First_Aid_for_the_USMLE_Step_1_2023_Compressed_-1-450

["230 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014PHARMACOKINETICS and Pharmacodynamics Drug metabolism Geriatric patients lose phase I first. Patients who are slow acetylators have \u008f\u00a0adverse effects from certain drugs because of \uf090\u00a0rate of metabolism (eg, isoniazid). Drugs can be metabolized by either or both phase 1 and phase 2 reactions. These reactions serve to bioactivate or deactivate substances, and do not have to take place sequentially (eg, phase I can follow phase II, or take place as a single reaction). Lipophilic drugs Polar drugs (water-soluble) Phase I Phase II (predominantly CYP450-dependent) Reactive oxygen metabolites Reduction Oxidation Hydrolysis Methylation Glucuronidation Acetylation Sulfation Slightly polar metabolite (active or inactive) Very polar, hydrophilic metabolite Reactive oxygen metabolites (except acetylated metabolite) Excretion Serum (urine, sweat), bile (stool) Elimination of drugs Rate of elimination is constant regardless of Cp Capacity-limited elimination. Zero-order (ie, constant amount of drug eliminated per PEA (a pea is round, shaped like the \u201c0\u201d in elimination unit time). Cp \u0090 linearly with time. Examples of drugs\u2014Phenytoin, Ethanol, and Aspirin (at zero-order). First-order elimination high or toxic concentrations). Flow-dependent elimination. Rate of first-order elimination is directly proportional to the drug concentration (ie, constant fraction of drug eliminated per unit time). Cp \u0090\u00a0exponentially with time. Applies to most drugs. Zero-order elimination First-order elimination Elimination rate (=slope) Elimination rate (=slope) 4 U\/h Drug plasma concentration2 U\/h Drug plasma concentration Time of t1\/2 is constant as concentration Time of t1\/2 as \u2191 concentration \u2191\u2191 2 U\/h 2 U\/h First t1\/2 > First t1\/2 = 2 U\/h 1 U\/h 0.5 U\/h Second t1\/2 > Second t1\/2 = Third t1\/2 Third t1\/2 Time (h) Time (h)","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014PHARMACOKINETICS and Pharmacodynamics SEC TION II 231 Urine pH and drug Ionized species are trapped in urine and cleared quickly. Neutral forms can be reabsorbed. elimination Weak acids Examples: phenobarbital, methotrexate, aspirin (salicylates). Trapped in basic environments. Treat overdose with sodium bicarbonate to alkalinize urine. Weak bases \tRCOOH\t\tRCOO\u2013 + H+ pKa \t (lipid soluble)\t\t (trapped) Examples: TCAs, amphetamines. Trapped in acidic environments. \tRNH3+\t \tRNH2 + H+ \t (trapped)\t\t (lipid soluble) TCA toxicity is initially treated with sodium bicarbonate to overcome the sodium channel-blocking activity of TCAs. This treats cardiac toxicity, but does not accelerate drug elimination. pH at which drugs (weak acid or base) are Ionized species formation (%) 100 Weak acid 50% ionized and 50% nonionized. The pKa 50 Weak base represents the strength of the weak acid or base. 04 8 12 14 pH pKa: 9.2 pKa = more acidic pKa = more basic uploaded by medbooksvn","232 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014PHARMACOKINETICS and Pharmacodynamics Efficacy vs potency Maximal effect a drug can produce. Represented by the y-value (Vmax). \u008f\u00a0y-value = \u008f\u00a0Vmax = Efficacy \u008f\u00a0efficacy. Unrelated to potency (ie, efficacious drugs can have high or low potency). Partial agonists have less efficacy than full agonists. % Maximal e ect RELATIVE EFFICACY 100 Vmax Drug A \u0394 E cacy 50 Vmax Drug B Potency 0 Log (drug dose) Amount of drug needed for a given effect. Represented by the x-value (EC50). Left shifting = \uf090\u00a0EC50 = \u008f\u00a0potency = \uf090\u00a0drug needed. Unrelated to efficacy (ie, potent drugs can have high or low efficacy). RELATIVE POTENCY 100 % Maximal e ect Drug A Drug B 50 \u0394 Potency EC = E ective concentration EC50 EC50 0 Log (drug dose)","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014PHARMACOKINETICS and Pharmacodynamics SEC TION II 233 Receptor binding 100 100 100 Agonist Agonist + Agonist Agonist Reduced A competitive e cacy antagonist B Reduced e cacy Partial agonist 50 Reduced 50 50 Partial agonist potency C Agonist + noncompetitive antagonist 0 0 0 Independent Agonist dose Agonist dose potency Agonist dose AGONIST WITH POTENCY EFFICACY REMARKS EXAMPLE A \u0007Competitive \u0090 No change Can be overcome by Diazepam (agonist) + flumazenil antagonist \u008f agonist concentration (competitive antagonist) on GABAA No change \u0090 receptor. B N\u0007 oncompetitive Cannot be overcome by antagonist Independent \u0090 \u008f agonist concentration Norepinephrine (agonist) + phenoxybenzamine (noncompetitive C \u0007Partial agonist Acts at same site as full antagonist) on \u03b1-receptors. (alone) agonist Morphine (full agonist) vs buprenorphine (partial agonist) at opioid \u03bc-receptors. Therapeutic index Measurement of drug safety. TITE: Therapeutic Index = TD50 \/ ED50. Safer drugs have higher TI values. Drugs with TEDD5500\u2002=\u2002mmedeidainaneftfoexcitcivdeodseose lower TI values frequently require monitoring Therapeutic window\u2014range of drug concentrations that can safely and effectively (eg, warfarin, theophylline, digoxin, treat disease. antiepileptic drugs, lithium; Warning! These drugs are lethal!). LD50 (lethal median dose) often replaces TD50 in animal studies. 100 E cacy Toxicity % of patients responding 50 Therapeutic index ED50 ED = E ective dose TD = Toxic dose TD50 0 Log (drug concentration) uploaded by medbooksvn","234 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014PHARMACOKINETICS and Pharmacodynamics Drug effect modifi ations TERM DEFINITION EXAMPLE Additive Effect of substances A and B together is equal to Aspirin and acetaminophen the sum of their individual effects \u201c2 + 2 = 4\u201d Cortisol on catecholamine responsiveness Permissive Presence of substance A is required for the full effects of substance B Clopidogrel with aspirin \u201c2 + 2 > 4\u201d Synergistic Effect of substances A and B together is greater Carbidopa only blocks enzyme to prevent than the sum of their individual effects peripheral conversion of levodopa Potentiation Similar to synergism, but drug B with no \u201c2 + 0 > 2\u201d therapeutic action enhances the therapeutic Morphine with naloxone action of drug A Repeat use of intranasal decongestant (eg, Antagonistic Effect of substances A and B together is less oxymetazoline) \u008e \u0090 therapeutic response (with than the sum of their individual effects rebound congestion) Tachyphylactic Acute decrease in response to a drug after initial\/repeated administration","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs SEC TION II 235 `\u2009PHARMACOLOGY\u2014AUTONOMIC DRUGS AUTONOMIC SOMATIC Autonomic receptors Sympathetic Parasympathetic Spinal cord Brainstem Preganglionic Preganglionic Voluntary neuron (long) neuron (short) motor nerve ACh ACh ACh ACh Nn Adrenal gland Sympathetic chain Nn ACh Blood (catecholamine transmission) Postganglionic Postganglionic NE NE Neuromuscular neuron (short) neuron (long) NE D Epi junction ACh ACh ACh M\u2081, M\u2082, M\u2083 M\u2083 \u03b11, \u03b12, \u03b21, \u03b22 \u03b11, \u03b12, \u03b21, D1 \u03b11, \u03b12, \u03b21, \u03b22 Nm Smooth muscle, Sweat glands Smooth muscle, Renal vasculature Cardiac muscle, Skeletal muscle gland cells, nerve gland cells, nerve smooth muscle vessels terminals, terminals, cardiac muscle cardiac muscle Pelvic splanchnic nerves and CNs III, VII, IX and X are part of the parasympathetic nervous system. Adrenal medulla is directly innervated by preganglionic sympathetic fibers. Sweat glands are part of the sympathetic pathway but are innervated by cholinergic fibers (sympathetic nervous system results in a \u201cchold\u201d sweat). Acetylcholine Nicotinic ACh receptors are ligand-gated channels allowing efflux of K+ and influx of Na+ and in receptors some cases Ca2+. Two subtypes: NN (found in autonomic ganglia, adrenal medulla) and NM (found in neuromuscular junction of skeletal muscle). Muscarinic ACh receptors are G-protein\u2013coupled receptors that usually act through 2nd messengers. 5 subtypes: M1\u20135 found in heart, smooth muscle, brain, exocrine glands, and on sweat glands (cholinergic sympathetic). uploaded by medbooksvn","236 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs Micturition control M\u2083-receptor Micturition center in pons regulates involuntary bladder function via Pelvic nerve Detrusor muscle coordination of sympathetic and (parasympathetic \u03b2\u2083-receptor parasympathetic nervous systems. \u03b1\u2081-receptor input) \u2295\u00a0sympathetic \u008e\u00a0\uf08f\u00a0urinary retention. \u2295\u00a0parasympathetic \u008e\u00a0\uf08f\u00a0urine voiding. Some autonomic drugs act on smooth muscle receptors to treat bladder dysfunction. Hypogastric nerve Internal urethral (sympathetic input) sphincter Pudendal nerve External urethral (somatic input) sphincter Nicotinic receptor DRUGS MECHANISM APPLICATIONS \u0007Muscarinic \u229d M3 receptor \u008e\u00a0relaxation of detrusor smooth muscle Urgency incontinence antagonists \u008e\u00a0\uf090\u00a0detrusor overactivity (eg,\u00a0oxybutynin) Urinary retention \u2295\u00a0M3 receptor \u008e\u00a0contraction of detrusor smooth M\u0007 uscarinic muscle \u008e\u00a0\uf08f\u00a0bladder emptying Urgency incontinence agonists BPH (eg,\u00a0bethanechol) \u2295\u00a0\u03b23 receptor \u008e\u00a0relaxation of detrusor smooth muscle \u008e\u00a0\uf08f\u00a0bladder capacity \u0007Sympathomimetics (eg, mirabegron) \u229d \u03b11-receptor \u008e\u00a0relaxation of smooth muscle (bladder neck, prostate) \u008e\u00a0\uf090\u00a0urinary obstruction \u0007\u03b11-blockers (eg,\u00a0tamsulosin) Tissue distribution of adrenergic receptors RECEPTOR TISSUE EFFECT(S) \u03b11 Vascular smooth muscle Vasoconstriction Visceral smooth muscle Smooth muscle contraction \u03b12 Pancreas Inhibition of insulin secretion Presynaptic terminals Inhibition of neurotransmitter release Inhibition of salivary secretion Salivary glands \uf08f heart rate, contractility \u03b21 Heart \uf08f renin secretion Kidney Bronchodilation \u03b22 Bronchioles \uf08f heart rate, contractility Cardiac muscle Glycogenolysis, glucose release Vasodilation Liver Stimulation of insulin secretion Arterial smooth muscle \uf08f lipolysis Pancreas \u03b23 Adipose","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs SEC TION II 237 G-protein\u2013linked second messengers RECEPTOR G-PROTEIN CLASS MAJOR FUNCTIONS Adrenergic \u2002\u2002\u03b11 q \u008f v\u0007 ascular smooth muscle contraction, \u008f pupillary dilator muscle contraction (mydriasis), \u008f intestinal and bladder sphincter muscle contraction \u2002\u2002\u03b12 i \u0090 s\u0007ympathetic (adrenergic) outflow, \u0090 insulin release, \u0090 lipolysis, \u008f platelet aggregation, \u0090\u00a0aqueous humor production \u2002\u2002\u03b21 s \u008f \u0007heart rate, \u008f contractility (one heart), \u008f renin release, \u008f lipolysis \u2002\u2002\u03b22 s Vasodilation, bronchodilation (two lungs), \u008f lipolysis, \u008f insulin release, \u008f\u00a0glycogenolysis, \u0090 uterine tone (tocolysis), \u008f\u00a0aqueous humor production, \u008f cellular K+ uptake \u2002\u2002\u03b23 s \u008f l\u0007ipolysis, \u008f\u00a0thermogenesis in skeletal muscle, \u008f bladder relaxation Cholinergic \u2002\u2002M1 q Mediates higher cognitive functions, stimulates enteric nervous system \u2002\u2002M2 i \u0090 heart rate and contractility of atria \u2002\u2002M3 q \u008f e\u0007 xocrine gland secretions, gut peristalsis, bladder contraction, bronchoconstriction, vasodilation, \u008f\u00a0pupillary sphincter muscle contraction (miosis), ciliary muscle contraction (accommodation) Dopamine \u2002\u2002D1 s Relaxes renal vascular smooth muscle, activates direct pathway of striatum \u2002\u2002D2 i Modulates transmitter release, especially in brain, inhibits indirect pathway of striatum Histamine \u2002\u2002H1 q \u008f b\u0007 ronchoconstriction, airway mucus production, \u008f vascular permeability\/vasodilation, pruritus \u008f g\u0007 astric acid secretion \u2002\u2002H2 s Vasopressin \u2002\u2002V1 q \u008f \u0007vascular smooth muscle contraction \u2002\u2002V2 s \u008f H\u0007 2O permeability and reabsorption via upregulating aquaporin-2 in collecting twobules (tubules) of kidney, \u008f reLligeanadse of vWF Extracellular H1, \u03b11, V1, M1, or M3 receptor space Ligand ExtracellCulealrl H1, \u03b11, V1, M1, or M3 receptor memsbprance CytoplaCsemll PIP2 DAG membrane Cytoplasm Gq protein PIP2 IP3 DAG Gq protein Phospholipase C CaI2P+3 Protein Phospholipase C kinase C SmcooonttrhCamcat2iu+osncle Protein kinase C Extracellular Ligand Smooth muscle space contraction B1, B2, B3, D1, H2, or V2 receptor M2, \u03b12, or D2 receptor ExtracellCulealrl Ligand M2, \u03b12, or D2 receptor memsbprance B1, B2, B3, D1, H2, or V2 receptor Gi protein Gi protein CytoplaCsemll Adenylyl Myosin light-chain kinase membrane cyclase (smooth muscle contraction) Myosin light-chain kinase Cytoplasm GS protein Adenylyl (smooth muscle contraction) cyclase ATP Cyclic AMP GS protein ATP Cyclic Protein AMP Ca2+ kinase A Ca2+ Protein kinase A uploaded by medbooksvn","238 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs Autonomic drugs Release of norepinephrine from a sympathetic nerve ending is modulated by NE itself, acting on presyn\u00adaptic \u03b12-autoreceptors \u008e\u00a0negative feedback. Amphetamines use the NE transporter (NET) to enter the presynaptic terminal, where they utilize the vesicular monoamine transporter (VMAT) to enter neurosecretory vesicles. This displaces NE from the vesicles. Once NE reaches a concentration threshold within the presynaptic terminal, the action of NET is reversed, and NE is expelled into the synaptic cleft, contributing to the characteristics and effects of \u008f\u00a0NE observed in patients taking amphetamines. Cholinergic Noradrenergic AXON Tyrosine AXON Tyrosine Choline Choline+ DOPA Acetyl-CoA Tetrabenazine Dopamine Release-modulating ChAT Ca2+ receptors - VMAT ACh AT II Ca2+ ACh + NE + \u03b12 Botulinum - toxin + Amphetamine, + - ephedrine Reuptake Choline Cocaine, TCAs, - NET feedback Acetate amphetamine Negative NE ACh Di usion, receptor metabolism - Adrenoreceptors \u03b1 or \u03b2 POSTSYNAPTIC MEMBRANE AChE inhibitors AChE POSTSYNAPTIC MEMBRANE represents transporters.","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs SEC TION II 239 Cholinomimetic Watch for exacerbation of COPD, asthma, and peptic ulcers in susceptible patients. agents DRUG ACTION APPLICATIONS Direct agonists Bethanechol Activates bladder smooth muscle; resistant Urinary retention. to AChE. Acts on muscarinic receptors; no nicotinic activity. \u201cBethany, call me to activate your bladder.\u201d Carbachol Carbon copy of acetylcholine (but resistant to Constricts pupil. Used for intraoperative miosis AChE). induction. Methacholine Stimulates muscarinic receptors in airway when Challenge test for diagnosis of asthma. inhaled. Pilocarpine Contracts ciliary muscle of eye (open-angle Potent stimulator of sweat, tears, and saliva glaucoma), pupillary sphincter (closed-angle Open-angle and closed-angle glaucoma, glaucoma); resistant to AChE, can cross blood- brain barrier. \u201cYou cry, drool, and sweat on xerostomia (Sj\u00f6gren syndrome). your \u2018pilow.\u2019\u2009\u201d Indirect agonists (anticholinesterases) Donepezil, \u008f ACh. 1st line for Alzheimer disease (Don Riva forgot rivastigmine, the gala). galantamine Neostigmine \u008f ACh. Postoperative and neurogenic ileus and Neo CNS = no CNS penetration due to positive urinary retention, myasthenia gravis, reversal of neuromuscular junction blockade charge. (postoperative). Pyridostigmine \u008f ACh; \u008f muscle strength. Does not penetrate Myasthenia gravis (long acting). Used with CNS. Pyridostigmine gets rid of myasthenia glycopyrrolate or hyoscyamine to control gravis. pyridostigmine adverse effects. Physostigmine \u008f ACh. Phreely (freely) crosses blood-brain Antidote for anticholinergic toxicity; barrier as not charged \u008e\u00a0CNS. physostigmine \u201cphyxes\u201d atropine overdose. Anticholinesterase Often due to organophosphates (eg, parathion) that irreversibly inhibit AChE. Organophosphates poisoning commonly used as insecticides; poisoning usually seen in farmers. Muscarinic effects Diarrhea, Urination, Miosis, Bronchospasm, DUMBBELSS. Nicotinic effects Bradycardia, Emesis, Lacrimation, Sweating, Reversed by atropine, a competitive inhibitor. Salivation. Atropine can cross BBB to relieve CNS CNS effects symptoms. Neuromuscular blockade (mechanism similar to Reversed by pralidoxime, regenerates AChE succinylcholine). via dephosphorylation if given early. Must be coadministered with atropine to prevent transient worsening of symptoms. Pralidoxime does not readily cross BBB. Respiratory depression, lethargy, seizures, coma. uploaded by medbooksvn","240 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs Muscarinic antagonists ORGAN SYSTEMS APPLICATIONS DRUGS Eye Produce mydriasis and cycloplegia Atropine, CNS Parkinson disease (\u201cpark my Benz\u201d) homatropine, GI, respiratory Acute dystonia tropicamide Parenteral: preoperative use to reduce airway Benztropine, secretions trihexyphenidyl Oral: reduces drooling, peptic ulcer Antispasmodics for irritable bowel syndrome Glycopyrrolate COPD, asthma Hyoscyamine, GI Duration: tiotropium > ipratropium dicyclomine Respiratory Reduce bladder spasms and urge urinary Genitourinary Ipratropium, incontinence (overactive bladder) tiotropium CNS Make bladder SOFT Solifenacin, Motion sickness Oxybutynin, Flavoxate, Tolterodine Scopolamine Atropine Muscarinic antagonist. Used to treat bradycardia and for ophthalmic applications. ORGAN SYSTEM ACTION NOTES Eye \u008f pupil dilation, cycloplegia Blocks muscarinic effects (DUMBBELSS) Airway of anticholinesterases, but not the nicotinic Stomach Bronchodilation, \u0090 secretions effects Gut Bladder \u0090 acid secretion Adverse effects: Hot as a hare ADVERSE EFFECTS \u0090 motility Fast as a fiddle Dry as a bone \u0090 urgency in cystitis Red as a beet Blind as a bat \u008f body temperature (due to \u0090 sweating); \u008f HR; Mad as a hatter dry mouth; dry, flushed skin; cycloplegia; Full as a flask constipation; disorientation Jimson weed (Datura) \u008e gardener\u2019s pupil Can cause acute angle-closure glaucoma (mydriasis) in older adults (due to mydriasis), urinary retention in men with prostatic hyperplasia, and hyperthermia in infants","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs SEC TION II 241 Sympathomimetics HEMODYNAMIC CHANGES APPLICATIONS DRUG SITE \u008f\u00a0HR (little effect) Albuterol for acute asthma\/COPD. Salmeterol for \u2013\/\u0090\u00a0BP, \u008f\u00a0HR, \u008f\u00a0CO serial (long-term) asthma\/COPD. Terbutaline Direct sympathomimetics for acute bronchospasm in asthma and tocolysis. Albuterol, salmeterol, \u03b22 > \u03b21 terbutaline Cardiac stress testing, acute decompensated heart failure (HF) with cardiogenic shock Dobutamine \u03b21 > \u03b22, \u03b1 (inotrope) Dopamine D1 = D2 > \u03b2 > \u03b1 \u008f\u00a0BP (high dose), \u008f\u00a0HR, Unstable bradycardia, shock; inotropic and Epinephrine \u008f\u00a0CO chronotropic effects at lower doses via \u03b2 effects; vasoconstriction at high doses via \u03b1 effects. \u03b2>\u03b1 \u008f\u00a0BP (high dose), \u008f\u00a0HR, \u008f\u00a0CO Anaphylaxis, asthma, shock, open-angle glaucoma; \u03b1 effects predominate at high Fenoldopam D1 \u0090\u00a0BP (vasodilation), \u008f\u00a0HR, doses. Stronger effect at \u03b22-receptor than \u008f\u00a0CO norepinephrine. Isoproterenol \u03b21 = \u03b22 \u0090\u00a0BP (vasodilation), \u008f\u00a0HR, Postoperative hypertension, hypertensive crisis. \u008f\u00a0CO Vasodilator (coronary, peripheral, renal, and splanchnic). Promotes natriuresis. Can cause Midodrine \u03b11 \u008f\u00a0BP (vasoconstriction), hypotension, tachycardia, flushing, headache. \u0090\u00a0HR, \u2013\/\u0090\u00a0CO Electrophysiologic evaluation of Mirabegron \u03b23 \u008f\u00a0BP, \u2013\/\u0090 HR (may have tachyarrhythmias. Can worsen ischemia. Has Norepinephrine \u03b11 > \u03b12 > \u03b21 minor reflexive change in negligible \u03b1 effect. response to \u008f BP due to \u03b11 Phenylephrine \u03b11 > \u03b12 agonism outweighing direct Autonomic insufficiency and postural \u03b21 chronotropic effect), hypotension. May exacerbate supine \u2013\/\u008f\u00a0CO hypertension. \u008f\u00a0BP (vasoconstriction), Urinary urgency or incontinence or overactive \u0090\u00a0HR, \u2013\/\u0090\u00a0CO bladder. Think \u201cmirab3gron.\u201d Indirect sympathomimetics Hypotension, septic shock. Amphetamine Indirect general agonist, reuptake inhibitor, also Hypotension (vasoconstrictor), ocular procedures releases stored catecholamines. (mydriatic), rhinitis (decongestant), ischemic priapism. Cocaine Indirect general agonist, reuptake inhibitor. Narcolepsy, obesity, ADHD. Causes vasoconstriction and local anesthesia. Causes mydriasis in eyes with intact sympathetic Caution when giving \u03b2-blockers if cocaine innervation \uf08e\u00a0used to confirm Horner intoxication is suspected (unopposed \u03b11 syndrome. activation \uf08e\u00a0\u008f\u2009\u008f\u2009\u008f\u00a0BP, coronary vasospasm). Nasal decongestion (pseudoephedrine), urinary Ephedrine Indirect general agonist, releases stored incontinence, hypotension. catecholamines. uploaded by medbooksvn","242 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs Physiologic effects of NE \u008f systolic and diastolic pressures as a result of \u03b11-mediated vasoconstriction \u008e\u00a0\u008f\u00a0mean arterial sympathomimetics pressure \u008e reflex bradycardia. However, isoproterenol (rarely used) has little \u03b1 effect but causes \u03b22-mediated vasodilation, resulting in \u0090 mean arterial pressure and \u008f\u00a0heart rate through \u03b21 and reflex activity. Norepinephrine (\u03b1 > \u03b2) Epinephrine (\u03b2 > \u03b1) Isoproterenol (\u03b21 \u02dc \u03b22) \u03b22 > \u03b11 Blood pressure Widened \u03b21 \u03b21 \u03b22 pulse \u03b21, re\ufb02ex tachycardia pressure Systolic \u03b11 MAP Diastolic Heart rate Re\ufb02ex bradycardia Peripheral resistance Unopposed \u03b11 CO \u2191 \u03b22 > \u03b11 Unopposed \u03b22 HR \u2191 CO \u2191 MAP \u2191\u2191 HR \u2191 CO \u2191\u2191 PP \u2191 \u2191MAP \u2191HR \u2191\u2191 \u2191 PP \u2191 MAP PP \u2191\u2191 Epinephrine Phenylephrine Before \u03b1-blockade After \u03b1-blockade Before \u03b1-blockade After \u03b1-blockade Blood pressure Net pressor Blood pressure Net pressor Net depressor \u03b11 e ect Systolic \u03b22 > \u03b11 Suppression of MAP Unopposed \u03b22 Diastolic Heart rate \u03b21 \u03b21, re\ufb02ex tachycardia Heart rate Re\ufb02ex bradycardia Time Time Epinephrine response exhibits reversal of mean arterial \t Phenylephrine response is suppressed but not reversed pressure from a net increase (the \u03b1 response) to a net \t\t because it is a \u201cpure\u201d \u03b1-agonist (lacks \u03b2-agonist decrease (the \u03b22 response).\t\t properties).","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs SEC TION II 243 Sympatholytics (\u03b12-agonists) ADVERSE EFFECTS DRUG APPLICATIONS CNS depression, bradycardia, hypotension, respiratory depression, miosis, rebound Clonidine, guanfacine Hypertensive urgency (limited situations), hypertension with abrupt cessation ADHD, Tourette syndrome, symptom control in opioid withdrawal Direct Coombs \u2295 hemolysis, drug-induced lupus, hyperprolactinemia \u03b1-methyldopa Hypertension in pregnancy Hypotension, weakness, xerostomia Tizanidine Relief of spasticity \u03b1-blockers APPLICATIONS ADVERSE EFFECTS DRUG Nonselective Phenoxybenzamine Irreversible. Pheochromocytoma (used Phentolamine preoperatively) to prevent catecholamine (hypertensive) crisis. Orthostatic hypotension, reflex tachycardia. Reversible. Given to patients on MAO inhibitors who eat tyramine-containing foods and for severe cocaine-induced hypertension (2nd line). Also used to treat norepinephrine extravasation. \u03b11 selective (-osin ending) Prazosin, terazosin, Urinary symptoms of BPH; PTSD (prazosin); 1st-dose orthostatic hypotension, dizziness, headache. doxazosin, hypertension (except tamsulosin). tamsulosin \u03b12 selective Depression. Sedation, \u008f serum cholesterol, \u008f appetite. Mirtazapine uploaded by medbooksvn","244 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs \u03b2-blockers Atenolol, betaxolol, bisoprolol, carvedilol, esmolol, labetalol, metoprolol, nadolol, nebivolol, propranolol, timolol. APPLICATION ACTIONS NOTES\/EXAMPLES Angina pectoris \u0090 heart rate and contractility \u008e\u00a0\u0090 O2 Glaucoma consumption Heart failure \u0090 production of aqueous humor Timolol Hypertension Blockade of neurohormonal stress \u008e\u00a0prevention Bisoprolol, carvedilol, metoprolol (\u03b2-blockers Hyperthyroidism\/ of deleterious cardiac remodeling curb mortality) thyroid storm \u008e\u00a0\u0090\u00a0mortality \u0090 cardiac output, \u0090 renin secretion (due to \u03b21- receptor blockade on JG cells) Symptom control (\u0090 heart rate, \u0090 tremor) Propranolol Hypertrophic \u0090 heart rate \u008e\u00a0\u008f\u00a0filling time, relieving Metoprolol, esmolol cardiomyopathy obstruction Myocardial infarction Nadolol, propranolol, carvedilol for no portal Supraventricular \u0090 O2 demand (short-term), \u0090 mortality (long- circulation tachycardia term) Variceal bleeding Use of \u03b2-blockers for acute cocaine-associated \u0090 AV conduction velocity (class II chest pain remains controversial due to ADVERSE EFFECTS antiarrhythmic) unsubstantiated concern for unopposed \u03b1-adrenergic stimulation SELECTIVITY \u0090 hepatic venous pressure gradient and portal hypertension (prophylactic use) Selective antagonists mostly go from A to M (\u03b21 with 1st half of alphabet) Erectile dysfunction, cardiovascular (bradycardia, AV block, HF), CNS (seizures, NonZelective antagonists mostly go from N to Z sleep alterations), dyslipidemia (metoprolol), (\u03b22 with 2nd half of alphabet) masked hypoglycemia, asthma\/COPD exacerbations Nonselective \u03b1- and \u03b2-antagonists have modified suffixes (instead of \u201c-olol\u201d) \u03b21-selective antagonists (\u03b21 > \u03b22)\u2014atenolol, betaxolol, bisoprolol, esmolol, metoprolol NebivOlol increases NO Nonselective antagonists (\u03b21 = \u03b22)\u2014nadolol, propranolol, timolol Nonselective \u03b1- and \u03b2-antagonists\u2014carvedilol, labetalol Nebivolol combines cardiac-selective \u03b21\u2011adrenergic blockade with stimulation of \u03b23\u2011receptors (activate NO synthase in the vasculature and \u0090\u00a0SVR)","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Autonomic Drugs SEC TION II 245 Phosphodiesterase Phosphodiesterase (PDE) inhibitors inhibit PDE, which catalyzes the hydrolysis of cAMP and\/or inhibitors cGMP, and thereby increase cAMP and\/or cGMP. These inhibitors have varying specificity for PDE isoforms and thus have different clinical uses. TYPE OF INHIBITOR MECHANISM OF ACTION CLINICAL USES ADVERSE EFFECTS Nonspecific PDE \u0090\u00a0cAMP hydrolysis \u008e\u00a0\u008f\u00a0cAMP COPD\/asthma (rarely used) Cardiotoxicity (eg, tachycardia, inhibitor \u008e\u00a0bronchial smooth muscle arrhythmia), neurotoxicity Theophylline relaxation \u008e\u00a0bronchodilation (eg, seizures, headache), abdominal pain PDE-5 inhibitors \u0090\u00a0hydrolysis of cGMP Erectile dysfunction Facial flushing, headache, Sildenafil, vardenafil, \u008e\u00a0\u008f\u00a0cGMP \u008e\u00a0\u008f\u00a0smooth Pulmonary hypertension dyspepsia, hypotension in tadalafil, avanafil muscle relaxation by Benign prostatic hyperplasia patients taking nitrates; \u201chot enhancing NO activity and sweaty,\u201d then headache, \u008e\u00a0pulmonary vasodilation (tadalafil only) heartburn, hypotension and \u008f\u00a0blood flow in corpus cavernosum fills the penis Sildenafil only: cyanopia (blue- tinted vision) via inhibition of PDE-6 (six) in retina PDE-4 inhibitor \u008f cAMP in neutrophils, Severe COPD Abdominal pain, weight loss, Roflumilast granulocytes, and bronchial depression, anxiety, insomnia epithelium PDE-3 inhibitor In cardiomyocytes: Acute decompensated HF with Tachycardia, ventricular Milrinone \u008f\u00a0cAMP \u008e\u00a0\u008f\u00a0Ca2+ influx cardiogenic shock (inotrope) arrhythmias, hypotension \u008e\u00a0\u008f\u00a0ionotropy and chronotropy In vascular smooth muscle: \u008f\u00a0cAMP \u008e\u00a0MLCK inhibition \u008e\u00a0vasodilation \u008e\u00a0\u0090\u00a0preload and afterload \u201cPlatelet inhibitors\u201d In platelets: \u008f\u00a0cAMP Intermittent claudication Nausea, headache, facial Cilostazola \u008e\u00a0inhibition of platelet Stroke or TIA prevention (with flushing, hypotension, Dipyridamoleb aggregation abdominal pain aspirin) Cardiac stress testing (dipyridamole only, due to coronary vasodilation) Prevention of coronary stent restenosis aCilostazol is a PDE-3 inhibitor, but due to its indications is categorized as a platelet inhibitor together with dipyridamole. bDipyridamole is a nonspecific PDE inhibitor, leading to inhibition of platelet aggregation. It also prevents adenosine reuptake by platelets \u008e\u00a0\u008f\u00a0extracellular adenosine \u008e\u00a0\u008f\u00a0vasodilation. uploaded by medbooksvn","246 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Toxicities and ADVERSE Effects `\u2009PHARMACOLOGY\u2014TOXICITIES AND ADVERSE EFFECTS Ingested seafood Toxin actions include histamine release, total block of Na+ channels, or opening of Na+ channels to toxins cause depolarization. TOXIN SOURCE ACTION SYMPTOMS TREATMENT Histamine Spoiled dark-meat Bacterial histidine Mimics anaphylaxis: oral Antihistamines (scombroid fish such as tuna, decarboxylase converts burning sensation, facial Albuterol +\/\u2013 poisoning) mahi-mahi, histidine to histamine flushing, erythema, mackerel, and urticaria, itching; may epinephrine Tetrodotoxin bonito Frequently progress to bronchospasm, misdiagnosed as fish angioedema, hypotension Supportive Ciguatoxin Pufferfish allergy Nausea, diarrhea, Supportive Reef fish such as Binds fast voltage-gated paresthesias, weakness, barracuda, snapper, Na+ channels in nerve dizziness, loss of reflexes and moray eel tissue, preventing depolarization Nausea, vomiting, diarrhea; perioral numbness; Opens Na+ channels, reversal of hot and cold causing depolarization sensations; bradycardia, heart block, hypotension Age-related changes in Aging alters the passage of drugs through the body and standard doses can result in \u008f plasma pharmacokinetics concentrations. Older patients often require reduced doses to prevent toxicity. \u0083\t Absorption\u2014mostly unaffected. \u0083\t Distribution\u2014\u0090 total body water (\u0090 Vd of hydrophilic drugs \u008e \u008f concentration), \u008f total body fat (\u008f Vd of lipophilic drugs \u008e \u008f half-life). \u0083\t Metabolism\u2014\u0090 hepatic mass and blood flow \u008e \u0090 first-pass metabolism, \u0090 hepatic clearance. Phase I of drug metabolism is decreased; phase II is relatively preserved. \u0083\t Excretion\u2014\u0090 renal mass and blood flow (\u0090 GFR) \u008e \u0090 renal clearance.","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Toxicities and ADVERSE Effects SEC TION II 247 Specific oxicity TOXIN TREATMENT treatments Acetaminophen N-acetylcysteine (replenishes glutathione) AChE inhibitors, organophosphates Antimuscarinic, anticholinergic agents Atropine > pralidoxime Arsenic Physostigmine (crosses BBB), control Benzodiazepines hyperthermia \u03b2-blockers Carbon monoxide Dimercaprol, succimer Copper Flumazenil Cyanide Atropine, glucagon, saline Dabigatran Digoxin 100% O2, hyperbaric O2 Direct factor Xa inhibitors (eg, apixaban) \u201cPenny\u201dcillamine (penicillamine), trientine Heparin Iron (Fe) (3\u00a0copper pennies) Lead Hydroxocobalamin, nitrites + sodium Mercury thiosulfate Methanol, ethylene glycol (antifreeze) Methemoglobin Idarucizumab Methotrexate Opioids Digoxin-specific antibody fragments Salicylates TCAs Andexanet alfa Warfarin Protamine sulfate Deferoxamine, deferasirox, deferiprone Penicillamine, calcium disodium EDTA, Dimercaprol, Succimer, (correct lead poisoning in PEDS patients) Dimercaprol, succimer Fomepizole > ethanol, dialysis Methylene blue, vitamin C (reducing agent) Leucovorin Naloxone NaHCO3 (alkalinize urine), dialysis NaHCO3 (stabilizes cardiac cell membrane) Vitamin K (delayed effect), PCC (prothrombin complex concentrate)\/FFP (immediate effect) Drug reactions\u2014cardiovascular DRUG REACTION CAUSAL AGENTS Coronary vasospasm Cocaine, Amphetamines, Sumatriptan, Ergot alkaloids (CASE) Cutaneous flus ing Vancomycin, Adenosine, Niacin, Ca2+ channel blockers, Echinocandins, Nitrates (flushed from VANCEN [dancing]) Vancomycin infusion reaction (formerly called red man syndrome)\u2014rate-dependent infusion reaction to vancomycin causing widespread pruritic erythema due to histamine release. Manage with diphenhydramine, slower infusion rate. Dilated cardiomyopathy Alcohol, anthracycline (eg, doxorubicin, daunorubicin; prevent with dexrazoxane), trastuzumab Torsades de pointes Agents that prolong QT interval: antiArrhythmics (class IA, III), antiBiotics (eg, macrolides, fluoroquinolones), anti\u201cC\u201dychotics (eg, ziprasidone), antiDepressants (eg, TCAs), antiEmetics (eg, ondansetron), antiFungals (eg, fluconazole) (ABCDEF) uploaded by medbooksvn","248 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Toxicities and ADVERSE Effects Drug reactions\u2014endocrine\/reproductive DRUG REACTION CAUSAL AGENTS NOTES Adrenocortical HPA suppression 2\u00b0 to glucocorticoid The people need High glucose insufficiency withdrawal Presents with hypogonadism (eg, infertility, Diabetes insipidus Lithium, demeclocycline amenorrhea, erectile dysfunction) and galactorrhea Gynecomastia Ketoconazole, cimetidine, spironolactone, I am lethargic GnRH analogs\/antagonists, androgen receptor Can\u2019t Concentrate Serum Sodium inhibitors, 5\u03b1-reductase inhibitors Hot flashes SERMs (eg, tamoxifen, clomiphene, raloxifene) Hyperglycemia Tacrolimus, protease inhibitors, niacin, HCTZ, glucocorticoids Hyperprolactinemia Typical antipsychotics (eg, haloperidol), atypical antipsychotics (eg, risperidone), metoclopramide, methyldopa, verapamil Hyperthyroidism Amiodarone, iodine, lithium Hypothyroidism Amiodarone, lithium SIADH Carbamazepine, Cyclophosphamide, SSRIs Drug reactions\u2014gastrointestinal DRUG REACTION CAUSAL AGENTS NOTES Acute cholestatic Macrolides (eg, erythromycin) hepatitis, jaundice Constipation Antimuscarinics (eg, atropine), antipsychotics, opioids, non-dihydropyridine CCBs, ranolazine, amiodarone, aluminum hydroxide, loperamide, 5HT3 receptor antagonist (ondansetron), vincristine Diarrhea Acamprosate, antidiabetic agents (acarbose, metformin, pramlintide), colchicine, cholinesterase inhibitors, lipid-lowering agents (eg, ezetimibe, orlistat), macrolides (eg, erythromycin), SSRIs, chemotherapy (eg, irinotecan) Focal to massive Amanita phalloides (death cap mushroom), hepatic necrosis valproate, acetaminophen Hepatitis Rifampin, isoniazid, pyrazinamide, statins, fibrates Pancreatitis Diuretics (eg, furosemide, HCTZ), Drugs generate a violent abdominal distress glucocorticoids, alcohol, valproate, azathioprine Medication-induced Potassium chloride, NSAIDs, bisphosphonates, Usually occurs at anatomic sites of esophageal esophagitis ferrous sulfate, tetracyclines narrowing (eg, near level of aortic arch); caustic effect minimized with upright posture Pills Not beneficial for food tube and adequate water ingestion Pseudomembranous Ampicillin, cephalosporins, clindamycin, Antibiotics predispose to superinfection by colitis fluoroquinolones, PPIs resistant C difficile","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Toxicities and ADVERSE Effects SEC TION II 249 Drug reactions\u2014hematologic DRUG REACTION CAUSAL AGENTS NOTES Agranulocytosis Dapsone, clozapine, carbamazepine, Drugs can cause pretty major granulocytes propylthiouracil, methimazole, ganciclovir, collapse colchicine Can\u2019t make New blood cells properly Aplastic anemia Carbamazepine, methimazole, NSAIDs, P Diddy Coombs benzene, chloramphenicol, propylthiouracil DRESS is a delayed (type IV) hypersensitivity Direct Coombs \u2295 Penicillin, methylDopa, Cephalosporins reaction hemolytic anemia DRESSes partially cover my skin and viscera Drug Reaction with Phenytoin, carbamazepine, minocycline, sulfa You\u2019re having a mega blast with PMS Eosinophilia and drugs, allopurinol, vancomycin Systemic Symptoms Estrogen-mediated adverse effect Gray baby syndrome Chloramphenicol Hemolysis in G6PD Sulfonamides, dapsone, primaquine, aspirin, deficiency nitrofurantoin Megaloblastic anemia Hydroxyurea, Phenytoin, Methotrexate, Sulfa drugs Thrombocytopenia Heparin, quinidine, ganciclovir, vancomycin, linezolid Thrombotic Combined oral contraceptives, hormone complications replacement therapy, SERMs, epoetin alfa Drug reactions\u2014musculoskeletal\/skin\/connective tissue DRUG REACTION CAUSAL AGENTS NOTES Drug-induced lupus Hydralazine, procainamide, quinidine Fat protects glutes Can Cause puffy gums Fat redistribution Protease inhibitors, glucocorticoids Painful tophi and feet need care Gingival hyperplasia Cyclosporine, Ca2+ channel blockers, phenytoin Sat For photo Steven Johnson has epileptic allergy to sulfa Hyperuricemia (gout) Pyrazinamide, thiazides, furosemide, niacin, cyclosporine drugs and penicillin Teethracyclines Myopathy Statins, fibrates, niacin, colchicine, daptomycin, hydroxychloroquine, interferon-\u03b1, penicillamine, glucocorticoids Osteoporosis Glucocorticoids, depot medroxyprogesterone acetate, GnRH agonists, aromatase inhibitors, anticonvulsants, heparin, PPIs Photosensitivity Sulfonamides, amiodarone, tetracyclines, 5-FU Rash (Stevens-Johnson Anti-epileptic drugs (especially lamotrigine), syndrome) allopurinol, sulfa drugs, penicillin Teeth discoloration Tetracyclines Tendon\/cartilage Fluoroquinolones damage uploaded by medbooksvn","250 SEC TION II Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Toxicities and ADVERSE Effects Drug reactions\u2014neurologic DRUG REACTION CAUSAL AGENTS NOTES Cinchonism Quinidine, quinine Can present with tinnitus, hearing\/vision loss, psychosis, and cognitive impairment Parkinson-like Antipsychotics, metoclopramide syndrome Cogwheel rigidity of arm Peripheral neuropathy Platinum agents (eg, cisplatin), isoniazid, vincristine, paclitaxtel, phenytoin Cis, it\u2019s very painful peripherally Idiopathic intracranial hypertension Vitamin A, growth hormones, tetracyclines Always grow head tension Seizures Isoniazid, bupropion, imipenem\/cilastatin, With seizures, I bit my tongue Tardive dyskinesia tramadol Visual disturbances These horrible drugs iirritate Precious eyes Antipsychotics, metoclopramide Topiramate (blurred vision\/diplopia, haloes), hydroxychloroquine (\u0090\u00a0visual acuity, visual field defects), digoxin (yellow-tinged vision), isoniazid (optic neuritis), ivabradine (luminous phenomena), PDE-5 inhibitors (blue-tinged vision), ethambutol (color vision changes) Drug reactions\u2014renal\/genitourinary DRUG REACTION CAUSAL AGENTS NOTES Fanconi syndrome Cisplatin, ifosfamide, expired tetracyclines, Prevent by coadministering with mesna tenofovir Remember the 5 P\u2019s Hemorrhagic cystitis Cyclophosphamide, ifosfamide Interstitial nephritis Diuretics (Pee), NSAIDs (Pain-free), Penicillins and cephalosporins, PPIs, rifamPin, sulfa drugs Drug reactions\u2014respiratory DRUG REACTION CAUSAL AGENTS NOTES Dry cough ACE inhibitors My nose cannot breathe bad air Pulmonary fibrosis Methotrexate, nitrofurantoin, carmustine, bleomycin, busulfan, amiodarone Drug reactions\u2014multiorgan DRUG REACTION CAUSAL AGENTS NOTES Antimuscarinic Atropine, TCAs, H1-blockers, antipsychotics Sorry pals, can\u2019t go mingle Disulfi am-like reaction 1st-generation sulfonylureas, procarbazine, Listen cis, always adjust vancomycin in CKD. certain cephalosporins, griseofulvin, Cisplatin toxicity may respond to amifostine metronidazole Nephrotoxicity\/ Loop diuretics, cisplatin, aminoglycosides, ototoxicity amphotericin, vancomycin","Pharmacology\u2003 \uf07d\u2009PHARMACOLOGY\u2014Toxicities and ADVERSE Effects SEC TION II 251 Drugs affecting pupil \u008f pupil size (mydriasis) \u0090 pupil size (miosis) size Anticholinergics (eg, atropine, TCAs, Sympatholytics (eg, \u03b12-agonists) tropicamide, scopolamine, antihistamines) Opioids (except meperidine) Parasympathomimetics (eg, pilocarpine), Indirect sympathomimetics (eg, amphetamines, cocaine, LSD), meperidine organophosphates Direct sympathomimetics Radial muscleRacdoinatlrmacutisocnle contraction Sphincter muSspclheinccotnetrrmacutisocnle contraction (\u03b11 receptor m(\u03b1e1drieatceedp)tor mediated) (M3 receptor m(Me3drieatceedp)tor mediated) Cytochrome P-450 Inducers (+) Substrates Inhibitors (\u2013) interactions (selected) St. John\u2019s wort Theophylline Sodium valproate Phenytoin OCPs Isoniazid Phenobarbital Anti-epileptics Cimetidine Modafinil Warfarin Ketoconazole Nevirapine Fluconazole Rifampin Acute alcohol overuse Griseofulvin Chloramphenicol Carbamazepine Erythromycin\/clarithromycin Chronic alcohol overuse Sulfonamides Ciprofloxacin St. John\u2019s funny funny (phen- The OCPs are anti-war Omeprazole phen) mom never refuses Amiodarone greasy carbs and chronic Ritonavir alcohol Grapefruit juice SICK FACES come when I am really drinking grapefruit juice Sulfa drugs Sulfonamide antibiotics, Sulfasalazine, Scary Sulfa Pharm FACTS Probenecid, Furosemide, Acetazolamide, Celecoxib, Thiazides, Sulfonylureas. Patients with sulfa allergies may develop fever, urinary tract infection, Stevens- Johnson syndrome, hemolytic anemia, thrombocytopenia, agranulocytosis, acute interstitial nephritis, and urticaria (hives), and photosensitivity. uploaded by medbooksvn","252 SEC TION II Pharmacology\u2003 \uf07d\u2009pharmacology\u2014Miscellaneous ` \u2009P H A R M A C O LO G Y \u2014 M I S C E L L A N E O U S Drug names CATEGORY EXAMPLE ENDING NS5A inhibitor Ledipasvir Antiparasitic\/antihelminthic Mebendazole Antimicrobial NS5B inhibitor Sofosbuvir -asvir Transpeptidase inhibitor Ampicillin -bendazole Ergosterol synthesis inhibitor Ketoconazole -buvir Protein synthesis inhibitor Tetracycline -cillin Fluoroquinolone Ciprofloxacin -conazole Neuraminidase inhibitor Oseltamivir -cycline Protease inhibitor Ritonavir -floxacin Viral DNA polymerase inhibitor Acyclovir -mivir NS3\/4A inhibitor\t Grazoprevir -navir Integrase inhibitor Dolutegravir -ovir Macrolide Azithromycin -previr -tegravir Recombinant uricase Rasburicase -thromycin Nitrosourea Carmustine Antineoplastic Platinum compound Cisplatin -case Topoisomerase II inhibitor Etoposide -mustine Anthracycline Doxorubicin -platin Taxane Paclitaxel -poside Topoisomerase I inhibitor Irinotecan -rubicin -taxel Inhaled anesthetic Sevof lurane -tecan Atypical antipsychotic Quetiapine, risperidone CNS Typical antipsychotic Thioridazine -flurane Barbiturate Phenobarbital -apine, -idone VMAT inhibitor Tetrabenazine -azine Local anesthetic Lidocaine -barbital COMT inhibitor Entacapone -benazine Nondepolarizing neuromuscular blocker Atracurium, pancuronium -caine MAO-B inhibitor Selegiline -capone TCA Imipramine, amitriptyline -curium, -curonium 5-HT1B\/1D agonist Sumatriptan -giline Benzodiazepine Diazepam, alprazolam -ipramine, -triptyline -triptan -zepam, -zolam","Pharmacology\u2003 \uf07d\u2009pharmacology\u2014Miscellaneous SEC TION II 253 Drug names (continued) ENDING CATEGORY EXAMPLE Autonomic Bethanechol Propranolol -chol Cholinergic agonist Neostigmine Albuterol -olol \u03b2-blocker Prazosin -stigmine AChE inhibitor Sildenafil Amlodipine -terol \u03b22-agonist Enoxaparin -zosin \u03b11-blocker Alteplase Cardiovascular Captopril Losartan -afil PDE-5 inhibitor Apixaban -dipine Dihydropyridine Ca2+ channel blocker Dapagliflozin Repaglinide -parin Low-molecular-weight heparin Sitagliptin Pioglitazone -plase Thrombolytic Liraglutide Lovastatin -pril ACE inhibitor Lumacaftor -sartan Angiotensin-II receptor blocker Alendronate Montelukast -xaban Direct factor Xa inhibitor Flutamide Aprepitant Metabolic Omeprazole Latanoprost -gliflozin SGLT-2 inhibitor Bosentan Ondansetron -glinide Meglitinide Finasteride Loratadine -gliptin DPP-4 inhibitor Cimetidine Anastrozole -glitazone PPAR-\u03b3 activator Tolvaptan -glutide GLP-1 analog -statin HMG-CoA reductase inhibitor Other -caftor CFTR modulator -dronate Bisphosphonate -lukast CysLT1 receptor blocker -lutamide Androgen receptor inhibitor -pitant NK1 blocker -prazole Proton pump inhibitor -prost Prostaglandin analog -sentan Endothelin receptor antagonist -setron 5-HT3 blocker -steride 5\u03b1-reductase inhibitor -tadine H1-antagonist -tidine H2-antagonist -trozole Aromatase inhibitor -vaptan ADH antagonist uploaded by medbooksvn","254 SEC TION II Pharmacology\u2003 \uf07d\u2009pharmacology\u2014Miscellaneous Biologic agents ENDING CATEGORY EXAMPLE Monoclonal antibodies (-mab)\u2014target overexpressed cell surface receptors -ximab Chimeric human-mouse monoclonal antibody Rituximab -zumab Humanized monoclonal antibody Bevacizumab -umab Human monoclonal antibody Denosumab Small molecule inhibitors (-ib)\u2014target intracellular molecules -ciclib Cyclin-dependent kinase inhibitor Palbociclib -coxib COX-2 inhibitor Celecoxib -parib Poly(ADP-ribose) polymerase inhibitor Olaparib -rafenib BRAF inhibitor Vemurafenib -tinib Tyrosine kinase inhibitor Imatinib -zomib Proteasome inhibitor Bortezomib Interleukin receptor modulators (-kin)\u2014agonists and antagonists of interleukin receptors -leukin Interleukin-2 agonist\/analog Aldesleukin -kinra Interleukin receptor antagonist Anakinra","HIGH-YIELD PRINCIPLES IN Public Health Sciences \u201cMedicine is a science of uncertainty and an art of probability.\u201d `\tEpidemiology and \u2014Sir William Osler Biostatistics\t 256 \u201cOf all forms of discrimination and inequalities, injustice in health is the `\tEthics\t 267 most shocking and inhuman.\u201d `\tCommunication 270 \u2014Martin Luther King, Jr. Skills\t \u201cPeople will forget what you said, people will forget what you did, but `\tHealthcare Delivery\t 275 people will never forget how you made them feel.\u201d `\tQuality and Safety\t 277 \u2014Maya Angelou \u201cOn a long enough timeline, the survival rate for everyone drops to zero.\u201d \u2014Chuck Palahniuk, Fight Club A heterogenous mix of epidemiology, biostatistics, ethics, law, healthcare delivery, patient safety, quality improvement, and more falls under the heading of public health sciences. Biostatistics and epidemiology are the foundations of evidence-based medicine and are very high yield. Make sure you can quickly apply biostatistical equations such as sensitivity, specificity, and predictive values in a problem-solving format. Also, know how to set up your own 2 \u00d7 2 tables, and beware questions that switch the columns. Quality improvement and patient safety topics were introduced a few years ago on the exam and represent trends in health system science. Medical ethics questions often require application of principles. Typically, you are presented with a patient scenario and then asked how you would respond. In this edition, we provide further details on communication skills and patient care given their growing emphasis on the exam. Effective communication is essential to the physician- patient partnership. Physicians must seek opportunities to connect with patients, understand their perspectives, express empathy, and form shared decisions and realistic goals. 255 uploaded by medbooksvn","256 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics `\u2009PUBLIC HEALTH SCIENCES\u2014EPIDEMIOLOGY AND BIOSTATISTICS Observational studies DESIGN MEASURES\/EXAMPLE STUDY TYPE Describes several individual patients with the Description of clinical findings and symptoms. same diagnosis, treatment, or outcome. Has no comparison group, thus cannot show Case series risk factor association with disease. Cross-sectional study Frequency of disease and frequency of risk- Case-control study related factors are assessed in the present. Disease prevalence. Can show risk factor association with disease, Cohort study Asks, \u201cWhat is happening?\u201d but does not establish causality. Twin concordance Retrospectively compares a group of people with Odds ratio (OR). study disease to a group without disease. Control the case in the OR. Adoption study Patients with COPD had higher odds of a Ecological study Looks to see if odds of prior exposure or risk factor differ by disease state. smoking history than those without COPD. Asks, \u201cWhat happened?\u201d Disease incidence. Relative risk (RR). Compares a group with a given exposure or risk People who smoke had a higher risk of factor to a group without such exposure. developing COPD than people who do not. Looks to see if exposure or risk factor is Cohort = relative risk. associated with later development of disease. Measures heritability and influence of Can be prospective or retrospective, but risk environmental factors (\u201cnature vs nurture\u201d). factor has to be present prior to disease development. Measures heritability and influence of environmental factors. Compares the frequency with which both monozygotic twins vs both dizygotic twins Used to monitor population health. develop the same disease. COPD prevalence was higher in more polluted Compares behavioral traits\/genetics in siblings cities. raised by biological vs adoptive parents. Compares frequency of disease and frequency of risk-related factors across populations. Measures population data not necessarily applicable to individuals (ecological fallacy). Cross-sectional study Case-control study Retrospective cohort study Prospective cohort study Past Compare risk factor Risk factor Risk factor frequency Present Risk factor Risk factor Controls Diseased Compare disease Risk factor Risk factor without cases incidence Compare disease disease Compare disease prevalence Review previous incidence records Future","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics SECTION II 257 Clinical therapeutic Experimental study involving humans. Compares therapeutic benefits of \u2265 2 interventions (eg, trial treatment vs placebo, treatment vs treatment). Study quality improves when clinical trial is randomized, controlled, and double-blinded (ie, neither subject nor researcher knows whether the subject is in the treatment or control group). Triple-blind refers to additional blinding of the researchers analyzing the data. Crossover clinical trial\u2014compares the effect of a series of \u2265 2 treatments on a subject. Order in which subjects receive treatments is randomized. Washout period occurs between treatments. Allows subjects to serve as their own controls. Intention-to-treat analysis\u2014all subjects are analyzed according to their original, randomly assigned treatment. No one is excluded. Attempts to avoid bias from attrition, crossover, and nonrandom noncompliance, but may dilute the true effects of intervention. As-treated analysis\u2014all subjects are analyzed according to the treatment they actually received. \u008f risk of bias. Per-protocol analysis\u2014subjects who fail to complete treatment as originally, randomly assigned are excluded. \u008f risk of bias. Clinical trials occur after preclinical studies and consist of five phases (\u201cCan I SWIM?\u201d). FDA approval Preclinical Phase 0 Phase 1 Phase 2 Phase 3 Phase 4 Test drug in lab animals Initial pharmacokinetic and Safety assessment via dose E cacy assessment (does it E ectiveness assessment via Provides data on long-tern or and in vitro experiments pharmacodynamic assessment via Work?) Provides additional comparison with current standard of rare adverse e ects (can it microdosing. Often skipped. escalation. Determine care\/placebo (any Improvement?) maximum tolerable dose. data on short-term stay on the Market?) adverse e ects. ? ? Sample Very small number of healthy Small number of healthy Moderate number of patients with Large number of patients with Postmarketing surveillance of volunteers or patients volunteers or patients disease of interest. Randomized, disease of interest. Randomized, patients with disease of interest. with disease of interest. with disease of interest. Open label. controlled, anonymized. controlled, anonymized. Open label. Open label. Off-label drug use Use of a drug to treat a disease in a form, population group, or dosage that is not specifically approved by the FDA. Reasons for off-label use include treatment of an illness with no approved pharmacologic treatment or exploring alternative treatments after failure of approved options. Example: use of tricyclic antidepressants for treating neuropathic\/chronic pain. Bradford Hill criteria A group of principles that provide limited support for establishing evidence of a causal relationship between presumed cause and effect. Strength Association does not necessarily imply causation, but the stronger the association, the more Consistency evidence for causation. Specificity Temporality Repeated observations of the findings in multiple distinct samples. Biological gradient The more specific the presumed cause is to the effect, the stronger the evidence for causation. Plausibility The presumed cause precedes the effect by an expected amount of time. Coherence Greater effect observed with greater exposure to the presumed cause (dose-response relationship). Experiment A conceivable mechanism exists by which the cause may lead to the effect. Analogy The presumed cause and effect do not conflict with existing scientific consensus. Empirical evidence supporting the presumed cause and effect (eg, animal studies, in vitro studies). The presumed cause and effect are comparable to a similar, established cause and effect. uploaded by medbooksvn","Odds ratio = a\/c = ad b\/d bc 258 SECTION II Public Health Sciences\u2003 \uf07d \u2009P U B L I C HEALTH S C I E N C E S \u2014RelEaptiivedreismk =io a\/(a + b) d B i o statistics lc\/o(cg+yd)an Attributable risk = a c a+b c+d Quantifying risk Definitions and formulas are based on the classic Disease or outcome 2 \u00d7 2 or contingency table. Exposure ab or intervention cd TERM DEFINITION EXAMPLE FORMULA Odds ratio Typically used in case-control If in a case-control study, 20\/30 patients O\t\tR = a\/c =\u2002 ad studies. Represents the odds of with lung cancer and 5\/25 healthy b\/d bc Relative risk exposure among cases (a\/c) vs odds individuals report smoking, the OR is of exposure among controls (b\/d). 8; so the patients with lung cancer are a b Relative risk 8 times more likely to have a history of 20 5 reduction OR = 1 \u008e\u00a0odds of exposure are smoking. equal in cases and controls. c d Attributable You take a case to the OR. 10 20 risk OR > 1 \u008e\u00a0odds of exposure are greater in cases. If 5\/10 people exposed to radiation are \tR\tR = a\/(a + b) Absolute diagnosed with cancer, and 1\/10 people c\/(c + d) risk OR < 1 \u008e\u00a0odds of exposure are not exposed to radiation are diagnosed reduction greater in controls. with cancer, the RR is 5; so people a b Number exposed to radiation have a 5 times 5 5 needed to Typically used in cohort studies. greater risk of developing cancer. treat Risk of developing disease in the c d Number exposed group divided by risk in For rare diseases (low prevalence), OR 1 9 needed to the unexposed group. approximates RR. harm R\t\tRR =\t(ARCAR\u2013CA\tRT) Case fatality RR = 1 \u008e\u00a0no association between If 2% of patients who receive a flu rate exposure and disease. shot develop the flu, while 8% of \tA\tR = \t a\t \u2212 c c d unvaccinated patients develop the flu, a +b + RR > 1 \u008e\u00a0exposure associated with then RR = 2\/8 = 0.25, and RRR = 0.75. \u008f\u00a0disease occurrence. \tA\tR% = \u2009\tRR \u2212 1\u2009 \u00d7 100 If risk of lung cancer in people who RR RR < 1 \u008e\u00a0exposure associated with smoke is 21% and risk in people who \u0090\u00a0disease occurrence. don\u2019t smoke is 1%, then the attributable \tA\tRR = \t\t c\t d \u2212 a a b risk is 20%. c + + The proportion of risk reduction attributable to the intervention If 8% of people who receive a placebo NNT = 1\/ARR (ARI) as compared to a control vaccine develop the flu vs 2% of people (ARC). who receive a flu vaccine, then ARR = NNH = 1\/AR 8%\u20132% = 6% = 0.06. The difference in risk between C\t\tFR% = \u2009deaths\u2009 \u00d7 100 exposed and unexposed groups. If 4 patients die among 10 cases of cases meningitis, case fatality rate is 40%. The difference in risk (not the proportion) attributable to the intervention as compared to a control. Number of patients who need to be treated for 1 patient to benefit. Lower number = better treatment. Number of patients who need to be exposed to a risk factor for 1 patient to be harmed. Higher number = safer exposure. Percentage of deaths occurring among those with disease.","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics SECTION II 259 Quantifying risk (continued) TERM DEFINITION EXAMPLE FORMULA Mortality Number of deaths (in general or If 80 people in a town of 10,000 die over Deaths\/1000 people per rate due to specific cause) within a 2 years, mortality rate is 4 per 1000 per year. population over a defined period. year. People who become ill Attack rate Proportion of exposed people who If 80 people in a town are exposed and \t Total people exposed become ill. 60\u00a0people become ill, attack rate is 75%. Demographic As a country proceeds to higher levels of development, birth and mortality rates decline to varying transition degrees, changing the age composition of the population. Population pyramid Male FemalMeale FemalMeale PoFpemulatleion % Population % Population %Age Age Birth rate \u008f\u008f Age\u0090 \u0090\u0090 Mortality rate \u008f Survival probability\u0090 \u0090 Life expectancy Short Long Long Population Growing Stable Declining Likelihood ratio \tL\tR+ =\t prporboabbaibliitlyityofopf opsoitsiivtievererseuslut litninpaptaietinetnwt withitohudt idsoisrodredre\tr\t=\t\t1 \u2013sesnpseitciivfiitcyi\tty\t=\t\t TP rate FP rate L\t\tR\u2013 = \tprporboabbaibliitlyityofonf engeagtaivtievererseuslut litninpaptaietinetnwt withitohudt idsoisrodredre\tr\t=\t\t 1 s\u2013pseecnifsiictiitvyit\ty\t \t=\t TFNN rate rate LR+ >\u00a010 indicates a highly specific test, while LR\u2013 < 0.1 indicates a highly sensitive test. Pretest probability \u00d7 LR = posttest odds. Posttest probability = posttest odds \/ (posttest odds + 1). Kaplan-Meier curve Graphic representation of event probability 1.0 (y-axis) vs length of time (x-axis). Useful for displaying \u201ctime-to-event\u201d data. Outcomes 0.9 Drug examined may include any event, but 0.8 frequently include mortality. 0.7 Survival probability = 1 \u2013 (event probability). 0.6 Control 0.5 0.4 0.3 0.2 X Y Time Z uploaded by medbooksvn","260 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics Evaluation of Sensitivity and specificity are fixed properties Disease diagnostic tests of a test. PPV and NPV vary depending on \u2013 disease prevalence in population being tested. Sensitivity (true- TP FP PPV positive rate) Test efficiency = (TP + TN)\/(TP + FN + FP + TN) = TP\/(TP + FP) Specificity (true- Number of people negative rate) TP rate (sensitivity) \u2013 FN TN NPV Positive predictive Test = TN\/(TN + FN) value Actual tes Sensitivity Speci\u00ffcity Prevalence Negative predictive TP + FN value = TP\/(TP + FN) = TN\/(TN + FP) (TP + FN + FP + TN) Proportion of all people with disease who test = TP \/ (TP + FN) positive, or the ability of a test to correctly = 1 \u2013 FN rate identify those with the disease. SN-N-OUT = highly SeNsitive test, when Value approaching 100% is desirable for ruling Negative, rules OUT disease out disease and indicates a low false-negative High sensitivity test used for screening rate. = TN \/ (TN + FP) Proportion of all people without disease who = 1 \u2013 FP rate test negative, or the ability of a test to correctly SP-P-IN = highly SPecific test, when Positive, identify those without the disease. rules IN disease Value approaching 100% is desirable for ruling High specificity test used for confirmation after a in disease and indicates a low false-positive rate. positive screening test Probability that a person who has a positive test PPV = TP \/ (TP + FP) result actually has the disease. PPV varies directly with pretest probability Probability that a person with a negative test (baseline risk, such as prevalence of disease): result actually does not have the disease. high pretest probability \u008e\u00a0high PPV NPV = TN \/ (TN + FN) NPV varies inversely with prevalence or pretest probability Disease Disease Possible cuto values for vs \u2013 test result absent present A = 100% sensitivity cuto value B = practical compromise between speci\ufb01city and sensitivity C = 100% speci\ufb01city cuto value TN TP Lowering the cuto value: \u2191 Sensitivity \u2191 NPV B A (\u2191 FP FN)\u2191\u2191 \u2191 \u2191\u2191 \u2191 \u2191\u2191 Speci\ufb01city PPV FN FP Raising the cuto value: \u2191 Speci\ufb01city \u2191 PPV AB C B C (\u2191 FN FP) Sensitivity NPV Test results Note: In diseases where diagnosis is based on lower values (eg, anemia), the TP and TN are switched in the graph, ie, \uf090 sensitivity and \uf090 NPV, and vice-versa. Receiver operating ROC curve demonstrates how well a diagnostic 1 Ideal test (AUC = 1) characteristic curve test can distinguish between 2 groups (eg, (0.5 < AUC < 1) disease vs healthy). Plots the true-positive rate No predictive (sensitivity) against the false-positive rate t 0.5) (1 \u2013 specificity). The better performing test will have a higher (AUC = area under the curve (AUC), with the curve closer to the upper left corner. value FP rate (1 \u2013 speci\ufb01city) 1","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics SECTION II 261 Precision vs accuracy The consistency and reproducibility of a test. Random error \u0090 precision in a test. Precision (reliability) The absence of random variation in a test. \u008f\u00a0precision \u008e \u0090 standard deviation. \u008f precision \u008e \u008f statistical power (1 \u2212 \u03b2). Accuracy (validity) The closeness of test results to the true values. Systematic error \u0090 accuracy in a test. The absence of systematic error or bias in a test. Accuracy Accuracy High Low High Low High High Low Low Precision Precision Incidence vs I\tnci\tdence = \t # of new cases \t (per unit of time) Incidence looks at new cases (incidents). prevalence # of people at risk Prevalence looks at all current cases. Recurrence P\t revalence = \t# of existing cases\t (at a point in Prevalence \u223c pretest probability. Incidence Total # of people\t\u2002\u2002 time) \u008f\u00a0prevalence \u008e\u00a0\u008f\u00a0PPV and \u0090\u00a0NPV. Prevalence \t in a population Mortality Cure \t Prevalence \t = \t Incidence rate \u00d7 average duration 1 \u2013 prevalence of disease Prevalence \u2248 incidence for short duration disease (eg, common cold). Prevalence > incidence for chronic diseases, due to large # of existing cases (eg, diabetes). SITUATION INCIDENCE PREVALENCE \u008f\u00a0survival time \u2014 \u008f \u008f\u00a0mortality \u2014 \u0090 Faster recovery time \u2014 \u0090 Extensive vaccine administration \u0090 \u0090 \u0090 \u0090 \u0090\u00a0risk factors \u008f \u008f \u008f\u00a0diagnostic sensitivity \u2014 \u0090 New effective treatment started \u0090 \u0090 \u0090 contact between infected and noninfected patients with airborne infectious disease uploaded by medbooksvn","262 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics Bias and study errors DEFINITION EXAMPLES STRATEGIES TO REDUCE BIAS TYPE Nonrandom sampling Berkson bias\u2014cases and\/ Randomization (creates groups or treatment allocation or controls selected from with similar distributions Recruiting participants of subjects such that hospitals (bedside bias) are of known and unknown Selection bias study population is not less healthy and have different variables) representative of target exposures Performing study population Ensure the choice of the right Recall bias Attrition bias\u2014participants lost comparison\/reference group Measurement bias Most commonly a sampling to follow up have a different bias prognosis than those who Procedure bias complete the study Observer-expectancy Convenience sampling\u2014 bias patients are enrolled on basis Interpreting results of ease of contact Lead-time bias Awareness of disorder alters Patients with disease recall Decrease time from exposure Length-time bias recall by subjects; common in exposure after learning of to follow-up; use medical retrospective studies similar cases records as sources Information is gathered in a Using a faulty automatic Use objective, standardized, systemically distorted manner sphygmomanometer and previously tested methods of data collection that are Subjects in different groups are Hawthorne effect\u2014participants planned ahead of time not treated the same change behavior upon awareness of being observed Use placebo group Researcher\u2019s belief in the efficacy of a treatment changes Patients in treatment group Blinding (masking) and the outcome of that treatment spend more time in highly use of placebo reduce (also called Pygmalion effect) specialized hospital units influence of participants and researchers on procedures and An observer expecting interpretation of outcomes treatment group to show signs as neither are aware of group of recovery is more likely to assignments document positive outcomes Early detection interpreted as Breast cancer diagnosed early Measure \u201cback-end\u201d survival \u008f\u00a0survival, but the disease by mammography may (adjust survival according to course has not changed appear to exaggerate survival the severity of disease at the time because patients are time of diagnosis) Screening test detects diseases known to have the cancer for with long latency period, longer A randomized controlled trial while those with shorter assigning subjects to the latency period become A slowly progressive cancer screening program or to no symptomatic earlier is more likely detected by a screening screening test than a rapidly progressive cancer","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics SECTION II 263 Confounding vs effect modifi ation TYPE DEFINITION EXAMPLES STRATEGIES TO REDUCE BIAS Confounding Factor related to both An uncontrolled study shows Crossover studies (with subject exposure and outcome (but association between drinking as their own controls) not on causal path) distorts coffee and lung cancer; effect on outcome however, people who drink Matching (patients with coffee may smoke more, similar characteristics in both No true association exists which could account for the treatment and control groups) association Effect modification Exposure leads to different Analytic techniques (eg, outcomes in subgroups A study among women using regression analysis when stratified by factor OCPs showed significant risk confounding variables are of DVT, but when these data known and were measured) True association exists were stratified by smoking habits, there was a very strong Stratified analysis (eg, after association between smoking testing for interaction and OCP use with DVT, between OCP and smoking, but there was no association analyze risk amongst smokers between OCP and DVT risk and nonsmokers) in people who do not smoke Confounding Crude analysis Drinking co ee Lung cancer Lung cancer Strati\ufb01ed analysis Smokers Drinking co ee Nonsmokers Drinking co ee Lung cancer Note: Association disappeared after strati\ufb01cation. E ect modi\ufb01cation Crude analysis OCP use DVT DVT Strati\ufb01ed analysis Smokers OCP use Nonsmokers OCP use DVT Note: Association was strong in one subgroup with weak\/no association in the other subgroup. Strong association Signi\ufb01cant association Weak\/no association uploaded by medbooksvn","264 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics Statistical distribution Mean = (sum of values)\/(total number of values). Most affected by outliers (extreme values). Measures of central tendency Median = middle value of a list of data sorted If there is an even number of values, the median from least to greatest. will be the average of the middle two values. Measures of dispersion Mode = most common value. Least affected by outliers. Normal distribution Standard deviation = how much variability \u03c3 = SD; n = sample size. exists in a set of values, around the mean of Variance = (SD)2. these values. SE = \u03c3\/\u221an. SE \u0090 as n \u008f. Standard error = an estimate of how much variability exists in a (theoretical) set of sample \u20131\u03c3 +1\u03c3 means around the true population mean. \u20132\u03c3 +2\u03c3 Gaussian, also called bell-shaped. \u20133\u03c3 +3\u03c3 Mean = median = mode. For normal distribution, mean is the best 68% measure of central tendency. 95% For skewed data, median is a better measure of central tendency than mean. Nonnormal distributions 99.7% \u20131\u03c3 +1\u03c3 Bimodal distribution Suggests two different populations (eg, \u20132\u03c3\u20131\u03c3 +1\u03c3 +2\u03c3 metabolic polymorphism such as fast vs slow acetylators; age at onset of Hodgkin \u20133\u03c3\u20132\u03c3 +2\u03c3 +3\u03c3 lymphoma; suicide rate by age). \u20133\u03c3 68% +3\u03c3 6985%% Positive skew Typically, mean > median > mode. 9995.%7% Asymmetry with longer tail on right; mean falls Mode 9M9e.d7i%an closer to tail. Mode MedianMean Negative skew Typically, mean < median < mode. Mean Asymmetry with longer tail on left; mean falls Median Mode closer to tail. MeaMnedian Mode Mean Statistical hypothesis testing Null hypothesis Also called H0. Hypothesis of no difference or relationship (eg, there is no association between the disease and the risk factor in the population). Alternative hypothesis Also called H1. Hypothesis of some difference or relationship (eg, there is some association between the disease and the risk factor in the population). P value Probability of obtaining test results at least as extreme as those observed during the test, assuming that H0 is correct. Commonly accepted as 0.05 (< 5% of results occur due to chance).","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics SECTION II 265 Outcomes of statistical hypothesis testing Correct result Stating that there is an effect or difference when Reality H1 H0 one exists (H0 rejected in favor of H1). Stating that there is no effect or difference when Study rejects H0 Power \u03b1 (1 \u2013 \u03b2) Type I error none exists (H0 not rejected). Study does not reject H0 \u03b2 Type II error Blue shading = correct result. Testing errors Stating that there is an effect or difference when Also called false-positive error. Type I error (\u03b1) none exists (H0 incorrectly rejected in favor of 1st time boy cries wolf, the town believes there H1). Type II error (\u03b2) is a wolf, but there is not (false positive). \u03b1 is the probability of making a type I error You can never \u201cprove\u201d H1, but you can reject the Statistical vs clinical (usually 0.05 is chosen). If P < \u03b1, then signifi ance assuming H0 is true, the probability of H0 as being very unlikely. obtaining the test results would be less than the probability of making a type I error. H0 is Also called false-negative error. therefore rejected as false. 2nd time boy cries wolf, the town believes there is Statistical significance \u2260 clinical significance. no wolf, but there is one. If you \u008f sample size, you \u008f power. There is power Stating that there is not an effect or difference when one exists (H0 is not rejected when it is in numbers. in fact false). Generally, when type I error increases, type II \u03b2 is the probability of making a type II error. \u03b2 is error decreases. related to statistical power (1 \u2013 \u03b2), which is the probability of rejecting H0 when it is false. \u008f power and \u0090 \u03b2 by: \u0083\t \u008f sample size \u0083\t \u008f expected effect size \u0083\t \u008f precision of measurement \u0083\t \u008f \u03b1 level (\u008f statistical significance level). Statistical significance\u2014defined by the likelihood of study results being due to chance. If there is a high statistical significance, then there is a low probability that the results are due to chance. Clinical significance\u2014measure of effect on treatment outcomes. An intervention with high clinical significance is likely to have a large impact on patient outcomes\/measures. Some studies have a very high statistical significance, but the proposed intervention may not have any clinical impact\/significance. uploaded by medbooksvn","266 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Epidemiology and Biostatistics Confiden e interval Range of values within which the true mean H0 is rejected (and results are significant) when: of the population is expected to fall, with a \u0083\t 95% CI for mean difference excludes 0 specified probability. \u0083\t 95% CI OR or RR excludes 1 CI = 1 \u2013 \u03b1. The 95% CI (corresponding to \u03b1 = 0.05) is often used. As sample size \u0083\t CIs between two groups do not overlap increases, CI narrows. H0 is not rejected (and results are not significant) CI for sample mean = x \u00b1 Z(SE) when: For the 95% CI, Z = 1.96. For the 99% CI, Z = 2.58. \u0083\t 95% CI for mean difference includes 0 \u0083\t 95% CI OR or RR includes 1 \u0083\t CIs between two groups do overlap Meta-analysis A method of statistical analysis that pools summary data (eg, means, RRs) from multiple studies for a more precise estimate of the size of an effect. Also estimates heterogeneity of effect sizes between studies. Improves power, strength of evidence, and generalizability (external validity) of study findings. Limited by quality of individual studies and bias in study selection. Common statistical tests t-test Checks differences between means of 2 groups. Tea is meant for 2. Example: comparing the mean blood pressure ANOVA Checks differences between means of 3 or more Fisher\u2019s exact test groups. between men and women. Chi-square (\u03c7\u00b2) 3 words: ANalysis Of VAriance. Checks differences between 2 percentages or Example: comparing the mean blood pressure proportions of categorical, nominal outcomes. Use instead of chi-square test with small between members of 3 different ethnic groups. populations. Example: comparing the percentage of 20 men Checks differences between 2 or more and 20 women with hypertension. percentages or proportions of categorical outcomes (not mean values). Pronounce chi-tegorical. Example: comparing the proportion of members of 3 age groups who have essential hypertension. Variables to be compared Numerical (means) Categorical (proportions) 2 groups \u2265 3 groups Small sample size Large sample size t-test ANOVA Fisher\u2019s exact test Chi-square test","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Ethics SECTION II 267 Pearson correlation A measure of the linear correlation between two variables. r is always between \u22121 and +1. The coeffici t closer the absolute value of r is to 1, the stronger the linear correlation between the 2 variables. Variance is how much the measured values differ from the average value in a data set. Positive r value \u008e positive correlation (as one variable \u008f, the other variable \u008f). Negative r value \u008e negative correlation (as one variable \u008f, the other variable \u0090). Coefficient of determination = r\u200a2 (amount of variance in one variable that can be explained by variance in the other variable). r = \u20130.8 r = \u20130.4 r=0 r = +0.4 r = +0.8 Strong negative Weak negative No correlation Weak positive Strong positive correlation correlation correlation correlation `\u2009PUBLIC HEALTH SCIENCES\u2014ETHICS Core ethical principles Obligation to respect patients as individuals (truth-telling, confidentiality), to create conditions Autonomy necessary for autonomous choice (informed consent), and to honor their preference in accepting Beneficence or not accepting medical care. Nonmaleficence Physicians have a special ethical (fiduciary) duty to act in the patient\u2019s best interest. May conflict Justice with autonomy (an informed patient has the right to decide) or what is best for society (eg, mandatory TB treatment). Traditionally, patient interest supersedes. Principle of double effect\u2014facilitating comfort is prioritized over potential side effects (eg, respiratory depression with opioid use) for patients receiving end-of-life care. \u201cDo no harm.\u201d Must be balanced against beneficence; if the benefits outweigh the risks, a patient may make an informed decision to proceed (most surgeries and medications fall into this category). To treat persons fairly and equitably. This does not always imply equally (eg, triage). Decision-making Physician must determine whether the patient is Four major components of decision-making: capacity psychologically and legally capable of making \u0083\t Understanding (what do you know about a particular healthcare decision. your condition\/proposed procedure\/ treatment?) Note that decisions made with capacity cannot be \u0083\t Appreciation (what does your condition revoked simply if the patient later loses capacity. mean to you? why do you think your doctor is recommending this course of treatment?) Intellectual disabilities and mental illnesses \u0083\t Reasoning (how are you weighing your are not exclusion criteria unless the patient\u2019s options?) condition presently impairs their ability to \u0083\t Expressing a choice (what would you like make healthcare decisions. to do?) Capacity is determined by a physician for a specific healthcare-related decision (eg, to refuse medical care). Competency is determined by a judge and usually refers to more global categories of decision-making (eg, legally unable to make any healthcare-related decision). uploaded by medbooksvn","268 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Ethics Informed consent A process (not just a document\/signature) that Exceptions to informed consent (WIPE it away): requires: \u0083\t Waiver\u2014patient explicitly relinquishes the \u0083\t Disclosure: discussion of pertinent right of informed consent information, including risks\/benefits (using \u0083\t Legally Incompetent\u2014patient lacks decision- medical interpreter, if needed) making capacity (obtain consent from legal \u0083\t Understanding: ability to comprehend surrogate) \u0083\t Capacity: ability to reason and make one\u2019s \u0083\t Therapeutic Privilege\u2014withholding own decisions (distinct from competence, a information when disclosure would severely legal determination) harm the patient or undermine informed \u0083\t Voluntariness: freedom from coercion and decision-making capacity manipulation \u0083\t Emergency situation\u2014implied consent may apply Patients must have a comprehensive understanding of their diagnosis and the risks\/ benefits of proposed treatment and alternative options, including no treatment. Patients must be informed of their right to revoke written consent at any time, even orally. Consent for minors A minor is generally any person < 18 years old. Situations in which parental consent is usually Parental consent laws in relation to healthcare not required: vary by state. In general, parental consent \u0083\t Sex (contraception, STIs, prenatal care\u2014 should be obtained, but exceptions exist for usually not abortion) emergency treatment (eg, blood transfusions) \u0083\t Drugs (substance use disorder treatment) or if minor is legally emancipated (eg, married, \u0083\t Rock and roll (emergency\/trauma) self-supporting, or in the military). Physicians should always encourage healthy minor-guardian communication. Physician should seek a minor\u2019s assent (agreement of someone unable to legally consent) even if their consent is not required. Advance directives Instructions given by a patient in anticipation of the need for a medical decision. Details vary per state law. Oral advance directive Incapacitated patient\u2019s prior oral statements commonly used as guide. Problems arise from variance Written advance in interpretation. If patient was informed, directive was specific, patient made a choice, and directive decision was repeated over time to multiple people, then the oral directive is more valid. Medical power of attorney Delineates specific healthcare interventions that patient anticipates accepting or rejecting during treatment for a critical or life-threatening illness. A living will is an example. Do not resuscitate order Patient designates an agent to make medical decisions in the event that the patient loses decision- making capacity. Patient may also specify decisions in clinical situations. Can be revoked by patient if decision-making capacity is intact. More flexible than a living will. DNR order prohibits cardiopulmonary resuscitation (CPR). Patient may still consider other life- sustaining measures (eg, intubation, feeding tube, chemotherapy).","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014Ethics SECTION II 269 Ventilator-assisted life Ideally, discussions with patients occur before ventilator support is necessary. However, information support about patient preferences may be absent at the time patients require this intervention to survive. Medical decision-making frequently relies on surrogate decision-makers (patient identified or legally appointed) when discussing the continuation or withdrawal of ventilatory support, focusing on both the prognosis of the condition and the believed wishes of the patient. If surrogates indicate patient would not have wanted to receive life support with ventilation \u008e withhold or withdraw life support regardless of what the surrogate prefers. If the decision is made to withhold or withdraw life support, involve palliative care, chaplain services, and the primary care physician in medical discussions with the family and provide emotional support. Surrogate decision- If a patient loses decision-making capacity and has not prepared an advance directive, individuals maker (surrogates) who know the patient must determine what the patient would have done. Priority of surrogates: spouse \u008e\u00a0adult children \u008e\u00a0parents \u008e\u00a0adult siblings \u008e\u00a0other relatives (the spouse chips in). Confide tiality Confidentiality respects patient privacy and autonomy. If the patient is incapacitated or the situation is emergent, disclosing information to family and friends should be guided by professional judgment of patient\u2019s best interest. The patient may voluntarily waive the right to confidentiality (eg, insurance company request). General principles for exceptions to confidentiality: \u0083\t Potential physical harm to self or others is serious and imminent \u0083\t Alternative means to warn or protect those at risk is not possible \u0083\t Steps can be taken to prevent harm Examples of exceptions to patient confidentiality (many are state specific) include the following (\u201cThe physician\u2019s good judgment SAVED the day\u201d): \u0083\t Patients with Suicidal\/homicidal ideation \u0083\t Abuse (children, older adults, and\/or prisoners) \u0083\t Duty to protect\u2014state-specific laws that sometimes allow physician to inform or somehow protect potential Victim from harm \u0083\t Patients with Epilepsy and other impaired automobile drivers \u0083\t Reportable Diseases (eg, STIs, hepatitis, food poisoning); physicians may have a duty to warn public officials, who will then notify people at risk. Dangerous communicable diseases, such as TB or Ebola, may require involuntary treatment. Accepting gifts from A complex subject without definitive regulations. Some argue that the patient-physician patients relationship is strengthened through accepting a gift from a patient, while others argue that negative consequences outweigh the benefits of accepting any gift. In practice, patients often present items such as cards, baked goods, and inexpensive gifts to physicians. The physician\u2019s decision to accept or decline is based on an individual assessment of whether or not the risk of harm outweighs the potential benefit. \u0083\t Physicians should not accept gifts that are inappropriately large or valuable. \u0083\t Gifts should not be accepted if the physician identifies that the gift could detrimentally affect patient care. \u0083\t Gifts that may cause emotional or financial stress for the patient should not be accepted. If a gift violates any of the guidelines above, the best practice is to thank the patient for offering a kind gift, but politely indicate that it must be declined. During this conversation it should be emphasized that the incident does not influence the physician-patient relationship in any way. uploaded by medbooksvn","270 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014communication skills `\u2009PUBLIC HEALTH SCIENCES\u2014COMMUNICATION SKILLS Patient-centered interviewing techniques Introduction Introduce yourself and ask the patient their name and how they would like to be addressed. Address the patient by the name and pronouns given. Avoid making gender assumptions. Sit at eye level near the patient. Agenda setting Identify concerns and set goals by developing joint agenda between the physician and the patient. Reflection Actively listen and synthesize information offered by the patient, particularly with respect to primary concern(s). Validation Legitimize or affirm the patient\u2019s perspectives. Recapitulation Summarize what the patient has said so far to ensure correct interpretation. Facilitation Encourage the patient to speak freely without guiding responses or leading questions. Allow the patient to ask questions throughout the encounter. Establishing rapport PEARLS Partnership Empathy Work together with patient to identify primary concerns and develop preferred solutions. Apology Acknowledge the emotions displayed and demonstrate understanding of why the patient is feeling Respect that way. Legitimization Take personal responsibility when appropriate. Support Commend the patient for coming in to discuss a problem, pushing through challenging circumstances, keeping a positive attitude, or other constructive behaviors. Assure patient that emotional responses are understandable or common. Reassure patient that you will work together through difficult times and offer appropriate resources. Delivering bad news SPIKES Setting Offer in advance for the patient to bring support. Eliminate distractions, ensure privacy, and sit Perception down with the patient to talk. Invitation Knowledge Determine the patient\u2019s understanding and expectations of the situation. Emotions Obtain the patient\u2019s permission to disclose the news and what level of detail is desired. Strategy Share the information in small pieces without medical jargon, allowing time to process. Assess the patient\u2019s understanding. Acknowledge the patient\u2019s emotions, and provide opportunity to express them. Listen and offer empathetic responses. If the patient feels ready, discuss treatment options and goals of care. Offer an agenda for the next appointment. Giving control to the patient may be empowering. Ask how they feel a problem might be solved and what they would like to do about the plan of action.","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014communication skills SECTION II 271 Gender- and sexuality- Avoid making assumptions about sexual orientation, gender identity, gender expression, and inclusive history behavior (eg, a patient who identifies as heterosexual may engage in same-sex sexual activity). taking Use gender-neutral terms (eg, refer to a patient\u2019s \u201cpartner\u201d rather than assuming a spouse\u2019s gender). A patient\u2019s sex assigned at birth and gender identity may differ. Consider stating what pronouns you use when you introduce yourself (eg, \u201cI\u2019m Dr. Smith, and I use she\/her pronouns\u201d) and asking patients how they would like to be addressed. Reassure them about the confidentiality of their appointments and be sensitive to the fact that patients may not be open about their sexual orientation or gender identity to others in their life. Do not bring up gender or sexuality if it is not relevant to the visit (eg, a gender-nonconforming patient seeking care for a hand laceration). Cultural formulation Identify the problem through the patient\u2019s perspective. Ask the patient to describe the problem in interview their own words, or how the patient would describe the problem to their family and friends. Identify cultural perceptions of factors leading to a problem. Ask the patient to explain why they think they are experiencing their problem. Identify how the patient\u2019s background influences their problem. Ask the patient about what makes their problem better or worse. Investigate roles of family, community, and spirituality. Identify how culture may impact current and future interventions. Ask the patient if they have any concerns about the current plan of treatment and if they have any suggestions. If they do not want to follow medical advice, investigate if there is a way to combine their plans with the standard medical regimen. Identify possible barriers to care based on culture. Ask the patient if there is anything that would prevent them from seeking care in a standard medical institution. Probe for explanations and what may increase the chance of maintaining a good patient-physician relationship. Motivational Counseling technique to facilitate behavior modification by helping patients resolve ambivalence interviewing about change. Useful for many conditions (eg, nicotine dependence, obesity). Helpful when patient has some desire to change, but it does not require that the patient be committed to making the change. May involve asking patients to examine how their behavior interferes with their life or why they might want to change it. Assess barriers (eg, food access, untreated trauma) that may make behavior change difficult. Assessing a patient\u2019s readiness for change is also important for guiding physician-suggested goals. These goals should be Specific, Measurable, Achievable, Relevant, and Time bound (SMART). Trauma-informed care Patients with history of psychological trauma should receive thorough behavioral health screenings. Regularly assess mood, substance use, social supports, and suicide risk. Focus assessments on trauma-related symptoms that interfere with social and occupational function. Do not probe into details of the incident. Always be empathetic. Do not ask invasive questions requiring the patient to describe trauma in detail. Ask permission prior to discussion. Before the physical exam, reassure patients that they may signal to end it immediately if they experience too much physical or emotional discomfort. Offer the presence of additional staff for support. Psychological counseling may be indicated. Follow-up counseling is offered (or advised) as appropriate. The 4 Rs of trauma-informed care: Realize, Recognize, Respond, Resist retraumatization. uploaded by medbooksvn","272 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014COMMUNICATION SKILLS Challenging patient and ethical The most appropriate response is usually one that acknowledges the issues, validates scenarios emotions, and is open ended, empathetic, and patient centered. It often honors one or more of the principles of autonomy, beneficence, nonmaleficence, and justice. SITUATION Appropriate responses are respectful of patients and other members of the healthcare team. Patient does not follow the medical plan. APPROPRIATE RESPONSE Patient desires an unnecessary Determine whether there are financial, logistical, or other obstacles preventing the procedure. patient\u2019s adherence. Do not coerce the patient into adhering or refer the patient to another physician. Schedule regular follow-up visits to track patient progress. Patient has difficulty taking medications. Attempt to understand why the patient wants the procedure and address underlying concerns. Do not refuse to see the patient or refer to another physician. Avoid Family members ask for information performing unnecessary procedures. about patient\u2019s prognosis. Determine what factors are involved in the patient\u2019s difficulties. If comprehension or A patient\u2019s family member asks you memory are issues, use techniques such as providing written instructions, using the not to disclose the results of a test teach-back method, or simplifying treatment regimens. if the prognosis is poor because the patient will be \u201cunable to Avoid discussing issues with relatives without the patient\u2019s permission. handle it.\u201d Explore why the family member believes this would be detrimental, including A 17-year-old is pregnant and possible cultural factors. Explain that if the patient would like to know information requests an abortion. concerning care, it will not be withheld. However, if you believe the patient might seriously harm self or others if informed, you may invoke therapeutic privilege and A 15-year-old is pregnant and wants withhold the information. to raise the child. The patient\u2019s parents want you to tell the patient Many states require parental notification or consent for minors for an abortion. Unless to give the child up for adoption. there are specific medical risks associated with pregnancy, a physician should not sway the patient\u2019s decision for, or against, an elective abortion (regardless of patient\u2019s A terminally ill patient requests age or fetal condition). Discuss options for terminating the pregnancy and refer to physician-assisted dying. abortion care, if needed. Patient is suicidal. The patient retains the right to make decisions regarding the child, even if the patient\u2019s parents disagree. Provide information to the teenager about the practical aspects Patient states that you are attractive of caring for a baby. Discuss options for terminating the pregnancy, if requested. and asks if you would go on a date. Encourage discussion between the patient and parents to reach the best decision. A woman who had a mastectomy The overwhelming majority of states prohibit most forms of physician-assisted dying. says she now feels \u201cugly.\u201d Physicians may, however, prescribe medically appropriate analgesics even if they potentially shorten the patient\u2019s life. Patient is angry about the long time spent in the waiting room. Assess the seriousness of the threat. If patient is actively suicidal with a plan, suggest remaining in the hospital voluntarily; patient may be hospitalized involuntarily if needed. Patient is upset with treatment received from another physician. Use a chaperone if necessary. Romantic relationships with patients are never appropriate. Set firm professional boundaries with direct communication. Transition care to another physician if necessary. Find out why the patient feels this way. Do not offer falsely reassuring statements (eg, \u201cYou still look good\u201d). Acknowledge the patient\u2019s anger, but do not take a patient\u2019s anger personally. Thank the patient for being patient and apologize for any inconvenience. Stay away from efforts to explain the delay. Suggest that the patient speak directly to that physician regarding the concern. If the problem is with a member of the office staff, reassure the patient you will speak to that person.","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014communication skills SECTION II 273 Challenging patient and ethical scenarios (continued) SITUATION APPROPRIATE RESPONSE An invasive test is performed on the Regardless of the outcome, a physician is ethically obligated to inform a patient that a wrong patient. mistake has been made. A patient requires a treatment not Discuss all treatment options with patients, even if some are not covered by their covered by insurance. insurance companies. Inform patient of financial assistance programs. A 7-year-old boy loses a sister to At ages 5\u20137, children begin to understand that death is permanent, all life functions cancer and now feels responsible. end completely at death, and everything that is alive eventually dies. Provide a direct, concrete description of his sister\u2019s death. Avoid clich\u00e9s and euphemisms. Reassure the boy that he is not responsible. Identify and normalize fears and feelings. Encourage play and healthy coping behaviors (eg, remembering her in his own way). Patient is victim of intimate partner Ask if patient is safe and help devise an emergency plan if there isn\u2019t one. Ask patient violence. direct, open-ended questions about exam findings and summarize patient\u2019s answers back to them. Ask if patient has any questions. Do not necessarily pressure patient to leave a partner or disclose the incident to the authorities (unless required by state law). Patient wants to try alternative or Explore any underlying reasons with the patient in a supportive, nonjudgmental manner. holistic medicine. Advise the patient of known benefits and risks of treatment, including adverse effects, contraindications, and medication interactions. Consider referral to an appropriate complementary or alternative medicine provider. Physician colleague presents to This presents a potential risk to patient safety. You have an ethical and usually a legal work impaired. obligation to report impaired colleagues so they can cease patient care and receive appropriate assistance in a timely manner. Seek guidance in reporting as procedures and applicable law vary by institution and state. Patient\u2019s family insists on Gently explain to family that there is no chance of recovery, and that brain death is maintaining life support after brain equivalent to death. Movement is due to spinal arc reflex and is not voluntary. Bring death has occurred, citing patient\u2019s case to appropriate ethics board regarding futility of care and withdrawal of life movements when touched. support. A pharmaceutical company offers Reject this offer. Generally, decline gifts and sponsorships to avoid any conflict of you a sponsorship in exchange for interest. The AMA Code of Ethics does make exceptions for gifts directly benefitting advertising its new drug. patients; special funding for medical education of students, residents, fellows; grants whose recipients are chosen by independent institutional criteria; and funds that are distributed without attribution to sponsors. Patient requests a nonemergent Provide accurate and unbiased information so patients can make an informed decision. procedure that is against your In a neutral, nonjudgmental manner, explain to the patient that you do not perform personal or religious beliefs. the procedure but offer to refer to another physician. Mother and 15-year-old daughter Transfuse daughter, but do not transfuse mother. Emergent care can be refused by the are unresponsive and bleeding healthcare proxy for an adult, particularly when patient preferences are known or heavily, but father refuses reasonably inferred, but not for a minor based solely on faith. transfusion because they are Jehovah\u2019s Witnesses. A dependent patient presents Document detailed history and physical. If possible and appropriate, interview the with injuries inconsistent with patient alone. Provide any necessary medical care. If suspicion remains, contact caretaker\u2019s story. the appropriate agencies or authorities (eg, child or adult protective services) for an evaluation. Inform the caretaker of your obligation to report. Physicians are required by law to report any reasonable suspicion of abuse, neglect, or endangerment. A pediatrician recommends standard Address any concerns the parent has. Explain the risks and benefits of vaccinations vaccinations for a patient, but the and why they are recommended. Do not administer routine vaccinations without the child\u2019s parent refuses. parent\u2019s consent. uploaded by medbooksvn","274 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014communication skills Communicating Patients may identify with person-first (ie, \u201ca person with a disability\u201d) or identity-first (ie, \u201ca with patients with disabled person\u201d) language. Ask patients what terms they use. disabilities Under most circumstances, talk directly to the patient. Do not assume that nonverbal patients do not understand. Accompanying caregivers can add information to any discussion as needed. Ask if assistance is desired rather than assuming the patient cannot do something alone. Most people, including people with disabilities, value their independence. For patients with speech difficulties, provide extra time for the interview. If their speech is difficult to understand, consider asking them to write down a few words or ask them to rephrase their sentence. Repeat what they said to ensure you understood it correctly. For patients with a cognitive impairment, use concrete, specific language. Ask simple, direct questions. Eliminate background noise and distractions. Do not assume the patient can read. Adjust to how the patient understands best (eg, use hand gestures or ask them to demonstrate a task). Ask patients who are deaf or hard of hearing their preferred mode of communication. Use light touch or waving to get their attention. For patients who prefer to speak and lipread, eliminate background noise, face the patient, and do not change your mode of speaking. Consider using an interpreter when necessary. As with other parts of a medical history, do not bring up a disability if it is not relevant to a visit (eg, a patient in a wheelchair with an ear infection). Do not skip relevant parts of the physical exam even if the disability makes the exam challenging. Use of interpreters Visits with a patient who speaks little English should utilize a professionally trained medical interpreter unless the physician is conversationally fluent in the patient\u2019s preferred language. If an interpreter is unavailable in person, interpretation services may be provided by telephone or video call. If the patient prefers to utilize a family member, this should be recorded in the chart. Do not assume that a patient is a poor English speaker because of name, skin tone, or accent. Ask the patient what language is preferred. The physician should make eye contact with the patient and speak to them directly, without use of third-person statements such as \u201ctell him.\u201d Allow extra time for the interview, and ask one question at a time. For in-person spoken language interpretation, the interpreter should ideally be next to or slightly behind the patient. For sign language interpretation, the interpreter should be next to or slightly behind the physician. In cases of emergency, facilitate communication by any tools available (eg, friends, family, sketches, interpreter apps) even though they do not comprise standard procedure otherwise.","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014HEALTHCARE DELIVERY SECTION II 275 `\u2009PUBLIC HEALTH SCIENCES\u2014HEALTHCARE DELIVERY Goals Disease prevention Target population Quaternary Decrease overtreatment and iatrogenic harm Symptomatic patients Quit unnecessary eg, discontinuing sulfonylurea medical after multiple hypoglycemic events interventions to minimize incidental harm Tertiary Decrease associated morbidity, mortality, and disability Treat to reduce eg, hemoglobin Aan1cdmporneivteonritng to complications from disease guide treatment Asymptomatic and complications early disease patients that is ongoing Susceptible population Secondary Decrease prevalence and severity of disease Screen for and manage eg, glucose screening for presymptomatic disease type 2 diabetes mellitus Primary Decrease incidence eg, healthy diet and exercise Prevent disease before it occurs to prevent diabetes General population Major medical insurance plans PLAN PROVIDERS PAYMENTS SPECIALIST CARE Exclusive provider Restricted to limited panel No referral required organization (except emergencies) Health maintenance Restricted to limited panel Most affordable Requires referral from primary care provider organization (except emergencies) Higher copays and deductibles for out-of-network services Requires referral from Point of service Patient can see providers primary care provider outside network Higher copays and deductibles for all services No referral required Preferred provider Patient can see providers organization outside network Medicare Specialists voluntarily enroll Accountable care Providers voluntarily enroll organization uploaded by medbooksvn","276 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014HEALTHCARE DELIVERY Healthcare payment models Bundled payment Healthcare organization receives a set amount per service, regardless of ultimate cost, to be divided among all providers and facilities involved. Capitation Physicians receive a set amount per patient assigned to them per period of time, regardless of how much the patient uses the healthcare system. Used by some HMOs. Discounted fee-for- Insurer and\/or patient pays for each individual service at a discounted rate predetermined by service providers and payers (eg, PPOs). Fee-for-service Insurer and\/or patient pays for each individual service. Global payment Insurer and\/or patient pays for all expenses associated with a single incident of care with a single payment. Most commonly used during elective surgeries, as it covers the cost of surgery as well as the necessary pre- and postoperative visits. Medicare and Medicare and Medicaid\u2014federal social MedicarE is for Elderly. Medicaid healthcare programs that originated from MedicaiD is for Disadvantaged. amendments to the Social Security Act. The 4 parts of Medicare: Medicare is available to patients \u2265 65 years old, \u0083\t Part A: hospital Admissions, including < 65 with certain disabilities, and those with hospice, skilled nursing end-stage renal disease. \u0083\t Part B: Basic medical bills (eg, physician fees, diagnostic testing) Medicaid is joint federal and state health \u0083\t Part C: (parts A + B = Combo) delivered by assistance for people with limited income and\/ approved private companies or resources. \u0083\t Part D: prescription Drugs Palliative care Medical care aiming to provide comfort, relieve suffering, and improve quality of life in patients with serious illness regardless of their diagnosis or prognosis. Often concurrent with curative or life-prolonging treatment. Delivered by interdisciplinary team (eg, physicians, nurses, social workers) in hospitals, outpatient clinics, or at home. Hospice care (end-of-life care)\u2014form of palliative care for patients with prognosis \u2264 6 months when curative or life-prolonging treatment is no longer beneficial. Common causes of death (US) by age < 1 YR 1\u201314 YR 15\u201334 YR 35\u201344 YR 45\u201364 YR 65+ YRa #1 Congenital Unintentional Unintentional Unintentional Cancer Heart disease injury injury malformations injury #2 Preterm birth Cancer Suicide Cancer Heart disease Cancer #3 Sudden Congenital Homicide Heart disease Unintentional Chronic lower unexpected injury respiratory infant death malformations disease aWith the ongoing pandemic, COVID-19 has been included as one of the most common causes of death among people 65+ years old.","Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014QUALITY AND SAFETY SECTION II 277 `\u2009PUBLIC HEALTH SCIENCES\u2014QUALITY AND SAFETY Safety culture Organizational environment in which everyone can freely bring up safety concerns without fear of penalty. Human factors design Forcing functions (those that prevent Deficient designs hinder workflow and lead to undesirable actions [eg, connecting feeding staff workarounds that bypass safety features syringe to IV tubing]) are the most effective. (eg, patient ID barcodes affixed to computers due to unreadable wristbands). Standardization improves process reliability (eg, clinical pathways, guidelines, checklists). Simplification reduces wasteful activities (eg, consolidating electronic medical records). PDSA cycle Process improvement model to test changes in real clinical setting. Impact on patients: \u0083\t Plan\u2014define problem and solution Do \u0083\t Do\u2014test new process \u0083\t Study\u2014measure and analyze data Plan \u0083\t Act\u2014integrate new process into workflow Study Act Quality measurements MEASURE EXAMPLE Structural Physical equipment, resources, facilities Number of diabetes educators Process Performance of system as planned Percentage of patients with diabetes whose Outcome Impact on patients HbA1c was measured in the past 6 months Balancing Impact on other systems\/outcomes Average HbA1c of patients with diabetes Incidence of hypoglycemia among patients who tried an intervention to lower HbA1c Swiss cheese model Focuses on systems and conditions rather than Potential failures an individual\u2019s error. The risk of a threat in defense strategy becoming a reality is mitigated by differing layers and types of defenses. Patient harm can Hazard occur despite multiple safeguards when \u201cthe holes in the cheese line up.\u201d Defense Harm strategies uploaded by medbooksvn","278 SECTION II Public Health Sciences\u2003 \uf07d\u2009PUBLIC HEALTH SCIENCES\u2014QUALITY AND SAFETY Types of medical May involve patient identification, diagnosis, monitoring, healthcare-associated infection, errors medications, procedures, devices, documentation, handoffs. Medical errors should be disclosed to patients, independent of immediate outcome (harmful or not). Active error Latent error Burnout\u2014prolonged, excessive stress \u008e\u00a0medical errors due to reduced professional efficacy. Never event Fatigue\u2014sleep\/rest deprivation \u008e\u00a0medical errors due to cognitive impairment. Near miss Occurs at level of frontline operator (eg, wrong Immediate impact. IV pump dose programmed). Occurs in processes indirect from operator but Accident waiting to happen. impacts patient care (eg, different types of IV pumps used within same hospital). Adverse event that is identifiable, serious, and Major error that should never occur. usually preventable (eg, scalpel retained in a Sentinel event\u2014a never event that leads to surgical patient\u2019s abdomen). death, permanent harm, or severe temporary harm. Unplanned event that does not result in harm Narrow prevention of harm that exposes dangers. but has the potential to do so (eg, pharmacist recognizes a medication interaction and cancels the order). Medical error analysis DESIGN METHODS Root cause analysis Retrospective approach. Applied after failure Uses records and participant interviews (eg, event to prevent recurrence. 5 whys approach, fishbone\/cause-and- effect diagrams, process maps) to identify Failure mode and Forward-looking approach. Applied before all the underlying problems (eg, process, effects analysis process implementation to prevent failure people, environment, equipment, materials, occurrence. management) that led to an error. Uses inductive reasoning to identify all the ways a process might fail and prioritizes them by their probability of occurrence and impact on patients.","SECTION III High-Yield Organ Systems \u201cSymptoms, then, are in reality nothing but the cry from suffering organs.\u201d `\tApproaching the 280 \u2014Jean-Martin Charcot Organ Systems\b \u201cMan is an intelligence in servitude to his organs.\u201d `\tCardiovascular\b 283 \u2014Aldous Huxley \u201cWhen every part of the machine is correctly adjusted and in perfect `\tEndocrine\b 329 harmony, health will hold dominion over the human organism by laws as natural and immutable as the laws of gravity.\u201d `\tGastrointestinal\b 363 \u2014Andrew T. Still `\tHematology and Oncology\b 409 `\tMusculoskeletal, Skin, and Connective Tissue\b 449 `\tNeurology and 499 Special Senses \b `\tPsychiatry\b 571 `\tRenal\b 597 `\tReproductive\b 631 `\tRespiratory\b 679 279 uploaded by medbooksvn"]