USMLE Step 1 - High-Yield Autonomic & Cardiovascular Pharmacology Flashcards

Question 1

Autonomic Receptor G-Protein Coupling Mnemonic ($G_q, G_i, G_s$)

Accepted Answer

**$G_q$**: "HAV 1 M&M" ($\alpha_1, M_1, M_3$) $\	o$ activates phospholipase C ($\uparrow IP_3, DAG, Ca^{2+}$).
**$G_i$**: "MAD 2s" ($M_2, \alpha_2, D_2$) $\	o$ inhibits adenylyl cyclase ($\downarrow cAMP$).
**$G_s$**: All $\beta$ receptors ($\beta_1, \beta_2, \beta_3$) + $D_1$ $\	o$ activates adenylyl cyclase ($\uparrow cAMP$).

Question 2

$\alpha_1$ Receptor Mechanism and Vascular Effects

Accepted Answer

**Coupling**: $G_q$ ($\uparrow IP_3 / DAG / Ca^{2+}$).
**Location & Action**: Vascular smooth muscle constriction ($\uparrow SVR$, $\uparrow MAP$), pupillary dilator muscle contraction (mydriasis), intestinal and urinary sphincter contraction.

Question 3

$\alpha_2$ Receptor Mechanism and Central Effects

Accepted Answer

**Coupling**: $G_i$ ($\downarrow cAMP$).
**Location & Action**: Presynaptic sympathetic nerve terminals (decreases norepinephrine and insulin release), CNS sympathetic outflow reduction.
**Key Agonists**: Clonidine, $\alpha$-methyldopa (first-line in pregnancy hypertension).

Question 4

$\beta_1$ Receptor Signal Transduction & Cardiac Effects

Accepted Answer

**Coupling**: $G_s$ ($\uparrow cAMP \	o \uparrow$ Protein Kinase A).
**Location & Action**: Heart (SA node $\uparrow$ HR, AV node $\uparrow$ conduction velocity, myocardium $\uparrow$ inotropy) and renal juxtaglomerular cells ($\uparrow$ renin release).

Question 5

$\beta_2$ Receptor Signal Transduction & Physiological Effects

Accepted Answer

**Coupling**: $G_s$ ($\uparrow cAMP \	o \uparrow$ PKA $\	o$ smooth muscle relaxation).
**Location & Action**: Bronchodilation, vasodilation ($\downarrow SVR$, $\downarrow DBP$), uterine relaxation (tocolysis), $\uparrow$ aqueous humor production, and $\uparrow$ hepatic glycogenolysis (causes intracellular $K^+$ shift).

Question 6

Muscarinic Receptor Subtypes ($M_1, M_2, M_3$) Summary

Accepted Answer

**$M_1$** ($G_q$): CNS and enteric nervous system.
**$M_2$** ($G_i$): Heart (SA node $\downarrow$ HR, AV node $\downarrow$ conduction velocity).
**$M_3$** ($G_q$): Exocrine glands ($\uparrow$ secretions), smooth muscle (bronchoconstriction, gut motility, bladder detrusor contraction), endothelial nitric oxide release ($\	o$ vasodilation).

Question 7

Bethanechol: Class, Mechanism, & Clinical Indications

Accepted Answer

**Class**: Direct-acting muscarinic agonist.
**Mechanism**: Resistant to acetylcholinesterase; selectively activates $M_3$ receptors in bowel and bladder.
**Indications**: Non-obstructive urinary retention (e.g., postoperative or neurogenic bladder) and neurogenic ileus.
**Adverse Effects**: Parasympathetic overload (diaphoresis, diarrhea, bradycardia, bronchospasm).

Question 8

Atropine: Mechanism, Indications, & Toxicity Symptoms

Accepted Answer

**Mechanism**: Competitive muscarinic receptor antagonist ($M_1, M_2, M_3$).
**Indications**: Severe bradycardia, organophosphate poisoning antidote.
**Toxicity Mnemonic**: "Blind as a bat (mydriasis), mad as a hatter (delirium), red as a beet (flushing), hot as a hare (hyperthermia), dry as a bone (anhidrosis), bowel and bladder lose tone."

Question 9

Hemodynamic Profiles: Isoproterenol vs. Phenylephrine

Accepted Answer

**Isoproterenol** ($\beta_1, \beta_2$ agonist): $\uparrow$ HR, $\uparrow$ contractility, $\downarrow\downarrow$ SVR and DBP, slight $\downarrow$ or unchanged MAP, $\uparrow$ pulse pressure.
**Phenylephrine** (pure $\alpha_1$ agonist): $\uparrow\uparrow$ SVR, $\uparrow$ MAP, reflex bradycardia ($\downarrow$ HR due to carotid sinus baroreceptor reflex).

Question 10

Hemodynamic Profiles: Epinephrine vs. Norepinephrine

Accepted Answer

**Epinephrine** ($\beta_1 = \beta_2 > \alpha_1$ at low dose; $\alpha_1 > \beta_1$ at high dose): Low dose $\	o \downarrow$ SVR ($\beta_2$), $\uparrow$ HR/CO ($\beta_1$). High dose $\	o \uparrow$ SVR ($\alpha_1$).
**Norepinephrine** ($\alpha_1 > \alpha_2 > \beta_1$): Prominent vasoconstriction ($\uparrow SVR$, $\uparrow MAP$) with reflex bradycardia; $\beta_1$ activity counteracts bradycardia to keep HR relatively stable.

Question 11

ACE Inhibitors (-pril): Mechanism & Key Adverse Effects

Accepted Answer

**Mechanism**: Inhibits Angiotensin-Converting Enzyme $\	o \downarrow$ Angiotensin II (prevents efferent arteriolar constriction) and prevents bradykinin degradation ($\uparrow$ bradykinin).
**Clinical Uses**: HTN, Heart Failure, diabetic nephropathy.
**Adverse Effects Mnemonic (CATCHH)**: **C**ough, **A**ngioedema, **T**eratogen, $\uparrow$ **C**reatinine ($\downarrow$ GFR), **H**yperkalemia, **H**ypotension.

Question 12

Calcium Channel Blockers: Dihydropyridines vs. Non-Dihydropyridines

Accepted Answer

**Dihydropyridines** (Amlodipine, Nifedipine): Act on vascular smooth muscle $L$-type $Ca^{2+}$ channels. Indicated for HTN, angina. Cause peripheral edema and reflex tachycardia.
**Non-Dihydropyridines** (Verapamil, Diltiazem): Act on cardiac $L$-type $Ca^{2+}$ channels. Indicated for AFib rate control, angina. Cause bradycardia, heart block, HF exacerbation, and constipation (Verapamil).

Question 13

Hydralazine: Mechanism, Indication, & Drug-Induced Lupus

Accepted Answer

**Mechanism**: Direct arteriolar vasodilator ($\uparrow cGMP$) $\	o \downarrow$ afterload.
**Clinical Use**: Severe HTN, HF (in combination with nitrates), pregnancy-induced HTN.
**Adverse Effects**: Reflex tachycardia (co-administer with $\beta$-blocker), fluid retention, **Drug-induced Lupus Erythematosus** (associated with slow acetylators; anti-histone antibodies positive).

Question 14

Class IA Anti-arrhythmics: Agents, Mechanism, & ECG Findings

Accepted Answer

**Agents**: Quinidine, Procainamide, Disopyramide ("The **Queen** **Proclaims** **Diso** is **1A**").
**Mechanism**: Moderate $Na^+$ channel blockade (decreases Phase 0 depolarization slope) + $K^+$ channel blockade (prolongs action potential duration [APD] and effective refractory period [ERP]).
**ECG**: $\uparrow$ QRS duration, $\uparrow$ QT interval (risk of Torsades de Pointes).

Question 15

Class IB Anti-arrhythmics: Agents, Mechanism, & Tissue Preference

Accepted Answer

**Agents**: Lidocaine, Mexiletine ("**1B** **L**ikes **M**exican food").
**Mechanism**: Weak $Na^+$ channel blockade + accelerates repolarization ($\downarrow$ APD and ERP).
**Key Characteristic**: Highly selective for **ischemic or depolarized ventricular tissue**; minimal effect on normal atrial tissue. Used for post-MI ventricular arrhythmias.

Question 16

Class IC Anti-arrhythmics: Agents, Mechanism, & Contraindications

Accepted Answer

**Agents**: Flecainide, Propafenone ("**1C** **F**ries **P**otatoes").
**Mechanism**: Strong $Na^+$ channel blockade (markedly depresses Phase 0 slope); no effect on APD.
**ECG**: Significantly $\uparrow$ QRS duration.
**Contraindication**: Strictly **contraindicated in structural or ischemic heart disease** due to high risk of fatal proarrhythmias (CAST trial).

Question 17

Class II & Class IV Anti-arrhythmics: Nodal Mechanisms & ECG Changes

Accepted Answer

**Class II ($\beta$-blockers)**: Decreases $cAMP \	o \downarrow Ca^{2+}$ currents $	o \downarrow$ SA/AV node activity ($\downarrow$ Phase 4 slope).
**Class IV (Verapamil, Diltiazem)**: Blocks $L$-type $Ca^{2+}$ channels $	o \downarrow$ conduction velocity and $\uparrow$ ERP at AV node.
**ECG Effect**: Both cause **$\uparrow$ PR interval**; used for rate control in atrial fibrillation and flutter.

Question 18

Class III Anti-arrhythmics & Amiodarone Adverse Profile

Accepted Answer

**Class III Agents**: Amiodarone, Dofetilide, Ibutilide, Sotalol ("**A** **D**IS **3**"). Mechanism: $K^+$ channel blockers $\	o \uparrow$ APD, $\uparrow$ ERP, $\uparrow$ QT interval.
**Amiodarone Adverse Effects**: Pulmonary fibrosis, thyroid dysfunction (hypo/hyperthyroidism due to iodine content), hepatotoxicity, corneal microdeposits, blue-gray skin discoloration, bradycardia/heart block (Note: low Torsades risk despite long QT).

Question 19

Adenosine & Digoxin: Mechanisms & Clinical Indications

Accepted Answer

**Adenosine**: Activates $A_1$ receptors $	o \uparrow K^+$ efflux $	o$ hyperpolarizes AV node. First-line for acute **Paroxysmal Supraventricular Tachycardia (PSVT)**. Blocked by theophylline and caffeine.
**Digoxin**: Inhibits $Na^+/K^+$-ATPase $	o \uparrow$ intracellular $Na^+ \	o \downarrow Na^+/Ca^{2+}$ exchanger activity $	o \uparrow$ intracellular $Ca^{2+} \	o \uparrow$ inotropy. Stimulates vagus nerve ($\downarrow$ AV conduction). Used in systolic HF and AFib.

Question 20

HMG-CoA Reductase Inhibitors (Statins): Mechanism & Adverse Effects

Accepted Answer

**Mechanism**: Competitive inhibition of HMG-CoA reductase (converts HMG-CoA to mevalonate). Up-regulates hepatic LDL receptors $	o$ marked clearance of LDL from blood.
**Lipid Profile**: $\downarrow\downarrow\downarrow$ LDL, $\uparrow$ HDL, $\downarrow$ Triglycerides.
**Adverse Effects**: Hepatotoxicity (check baseline LFTs), myopathy/rhabdomyolysis (risk increases when combined with fibrates or CYP450 inhibitors).

Question 21

Non-Statin Lipid-Lowering Drugs: Key Mechanisms & Targets

Accepted Answer

**Fibrates (Gemfibrozil, Fenofibrate)**: Activate **PPAR-$\alpha$** $	o \uparrow$ LPL activity ($\downarrow\downarrow\downarrow$ Triglycerides). Increases risk of cholesterol gallstones and myopathy.
**Ezetimibe**: Inhibits **NPC1L1** transporter at intestinal brush border $	o \downarrow$ cholesterol absorption ($\downarrow$ LDL).
**PCSK9 Inhibitors (Evolocumab, Alirocumab)**: Inactivate PCSK9 protein $	o \uparrow$ LDL receptor recycling and density on hepatocytes ($\downarrow\downarrow\downarrow$ LDL).

USMLE Step 1 - High-Yield Autonomic & Cardiovascular Pharmacology

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