Cardiovascular Pharmacology: Excitation-Contraction Coupling, Hypertension, and Ischemic Heart Disease

Comprehensive practice flashcards reviewing excitation-contraction coupling across muscle types, first-line and add-on antihypertensive pharmacology, and therapies for ischemic heart disease and myocardial infarction.

Electromechanical Coupling

A physiological coupling mechanism linking muscle stimulation to contraction wherein membrane depolarization opens L-type $Ca^{2+}$ channels, triggering the release of intracellularly stored $Ca^{2+}$ from the sarcoplasmic reticulum.

Pharmacomechanical Coupling

A mechanism that initiates muscle contraction through receptor activation (such as G-protein coupled receptor stimulation yielding $IP_3$) without requiring prior membrane depolarization.

Calcium-Induced Calcium Release (CICR)

A biological process operating in cardiac myocytes and vascular smooth muscle wherein extracellular $Ca^{2+}$ influx through L-type $Ca^{2+}$ channels activates ryanodine receptor channels ($RyR2$) on the sarcoplasmic reticulum to discharge stored intracellular $Ca^{2+}$.

Malignant Hyperthermia (MH)

A life-threatening hereditary reaction triggered by volatile anesthetics (such as sevoflurane) in susceptible individuals, causing continuous, uncontrolled $Ca^{2+}$ leakage through mutated $RyR1$ channels, leading to sustained muscle rigidity, rapid ATP depletion, and extreme heat production.

Dantrolene

A pharmacological antagonist at $RyR1$ channels administered intravenously in emergency situations or as surgical prophylaxis to treat malignant hyperthermia by halting $Ca^{2+}$ release from the sarcoplasmic reticulum.

Dobutamine

A $\beta_1$-adrenergic receptor agonist administered intravenously in acute heart failure to improve cardiac output by elevating cAMP and activating PKA, which prolongs the opening duration of voltage-dependent L-type $Ca^{2+}$ channels during depolarization.

Myosin Light Chain Kinase (MLCK)

The calcium-calmodulin-activated kinase in smooth muscle that phosphorylates myosin light chains to permit actin-myosin interaction and contraction, substituting functionally for troponin C.

Blood Pressure Formula and Stages

The physiological relationship defined as $\text{Blood Pressure} = \text{Cardiac Output (CO)} \times \text{Total Peripheral Resistance (TPR)}$, categorized clinically into Stage 1 ($130\text{--}139 / 80\text{--}89\,mmHg$) and Stage 2 ($\ge 140 / \ge 90\,mmHg$).

Chlorthalidone

A thiazide-like diuretic that blocks the $\text{Na}^+\text{-Cl}^-$ cotransporter in the distal convoluted tubule, initially reducing blood pressure via decreased cardiac output, followed after $6\text{--}8\text{ weeks}$ by sustained pressure reduction mediated through lowered total peripheral resistance.

Thiazide-Induced Hypokalemia

A decline in serum potassium occurring when unabsorbed $\text{Na}^+$ reaches the collecting duct and enters epithelial sodium channels ($\text{ENaC}$), generating a negative luminal potential that accelerates $\text{K}^+$ secretion into urine via ROMK channels.

Thiazide-Induced Hyperuricemia

An elevation in plasma uric acid precipitated when thiazides exchange into the tubular lumen via the $OAT1$ and $URAT1$ antiporters in proximal tubules, simultaneously driving urate reabsorption into tubular cells for subsequent blood entry via $GLUT9$.

Lisinopril

An angiotensin-converting enzyme (ACE) inhibitor that lowers systemic blood pressure primarily by decreasing total peripheral resistance through reduced Angiotensin II synthesis and reduced aldosterone secretion.

ACE Inhibitor-Induced Cough and Angioedema

Adverse effects caused by the inhibition of bradykinin breakdown by ACE, resulting in bradykinin accumulation that sensitizes tracheal sensory nerves (inducing persistent dry cough) and increases post-capillary venular permeability (inducing angioedema of the lips, tongue, and throat).

Losartan

An angiotensin receptor blocker (ARB) targeting $AT_1$ receptors on vascular smooth muscle to block Angiotensin II-mediated vasoconstriction without elevating bradykinin, which uniquely features a uricosuric action by inhibiting the luminal $URAT1$ transporter in proximal tubules.

Efferent Arteriolar Vasodilation by RAAS Inhibitors

The therapeutic mechanism protecting kidneys in chronic kidney disease wherein ACE inhibitors or ARBs antagonize Angiotensin II-mediated constriction of efferent arterioles, reducing intraglomerular capillary hydrostatic pressure and preventing albuminuria.

Amlodipine-Induced Peripheral Edema

A characteristic adverse effect of dihydropyridine calcium channel blockers resulting from selective vasodilation of precapillary arterioles relative to postcapillary venules, driving up capillary hydrostatic pressure and causing fluid extravasation into dependent interstitial areas like the ankles.

Preload

The degree of stretch experienced by ventricular myocardium at the end of diastole as a consequence of venous filling, for which left ventricular end-diastolic pressure ($\text{LVEDP}$) functions as an indirect clinical parameter.

Afterload

The hydraulic resistance that opposes ventricular blood ejection during systole, directly determined by aortic blood pressure and demanding greater myocardial contractile force when elevated.

Prazosin

An $\alpha_1$-adrenergic receptor antagonist used as an add-on antihypertensive that lowers total peripheral resistance by preventing $\alpha_1$-mediated $IP_3$ generation and subsequent calcium release in vascular smooth muscle.

Ischemic Heart Disease (IHD)

A spectrum of cardiac pathologies encompassing stable angina pectoris and myocardial infarction, defined by an imbalance between myocardial oxygen supply and myocardial oxygen demand.

Coronary Perfusion Driving Pressure

The net hemodynamic gradient propelling myocardial blood flow during ventricular diastole, calculated as coronary artery pressure minus left ventricular end-diastolic pressure ($\text{Coronary Pressure} - \text{LVEDP}$).

Glyceryl Trinitrate (GTN)

A rapid-acting nitrate that donates nitric oxide ($\text{NO}$) to activate smooth muscle cGMP and PKG, thereby enhancing myocardial $O_2$ supply via coronary collateral dilation and lowering myocardial $O_2$ demand by preferentially dilating systemic veins to decrease preload.

Coronary Steal

An adverse hemodynamic phenomenon provoked by arteriolar dilators such as dipyridamole, which dilate healthy vessels while leaving autoregulated ischemic vessels unaffected, thereby diverting perfusion away from ischemic myocardium.

Metoprolol and Diltiazem Contraindication

A drug combination generally avoided in clinical practice due to dual inhibition of cardiac L-type $Ca^{2+}$ channels and AV node conduction, which produces profound bradycardia and severe hypotension.

Non-ST-Segment Elevation Myocardial Infarction (NSTEMI)

An acute presentation of myocardial necrosis diagnosed by severe prolonged chest pain unresponsive to sublingual nitrates, EKG findings of ST-segment depression with T-wave inversion, and elevated high-sensitivity cardiac troponin ($\text{hs-cTn}$).

Aspirin Mechanism in Acute Myocardial Infarction

The irreversible acetylation and inhibition of cyclooxygenase-1 ($\text{COX-1}$) in platelets, preventing the conversion of arachidonic acid to prostaglandin $H_2$ ($\text{PGH}_2$) and blocking thromboxane $A_2$ ($\text{TXA}_2$) formation to halt platelet aggregation.