Cardiovascular Pharmacology Quiz

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Questions and Answers

What happens to the contractile function of a healthy heart when venous return increases?

It remains unchanged.

It decreases due to increased pressure.

It increases, thereby pumping more blood. (correct)

It fluctuates depending on heart rate.

Which system regulates the cardiovascular system, particularly the heart?

Somatic nervous system

Autonomic nervous system (correct)

Endocrine system

Central nervous system

What is the role of calcium in excitation–contraction coupling in the myocardium?

Calcium solely regulates heart rate.

Calcium is crucial for muscle contraction. (correct)

Calcium inhibits muscle contraction.

Calcium promotes the release of energy from ATP.

Which group of drugs directly affects myocardial cells?

Cardiac glycosides and other inotropic drugs Signup and view all the answers

How do calcium antagonists affect cardiac function?

By affecting myocardial cells and relaxing vascular smooth muscle. Signup and view all the answers

What type of change is referred to as inotropy?

Change in myocardial contractility. Signup and view all the answers

Which of the following statements regarding heart regulation is incorrect?

Heart rate is not influenced by the autonomic nervous system. Signup and view all the answers

Which type of drugs is most likely to be used indirectly to treat heart function?

Diuretics and ACE inhibitors Signup and view all the answers

What is the primary enzymatic action inhibited by Milrinone?

Inhibition of phosphodiesterase 3 Signup and view all the answers

Which formulation of Pimobendan has the highest oral bioavailability when administered correctly?

60-70% Signup and view all the answers

What is the effect of inhibiting PDE III in vascular smooth muscle?

Vasodilation Signup and view all the answers

Which of the following statements about Inamrinone and Milrinone is true?

They have both inotropic and vasodilatory effects. Signup and view all the answers

What major metabolite of Pimobendan is known to be more potent in inhibiting PDE III than Pimobendan itself?

Desmethylpimobendan Signup and view all the answers

Which class of drugs are considered alternatives to digoxin for treating congestive heart failure?

Inodilators Signup and view all the answers

What is a major consequence of increased cAMP due to PDE III inhibition?

Increased inotropic effects Signup and view all the answers

Which of the following is not a recommended practice when administering Pimobendan?

Administering with a high-fat meal Signup and view all the answers

What is the primary factor that determines cardiac output?

Stroke volume and heart rate Signup and view all the answers

Which phase of the action potential is associated with rapid depolarization?

Phase 0 Signup and view all the answers

What influences preload in the cardiovascular system?

Volume of blood returning to the heart Signup and view all the answers

What does afterload refer to in cardiac physiology?

The pressure that the heart must work against to eject blood Signup and view all the answers

Which part of the heart lacks a fast Na+ current during action potentials?

Atrioventricular node Signup and view all the answers

Which of the following systems is involved in the neurohormonal control of cardiac output?

Renin-angiotensin-aldosterone system (RAAS) Signup and view all the answers

What percentage of horses in a study were reported to have cardiac diseases?

8.3% Signup and view all the answers

Which class of drugs is primarily used to improve cardiac contractility?

Positive inotropes Signup and view all the answers

During which phase of the action potential does calcium influx primarily occur?

Phase 2 Signup and view all the answers

Which aspect is NOT part of the basic functions of the cardiovascular system?

Regulating blood oxygen levels Signup and view all the answers

What is the main clinical drug derived from the Digitalis purpurea plant?

Digoxin Signup and view all the answers

What is the mechanism of action of digitalis in cardiac cells?

Inhibition of Na+,K+-ATPase Signup and view all the answers

What is a positive inotropic effect of digitalis?

Improved myocardial contractility Signup and view all the answers

Which of the following is a potential risk associated with the use of digitalis?

Arrhythmias Signup and view all the answers

How does digitalis affect heart rate in patients with heart failure?

Decreases heart rate due to vagal stimulation Signup and view all the answers

Digitalis can enhance automaticity in cardiac cells. This effect can lead to which of the following?

Arrhythmias due to increased depolarization slope Signup and view all the answers

What effect does digitalis have on cardiac output?

It increases cardiac output by improving contractility Signup and view all the answers

What is one of the main challenges in using cardiac glycosides like digitalis in clinical practice?

Narrow therapeutic margin between effective and toxic doses Signup and view all the answers

Which of the following effects of digitalis does NOT contribute to cardiac performance enhancement?

Increase in afterload Signup and view all the answers

What outcome results from the positive inotropic effect of digitalis in heart failure patients?

Heart size reduction Signup and view all the answers

What is the primary action of ACE inhibitors in the treatment of chronic heart failure?

Blunt the negative effects of pathological remodeling Signup and view all the answers

Which ACE inhibitor is noted for being quickly converted to its active form in the liver?

Enalapril Signup and view all the answers

What are the main effects of ACE inhibitors on plasma volume and heart load?

Decrease plasma volume and cardiac load Signup and view all the answers

Which adverse effect is less common when administering ACE inhibitors in animals?

Fluid retention Signup and view all the answers

What characterizes Angiotensin II Receptor Blockers (ARBs) compared to ACE inhibitors?

They bind to angiotensin II receptors directly Signup and view all the answers

What is a key indication for prescribing ARBs in veterinary medicine?

Control of systemic hypertension in cats Signup and view all the answers

Which statement regarding the pharmacokinetics of benazepril is true?

The active metabolite can be given to animals with kidney disease Signup and view all the answers

What are the consequences of chronic use of ACE inhibitors in animals?

Long-term beneficial effects despite renal failure Signup and view all the answers

Which of the following is a common practice regarding the dosage of ARBs in veterinary medicine?

Administered at 1.5 mg/kg PO q12h for the first 14 days Signup and view all the answers

Which of the following is an outcome expected from the use of ACE inhibitors in managing glomerular hypertension?

Stabilization of the glomerular basal membrane Signup and view all the answers

What is the main benefit of using mixed or balanced vasodilators in heart failure?

They decrease the workload of the heart. Signup and view all the answers

Which of the following is an example of an α1-adrenergic selective blocking agent?

Prazosin Signup and view all the answers

What is the primary clinical use of hydralazine hydrochloride?

Improvement of cardiac output in congestive heart failure. Signup and view all the answers

What adverse effect is most frequently associated with calcium channel blockers?

Tachycardia Signup and view all the answers

Which of the following is true regarding the mechanism of action of organic nitrates?

They increase intracellular cyclic-GMP levels. Signup and view all the answers

Which drug is primarily used for the management of systemic hypertension in cats?

Amlodipine Signup and view all the answers

What is a notable side effect of nitrovasodilators?

Hypotension Signup and view all the answers

Which calcium channel blocker primarily affects cardiac electric conduction?

Diltiazem Signup and view all the answers

What class of drugs does carvedilol belong to?

Nonselective β1 and β2 receptor antagonist Signup and view all the answers

What is the effect of calcium channel blockers regarding ventricular wall tension?

Decrease wall tension Signup and view all the answers

What is the primary therapeutic goal of antihypertensive therapy?

Restoration of normal blood pressure Signup and view all the answers

Which condition is least likely to contribute to secondary hypertension?

Systolic dysfunction Signup and view all the answers

Which of the following best describes the effect of sildenafil in veterinary medicine?

It treats pulmonary hypertension by preventing degradation of cGMP. Signup and view all the answers

What is a common formulation route for nitroglycerin in veterinary use?

Topical ointment Signup and view all the answers

Study Notes

Cardiovascular Pharmacology I

Presented by Nuno Coelho, DVM, PhD
Part of a Pharmacology and Therapeutics II Master's Degree program in Veterinary Medicine
Course content focused on cardiovascular pharmacology
Covers basic cardiac function, modulation, and related drugs.

Summary of Topics

Introduction: Covers basic aspects of cardiac function and the need for pharmacological modulation.
Digitalis: Discussion of digitalis.
Positive inotropes: Information on positive inotropic drugs.
Vasodilators: Details on vasodilator drugs.
Antihypertensive drugs: Information on antihypertensive drugs.
Antiarrhythmics: Discussion of antiarrhythmic drugs.

Abbreviations

AV: atrioventricular
Ca: calcium
CHF: congestive heart failure
CNS: central nervous system
CO: Cardiac output
CRI: constant rate infusion
EDV: end diastolic volume
ESV: end systolic volume
HCM: hypertrophic cardiomiopathy
HR: heart rate
LA: left atria
LV: left ventricle
MMVD: myxomatous vitral valve disease
PS: parasympathetic nervous system
RA: right atria
RAAS: renin-angiotensin-aldosterone system
RV: right ventricle
S: sympathetic nervous system
SV: Stroke volume
V: ventricle

Introduction

Cardiac disease is common in dogs and cats (10% in dogs, 15% in cats), and cardiomyopathies are common in cats
Smaller breeds of dogs are more prone to myxomatous mitral valve disease (MMVD); larger breeds to dilated cardiomyopathy (DCM)
In horses, 8.3% have cardiac diseases.

Introduction: Basic Aspects of Cardiovascular Function

Electrophysiological features of cardiac muscle: pacemaker activity, absence of fast Na+ current in SA and AV nodes, long plateau phase, and influx of calcium during the plateau
Phases of action potential: rapid depolarization, partial repolarization, plateau, repolarization, and resting membrane potential.
Cardiac output (CO): total volume of blood pumped by one ventricle per minute, depends on stroke volume (SV) and heart rate (HR). Neurohormonal control plays a critical role affecting the CO with factors including pressure sensors, CNS, sympathetic and parasympathetic systems, and RAAS.
Preload: initial stretching of cardiac myocytes at the end of ventricular filling influenced by venous return; affects the initial stretch of the ventricular muscle cells
Afterload: pressure the heart must work against to eject blood during systole affecting the pressure against which the heart pumps blood.
Heart adjusts its pumping activity with venous return affecting contractile function and pumping blood into arterial system. Adjusting pumping capacity to filling volume.
Frank-Starling law of the heart: within physiological limits, the heart pumps all the blood that returns to it, and stroke volume increases with increased end-diastolic volume. Increasing ventricular filling leads to more optimal sarcomere length increasing stroke volume. The heart can adjust its pumping force to match incoming blood volume.
Sympathetic and parasympathetic modulation affect heart rate, vascular volume, and myocardial contractility adjusting cardiac function via inotropy (contractility) and chronotropy (heart rate)
Excitation-contraction coupling: action potential spreads into the cell via T tubules, voltage-dependent calcium channels open, extracellular calcium enters the cell promoting release of more calcium from the sarcoplasmic reticulum - Ca crucial for muscle contraction.
Vascular resistance: Map (mean arterial pressure) ≈ CO x SVR (systemic vascular resistance). Arterial pressure in hypertension due to increased SVR, decrease arterial pressure in hemorrhage or dehydration from decreased CO and increased SVR.
Important to minimize fall in BP and ensure diversion to critical organs is maintained in short-term situations like hemorrhage or dehydration.

Drugs Affecting Cardiac Function

Drugs affecting the heart and vessels can be grouped into: drugs that affect myocardial cells directly (cardiac glycosides, autonomic neurotransmitters, antidysrhythmics, miscellaneous, and hormones), drugs affecting cardiac function indirectly affecting the vascular system, calcium antagonists, and vasodilatory agents.
Calcium antagonists affect myocardial cells directly and indirectly by relaxing vascular smooth muscle.
Vasodilatory agents and antihypertensive drugs.

Inotropic Drugs - Cardiac Glycosides

Digitalis, derived, leaf from purple foxglove plant, contains digoxin, digitoxin, and gitoxin for clinical use. Only digoxin is relevant.
Digitalis designated the cardiac glycoside group also linked by oxygen to a sugar molecule.
Mechanism of action: inhibition of Na+,K+-ATPase. Increase in intracellular Na reduces Ca2+ extrusion. Increasing intracellular Ca2+ delivery to contractile proteins is increased, resulting in a positive inotropic effect.
Decrease in K+ can lead to arrhythmogenic properties of digitalis
Cardiovascular effects improve myocardial contractility.
Other effects: facilitate neurohormonal normalization, slows AV conduction, reduced conduction rate, prolongs AV node refractory period, and some diuresis.
PK in dogs: good oral absorption (75-90%), peak concentrations in serum in about 90 minutes. Significant variable half-lives (15-50 hours) thus needing individualised dosage.
PK in horses: less oral absorption and a half life of 17 hours; similar metabolism to dogs.
Therapeutic indications: congestive heart failure, atrial fibrillation with rapid ventricular response.
Toxicity: inappetence, depression, mild gastrointestinal upset (loose stools, vomiting, diarrhea, nausea), neurological signs, ECG abnormalities, and eventually death.
Therapeutic drug monitoring: monitoring plasma concentrations to ensure efficacy and minimise toxicity.

Sympathomimetic Agents

Inodilators: improving cardiac performance primarily with myocardial B1 receptors, activation of second messengers, and increasing intracellular calcium to enhance contractility.
Dobutamine: primarily used for positive inotropic effects in emergency heart failure management in dogs (minimally proarrhythmic), with a short half-life requiring continuous infusion.
Dopamine: although its interactions with receptors (dopaminergic DA1 and DA2) also affect cardiac B1 receptors, having significant positive inotropic, chronotropic, dromotropic, and vasoconstrictive effects that vary dependent upon dose.
Dopamine can have a positive or negative effect on blood pressure, renal blood flow and systemic resistance depending upon dose. Can also be used in hypotension associated with anesthetic and noncardiogenic shock.

Inodilators

Pimobendan: positive inotropic and vasodilatory properties, commonly used in veterinary medicine to manage congestive heart failure and showed an improved survival profile.
Clinical implications: used in clinical management of canine heart failure secondary to DCM or myxomatous mitral valve disease (MMVD) in dogs and also has some efficacy in cats, with no arrhythmogenic activity
Mechanism of action: a phosphodiesterase (PDE) III inhibitor which mediates via sensitization of the myocardial contractile apparatus to intracellular calcium and inhibits PDE III. Calcium sensitization allows for positive inotropic effects without increasing myocardial oxygen demand. Also results in vasodilation.
PK and formulations: quick oral absorption with peak plasma levels within an hour, oral bioavailability of 60-70%, reduced when taken with food
Administer at least 1 hour after feeding - excreted via bile into feces.
Major metabolite (desmethylpimobendan) is more potent as an inhibitor of PDE III than pimobendan and with slightly longer half-life.

Other Inotropic Agents

Innamrinone (formerly amrinone) and milrinone are bipyridine derivatives and often called nonglycoside, noncatecholamine inotropic drugs which have inotropic action also with peripheral vasodilator effects, typically alternatives to digoxin in congestive heart failure.
Mechanism of action: milrinone is an effective and selective inhibitor of phosphodiesterase 3 (PDE-III) which is responsible for the breakdown of cAMP - increasing cAMP results in inotropic effects and adverse effects.

Drugs that Inhibit RAAS

Angiotensin-converting enzyme (ACE) inhibitors: reduce angiotensin II and aldosterone secretion, commonly used as long-acting effects. Include captopril, enalapril, and benazepril. ACE inhibitors prevent conversion of angiotensin I to angiotensin II, reducing blood pressure.
Angiotensin receptor blockers (ARBs): block the angiotensin II receptor, affecting vasoconstriction and aldosterone secretion, often used due to improved efficacy compared to ACE inhibitors in cases of over-activation of RAAS. Include telmisartan, valsartan, and others.
Blocks angiotensin II (potent vasoconstrictor) which causes vasoconstriction of the blood vessels and also increases aldosterone secretion to promote Na+ and water retention in the kidneys ultimately increasing blood pressure.
Chronic use of these drugs can have adverse effect, including hypotension and a negative inotropic effect. ACE inhibitors may cause cough in some instances

ARBs

Clinical indications: systemic hypertension in cats and proteinuria caused by CKD, more effective than ACE Inhibitors
In dogs, less studies, but may be used similar to cats in ineffective cases of ACE inhibitors.
Available in 4 mg/ml oral solution.
Adverse events: transient hypotension
Mechanism of action: directly blocks angiotensin II receptor rather than inhibiting synthesis of angiotensin II (as ACEIs); high affinity and selectivity for angiotensin II subtype 1 (AT-1) receptor.

Mineralocorticoid Receptor Blockers

Spironolactone: a synthetic 17-lactone drug, a competitive blocker of aldosterone receptor, increases urinary Na+ and H2O excretion and decreases K+ excretion which is important for pathological cardiac remodeling, (inflammation, hypertrophy, fibrosis); useful as adjunctive therapy with ACEIs for heart failure.
Mechanism: blocks aldosterone; increase in urinary Na+ and H2O excretion; decrease K+ excretion
Rationale for adding spironolactone as an adjunct is due to the role of aldosterone in cardiac remodelling which includes inflammation, hypertrophy, fibrosis.
Absorption: Relative quickly absorbed through the GI tract, with higher bioavailability with food (80-90%).

Other Vasodilators

Venous dilators/venodilators: reduce preload, eg. Nitroglycerin
Arteriolar dilators/arteriodilators: reducing afterload; eg. Hydralazine and amlodipine
Mixed or balanced vasodilators: dilate both arterioles and veins and include ACEIs, prazosin, pimobendan and nitroprusside for reducing cardiac workload as a treatment.
Rationale for vasodilators in heart failure is that decreasing workload of the heart is better than using drugs with potential toxic effects.
Calcium channel blockers: includes dihydropyridines (amlodipine, nifedipine, having greater vascular selectivity, and nondihydropyridines (diltiazem, verapamil). Mechanism: selectively inhibits L-type Ca++ channel preventing opening within smooth muscle.
Nitrodilators/nitrovasodilators: include nitroglycerin, isosorbide dinitrate, and nitroprusside, using exogenous NO as a source for vasodilation; increase intracellular cyclic GMP inhibiting vascular smooth muscle contraction
Sildenafil (Viagra): orally active PDE5 inhibitor, preventing degradation of cGMP for smooth muscle relaxation in pulmonary and systemic vasculature used for pulmonary hypertension.
Carvedilol: nonselective B1 and B2 receptor and a1-receptor antagonist reduces myocardial workload lowering heart rates; useful for hypertension and heart failure

Antihypertensive Therapy

Goal: progressive, gradual reduction in blood pressure.
Mechanism of action of antihypertensive drugs is based on 3 effects: altering cardiac output, reducing circulating blood volume, and promoting vasodilation.
Classification includes a and B blockers (prazosine, propanolol), calcium channel blockers (amlodipine and others), renin inhibitors, diuretics; important also to differentiate between different types of blockers.
Causes of hypertension in dogs and cats.
Practical considerations include monitoring blood pressure, and tailoring dosage to efficacy and adverse effects.

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Description

Test your knowledge on cardiovascular pharmacology, focusing on heart contractility, the role of calcium in cardiac function, and the impact of various drugs on myocardial cells. This quiz also covers the regulation of the cardiovascular system and enzymatic actions related to heart function.