Cardiovascular Drugs

Cardiovascular Drugs Overview

• Treats cardiovascular diseases such as atherosclerosis, ischemic heart disease, heart failure, and hypertension.

Cardiovascular Drug Classifications

• Inotropic drugs, vasopressors, vasodilators, antiadrenergic, antiarrhythmic, diuretics, antithrombotic, and lipid-regulating drugs

Inotropic Drugs and Vasopressors

• Strengthen ventricular contraction by increasing intracellular calcium levels and improving cardiac output, when systolic functions are compromised.
• Include digitalis, sympathomimetic amines, phosphodiesterase-3 inhibitors, and vasopressin.

Cardiac Glycosides (Digitalis)

• Extracted from the foxglove plant, Digitalis purpurea.
• Improves failing heart contractility and prolongs the AV node refractory period.
• Works by increasing intracellular calcium, achieved by inhibiting the sodium-potassium pump.
• Delays conduction from the AV node to the Bundle of HIS, enhancing ventricular contraction.
• Prescribed for heart failure, but has side effects due to its action on sodium-potassium pumps affecting resting potential, action potential duration, and heart rhythm.

Sympathomimetic Amines

• Bind to cardiac beta 1 receptors, increasing calcium entry and force production.
• Activating beta 1 receptors triggers a cascade that increases calcium availability.
• Examples include dopamine, dobutamine, norepinephrine, epinephrine, and isoprotrenol.

Sympathomimetic Amines - Specific Drugs

• Dopamine: Induces different effects at different doses.
• Dobutamine: Stimulates beta1, beta2, and alpha receptors, increasing contraction force without raising blood vessel resistance.
• Norepinephrine and epinephrine: Endogenous, acting on alpha and beta receptors, increasing contraction force and causing potent vasoconstriction.
• Isoprotrenol: Synthetic epinephrine that exclusively acts on beta receptors.

Phosphodiesterase-3 Inhibitors

• Work by inhibiting phosphodiesterase 3, preventing cAMP breakdown, leading to higher calcium levels and increased contractility.

Vasopressin

• An antidiuretic hormone from the posterior pituitary gland.
• Acts as a potent vasoconstrictor by stimulating smooth muscle contraction.

Vasodilator Drugs

• Vital for treating hypertension and heart failure.
• Resistance decreases with dilated blood vessels, increasing flow and cardiac output.
• Counteracts vasoconstriction in heart failure and hypertension.
• Include ACE inhibitors, angiotensin II receptor antagonists (ARBs), direct-acting vasodilators, calcium channel blockers (CCBs), organic nitrates, natriuretic peptides, phosphodiesterase-5 inhibitors, and endothelin receptor antagonists.

ACE Inhibitors

• Inhibit the renin-angiotensin system (RAS) to maintain cardiovascular homeostasis.
• Blocking RAS reduces sodium retention and vasoconstriction.
• Lowers blood pressure and vascular resistance without affecting cardiac output or glomerular filtration.
• Side effects: cough, hypotension, renal insufficiency, and hyperkalemia.

Angiotensin II Receptor Antagonists (ARBs)

• Block angiotensin II receptors (AT1), working on the RAS pathway.
• More potent than ACE inhibitors.

Direct-Acting Vasodilators

• Relax smooth muscles in blood vessels, leading to vasodilation.
  • Hydralazine: Acts on arterioles, reducing blood pressure, but has low bioavailability and causes headaches.
  • Minoxidil: Acts more on arterioles, but usage is not very common.
  • Sodium Nitroprusside: Potent, acts on arteries and veins, decreases venous return and cardiac output, ideal for hypertension.
  • Fenoldopam: Intravenous, treats hypertension, and acts as a dopamine receptor agonist.

Calcium Channel Blockers (CCBs)

• Lower intracellular calcium availability by blocking calcium channels, promoting relaxation and reducing muscle cell contractions.

Organic Nitrates

• Mimic nitric oxide's action as a potent vasodilator.
• Nitroglycerin: Affects veins more at low doses and arterioles at high doses.
• Available as tablets or spray.

Natriuretic Peptide

• Released from the atria, causes vasodilation and sodium excretion.
• Nesiritide mimics natriuretic peptide effects.

Phosphodiesterase-5 Inhibitors

• Prevent cGMP breakdown, enhancing vasodilation and used for erectile dysfunction.

Endothelin Receptors Antagonists

• Cancel endothelin-1, which is a vasoconstrictor released by endothelial cells resulting in vasodilation.

Antiadrenergic Drugs

• Interfere with the sympathetic nervous system (SNS) at the central nervous system, postganglionic nerve endings, and peripheral receptors.
• Alpha 1 receptor activation causes vasoconstriction, beta 2 stimulates vasodilation. Alpha 2 in the CNS inhibits SNS and cause vasodilation.
• Types: central adrenergic inhibitors (CNS alpha 2 agonists), sympathetic nerve ending antagonists, peripheral alpha adrenergic receptor antagonists, beta adrenergic receptor antagonists.

Central Adrenergic Inhibitors (CNS Alpha 2-Agonists)

• Stimulating alpha 2 receptors on presynaptic neurons lowers SNS outflow, reducing vascular resistance and causing vasodilation.

Sympathetic Nerve Ending Antagonists

• Prevent norepinephrine uptake into storage vesicles rendering it unavailable and degrading it, , thus decreasing cardiac output and vascular resistance.

Peripheral Alpha Adrenergic Receptor Antagonists

• Act on both alpha 1 and alpha 2 receptors, decreasing cardiac output and vascular resistance.
• Used to treat hypertension.

Beta Adrenergic Receptor Antagonists

• Beta blockers are used for ischemia, hypertension, heart failure, and tachyarrhythmia, and slow down heart rate.

Antiarrhythmic Drugs

• Dangerous drugs with lots of side effects. Treatments must be closely watched.
• Classes I, II, III, and IV

Antiarrhythmic Drugs - Class I

• Class IA: Moderate sodium channel blocking that depolarizes cardiac muscle cells, reducing conduction velocity.
• Class IB: Inhibit fast sodium channels and shorten the cardiac action potential duration.
• Class IC: Most potent voltage-gated sodium channel blockers and prolong the AV node refractory period.

Antiarrhythmic Drugs - Class II

• Beta-adrenergic receptor antagonists which inhibit sympathetic activities.

Antiarrhythmic Drugs - Class III

• Significantly prolong the action potential of the Purkinje cells

Antiarrhythmic Drugs - Class IV

• Block L-type calcium channels.

Diuretics

• Treat heart failure and hypertension by working on the renin-angiotensin system (RAS), decreasing sodium reabsorption, and secretion of potassium.
• Kidneys reabsorb sodium and retain water. Kidneys respond to aldosterone (sodium retention) and antidiuretic hormone (water retention).
• Loop Diuretics: Minimize sodium reabsorption at the loop of Henle by inhibiting Na-Cl-K cotransporters. Less sodium in the blood mean reduce blood pressure.
• Thiazide Diuretics: Act on the distal convoluted tubule to minimize about 5% sodium reabsorption
• Potassium-Sparing Diuretics: Weak medication that act on the distal convoluted tubule and collecting duct. They reduce potassium excretion.

Antithrombotic Drugs

• Platelet monitoring and coagulation is important in cardiovascular disease patients.
• Clots form when damage exposes collagen in blood vessels, leading to coagulation. Coagulation can lead to blocking small blood vessels (ischemia).
• Antithrombotic drugs dissolve clots.

Classes of Antithrombotic Drugs

• Platelet inhibitors (aspirin, P2Y12 receptor antagonists, thrombin receptor antagonists, glycoprotein IIb/IIIa receptor antagonists).
• Anticoagulant drugs (parenteral agents): unfractionated heparin, low molecular weight heparin, direct thrombin inhibitors, factor Xa inhibitors.
• Anticoagulant drugs (oral agents): warfarin, newer oral anticoagulants.

Platelets Inhibitors

• Normal function is adhere to injury sites, release aggregation chemicals which promote clustering.

Anticoagulant Drugs (Parenteral Agents)

• Interfere in coagulation cascade to prevent hemostasis.
• Inhibit many clotting factors.

Anticoagulant Drugs (Oral Agents)

• Act by inhibiting the enzyme vitamin K epoxide reductase.

Lipid Regulating Drugs

• Abnormal plasma lipid profile is a major marker when diagnosing cardiovascular diseases.
• Target cholesterol level lowering in the plasma.