Cardiovascular Agents

Question 1

Quinidine, Procainamide, Disopyramide

Answer 1

Class IA Antiarrhythmic Agents

Bind to activated Na+ channels and block the flow of Na+ into the cardiac myocyte. This prolongs phase 0 depolarization of the AP, slowing the rate of conduction and HR. Phase 3 repolarization delayed somewhat (prolonged QT interval on EKG) with small interaction with K+ channels, leads to longer refractory period and myocyte is unable to fire as frequently.

Rx and prevent variety of arrhythmias: A fib, V tach. SE: cause arrhythmias. Q - GI upset, cinchonism (vertigo, HA, tinnitus, psychosis). P - drug induced lupus, psychosis. D - urinary retention, diplopia, constipation.

All class I are use-dependent: more active at ion channels that are depolarizing more frequently.

Question 2

Lidocaine, Tochainide, Mexiletine

Answer 2

Class IB Antiarrhythmic Agents

Bind to both activated and inactivated Na+ channels and block the flow of Na+ into the cardiac myocyte. Blocked inactive channels cannot be activated, so phase 3 repolarization and the entire duration of the AP is shortened. This causes a diminished ability for the myocyte to be stimulated to contract.

Rx of ventricular arrhythmias: V fib, V tach. SE: cause arrhythmias, hypotension, tremor, fatigue, nausea. Lidocane also local anesthetic.

All class I are use-dependent: more active at ion channels that are depolarizing more frequently.

Question 3

Flecainide, Encainide, Propafenone

Answer 3

Class IC Antiarrhythmic Agents

Bind to activated Na+ channels and block the flow of Na+ into the cardiac myocyte. This prolongs phase 0 depolarization of the AP, slowing the rate of conduction and thus contraction. No effect on duration of AP like IA.

Rx of supraventricular arrhythmias. SE: exacerbate or induce life-threatening arrhythmias, heart failure exacerbation (avoid in pts with depressed ejection fraction).

All class I are use-dependent: more active at ion channels that are depolarizing more frequently.

Question 4

Propanolol, Metoprolol

Answer 4

Class II Antiarrhythmic Agents

Beta-blockers. Blocking B1 leads to decreased HR and contractility, lower CO leads to reflex peripheral vasoconstriction, net decreased BP. Metoprolol is B1 selective.

Rx of arrhythmias.

Question 5

Sotalol, Ibutilide, Dofetilide, Bretylium

Answer 5

Class III Antiarrhythmic Agents

Bind to K+ channels and block flow out of myocyte. This prolongs phase 3 repolarization (prolonged QT interval on EKG) and the entire AP, increasing the refractory period, and decreasing the contractile frequency. Sotalol also a potent Beta-blocker.

Rx of atrial arrhythmias, rarely ventricular in emergencies. SE: may cause arrhythmias, bradycardia, hypotension.

Question 6

Verapamil, Diltiazem

Answer 6

Class IV Antiarrhythmic Agents

Blocks voltage-gated Ca++ channels in cardiac and smooth muscle, blocking flow of Ca++ into cell. By blocking in SA and AV nodes, slows phase 4 spontaneous depolarization there and leads to delayed activation/contraction (prolonged PR interval on EKG). Also delay repolarization, prolonging the refractory period and decreasing contractile frequency.

Rx of supraventricular tachycardia (A fib). SE: hypotension, heart block. Since relax smooth muscle, also used to Rx HTN and angina (Ca++ channel blockers).

Question 7

Amiodarone

Answer 7

Class I-IV Type Antiarrhythmic Agent

Blocks Na+, K+, Ca++ channels, some a and B adrenergic blocking effects. Prolongs the AP and refractory period.

Rx of atrial and ventricular tachycardias. SE: pulmonary fibrosis, hepatotoxicity, thyroid dysfunction, arrhythmias, ataxia, photosensitivity.

Question 8

Adenosine, Potassium, Magnesium

Answer 8

Other Antiarrhythmic Agents

Adenosine: increases K+ efflux out of cells of the SA and AV nodes, hyperpolarizing the cell and decreasing frequency of activation. Used in diagnosis and Rx of supraventricular tachycardias. SE: flushing, dyspnea, hypotension, heart block.

Potassium: Increase extracellular concentration of K+, raising threshold of cradiac AP, making it more difficult to generate AP/contract. Used to suppress ectopic pacemakers, especially when associated with Digoxin toxicity. SE: hyperkalemia, arrhythmias, paralysis, shock.

Magnesium: MOA unclear, effects ion flow through Na+, K+, Ca++ channels. Used to Rx Torsades de Pointes and Digoxin toxicity. SE: hypermagnesmia, hypotension, delayed DTRs, paralysis, shock.

Question 9

__oxin

Answer 9

Cardiovascular Agent

Cardiac glycoside. Inhibits cardiac Na+/K+ ATPase pump, which increases intracellular Na+ that then inhibits the Na+/Ca++ exchanger, increasing intracellular Ca++ and ultimately increasing cardiac contractility. Also increases parasympathetic outflow at the SA/AV nodes, decreasing HR.

Rx for heart failure, atrial arrhythmias. SE: GI upset, blurry yellow vision, ECG changes ( long PR, short QT, ST-segment scooping, T-wave inversion), arrhythmias. Exacerbated by hypokalemia (compete), renal failure (high levels), and Quinidine use (displaces from albumin). Treat toxicity by stopping Digoxin, correcting hypokalemia, administer Dignoxin immune antibody (anti-dig Fab fragments).

Ex: Digoxin, Digitoxin, Ouabain.

Question 10

Nitroglycerin

Answer 10

Cardiovascular Agent. Venodilator.

Converted to NO which stimulates guanylate cyclase, increasing cGMP. This dephosphorylates and deactivates myosin light chains, resulting in smooth muscle relaxation, mostly veins (and coronary arteries). Blood pools in veins, reducing preload.

Rx of angina, pulmonary edema, heart failure. SE: transient compensatory tachycardia, HA, orthostatic hypotension.

Ex: Isosorbide dinitrate, Isosorbide mononitrate, Amyl nitrate

Question 11

Nitroprusside

Answer 11

Cardiovascular Agent. Vasodilator.

Converted to NO which stimulates guanylate cyclase, increasing cGMP. This dephosphorylates and deactivates myosin light chains, resulting in smooth muscle relaxation in BOTH arteries and veins. Results in a reduction in PVR and venous return (afterload and preload).

Used in acute management of hypertensive crisis or severe heart failure. SE: cyanide toxicity (metabolite, treat with Thiosulfate), orthostatic hypotension, metabolic acidosis, arrhythmia. Only given IV to avoid more cyanide formation in GI tract.

Question 12

__pril

Answer 12

Angiotensin-Converting Enzyme Inhibitors. Vasodilators.

Low blood pressure activates Angiotensinogen from liver to be cleaved by Renin from kidney to form Angiotensin1, which is cleaved by ACE (peptidyl dipeptidase) to Angiotensin2, a vasoconstrictor of the kidney efferents which stimulates release of Aldosterone from adrenals, which holds on to H2O and Na+ to increase BP and volume.

Blocking ACE blocks Aldosterone, which leads to dilated blood vessels with less volume, leading to lower PVR and BP, reduces afterload. Also results in more of the vasodilator Bradykinin (prevents degredation).

Rx for HTN, CHF, prevents and treats diabetic nephropathy, decreases mortality post-MI. Usually combined with a B-blocker, nitrate, and Ca++ channel blocker. SE: COUGH (excess bradykinin), renal failure in insufficient pts, hypotension, teratogen, angioedema.

Ex: Captopril, Elanapril, Lisinopril.

Question 13

__sartan

Answer 13

Angiotensin Receptor Blockers. Vasodilators.

Low blood pressure activates Angiotensinogen from liver to be cleaved by Renin from kidney to form Angiotensin1, which is cleaved by ACE (peptidyl dipeptidase) to Angiotensin2, a vasoconstrictor of the kidney efferents which stimulates release of Aldosterone from adrenals, which holds on to H2O and Na+ to increase BP and volume.

Blocks the Angiotensin II receptor, blocking the renal efferents vasoconstriction (increases perfusion pressure in glomeruli) and production of Aldosterone. Ultimately decrease PVR and circulating volume, reduces afterload. NO effect on Bradykinin = no cough or angioedema.

Rx of HTN, CHF, treat and prevent diabetic nephropathy. SE: hyperkalemia, renal failure in insufficient pts, hypotension, teratogen, rash.

Ex: Losartan, Valsartan, Candesartan, Eprosartan Irbesartan, Telmisartan.

Question 14

Hydralazine

Answer 14

Cardiovascular Agent. Arteriolar Vasodilator.

Direct relaxation of arteriolar smooth muscle, decreasing BP. May block the release of Ca++ from SR, inhibiting contraction, but MOA unknown. Reduces afterload.

Rx of HTN, heart failure. SE: HA, reflex tachycardia (may provoke angina in CAD), GI upset, drug-induced lupus, fluid retention and edema.

Question 15

Minoxidil

Answer 15

Cardiovascular Agent. Arteriolar Vasodilator.

Direct relaxation of arteriolar smooth muscle by opening K+ channels to hyperpolarize myocyte and inhibit contraction, decreasing BP and reducing afterload.

Rx of refractory HTN. SE: hair growth when applied topically. Rogain.

Question 16

__dipine

Answer 16

Calcium Channel Blockers. Arteriolar Vasodilator.

Block the voltage-gated Ca++ channels of cardiac and vascular smooth muscle, inhibiting flow of Ca++ into cells, leading to decreased contraction. Results in peripheral vasodilation and reduced afterload.

Rx: HTN, Prinzmetal angina (vasospasm). SE: hypotension, peripheral edema (A). Use caution in pts with decreased ejection fractions due to negative inotropic effects. Greater effect on vascular smooth muscle except Verapamil (cardiac tissue).

Ex: Nifedipine, Nicardipine, Amlodipine. Class IV Anti-A also Rx supraventricular tachycardias, cause bradycardia and heart block: Verapamil, Diltiazem.

Question 17

Mannitol

Answer 17

Osmotic Diuretic.

Acts on proximal tubule and descending limb of loop of Henle. Increases tubular osmolarity and draws water in to urine to decrease blood volume, decreases preload.

Rx: decreasing intracranial or intraocular pressure by volume depletion, acute renal failure (and prevent after toxin exposure, trauma, or shock). SE: GI upset, HA, dehydration. Contraindicated in CHF (early expansion of fluid leads to pulmonary edema)

Ex: Mannitol, Urea. Eye procedures only: Glycerin, Isosorbide.

Question 18

__zolamide

Answer 18

Diuretics. Carbonic-Anhydrase Inhibitors.

Carbonic Anhydrase catalyzes the CO2 to HCO3- reaction, allowing for bicarbonate resorption and keeping Na+. Inhibiting CA in the proximal convoluted tubule leads to less bicarb resorption, therefore more Na+ loss, leading to increased renal water and electrolyte loss (K, Na, Ca, HCO3). Decreases preload. CA is also in the eye, producing aqueous humor.

Rx: glaucoma, alkalizing urine in cases of toxin ingestion (Salicylate, Barbituates), treatment and prophylaxis of altitude sickness (decreases CSF production), adjunct therapy for epilepsy, diuresis in metabolic alkalosis. SE: hyperchloremic metabolic acidosis, hypokalemia, sedation.

Ex: Acetazolamide, Dorzolamide, Brinzolamide.

Question 19

__semide

Answer 19

Loop Diuretics

Sulfonamide derivative, inhibits the coupled Na+/K+/2Cl- transport system in the thick ascending portion of the loop of Henle. Retains NaCl , K+, and water in urine, leading to loss of water and electrolytes, decreases preload.

Rx: heart failure (with pulmonary edema), liver/renal failure, HTN, hypercalcemia. SE: hypokalemia, metabolic alkalosis, ototoxicity, hypovoleia, interstitial nephritis, hyperuricemia (Gout attacks from urea reabsorption), hypomagnesemia. If sulfa allergy or unable to tolerate or Gout, use Ethacrynic Acid.

Ex: Furosamide, Torsemide, Bumetanide

Question 20

Hydrochlorothiazide

Answer 20

Diuretic.

Inhibits Na+/Cl- transporter in early distal convoluted tubule, increasing retention of NaCl and water in urine, resulting in loss of water and salt, decreases preload. Increased Na+ and K+ loss, less Ca++ loss.

Rx: HTN, heart failure, nephrogenic diabetes insipidus, recurrent kidney Ca++ stones. SE: Hypokalemia, hyperglycemia/lipidemia/uricemia/calcemia, metabolic acidosis, hypersensitivity rxns.

Ex: Chlorothiazide, Metolazone, Chlorthalidone, Idapamide.

Question 21

Spironolactone

Answer 21

Potassium Sparing Diuretic.

Competitive Aldosterone receptor antagonist, binds in cortical collecting and late distal tubules. Salt and water retention decreases, decreases preload. Potassium sparing because no drive to exchange it for Na+ resorption.

Rx: hyperaldosteronism (adrenal tumors, heart/liver failure, nephrotic syndrome), HTN, hirsutism. SE: Hyperkalemia, metabolic acidosis, gynecomastia, GI upset.

Others: Triamterene, Amiloride. Block Na+ channels in distal cortical collecting tubules, stopping Na+ and water resorption. Used in patients without Aldosterone (Addison disease).

Question 22

__rione

Answer 22

Phosphodiesterase Inhibitors (PDE3). Cardiovascular Agents.

Inhibits phosphdiesterase isozyme III in cardiac and smooth muscle, resulting in increased cAMP, which opens Ca++ channels and allows Ca++ to enter cell and increase contractility.

Rx of acute decompensated heart failure. SE: nausea, vomiting, arrhythmias, thrombocytopenia.

Ex: Milrione, Amrione

Question 23

__afil

Answer 23

Phosphodiesterase Inhibitors (PDE5). ED Treatment

Inhibits type 5, which prevents degradation of cGMP in corpus cavernosum. Causes relaxation of the smooth muscle, leading to increased blood flow.

Rx erectile dysfunction, pulmonary hypertension. Contraindicated in patients on nitrates (severe hypotension due to potentiation).

Ex: Sildenafil, Tadalifil, Verdenafil.

Question 24

__parin

Answer 24

Anticoagulant Agent

Binds Antithrombin III to accelerate its action (degrading activated clotting factors like thrombin). Short half-life, rapid onset, check with PTT. LMW degrade activated factor X faster and have longer duration. Safe in pregancy.

Use to Rx and prevent DVTs, PE, thromboemboli, MI. SE: bleeding (treat with protamine sulfate), HIT Heparin-induced thrombocytopenia (Rx with Argatroban, from antiplatelet antibodies), allergy.

Ex: Heparin, LMW: Enoxaparin, Dalteparin

Question 25

Warfarin

Answer 25

Anticoagulant Agent

Inhibit vitamin K-dependent gamma-carboxylation of factors II, VII, IX, and X, and proteins C and S, leading to defective molecules. Long half-life and slow onset b/c have to use up the good molecules, Monitor with PT. Sensitive to P-450.

Used for chronic anticoagulation in pts at risk for thromboembolic events. SE: bleeding (stop or give vitamin K or FFP), skin changes, teratogen (avoid in pregnancy).

Question 26

__rudin, __gatran

Answer 26

Anticoagulant Agent. Direct Thrombin Inhibitors.

Directly inhibit Thrombin, interfering with both intrinsic and extrinsic coagulation cascade (increased PT and PTT).

Used as anticoagulation in pts with indications and are unable to take Heparin. SE: bleeding, anaphylaxis.

Ex: Hirudin, Bivalirudin, Leprudin, Desrudin, Argatroban (HIT Rx), Megagatran, Dabigatran.

Question 27

Acetylsalicylic Acid

Answer 27

Antiplatelet Agent and NSAID.

Irreversibly inhibit COX 1 and 2 (usually create PGE precursors), decreasing prostaglandin synthesis. This leads to less inflammation/pain, resets hypothalamus temperature setpoint in fever, decreases gastric mucus secretion (ulcers). Prevents formation of Thromboxane A2 (TXA2) (leads to decreased platelet aggregation) and Prostacyclin (PGI2) (increase in gastric acid).

Used as an antipyretic, analgesic, anti-inflammatory agent, antiplatelet drug (primary or secondary prevention in pts at risk). SE: Bleeding (GI tract), gastritis and gastric ulcers, Reye syndrome (when given to kids with flu virus), tinnitis. Overdose: respiratory and metabolic acidosis, Rx with sodium bicarbonate to promote excretion.

Question 28

__clopid__

Answer 28

Antiplatelet Agent

Inhibits ADP pathway (platelet plug formation, fibrinogen interacting with platelets) to decrease platelet aggregation.

Rx for acute coronary syndrome (add Aspirin to prevent stroke), used in patients undergoing coronary stent placement to prevent thrombosis, alternative to Aspirin. SE: GI upset, bleeding, neutropenia or thrombic thrombocytopenic purpura (Ticlopidine).

Ex: Clopidogrel, Ticlopidine.

Question 29

Dipyridamole

Answer 29

Antiplatelet Agent

Inhibits cyclic nucleotide phosphodiesterase (increases cAMP), which inhibits thromboxane A2 synthesis (normally increases thrombus formation and vasoconstriction) while promoting prostacyclin action (inhibits thrombus formation). They exist in a balance.

Used for pharmacologic cardiac stress tests, secondary prevention of stroke when used with Aspirin.

Question 30

Abciximab, Eptifibatide, Tirofiban

Answer 30

Antiplatelet Agent

Binds GP IIb/IIIa receptor complex on platelet surface, inhibiting binding of fibrinogen and von Willebrand factor. Impede platelet aggregation by inhibiting fibrinogen cross-linking between GP receptors on different platelets.

Rx of acute coronary syndome, adjunctive for prevention of thrombosis during coronary intervention. SE: Bleeding, thrombocytopenia.

Question 31

__okinase, __teplase

Answer 31

Fibrinolytic Agents

Overall promotes conversion of plasminogen to plasmin, which degrades fibrin and thus the thrombus. Most effective if given early (within a few hours of symptom onset) as older clot is harder to breakdown.

Rx in massive PE, stroke, acute MI, thromboembolic events. SE: bleeding, allergy.

Ex: Streptokinase, Urokinase, Anistreplase, Alteplase, Reteplase.

Question 32

Aminocaproic Acid, Tranexamic Acid

Answer 32

Hematologic Agent

Inhibit plasminogen activation, resulting in inhibited fribrinolysis.

Treatment of bleeding associated with post-operative, hemophilia. SE: Thrombosis, GI upset, hypotension.

Question 33

__epoetin

Answer 33

Synthetic Erythropoietin

Stimulates the bone marrow to enhance erythroid proliferation and differentiation, increasing Hct.

Rx of anemia associated with chronic renal insufficiency, chemotherapy, or critical illness. SE: CV events and thrombotic complications if Hgb raised over 13, teratogen, HTN.

Ex: Epoetin, Darbepoetin.