Drugs adv pharm test #2 Flashcards

Question

Dabigatran (Pradaxa)

Answer 1

directly inhibiting thrombin. Indication: stroke prevention in patients with non-valvular AF, DVT/PE (prevention & tx). Compared to Warfarin: Dabigatran has much faster onset (on day one), more predictable response, limited drug interactions, wider therapeutic window, no dosage adjustment, no lab monitoring, no CYP implications, no antidote*. Adverse effects: bleeding. *The newly introduce antidote for Dabigatran, Idarucizumab rapidly reverses the effects of dabigatran in bleeding patients.

Answer 2

All are orally active direct factor Xa inhibitors, which work on day one, NO monitoring required. Indications: stroke prevention in non-valvular AF, DVT/PE (prevention and tx) Adverse effects: internal bleeding. The FDA recently (May 2018) approved Andexanet alfa (AndexXa®) as the first and only antidote for the oral direct factor Xa inhibitors when reversal of anticoagulation is needed.

Answer 3

irreversible inhibitor of P2Y12 receptors. It is a prodrug: that needs to be activated by CYP2C19, the activity of which is genetically controlled & variable among populations. Omeprazole: is a strong inhibitor of CYP2C19, pantoprazole is NOT!

Answer 4

A newer reversible ADP inhibitor. Not a prodrug. Indicated for acute coronary syndromes. Causes dyspnea, and more bleeding than Plavix.

Answer 5

irreversibly inhibits cyclooxygenase enzyme (COX) ;resultant inhibition of platelet aggregation (for 7-10 days, needs lower doses) 2.  PGI2 production by endothelial cells, with resultant more platelet aggregation (for few hour turnover, needs higher doses) Indications: ACS, secondary prevention of ACSs (2 antiplatelets) Stroke & TIA (1 antiplatelet) Peripheral arterial disease (Aspirin and Cilostazole or Dipyridamole) Inflammatory arthritis (RA, gout) Antipyretic Kawasaki Disease: aspirin reduces the incidence of coronary aneurysms Essential thrombocythemia: Usually platelet count >1 million. For clotting use aspirin, for bleeding use Hydroxyurea and Anagrelide. Adverse effects: Bleeding due to platelet inactivation Inhibition of PGE2 causes peptic ulcers and renal insufficiency Asthma may result from altering leukotriene synthesis. (Samter’s Triad: is a combination of aspirin intolerance, asthma, and nasal polyps) Tinnitus: in chronic aspirin intoxication In toxic amounts aspirin leads to: hyperventilation, metabolic acidosis (with increased anion gap), encephalopathy and renal insufficiency.

Answer 6

Mechanism of action: Vorapaxar is a new anti-platelet drug that is part of the PAR-1antagonist (Protease-activated receptor) family, a new class of anti-platelet drug. It functions by inhibiting thrombin-related platelet aggregation. This mechanism works by a different pathway than other anti-platelet medications such as aspirin and P2Y12 inhibitors. Unlike many other medication, vorapaxar does not affect ADP-mediated platelet aggregation, coagulation parameters, or bleeding time Medical uses: Vorapaxar is used for persons with a history of myocardial infarction or persons with peripheral arterial disease Contraindications: Vorapaxar is contraindicated for people with a history of stroke, transient ischemic attack, or intracerebral hemorrhage

Answer 7

Mechanism of action: It inhibits phosphodiesterase enzyme (PDE), thus increasing cAMP in platelets which prevents their activation. Inhibiting PDE also causes increased cGMP, which leads to vasodilation. Therapeutic indications: It is a weak drug that is never the first line of therapy, it can be combined with aspirin for stroke or PAD. Aggrenox® is a combination of aspirin/extended-release dipyridamole was approved by FDA for stroke secondary prevention. Side effects: GI bleed (not too much risk). Dizziness and headache because of the vasodilation.

Answer 8

Mechanism of action: Cilostazol decreases platelet aggregation. It works by inhibiting a platelet enzyme known as phosphodiestarse III. As a result, there is a reversible inhibition of platelet aggregation, vasodilation and inhibition of vascular smooth muscle cell proliferation. Medical uses: Symptomatic management of peripheral vascular disease, primarily intermittent claudication (in addition to aspirin or clopidogrel). Side effects: Because of vasodilation it results in headache (most common adverse effect) as well as dizziness and vertigo. The most serious adverse effect is worsening CHF.

Answer 9

Mechanism of action: Inhibit platelet aggregation by blocking the glycoprotein receptors (GP IIb/IIIa) Indications: Acute coronary syndromes, ONLY iv Adverse effects: Bradycardia, hypotension, edema dizziness bleeding, thrombocytopenia

Answer 10

- Activated protein C/S complex inactivates an inhibitor of tPA - tPA converts plasminogen to plasmin - The circulating plasminogen is trapped in the fibrin clot - After approximately 24 hours, tPA becomes dis-inhibited , leading to plasmin formation - Plasmin dissolves the clot

Answer 11

Mechanism of action: Thrombolytics activate the conversion of plasminogen to plasmin which breaks down (lyses) the thrombus. Indications: MI, DVT, PE, and acute ischemic stroke Adverse effects: Bleeding (internal, superficial, and intracranial). Thrombolytics can also induce cardiac dysrhythmias

Answer 12

Mechanism of action: HMG CoA reductase inhibitors Usually given in the evening the ones with short t1/2; cholesterol synthesis is a nocturnal event Side effects: The most common side effect is elevated liver enzymes, also myositis, myalgia do occur, and rhabdomyolysis (rare/high doses). Contraindications: active liver disease, pregnancy (Category-X), & lactation Drug interactions: CYP inhibitors affect the more CYP3A4 dependent statins (simvastatin, atorvastatin, lovastatin). The statins that are less CYP dependent are pravastatin, rosuvastatin Monitoring: LFTs should be evaluated at the start of treatment, and monitored periodically (6-12 weeks), and the drug should be discontinued if the LFT increase to > 3 times normal. Also, recheck cholesterol in about 8 weeks once starting on a statin

Answer 13

suffix - "statins"

Answer 14

A vitamin B that has to be given in 100-300 times its dose as a vitamin to  LDL, and TG, and  HDL (Dose: >3g/day) Unknown mechanism of action(VLDL synthesis, LPLase activity) Drug of choice for young patients with no risk factors, yet with a polylipid disorders (Non-acute conditions) Flushing: major side-effect ( by pretx. with ASA, and SR forms) Other side-effects: vasodilation (may potentiate antihypertensives), diarrhea, drug-induced hepatitis. Contraindications/cautions: niacin can exacerbate insulin resistance, can precipitate gout, liver disease or concomitant use with other drugs that may affect the liver(e.g. statins).

Answer 15

Act to bind bile acids in the intestines, forming an insoluble complex that is excreted in the feces. This decreases the return of cholesterol to the liver, the latter will respond by up-regulating the LDL receptors, which  the plasma LDL uptake by the liver Two examples are: cholestyramine(Questran®)(4-16g/d) & colesevelam (Welchol®)(3.75g/d) [should be taken before meals] Adverse effects: flatulence, bloating& constipation. TG Interactions: bind other medications and  their absorption and bioavailability [oral anticoagulants, thyroid hormones, digoxin, penicillins, tetracyclins]. [take concomitant medications at least 1 hour before or 4 hours after the bile aid resins] Important! Questan is powder and has a gritty/sandy consistency – adherence is a real problem. Welchol tablet is large and hard to swallow.

Answer 16

Mechanism of action: stimulation of lipoprotein lipase, promoting catabolism of VLDL & TG = use it to treat hypertriglyceridemia Examples: Gemfibrozil (Lopid®), fenofibrate (TriCor®) Side effects: gall stones, LFT abnormalities Interactions: potentiate warfarin, insulin, sulfonylureas Indication: severe hypertriglyceridemia >500 (and NOT for high cholesterol) **Caution: Statin plus FAD can lead to severe myopathy and rhabdomyolysis. If choosing combo therapy, fenofibrate has been shown to be effective for mixed hyperlipidemia and is a safer option.

Answer 17

Lovaza, Vascepa These help with hypertriglyceridemia The direct mechanism of action is not accurately known, they lead to decreased triglyceride synthesis by the liver.

Answer 18

Mechanism of action: inhibits cholesterol absorption from small intestine, thus  the hepatic free cholesterol pool. Reduced Tchol and LDL Indications: HDL, mixed hyperlipidemia Less preferred than statins. Can be used with statins and FADs Adverse Effects: Arthralgias, diarrhea, fatigue Contraindications: moderate to severe hepatic insufficiency Important! has no effect on overall mortality or cardiovascular mortality, although it significantly reduces the risk of MI and stroke

Answer 19

PCSK9: Is an enzyme encoded by the PCSK9 gene in hypercholesterolemia pts. When PCSK9 is blocked, more LDL receptors are recycled and are present on the surface of liver cells to remove LDL from the blood Usually given with statins to further lower the LDL levels in patients with familial hypercholesterolemia or whenever maximally tolerated statin therapy is not sufficient to control LDL-C levels in “Very High Risk” ASCVD patients. Administration: Every 2 weeks or once monthly as SC injection Side effects: Injection site reaction, “flu” like symptoms, nausea, fatigue, diarrhea, might result in increased blood sugar levels.

Answer 20

Mechanism of action: Inhibits ATP citrate lyase enzyme, which is involved in the liver’s biosynthesis of cholesterol (upstream of HMG-CoA reductase) Examples: Bempedoic acid (Nexletol®), in combination with ezetimibe (Nexlizet®) Side effects: Muscle spasms, gout, diarrhea Indication: Treatment of hypercholesterolemia in adults with familial hypercholesterolemia or with established ASCVD who need additional lowering of LDL. Administered orally in combination with diet and the highest tolerated statin therapy.

Answer 21

suffix "prils" Mechanism of action: They inhibit ACE (in the lungs), thus block the conversion of angiotensin I to angiotensin II. This causes reduced afterload (vasodilation) and reduced preload (due to decreased aldosterone production). They slow down cardiac remodeling. Examples: (-prils) Captopril*, lisinopril*, enalapril, ramipril, perindopril, trandolapril. (* All are prodrugs EXCEPT captopril & lisinopril) Some of them can come combined with thiazide diuretics for treatment of hypertension. Clinical Use: CHF with reduced EF, hypertension, diabetic nephropathy Side effects (CATCHH): Cough (dry, irritating), Angioedema (Both are ￪bradykinin effect), Teratogen, ￪Creatinine, Hyperkalemia, and Hypotension. Absolute contraindication: bilateral renal artery stenosis. (Relatively CI in pregnancy 2/2 teratogenic affect).

Answer 22

suffix - "artan" Mechanism of action: They selectively block binding of angiotensin II to AT1 receptor. They have same effects of ACE-Is, but ARBs do NOT increase bradykinin ARBs do NOT cause the dry irritating cough or angioedema Clinical Use: Same indications of ACE-Is but for patients who do not tolerate the dry cough of ACE-Is Side effects: Hypotension, hyperkalemia, teratogen, ↓GFR NEVER COMBINE ACE-Is AND ARBs

Answer 23

Mechanism of action: Sacubitril inhibits the enzyme neprilysin thus, increasing the levels of natriuretic peptides. This causes vasodilation, reduction of preload via increased sodium excretion, and reduction of the maladaptive cardiac remodeling. The efficacy of sacubitril was found to increase when combined with an ARB. Clinical Use: - CHF (with reduced EF), now, preferred over ACE-Is & ARBs. It reduces mortality and hospital stay. Side effects: - Hyperkalemia, hypotension, dry cough, and reduced kidney function. - Angioedema, a rare but serious side effect, can occur in some patients

Answer 24

Mechanism of action: Competitive aldosterone receptor antagonists in the cortical collecting renal tubules. Examples (-ones): Spironolactone (Aldactone®), and eplerenone (Inspra®). Clinical Use: - 1st choice drug for CHF with systolic dysfunction (w/ EF <40%), hyperaldosteronism. - Spironolactone is used for ascites of hepatic failure (best initial diuretic therapy). - Spironolactone has antiandrogenic properties and can be used for acne, hirsutism, amenorrhea & PCOS Side effects: Hyperkalemia Spironolactone causes gynecomastia

Answer 25

Mechanism of action & Examples: - Nonselective (ɑ1 & ɑ2 blockers): Phenoxybenzamine, and phentolamine (OLD) - ɑ1 selective (-osin): Prazosin (Minipress®), Terazosin (Hytrin®), Doxazosin (Cardura®) - ɑ1 uro-selective: Tamsulosin (Flomax®) [Does NOT result in orthostatic hypotension] - ɑ2 selective: Mirtazapine used for depression Clinical Use: - Phenoxybenzamine: used for pheochromocytoma (preoperatively). - Phentolamine: for cocaine-induced hypertension & the hypertensive crisis with MAO-Is interaction with tyramine-containing food. - Tamsulosin: the preferred symptomatic treatment of BPH (Terazosin & doxazosin can lower BP). - Prazosin: Was originally introduced as antihypertensive medication (but causes significant OH, esp 1st dose, pts fell) Side effects: Orthostatic hypotension (especially with the 1st dose), dizziness, headache. Tamsulosin works more selectively on the ɑ1 receptors in the prostate and the bladder, hence, it does NOT cause hypotension.

Answer 26

Mechanism of action: Amiodarone is a potent antiarrhythmic medication that is primarily K+ channel blocker, but also has beta-blocking effect as well as blocking inactivated Na+ and Ca2+ channels Clinical Use: - Drug of choice for V-fib & V-tach in acute resuscitation when used with defibrillation. - It is the single best med. To maintain sinus rhythm with A-fib. - For chronic ventricular arrhythmias, it is used in conjunction with implantable defibrillator Side effects: - Hyperthyroidism & hypothyroidism - - Pulmonary fibrosis - Non-sight-threatening corneal deposits (bluish halos) - - Blue skin

Answer 27

Mechanism of action: Selective inhibition of funny sodium channels. Negative chronotropic effect (without affecting inotropy). Reduces cardiac O2 requirements. Clinical Use: - Chronic stable angina in patients who cannot tolerate beta-blockers. - CHF with reduced ejection fraction in patients who cannot tolerate beta-blockers. Ivabradine lowers mortality in this group of CHF. Side effects: - Luminous phenomena/visual brightness - Bradycardia (not to be used in HR ＜70 bpm)

Answer 28

Major or unique side effects-- prolonged QT, drug induced lupus; Common antiarrythmic indications: AVRT and preexisting a fib and a flutter

Answer 29

slows rate of depolorization in slow AP cells; major side effects/toxicity: bronchospasm, depression, exercise intolerance, sexual dysfunction; indicated for rate control of afib/aflutter, suppression of PVCs, PACs, and VT

Answer 30

side effects: pulmonary fibrosis, thyroid disease, hepatic dysfunction (increase LFTs); indications: cardio version of afib/aflutter, maintenance of SR in PAF, suppression pf VT

Answer 31

side effect- negative ionotropy, indications: rate control of Afib/afluttter, prevention of AVNRT

Answer 32

increase vagal tone, inhibits Na/K pump; slows rate of depolarization in slow AP cells, side effects: very pro arrhythmic indications: rate control of afib (second line)

Answer 33

MOA:Block voltage-dependent L-type calcium channels of cardiac muscle and smooth muscles → ↓ muscle contractility Site of action:Vascular smooth muscles > Heart Indications: mainly HTN;Hypertension, angina (including Prinzmetal), Raynaud phenomenon, Pulmonary HTN adverse effects: Postural hypotension, constipation, peripheral edema, dizziness, flushing

Answer 34

MOA: Block voltage-dependent L-type calcium channels of cardiac muscle and smooth muscles → ↓ muscle contractility Site of action:Heart > Vascular smooth muscles Indications: Mainly for cardiac arrhythmias & ischemia; Angina, Atrial fibrillation/flutter, hypertension Adverse effects: AV-block, cardiac depression, ↑prolactin, constipation, gingival hyperplasia

Answer 35

Sulfonamide loop diuretic (cannot be used in pts with sulfa allergy) Mechanism of action: Lasix inhibits Na+ reabsorption in the thick ascending limb of loop of Henle. It also has a PG-mediated vasodilatory effect on the afferent arteriole. Lasix increases Ca2+ excretion. Lasix does not need an adequate GFR to exert its diuretic effect. Clinical Use: - All Edema states: CHF, cirrhosis, nephrotic syndrome, pulmonary edema - Hypertension, hypercalcemia Side effects: Ototoxicity, Hypokalemia, Hypomagnesemia, Dehydration, Allery (sulfa), metabolic alkalosis, nephritis (interstitial).

Answer 36

Thiazide Diuretics: Mechanism of action: Inhibit Na+ reabsorption in the early distal tubule. They also ↓ Ca2+excretion = retains Ca2+ in the body Clinical Use: Hypertension, HF (with furosemide), idiopathic hypercalciuria, osteoporosis (as it inhibits Ca2+ excretion) Side effects: Hypokalemic metabolic alkalosis, hyponatremia, hyperglycemia, hyperlipidemia, hyperuricemia, hypercalcemia, sulfa allergy, and erectile dysfunction. To be used with caution in patients with gout.

Answer 37

Potassium-sparing Diuretics [aka: Aldosterone Antagonists] Mechanism of action: - - Spironolactone antagonizes aldosterone in the collecting tubule. - Triamterene and amiloride block the Na+ channels in the collecting tube as well. Clinical Use: HF, hepatic ascites (Spironolactone), nephrogenic DI (Amiloride), K+ depletion. The antiandrogenic activity of spironolactone helps with acne, hirsutism, amenorrhea, PCOS. Side effects: Hyperkalemia

Answer 38

Nitrates Mechanism of action: Vasodilate by ↑ NO in vascular smooth muscle → smooth muscle relaxation. Nitrates dilate veins much more than arteries leading to preload reduction. Clinical Use: - Angina, acute coronary syndromes, pulmonary edema. - Nitrate tolerance: The patient should be allowed a 12-hour nitrate free period when using the long-acting forms to replenish NO stores in the vascular endothelium * Have patients sit down before taking nitrates to reduce the risk of falling 2/2 OH Side effects: - Orthostatic hypotension, flushing, headache, reflex tachycardia.

Answer 39

Mechanism of action: Smooth muscle relaxation. Dilate arteries much more than veins → afterload reduction. Clinical Use: - Hypertensive emergencies - Hydralazine (Apresoline®), is safe to use during pregnancy. - The combination Hydralazine/Isosorbide dinitrate (BiDil®): is used for CHF (it was proved to achieve 43% mortality reduction in self-identified African-American patients. Side effects: - Reflex tachycardia & angina (contraindicated in angina/CAD). - Fluid retention, headache. - SLE-like syndrome (Drug-induced lupus)

Answer 40

when all other meds fail Mechanism of action: - Inhibits Na+ channels, and consequently the Na+/Ca2+ exchanger which reduces the wall tension and O2 consumption. - Does not affect heart rate or contractility (a plus!) Clinical Use: - Chronic stable angina as an add-on therapy when other medications fail Side effects: - Dizziness, headache - Nausea, constipation - QT prolongation

Answer 41

not just for diabetes Mechanism of action: Their protective effects in heart failure is attributed primarily to hemodynamic effects, where SGLT2 inhibitors potently reduce intravascular volume through osmotic diuresis and natriuresis. This consequently may lead to a reduction in preload and afterload, thereby alleviating cardiac workload and improving left ventricular function Clinical Use: - HFrEF: They reduce mortality - HFpEF: They reduce hospitalization Side effects: - Dehydration & orthostatic hypotension (due to their osmotic diuretic effect) - Rapid weight loss & tiredness (due to their heavy glycosuric effect) - UTI (due to increased amounts of glucose in urine)