Heart Disease, Coronary Artery Disease, Hyperlipidemia, CHD

Question 1

Isosorbide dinitrate (3-4 hour action)
Isosorbide mononitrate (longer action)

Answer 1

Nitrovasodilators

• Venodilation. Activation through p450 and NO – relaxes arteries (relieve vasospasm) and veins (decrease preload), inhibit platelet aggregation, increase coronary artery flow (enhance ventricular function)
• Headache (really bad), orthostatic hypotension, dizziness, flushing, syncope, reflex tachy, GI distress, don’t use with PDE5 inhibitors
• CHD and angina, heart failure (use in combination with hydralazine)

Question 2

Ranolazine

Answer 2

Antianginal

• Piperazine derivative – inhibits late sodium current to reduce Na and Ca overload in ischemic myocytes, shift ATP from fatty acid oxidation to glycolysis
• Avoid in pts with prolonged QT intervals or hepatic impairment
• Improves exercise tolerance, chronic angina refractory to traditional antianginal

Question 3

Tricagrelor

Answer 3

Non-thienopyridine platelet P2Y inhibitor (already active)

• ADP antagonists at P2Y receptor, block ADP mediated activation of GPIIb/IIIa, prevent platelet aggregation
• Increased bleeding
• In combination with aspirin in ACS, MI, and stroke

Question 4

Cholestyramine

Colesevelam HCl

Answer 4

Bile acid sequestrants

• Bind bile acids through ionic and hydrophobic interactions to prevent reabsorption, increase uptake of LDL, increase hepatic production of VLDL
• Dyspepsia, constipation, bloating, diarrhea, malabsorption of vitamin K, impaired absorption of other drugs
• Granular resins or tablets - hyperlipidemia

Question 5

Atorvastatin (3A4)
Simvastatin (3A4)
Lovastatin (3A4)
Fluvastatin (2C9)
Pravastatin

Answer 5

HMG CoA Reductase Inhibitors

• Liver is target site so high first pass uptake is good. Competitively inhibit HMG CoA reductase – decrease cholesterol synthesis and upregulate LDL receptors (decrease circulating LDL)
• Increase in LFTs, increase in CK, myopathy, worse with concurrent cyclosporine or niacin or erythromycin, don’t drink grapefruit juice (CYP3A4)
• Hyperlipidemia - take in the evening (when cholesterol synthesis occurs), absorption enhanced by food

Question 6

Clofibrate
Fenofibrate
Gemfibrozil

Answer 6

Fibric acids

• Ligands for PPARa – upregulate LPL, apo AI, apo AII (HDL components), clears chylomicrons and VLDL quickly, lowers triglycerids, raises HDL
• Rash, GI symptoms, arrhythmias, low potassium, elevated LFTs, risk of myopathy (w/statin), cholesterol gallstones
• Modest decrease in LDL, mostly used for treating hyper triglyceridemias (VLDL)

Question 7

Ezetimibe

Answer 7

Miscellaneous

• Impaires intestinal absorption of cholesterol, absorbed and glucorinated
• Excreted in bile and feces – not a CYP450 substrate
• Hyperlipidemia

Question 8

Nicotinic acid

Answer 8

Miscellaneous

• Inhibits VLDL secretion (decreased production of LDL), decrease triglycerides > cholesterol
• Flushing sensation (cutaneous vasodilation), elevations in LFTs, liver dysfunction, increase insulin resistance, hyperuricemia
• Regular or timed release – elevated triglycerides

Question 9

Rizatriptan
Sumatriptan
Zolmitriptan (more lipophilic, rapidly absorbed, longer ½ life)

Answer 9

Serotonin agonists

• 5HT1B,D,F agonists – activation of prejunctional 5HT1B/D receptors on sensory nerves (block trigeminovascular system → inhibit inflammatory peptides), vasoconstriction of cranial vessels (5HT1D
• Recurrent migraine, risk of coronary spasm in pts with CV disease, hepatic failure is contraindication
• Drug of choice for acute migraines and cluster headaches

Question 10

Cyproheptadine

Answer 10

Serotonin antagonists

• Nonselective 5HT1/2 antagonist, H1 receptor antagonist
• Drowsiness, GI distrubances
• Treatment of symptoms from carcinoid tumors, block diarrhea, platelet aggregation, and pressure increase

Question 11

Ketanserin

Answer 11

Serotonin antagonists

• 5HT2 receptor selective on VSM, block a1 adrenergic receptors on VSM
• Lowers arterial pressure in hypertensives (not in US)

Question 12

Ergonovine

Answer 12

Serotonin partial agonists

• 5HT2 receptor partial agonist
• Diagnostic tool vasospastic angina, control postpartum and postabortal hemorrhage

Question 13

Ergotamine

Answer 13

Serotonin partial agonists

• Partial agonist of 5HT1/2 receptors – VSM constrictor
• Prolonged vasospasm, GI disturbances
• Acute migraines, control postpartum bleeding

Question 14

Methysergide

Answer 14

Serotonin partial agonists

• Antagonists at 5HT2 receptor and partial agonist at 5HT1 receptor
• Prolonged vasospasm, GI distrubances, CNS issues (hallucinations)
• Treatment of symptoms for carcinoid tumors

Question 15

Digoxin

Digitoxin (never used)

Answer 15

Cardiac glycoside

• Increases force of cardiac contraction by increase intracellular Ca – decreases reflex SNS activity and increases renal perfusion (inhibition of Na/K ATPase), sensitizes cardiac baroreceptors, increase vagal tone
• Toxicity related to electrical properties (arrhythmogenic) of the heart – treat with anti-digoxin immunotherapy
• Heart failure (in patient and in Afib or those with severe symptoms), slows ventricular response in Afib/atrial flutter

Question 16

Dobutamine

Answer 16

B agonist - parenteral

• Stimulates B1 (inotropic) and B2 (vasodilation) – increase in renal blood flow
• Tachycardia and arrhythmias
• Choice for systolic dysfunction and congestion from heart failure

Question 17

Dopamine

Answer 17

B agonist - parenteral

• Stimulates B receptors and cardiac contractility at intermediate infusion rates, stimulates A receptors at high infusion to stimulate peripheral arterial/veous constriction
• Tachycardia can provoke ischemia in patients with CAD
• Refractory heart failure – improve cardiac performance, facilitate diuresis, and promote clinical stability (SHORT TERM)

Question 18

Inamrinone
Milrinone (best option with fewer side effects)

Answer 18

cAMP PDE inhibitors

• Stimulate myocardial contraction and accelerate myocardial relaxation by increasing cAMP (activates PKA → increased Ca), cardiac output increased, arterial and venous dilatio
• Short term support of circulation in advanced heart failure