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Pharm Chapter21
Pharmacology of Vascular Tone
| Question | Answer |
|---|---|
| Organic Nitrates | Isosorbide dinitrate, Isosorbide 5-mononitrate, Nitroglycerin |
| MOA organic nitrates | Donate NO, activates guanylyl cyclase and increases dephosphorylation of myosin light chain in vascular smooth muscle, causing vasodilation |
| MOA sodium nitroprusside | Donate NO, activates guanylyl cyclase and increases dephosphorylation of myosin light chain in vascular smooth muscle, causing vasodilation |
| Clinical applications isosorbide dinitrate | Angina, Chronic ischemic HD, Diffuse esophageal spasm |
| Adverse effects isosorbide dinitrate, isosorbide 5-mononitrate, nitroglycerin | refractory hypotension, syncope, palpitations, angina from reflex tachycardia, flushing, headache |
| Contraindications isosorbide dinitrate, isosorbide 5-mononitrate, nitroglycerin | Hypotension, Increased intracranial pressure, Coadministration with PDE-5 inhibitors |
| Clinical applications isosorbide 5-mononitrate | Prophlyaxis of angina, treatment of chronic ischemic HD (preffered over isosorbide dinitrate, less adverse effects, greater half-life) |
| Clinical application nitroglycerin | Angina, treatment of chronic ischemic HD, IV - unstable angina, Acute HF |
| Clinical application sodium nitroprusside | Hypertensive emergencies, Severe cardiac failure |
| Adverse effects sodium nitroprusside | cyanide toxicity, cardiac arrythmia, excessive hypotension |
| Contraindications sodium nitroprusside | preexisting hypotension, hepatic or renal failure |
| Phosphodiesterase type V inhibitors | Sildenafil, vardenafil, tadalafil(longest half-life) |
| MOA PDE-5 inhibitors | Inhibit PDE-5, leading to cGMP accumulation in target tissues |
| Clinical applications sildenafil, vardenafil, tadalafil | erectile dysfunction, pulmonary HTN(sildenafil) |
| Adverse effects sildenafil, vardenafil, tadalafil | MI, non-arteritic ischemic optic neuropathy, headache, flushing |
| Contraindications sildenafil, vardenafil, tadalafil | Concomitant use of organic nitrate vasodilators |
| MOA calcium channel blockers | Block voltage-gated L-type calcium channels and prevent the influx of calcium that promotes actin-myosin cross-bridge formation |
| Dihydropyridines (N-binding site, excreted by kidney) | nifedipine, amlodipine(higher bioavailability, longer time to peak plasma concentration, slower hepatic metabolism |
| Clinical applications nifedipine, amlodipine | exertional angina, unstable angina, hypertension |
| Adverse effects nifedipine, amlodipine | increased angina, rare MI, flushing, constipation, severe reflex tachycardia |
| Benzothiazapine (D-binding site, excreted by liver) | Diltiazem |
| Clinical applications diltiazem, verapamil | Prinzmetal's of variant angina, or chronic stable angina, hypertension |
| Adverse effects diltiazem, verapamil | AV block, bradyarrhythmia, exacerbation of HF |
| Contraindications diltiazem, verapamil | SIck sinus syndrome, 2nd or 3rd degree AV block, supraventricular tachycardia, left ventricular failure, Concomitant use of beta blockers |
| Phenylalkylamine (V-binding site, excreted by kidney) | Verapamil |
| Potassium channel openers | Minoxidil, pinacidil, nicorandil, cromakalim (typically used in combination with a beta-blocker, and a diuretic) |
| MOA potassium channel openers | Open ATP-modulated potassium channels and hyperpolarize plasma membrane, thereby inhibiting influx of calcium through voltage-gated calcium channels |
| Clinical applications minoxidil, pinacidil, nicoranidil, cromakalin | severe or refractory hypertension, male pattern alopecia(topical minoxidil) |
| Adverse affects minoxidil, pinacidil, nicoranidil, cromakalin | reflex tachycardia, headache, flushing (use with caution in patients with impaired renal function, dissecting aortic aneurysm, or after acute MI) |
| Hydralazine MOA | Arteriolar vasodilator |
| Clinical applications hydralazine | Moderate to severe hypertension (+ beta-blocker, diuretic), severe HF (+ isorbide dinitrate) |
| Adverse effects hydralazine | SLE |
| Alpha-1 adrenergic antagonists | Prazosin, terazosin, doxazosin |
| Clinical applications prazosin, terazosin, doxazosin | hypertension |
| Adverse effects prazosin, terazosin, doxazosin | orthostatic hypotension |
| Beta-adrenergic antagonists | Propranolol(non-selective), atenolol, metoprolol(selective) |
| Clinical applications propranolol, atenolol, metoprolol | HTN, angina, cardiac arrhythmias |
| ACE inhibitors | Captopril, enalopril, lisinopril |
| Clinical applications captopril, enalopril, lisinopril | HTN, HF |
| AT1 receptor antagonists | Losartan, Valsartan |
| Clinical applications losartan, valsartan | HF, HTN |
| MOA statins | Inhibit HMG-CoA reductase |
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