Antihypertensives Flashcards
Loop Diuretics
Furosemide, Torsemide, Ethacrynic acid.
MOA: Inhibit the Na/K/2Cl carrier in the thick ascending loop of henle
Thiazide Duretics
Hydrochlorthiazide, Chlorthiazide, Chlorthalidone, Indapamide.
MOA: Inhibit the Na+/Cl- carier in the distal convoluted tubule.
Adverse Effects of Thiazide and Loop
Hypokalemia
Appears in breast milk, so should be avoided in nursing mothers
Ischemic Ventricular Fibrillation and SCD. Caused by hypokalemia, hyponatremia, and calcium imbalance.
K+ Sparing Diuretics
Amiloride, Triamterene, Spironolactone, Eplerenone
MOA: Inhibits ENAC channels, preventing sodium resorption in the collecting duct.
Adverse Effect: Hyperkalemia.
Relevant Receptors
a1: vasoconstriction, tubular resorption of sodium
a2: Negative feedback inhibition for NE release
B1: Stimulation of renin release, Increased heart rate and force of contraction.
B2: Vasodilation (a1>B2)
Cardioselective B1 Blockers
Atenolol and Metoprolol selectively block B1 receptors in the myocardium and kidneys, decreasing HR, force, cardiac output, and renin release. Mild decrease in peripheral resistance.
Beta Blockers Adverse Effects
Rebound Hypertension due to upregulation of beta receptors, increasing tissue sensitivity to endogenous catecholamines.
Beta Blocker Contraindications
Reactive Airway Disease
Myocardial conduction defects
DDI with Epinephrine and SA/AV conduction inhibitors, ie Verapamil and Diltiazem.
a1 Antagonists
Prazosin, Terazosin, Doxazosin
MOA: a1 antagonists reduce arteriolar resistance and increase venous capacitance.
Adverse Effects:
-Postural Hypotension
-Retention of salt and water
-Peripheral edema.
Combined Beta and a1 Receptor Antagonists
Labetalol is and equimolar mixture of stereoisomers that impact a1 and B receptors respectively. Labetolol can be used in hypertensive crisis because of its ability to block a1.
Carvedilol also has a1 antagonist activity in addition to its B antagonism, but is much weaker at a ratio of 1:10. Oxidation in the liver via CYP2D6 and is used adjunctively with diuretics and ACE inhibitors. Contraindicated in patients with decompensated HF dependent on sympathetic stim.
Decrease Preload and Afterload Simultaneously.
Centrally Acting Adrenergic Agents
Clonidine, Guanabenz, Guanfacine stimulate a2A subtype receptors in the brain stem and reduce NE release.
Methyldopa is a prodrug, metabolized in adrenergic neruons to a-methylnorepinephrine, MNE acts on the presynaptic adrenergic neurons in the CNS by preventing further release of NE. Useful in pregnancy and renal insufficiency.
Adverse Effects Bradycardia, sinus arrest, and hepatotoxicity. 1-5% hemolytic anemia.
Guanadrel
Guanadrel inhibits postganglionic adrenergic neuronal activation by acting as a false neurotransmitter.
Adverse Effects Hypotension and sexual dysfunction
DDI: Drugs that compete for catecholamine transporter on the presynaptic region reduce Guanadrel’s effects.
Contraindications: Pheochromocytoma
Reserpine
Remains bound to CNS and peripheral neurons causing loss of function of VMAT which stores and accumulates catecholamines.
Adverse Effects: Psychotic depression
Contraindications: Depressive illness
Calcium Channel Blockers
Block L type calcium channels, decrease intracellular calcium and calcium induced calcium release
Affect mostly cardiac and vascular smooth muscle. Slow HR and decrease TPR
Adverse Effects: Potential Baroreceptor reflex causing tachycardia.
DDI: Chronotropic effect with beta blockers. Not advised to use in combination when patient has a history of rhythm disease or MI.
Dihydropyridines
Nifedipine, Isradipine, Nicardipine, Amlodipine, Felodipine.
Phenylalkylamines
Verapimil
Benzothiazepines
Diltiazem
Clevidipine
3rd gen dihydropyridine. Ultra short acting (within 1-3 minutes) with high specificity to vasculature.
Aliskiren
Direct Renin competitive inhibitor
Adverse Effects: Angioedema
Contraindicated in pregnant women
ACE Inhibitors
Suffix -pril
MOA: Inhibition of ACE, preventing generation of Ang II.
Prevention of vasoconstriction due to ANG II binding to AT1R. Decreased formation of aldosterone decreases Na+ reuptake.
Adverse Effects: Angioedema, cough due to bradykinin accumulation.
Contraindications: Pregnancy, renal disease.
DDI: Hyperkalemia when used in high doses with K+ sparing diuretics.
AT1 Receptor Antagonists
Suffix -sartan
Antagonists of AT1 receptors promoting relaxation of vascular smooth muscle. Also promote renal salt and water excretion. Leads to increased renin and Ang II in circulation due to decreased negative feedback.
Adverse Effects: Hypotension, Hyperkalemia, reduced renal function.
Hydralazine
Arterial vasodilator causing a decrease in intracellular calcium by preventing IP3 mediated release of Ca.
Minoxidil
Arterial Vasodilator
Prodrug that needs to by converted to minoxidil N-O sulfate.
MOA: Activates ATP modulated K+ channel, promoting efflux of K+ in smooth muscle causing relaxation
Adverse Effects: Hirsuitism, Pseudoacromegaly, Pericardial Effusion.
Nitroprusside
Arterial and Venous vasodilator.
MOA: Releases NO which activates guanylyl cyclase-cGMP-PKG leading to vasodilation.
Contraindicated in patients with compromised renal or liver function.
Metabolism: Reacts with Hgb to form cyan-methemoglobin and cyanide. Thiosulfate breaks cyanide down to thiocyanate which is less toxic and eliminated. Remaining cyanide binds to mitochondrial cytochrome enzymes and prevents oxidative phosphorylation causing toxicity.
Adverse Effects: Rare cyanide toxicity causing toxic psychosis. Administration of thiosulfate preventatively can mitigate this. Treated with administration of hydroxocobalamin.
Non Pharmacological Approaches
Reduction in weight in obese individuals
Restriction of excess sodium
Restriction of ethanol
Increase in physical activity
Avoid smoking
