Pharmacology Flashcards
Why are loop diuretics “K wasting”? 2 fold mechanism
- Inhibit ascending limb Na/K/2Cl co-transporter, thereby inhibiting reabsorption of 15% of filtered K load
- Inhibition of the Na/K/2Cl transporter decreases the passive following (reabsorption) of water; thus, more water remains in the tubule (increased tubular flow) which enhances K+ secretion in the distal segments via flow effects
Thiazide diuretic - Mechanism
Inhibit NaCl co-transporter in distal tubule; anti-hypertensive effect secondary to decreased plasma volume and decreased CO
Thiazides - Special considerations
Lose efficacy in later stages of CKD as less drug reaches the distal tubule; loop diuretics indicated at GFR < 30 ml/min
Spironolactone - Mechanism
Competitively inhibits the mineralocorticoid receptor from binding aldosterone, blocking the aldosterone-dependent up-regulation of Na/K exchange leading to reduced Na resorption and reduced K excretion
Eplerenone - Mechanism
Competitively inhibits the mineralocorticoid receptor from binding aldosterone
Binds more specifically than aldosterone
Mannitol - Mechanism, Uses, and Pharmacokinetics
Non-absorbed sugar, produces diuresis by elevating the osmolarity of the glomerular filtrate, decreasing tubular reabsorption of water
Used in management of elevated intracranial pressure
Administered IV
Acetazolamide - Mechanism, Pharmacokinetics, and Uses
Inhibits carbonic anhydrase in the proximal tubule; leads to sodium bicarbonate loss with increased loss of water
Oral administration
Used to treat metabolic alkalosis and acute mountain sickness
Loop Diuretics - Adverse Effects
Hypokalemia Hypomagnesemia Hypocalcemia Uric acid retention (precipitation of gout attack) Metabolic alkalosis
Loop diuretics - 3 individual agents
Furosemide (Lasix) - most commonly used
Ethacrynic Acid - only non-sulfa containing loop or thiazide
Torsemide - improved bioavailability
3 pharmacological classes for treatment of HTN
ACEIs/ARBs
Calcium Channel Blockers
Diuretics
Beta blockers - Adverse Effects
Bradycardia
Bronchospasm
Glucose/lipid changes
Decreased libido
Alpha/Beta blockers
Labetalol
Carvedilol
Metoprolol vs. Atenolol - elimination
Metoprolol - renal and hepatic elimination
Atenolol - renal elmination only
Acetazolamide - Uses
Primarily used for metabolic alkalosis, acute mountain sickness; infrequently used as diuretic
Vasodilators - Mechanism
Induce release of NO, which induces arterial vasodilation
Hydralazine and minioxidil
Alpha 1 receptor blockers - Adverse Effects & Uses
Orthostatic hypotension, headache, peripheral edema
Primarily used in BPH
Loop diuretics - Mechanism
Inhibits the Na/K/2Cl co-transporter in the water-impermeable ascending Loop of Henle; this decreases the tonicity of the interstitium, thereby reducing the driving force on the reabsorption of water in the collecting duct
Leads to the excretion of 15-25% of filtered sodium
Thiazide - Adverse Effects
Hypokalemia Hyponatremia Hypomagnesemia Hyperglycemia and lipid abnormalities Hypercalcemia Uric acid retention and precipitation of gout Metabolic alkalosis
Uses of spironolactone
Resistant HTN
Heart failure
Hyperaldosteronism
Spironolactone - Adverse effects
Hyperkalemia Gynecomastia (not seen with eplerenone)
Sodium channel blockers diuretics - 2 examples
Amiloride
Triamterene
Sodium channel blocker diuretics - Mechanism
Block reabsorption of Na+ in the distal tubule leading to decreased Na/water retention; less Na+ influx decreases the driving force on K+ secretion (K-sparing)
Sodium channel blocker diuretics - Adverse effects
Hyperkalemia
Hyperuricemia
Glucose intolerance in diabetes
ACE Inhibitors - Mechanism
Inhibits angiotensin converting enzyme (ACE), blocking the conversion of angiotensin I to angiotensin II; reduces angiotensin II-mediated vasoconstriction and stimulation of aldosterone release; also blocks degradation of bradykinin
ACEIs - Adverse effects
Cough
Hyperkalemia
Mild increase in serum creatinine; contraindicated with b/l renal artery stenosis
Contraindicated in pregnancy
Angiotensin II Receptor Blockers (ARBs)
Irreversibly blocks the actions of angiotensin II at its receptor, preventing vasoconstriction and aldosterone release
ARB - Adverse Effects
Hyperkalemia
Mild increase in serum creatinine; contraindicated in bilateral rental artery stenosis
Contraindicated in pregnancy
Does not cause cough
Dihydropyridine CCBs - 3 examples
Amlodipine
Felodipine
Nifedipine
DHPs - Mechanism
Block L-type Ca2+ channels, causing arterial vasodilation which lowers peripheral vascular resistance; selective for vascular smooth muscle over cardiac tissue (no significant effect on chronotropy or inotropy)
Non-dihydropyridines - 2 examples
Verapamil
Diltiazem
DHPs - Adverse Effects
Peripheral edema
Reflex tachycardia
Flushing
Headache
NDHPs - Mechanism
Block L-type Ca2+ channels, causing vasodilation and decreased peripheral vascular resistance; equally selective for cardiac and vascular L-type Ca2+ channels, also causing negative chronotropic and inotropic effects
NDHPs - Adverse Effects
Conduction defects; contraindicated in 2nd or 3rd degree heart block
Nausea
Headache
Selective Beta 1 Blockers 2 examples & Pharmacokinetics
Atenolol - eliminated by the kidney
Metoprolol - eliminated by the liver
Non-selective Beta-1/Beta-2 blockers - 2 examples
Propanalol
Timolol
Beta / alpha blockers - 2 examples & mechanism
Carvedilol
Labetalol
Block beta receptors on heart, decreasing CO; also block alpha receptors on vascular smooth muscle, causing arterial vasodilation and decreased peripheral resistance
Hydralazine
Direct vasodilator
Stimulate release of NO, which interferes with intracellular Ca2+ release causing peripheral vasodilation of arterioles
Minoxidil
Direct vasodilator
K+ channel opener; causes hyperpolarization of smooth muscle cells
Direct vasodilator - Adverse effects
Reflex tachycardia Reflex activation of RAAS leading to Na/H2O retention Headache Anorexia Nauseavomiting Diarrhea
Alpha 1 blockers - 3 examples
Prazosin
Terazosin
Doxazosin
Alpha 1 blockers - Mechanism & Uses
Selectively block alpha-1 adrenergic receptors causing decreased SVR; particularly strong effect on alpha-1 receptors in the prostatic stroma, decreasing urethral resistance and relieving obstruction
Most often used in symptomatic BPH
Alpha-1 blocker Adverse Effects
Orthostatic HTN
Headache
Peripheral edema
Classes of immunosuppression meds
Calcineurin inhibitor (Cyclosporine, Tacrolimus) Proliferation inhibitor (MMF, Sirolimus) Predisone
Calcineurin inhibitors
Ex: Cyclosporine, Tacrolimus
Prevents NFAT-mediated T-cell clonal expansion
Adverse effects (Cyclosporine): Nephrotoxicity, gout, HTN, hyperlipidemia
Proliferation Inhibitors - Transplant Meds
MMF, mTOR inhibitors (Sirolimus)
Inhibit purine synthesis
Adverse effects: leukopenia, anemia
Prednisone - Adverse Effects
HTN
Hyperlipidemia
Cataracts
Weight gain
