Antiarrhythmics class 1a Drug names
Quinidine
Procainamide
Disopyramide
Antiarrhythmics class 1b Drug names
Lidocaine
Mexiletine
(Phenytoin)
Antiarrhythmics class 1c Drug names
Flecainide
Propafenone
Antiarrhythmics class 1 Type
Na channel blockers
Antiarryhythmics class 1a MOA
Na channel blockers
Inc. AP duration
Inc. ERP (some K-channel blocking effects).
Prolongs QT interval.
Antiarrhythmics class 1a Clinical use
Na channel blockers
Atrial/ventricular arrhythmias (AFib, A-flutter; SVT, Vtach)
(esp. re-entrant and ectopic SVT, VT)
Antiarrhythmics class 1a Toxicity
Na channel blockers.
>Cinchonism (headache, tinnitus; Quinidine).
>SLE-like syndrome (procainamide).
>Heart failure (disopyramide).
>Torsades de pointes (prolonged QT interval).
Antiarrhythmics class 1b MOA
Na channel blockers
Dec. AP duration (preferential for ischemic or depolarized Purkinje and ventricular tissue).
Dec. ERP.
Antiarrhythmics class 1b Clinical use
Na channel blockers. Ventricular arrhythmias (post-MI)
Antiarrhythmics class 1b Toxicity
Na channel blockers
CNS stimulation/depression
Cardiovascular depression
Antiarrhythmics class 1c MOA
Na channel blockers
Markedly prolongs phase 0 depolarization.
Antiarrhythmics class 1c Clinical use
Na channel blockers
Life-threatening SVTs (atrial fibrillation).
Last resort in refractory Vtach.
Antiarrhythmics class 1c Toxicity
Na channel blockers
Pro-arrhythmic (CI in post-MI)
Antiarryhthmics class 2 Type
Beta-blockers
Antiarrhythmics class 2 Drug names
Metoprolol, Propanolol
Esmolol, Atenolol
Timolol, Carvedilol
Antiarrhythmics class 2 MOA
B-blockers (B1 antagonists at low doses, atenolol)
Dec. SA/AV node activity (dec. cAMP – dec. Ca – dec. phase 4 slope, dec. depolarization).
Inc. PR interval – dec. conduction through AV node.
Antiarrhythmics class 2 Clinical use
B-blockers
SVT
Ventricular rate control of A-fib and A-flutter.
Antiarrhythmics class 2 Toxicity
B-blockers. Impotence. Exacerbated COPD, asthma. CVS effects (bradycardia, HF, AV block). CNS effects (sedation, sleep disturbance). Can mask hypoglycemic signs.
Antiarrhythmics class 3 Type
K channel blockers
Antiarrhythmics class 3 Drug names
Amiodarone
Ibutilide
Dofetilide
Sotalol
Antiarrhythmics class 3 MOA
K channel blockers. Prolongs phase 3 repolarization. Prolongs AP duration. Prolongs ERP. Prolongs QT interval (ventricular contraction).
Antiarrhythmics class 3 Clinical use
K channel blockers.
A-fib, A-flutter
Vtach (amiodarone, sotalol)
Antiarrhythmics class 3 Toxicity
K channel blockers.
Torsades de pointes (sotalol, ibutilide).
B-blockade (sotalol).
>Amiodarone: pulmo fibrosis, hepatotoxicity, hypo/hyperthyroidism (40% iodine); photodermatitis, corneal deposits (acts as a hapten); CNS effects, CVS effects – check LFT, PFT, TFT.
Antiarrythmics class 4 Type
Ca channel blockers (nondihydropyridine)
Antiarrhythmics class 4 Drug names
Verapamil
Diltiazem
Antiarrhythmics class 4 MOA
Ca channel blockers. Prolongs phase 2. Dec. conduction velocity -- slow rise of AP, slow closing of Ca channels. Inc. ERP. Inc. PR interval.
Antiarrhythmics class 4 Clinical use
Ca channel blockers
Prevents nodal arrhythmias (SVT)
Rate control in A-fib
Antiarrhythmics class 4 Toxicity
Ca channel blockers Constipation, flushing, edema CVS effects (HF, AV block, sinus node depression)
Digoxin
Type
Cardiac glycoside
Digoxin
MOA
Inhibits Na/K ATPase – indirect inhibition of Na/Ca exchanger – Inc. intracellular Ca – positive inotropy (increases contractility)
Digoxin
Clinical use
> HF (inc. contractility).
>A-fib (decr. AV node conduction, depresses SA node).
Digoxin
Toxicity, Antidote
> Cholinergic: N/V, diarrhea, changes in color vision (blurry yellow vision), arrhythmias, AV block.
Hyperkalemia (poor prognosis).
Antidote: slowly normalize K; Mg, anti-digoxin Fab fragments.
Digoxin
Predisposing for toxicity
Renal failure.
Hypokalemia.
>Verapamil, Amiodarone, quinidine – decr. digoxin clearance, displaces digoxin at tissue-binding sites.
Calcium channel blockers
Dihydropyridines
Amlodipine, Clevidipine
Nicardipine, Nifedipine
Nimodipine
Calcium channel blockers
Non-dihydropyridines
Diltiazem
Verapamil
Calcium channel blockers
MOA
Blocks L-type calcium channels on cardiac and smooth muscle (decrease contractility).
>Vascular smooth muscle: amlodipine = nifedipine.
>Heart: verapamil > diltiazem > amlodipine = nifedipine.
Calcium channel blockers
Clinical use
> Dihydropyridines (except nimodipine): HTN, angina, Raynaud phenomenon.
Nimodipine: SAH (prevents cerebral vasospasm).
Clevidipine: HTN urgency/emergency
NDP: HTN, angina, A-fib/flutter.
Hydralazine
MOA
Arteriolar dilator – reduces afterload.
Inc. cGMP – smooth muscle relaxation.
Hydralazine
Clinical use
Severe HTN, HF.
Coadministered w/ B-blocker to prevent reflex tachycardia.
Safe in pregnancy.
Hydralazine
Toxicity
> Compensatory tachycardia (due to inc. venous return from baroreceptor reflex; CI in angina/CAD).
Fluid retention (sympathetic activation of RAAS).
Lupus-like syndrome.
Nitrates
Drug names
Nitroglycerin, isosorbide dinitrate, isosorbide mononitrate
Nitrates
MOA
Venous dilator – reduces preload.
Inc. NO in vascular smooth muscle – inc. cCMP – smooth muscle relaxation.
Nitrates
Clinical use
Angina, acute coronary syndrome
Pulmo edema
Nitrates
Toxicity
Reflex tachycardia (response to relative hypotension). >"Monday disease" in industrial exposure: tolerance for vasodilating affect during work week, loss of tolerance over weekend (tachycardia, dizziness, headache upon exposure).
Calcium channel blockers
Toxicity
Cardiac depression, peripheral edema.
AV block (NDPs)
Hyperprolactinemia (verapamil)
Gingival hyperplasia
Mannitol
MOA
Proximal tubule
Osmotic diuretic.
Inc. tubular osmolarity – inc. urine flow.
Dec. ICP, IOP
Mannitol
Clinical use
Elevated ICP, IOP (cerebral edema tx).
Drug overdose.
Mannitol
[Toxicity, CI]
> Pulmo edema (rapid rise in volume, overall inc. in hydrostatic pressure in vessels).
CI: anuria, HF.
[ex. Pt w/ cerebral edema is given mannitol, so all the fluid in the brain is drawn back into BVs – rapid inc. in hydrostatic pressure – pulmo edema]
Acetazolamide
MOA
Proximal tubule.
Carbonic anhydrase inhibitor.
Self-limited NaHCO3 diuresis – dec. total HCO3 stores.
Acetazolamide
Clinical use
Glaucoma.
Urinary alkalization, Metabolic alkalosis.
Altitude sickness.
Pseudotumor cerebri
Acetazolamide
Toxicity
Hyperchloremic metabolic acidosis (dehydration). NH3 toxicity (SE: urine alkalinization). "ACIDazolamide causes ACIDosis"
Sulfonamide Loop diuretics
Drug names
Furosemide
Bumetanide
Torsemide
Sulfonamide Loop diuretics
MOA
Thick ascending limb of Henle.
Inhibit Na/K/2Cl cotransport.
Excess excretion of Na, Cl, H2O – no hypertonicity of medullary interstitium – prevents urine concentration.
Inc. Ca excretion (paracellular Ca reabsorption w/ Na/K/Cl cotransport).
Sulfonamide Loop diuretics
Clinical use
Edematous states (HF, cirrhosis, nephrotic syndrome, pulmo edema).
HTN
Hypercalcemia
Sulfonamide Loop diuretics
Toxicity
Ototoxicity (similar symporters in ear)
Hypokalemia
Dehydration, Allergy
Nephritis, Gout
Thiazide diuretics
Drug names
Chlorthalidone
Hydrochlorothiazide
Thiazide diuretics
MOA
Distal convoluted tubule.
>Inhibits Na/Cl cotransporter – no Na/Cl reabsorption – Na/H20 excretion.
>Dec. diluting capacity.
>Dec. Ca excretion (Ca/Na antiporter exchanges Na from blood w/ reabsorbed Ca – dec. intracellular Ca during exchange prompts further inc. Ca reabsorption).
Thiazide diuretics
Clinical use
HTN, HF
Nephrogenic diabetes insipidus
Osteoporosis, Idiopathic hypercalciuria
Thiazide diuretics
Toxicity
Hypokalemic metabolic alkalosis
Hyponatremia, Hypercalcemia (hypocalciuria)
Hyperglycemia, Hyperlipidemia, Hyperurecemia
K-sparing diuretics
Drug names
Spironolactone, Eplerenone
Triamterene, Amiloride
K-sparing diuretics
MOA
Collecting tubules.
>Spironolactone, eplerenone: competitive aldosterone receptor antagonists.
>Triamterene, Amiloride: Na channel blockers – block ENaC, w/c drives Na/K pump.
K-sparing diuretics
Clinical use
Hyperaldosteronism
K depletion
HF
K-sparing diuretics
Toxicity
Hyperkalemia (maybe arrhythmias).
Endocrine effects w/ spironolactone (gynecomastia, antiandrogen).
ACE inhibitors
Drug names
Captopril, Enalapril
Lisinopril, Ramipril
ACE inhibitors
MOA
Inhibit ACE – dec. ATII – prevent constriction of efferent arteriole – dec. GFR.
Inc. Renin.
Prevents bradykinin inactivation (vasodilator).
ACE inhibitors
Clinical use
HTN, HF (prevent heart remodelling due to chronic HTN).
Proteinuria (no ATII, no vasoconstriction).
Diabetic nephropathy – dec. intraglomerular pressure – slow GBM thickening.
ACE inhibitors
Toxicity
Cough, Angioedema (bradykinin accumulation –vasodilation).
Teratogen.
Inc. creatinine (due to dec. GFR).
Hyperkalemia, Hypotension.
*CI in bilateral renal artery stenosis – renal failure.
Angiotensin II receptor blockers (ARBs)
Drug names
Losartan
Candesartan
Valsartan
ARBs
MOA
Blocks binding of ATII to AT1 receptor – similar effects of ACEi (prevents peripheral vasoconstricting effects of ATII).
Dec. GFR, inc. renin.
Don’t inc. bradykinin.
ARBs
Clinical use
For intolerance of ACEi (cough, angioedema).
HTN, HF
Proteinuria
Diabetic nephropathy
ARBs
Toxicity
Hyperkalemia
Dec. renal function
Hypotension
Teratogen
HMG-CoA reductase inhibitors (-statin)
[Names]
Lovastatin, Simvastatin
Pravastatin, Atorvastatin
Rosuvastatin
HMG-CoA reductase inhibitors
[MOA, effect on lipid levels, toxicity]
> Inhibits conversion of HMG-CoA to mevalonate (cholesterol precursor).
Super dec. LDL, inc. HDL, dec. TGL.
Dec. mortality in CAD
Tox: hepatotoxic, myopathy (esp. w/ fibrates or niacin)
Bile acid resins
[Names]
Cholestyramine
Colestipol
Colesevelam
Bile acid resins
[MOA, effect on lipid levels, toxicity]
> Prevents intestinal reabsorption of bile acids – liver uses cholesterol to make more.
Dec. LDL, slightly inc. HDL.
SE: dec. absorption of other drugs and fat-soluble vitamins
Ezetimibe
[MOA, effect on lipid levels]
> Prevents cholesterol absorption at SI brush border.
>Dec. LDL
Fibrates
[Names]
Gemfibrozil
Clofibrate
Bezafibrate
Fenofibrate
Fibrates
[MOA, effect on lipid levels, toxicity]
> Upregulates LPL – inc. TG clearance.
Activates PPAR-alpha to induce HDL synthesis.
Super dec. TG, inc. HDL, dec. LDL
SE: myopathy (inc. risk w/ statins), cholesterol gallstones
Niacin (B3)
[MOA, effect on lipid levels, SE]
> inhibits lipolysis (HPL) in adipose, reduces hepatic VLDL synthesis.
Inc. HDL, dec. LDL
SE: red, flushed faced (PGs); Hyperglycemia, hyperuricemia