Calcium Channel Blockers

Mechanism: Reduce muscle contractility via blocking voltage dependent L-type Ca+ channels on cardiac+smooth muscle

Clinical use: 

Dihydropyridine (not nimodipine): HTN, angina (including prinzmetal), Raynaud phenomenon

Non-dihydropyridine: SA hemorrhage (prevents cerebral vasospasm

Nimodipine: SA hemorrhage (prevents cerebral vasospasm)

Tox: Cardiac depression, AV block, peripheral edema, flushing, dizziness, hyperprolactinemia and constipation; note no reflex tachy!

Use: Severe HTN, CHF. First line therapy for HTN in pregnancy, with methyldopa. Frequently coadministered with β-blocker to prevent reflex tachy.

Mechanism: ↑cGMP -> smooth muscle relaxation. Vasodilates arteriole > veins; afterload reductions.

Tox: Compensatory tachy (contraindicated in angina/CAD), fluid retention, nausea, headache, angina. Lupus-like syndrome

Use: Angina (causes angina in OD too), pulmonary edema

Mechanism: Vasodilate by releasing NO in smooth muscle, causing ↑ in cGMP and smooth muscle relaxation. Dilate veins >> arteries ↓ preload

Tox: Reflex tachy, hypotension, flushing, headache, "Monday disease" in industrial exposure i.e. develope tolerance during week and lose it over the weekend, results in tachy, dizziness and headache upon reexposure.

HMG-CoA reductase inhibitors

Use: Lipid Lowering Agent

Mechanism: Inhibits cholesterol precursor, mevulonate

Effects: ↓↓↓ LDL; ↑HDL; ↓TAG

Side effects: Hepatotoxicity (↑ LFTs), rhabdomyolysis

Use: Lipid Lowering Agent

Mechanism: Inhibits lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation

Effects: ↓↓ LDL; ↑↑HDL; ↓TAG

Side effects: Red, flushed face, which is ↓ by aspirin or long-term use; Hyperglycemia (acanthosis nigricans); Hyperuricemia (exacerbates gout)

Bile acid resins

Use: Lipid lowering agents

Mechanism: Prevent intestinal reabsorpiton of bile (and all other) acids; liver must use cholesterol to make more

Effects: ↓↓ LDL; slight ↑ HDL; slight ↑ TAG

Side effects: Pts hate it- tastes bad adn causes GI discomfort, ↓ absorption of fat-soluble vitamins; Cholesterol gallstones; Dx interactions with acidic drugs

Cholesterol absorption blocker

Use: Lipid lowering agent

Mechanism: Prevent cholesterol reabsorption at small intestine

Effects: ↓↓ LDL; No HDL or TAG effect

Side effects: Rare ↑ LFT's

"Fibrates"

Use: Lipid lowering agents

Mechanism: Upregulate LPL -> ↑TAG clearance

Effects: ↓ LDL; ↑HDL; ↓↓↓ TAG

Side effects: Myositis, hepatotoxicity (↑LFTs, cholesterol gallstones)

Cardiac Glycoside

Use: CHF (↑ contractility); a-fib (↓ conduction at AV node and depression of SA node)

Mechanism: Direct inhibition of Na+/K+ ATPase leads to indirect inhibition of Na/Ca exchanger/antiport. ↑Ca -> positive inotropy. Stimulate Vagus n.

PHK: Digox - 75% bioavailable, 20-40% protein bound, t1/2 = 40 hrs, urinary excretion

Tox:

Cholinergic (nausea, vomiting, diarrhea, blurry yellow vision (think van gogh)

ECG-↑PR, ↓QT, scooping, T-wave inversion, arrhythmias, hyperkalemia.

Worsened by renal failure (↓excretion), hypokalemia (permissive for digoxin binding of K-binding site on Na/K ATPase), quinidine (↓digoxin clearance; displaces digosin from tissue binding sites)

Antidote: Slowly normalize K+, lidocaine, cardiace pacer, anti-dig Fab fragments, Mg2+

Use: Acute decompensated HF

Mechanism: Recombinant B-type natriuretic peptide. Causes ↑ in cGMP and vasodilation

Tox: Hypotension

Class IA Antiarrhythmic: Na channel blockers

"The Queen Proclaims Disco's pyramid"

Mechanism: Slow or block conduction (especially in depolarized cells). 

Effects: ↑AP duration, ↑ effective refractory period (ERP), ↑QT interval. Affect both atrial and ventricular arrhytmias, especially recentrant and ectopic supraventricular and ventricular tachy. 

Tox: quinidine (cinchonism- headache, tinnitus); procainamide (reversible SLE-like syndrom); disopyramide (HF); thrombocytopenia; torsades de pointes due to ↑QT interval