Hydralazine

acetylated by the liver

increases cGMP thus smooth mm relaxation

vasodilates arterioles > veins thus afterload reduction

USE: severe htn, CHF; 1st line for htn in pregnancy (w/ methyldopa); admin w/ B-blocker to prevent reflex tachycradia

Toxicity: compensatory tachycardia (angina, CAD); fluid retention; Nausea; HA; angina; drug-induced SLE (anit-histone Ab)

Tx of high BP in pregnancy

hydralazine

methyldopa

labetolol

Nifedipine

Mask signs of hypoglycemia

(cautionin DM)

K+ channel opener thus hyperpolarizes and relaxes vascular smooth mm

USED in severe htn

Toxicity: hypertrichosis, pericardial effusion, reflex tachycardia, angina, salt retention

"dipine"

- nifedipine, amilodipine, felodipine

- act like nitrates and dilate veins thus decrease preload

- block voltage-gated L-type Ca channels of smooth mm and reduce mm contractility

USE: htn, Prinzmetal's angina, Raynaud's, esophafeal spasms, angina

Toxicity: peripheral edema, flushing, dizziness, constipation

Verapamil

- anti-arrhythmic, works directly on heart

- blocks voltage-gated L-type Ca channels of cardiac mm thus decreases mm conractility

USE: angina, arrhythmias

Toxicity: cardiac depression, AV block

- vasodilate by releasing NO in smooth mm, causing inc cGMP and smooth mm relaxation

- dilates veins >> arteries thus decreases preload

USE: angina, pulmonary edema, and as an aphrodisiac and erection enhancer

Toxicity: reflex tachycardia, hypotension, flushing, HA

- "Monday dz" in industrial exposure (tolerance during wk and loss of tolerance over the weekend thus tachycardia, dizziness, and HA on re-exposure on Mondays)

-short acting; tx of malignant htn

- inc cGMP via direct release of NO; vasodilates arteries and veins thus dec preload and dec afterload

- can cause CN toxicity

D1 receptor agonist

relaxes renal vascular smooth mm

tx of malignant htn

- K+ channel opener thus hyperpolarizes and relaxes vascular smooth mm

- may cause hyperglycemia b/c decreases insulin release

- tx of malignant htn

"statins"

- HMG-CoA reductase inhibitors

- inhibit colesterol precursor mevalonate

- best effect on lowering LDL

- also inc HDL and decrease TGs

Toxicity: cardio and hepatotoxic

- inc LFTs, rhabdomyolysis (myositis)

DOC to raise HDL

- also decreases LDL and TGs

- inhibits lipolysis in adipose tissue; reduces hepatic VLDL secretion into circulation

Toxicity: red, flushed face b/c inc PGs (inhibited by aspirin or long-term use) - take before bedtime

- hyperglycemia --> acanthosis nigricans

- hyperuricemia --> exacerbates gout

Resins

- cholestyramine (binds C. diff toxin)

- colestipol and colesevelam

- decreases LDL, inc HDL, inc TGs

- prevents intestinal resorption of bile acids; liver must use cholesterol to make more

Toxicity: patients hate it b/c tastes bad and causes GI discomfort

- dec absorption of ADEK

-cholesterol gallstones

- cholesterol absorption blocker

- not used much b/c may actually increase plaque thickness

- lowers LDL --> prevents cholesterol reabsorption at small intestine brush border

Toxicity: inc LFTs

DOC for lowering TGs

- also decreases LDL and inc HDL

- upregulates LDL thus inc TG clearance

Toxicity: cardio and hepatotoxic (dangerous to combine w/ statins)

- also causes cholesterol gallstones

lowers TGs and reduces risk for arrythmias and decreases rheumatoid arthritis severity

found in salmon, halibut, and flax seedoil

- cardiac glycoside

- 75% bioavail, 20-40% protein bound

- t1/2 = 40 hrs

- urinary exretion

Mech: direct inhibition of Na/K ATPase leads to indirect inhibition of of Na/Ca exchanger antiport thus inc intracellular Ca and positive inotropy; also stimulates vagus nerve (PSNS); dec resting HR not exercise HR

- USE: CHF to in contractility; atrial fib to dec conduction at AV node and depression of the SA node

Toxicity: cholinergic agonist, inc PR interbal, dec QT interval, scooping, T-wave inversion, arrhythmia, hyperkalemia --> toxicity worsened by renal failure b/c dec excretion or by hypokalemia or by quinidine

Tx of toxicity: K+, Mg2+, lidocaine (tachy), atropine (brady), cardiac pacer, anti-dig Fab fragments (cardioroxicity)

CLASS 1A Antiarrhymics

Na+ channel blockers --> dec slope of phase 4 depol and inc threshold for firing in abn pacemaker

- POLICE DEPT QUESTIONS --> procainamide, quinidine, disopyramide

- inc AP duration, inc ERP, inc QT interval

- affect both atrial and ventrical arrhythmias especially re-entrant and ectopic SVT and ventricular tachycardia --> use procainamide for WPW syndrome

Toxicity: Quinidine --> cinchonism, thrombocytopenia, torsades

- Procainamide --> drug-induce SLE

Na channel blockers --> dec slope of phase 4 depol and inc threshold for firing in abn pacemaker cells

- The Little Man --> Tocainide, Lidocaine, Mexiletine

- preferentially affects ischemic or depol Purkinje and Ventricular tissue

- useful in acute ventricular arrhythmias and in digitalis induced arrhythmias --> SVT

- BEST POST-MI

toxicity: local anesthetic; CNS stimulation/depression; CV depression

Na channel blockers - dec slope of phase 4 depol and inc threshold for firing abn pacemaker cells

- For Pushing Ecstasy --> Flecainide, Propafenone, Encainide

- no affect on AP duration

- useful in V-tachs that progress to Vfib and in intractable SVT; last resort in refractory tachyarrhythmias; pt w/ no structural abn - contraindicated post-MI

Toxicity: proarrhythmic - esp post-MI, prolongs refractory period in AV node

B-blockers --> "olol"

- dec cAMP thus dec Ca currents

- suppresses abn pacemakers by dec slope of phase 4

- AV node particularly sensitive thus inc PR interval

- esmolol: very short acting

USE: V-tach, SVT, slow ventricular rate during a.fib/a.flutter

Toxicity: impotence, exacerbation of asthma, bradycardia, AV block, CHF decompensated, sedations, sleep alt, masks signs of hypoglycemia

- metoprolol can cause dyslipidemia

Tx of OD w/ glucagon

K channel blockers --> inc AP duration, inc ERP, used when other antiarrhythmics fail, inc QT interval

- Bret SAID K+ is a last resort --> Bretylium, Sotalol, Amiodarone, Ibutilide, Dofetilide

Toxicity: sotalol: torsades, excessive B-block

- amiodarone: pulm fibrosis, hepatotoxic, thyrotoxic (check PFTs, LFTs, TFTs) and corneal or skin deposits (photodermatitis), neuro efects, constipation, bradycardia, CHF, heart block

- ibutilide: torsades

- bretylium: hypotension, new arrhythmias

Class IV Anitarrhythmic

CCB: verampil and dilitiazem

- non-dihydropyridine

- primarily affect AV nodal cells; dec conduction velocity, inc ERP, inc PR interval

- used in prevention of nodal arrythmias

toxicity: constipation, flushing, edema, CHF, AV block, sinus node depression

- inc K+ out of cells thus hyperpolarize the cell and dec Phase 0 (influx Ca)

- DOC for dx/abolishign SVT

- very short acting (~15 sec)

- effects blocked by theophylline used by COPD pts

- efective in torsades and dig toxicity (hypoK+)

Toxicity: flushing, hypotension, chest pain