Class 1A (procainamide) 

• Pacemaker cells: decreased slope of phase 4, increse firing threshold.
• purkinje cells: moderate Na block, prolongs repolarization.
• clinical uses: AF/AFl

Class 1B (lidocaine)

• Pacemaker cells: decreased slope of phase 4, increase firing threshold.
• Purkinje cells: mild Na block, shortens repolarization.
• clinical use: Post-MI ventricular arrhythmias.

Class 1C (Flecanide)

• Pacemaker cells: decreased slope of phase 4, increased firing threshold.
• Purkinje cells: marked Na block, no change in repolarization.
• clinical use: AF and WPW in patients with structurally normal hearts.

Class 2 (beta-blockers, metoprolol)

• Pacemaker cells: decreased slope of phase 4, prolong repolarization at AV node
• Purkinje cells: no effect.
• clinical use: Rate control AF/AFl, PSVT, VT

Class 3 (qt prolonging, ibutilide, amiodarone)

• Pacemaker cells: no effect.
• Purkinje cells: prolonged repolarization
• clinical use: ibutilide- AF/AFl, Amiodarone- AF, VT

Class 4 (CCB, verapamil)

• Pacemaker cells: slow AP rise, prolong repolarization at AV node.
• Purkinje cells: no effect
• Clinical use: rate control of AF/AFl, PSVT

Pacemaker cell:

• Pacemaker current - If (spontaneous depolarization by Na influx)
• Ca influx by L type and T type Ca channels. 
• repolarizatoin by K efflux.

Purkinje cell:

• Phase 0 - fast Na influx
• Phase 1 - Cl- influx
• Phase 2 - Ca influx balances K efflux (prolonged horizontal phase)
• Phase 3 - K efflux
• Phase 4 - resting membrane potential

Loop Diuretics (Furosemide)

• decreased K+, Ca, Mg
• increased HCO3-, Urate

CA inhibitor

blocks reuptake of HCO3- in proximal tubule.

Furosemide

blocks Na, K, 2Cl- symporter in distal loop of henle

blocks Na Cl symporter in distal tubule.

spironolactone

blocks K+, H+, Na+ (out) exchanger in distal collecting duct.

Overview: Pharmacokinetics refers to movement of drugs through the body (input, distribution, output). What the body does to the drug.

Input: availability refers to the fraction of a dose that reaches the systemic circulation. IV drugs have 100% availability. Oral availability is a function of not only absorption from the gut but also first pass metabolism in the liver.

Distribution: volume of distribution relates plasma concentration of the drug (C) to the total amoun tin the body. Drugs that extensively distribute in the tissues (lipids) can have a Vd substantially greater than actual volume of the body and higher tissue concentrations than serum concentrations.

Output: Renal excretion is the primary route of elimination for most water soluble compounds. influenced by GFR. acidification will enhance excretion of weak bases. alkalinization of urine will enhace secretion of weak acids.

Hepatic clearance eliminates lipophilic compounds. phase I reactions add oxygen moities via P450 enzyme. phase II reactions conjugate large hydrophilic groups to these oxygen moities. resulting in more hydrophilic compounds (bile, urine, both). 

the rate of elimination is directly proportional to the serum drug concentration.

clearance = output/concentration.

elimination at a fixed rate regardless of concentration is zero order kinetics.

a multisubstrate transporter that uses ATP hydrolysis to pump xenobiotics (durgs, toxins) out of cells against steep concentration gradients. primary function is to prevent absorption of toxic compounds by the gut and to facilitate their excretion into bile and the renal proximal tubules. P-gp expression in brain and testis capillary endothelium limits the ability of toxins to enter these sensitive tissues.

• expressed by colonic epithelium
• overexpression in tmor cells confers MDR phenotype. sometimes refered to as MDR1

Arteriolar dilators:

• decrease afterload
• Hydralazine, minoxidil, CCBs, Fenoldopam

Mixed vasodilators

• decrease afterload and preload
• ACEIs, ARBs, renin inhibitors
• Nitroprusside, nesiritide, alpha1 blockers, alpha2 central agonists.

Venodilators

• decrease preload
• nitrates