41: Drug Action on Ion Channels and Pumps

local anesthetics:

bind to voltage gated sodium channels → inactivates channel → prevents propagation of action potential

Examples of local anesthetic agents:

• short duration: procaine, chloroprocaine

• medium: lidocaine, prilocaine

• high: tetracaine, bupivacaine

What drugs interact with the GABA A receptor?

allosteric modulators like:

• barbiturates: interior binding sites

• general anesthetics (propofol, steroids, etc.): lowest binding sites

• benzodiazepines: most exterior binding sites

antiepileptic agents:

blocks sodium channel in neuronal membranes → prevents neuronal firing since sodium levels are decreased (i.e. phenytoin, carbamazepine, oxcarbazepine etc.)

SSRIs:

delays re-uptake of serotonin → increases in synaptic cleft → serotonin more likely to bind to serotonin receptors in postsynaptic cell (i.e. Paxil, Prozac, Zoloft)

Vaughan Williams Classification on antiarrhythmic agents:

• class 1: sodium channel blockers

• class 2: beta blockers

• class 3: potassium channel blockers

• class 4: calcium channel blockers

effective refractory period (ERP):

period of time during which a new action potential can’t be initiated

How does Class 1 antiarrhythmic agents affect ERP?

• 1A → increases ERP (lidocaine, phenytoin)

• 1B → decreases ERP

• 1C → prolongs ERP

How does Class 3 antiarrhythmic agents affect ERP?

delays repolarization (increases ERP) by inhibiting efflux of K+ ions

How does Class 4 antiarrhythmic agents affect ERP?

as calcium channel blockers, DECREASES heart rate and allows left ventricle to fill completely to lower heart workload

• dihydropyridine: anything ending with -dipine

• non-dihydropyridine: verapamil, dilitazem

ouabain:

also called g-strophanthin, inhibits Na+/K+ pump as a cardiac glycoside and can be used to treat hypotension and arrhythmias

digoxin:

from digitalis plant, inhibits Na⁺/K⁺ pump to decrease activity of Na⁺/Ca²⁺ exchanger, used to treat various heart conditions like AF and heart failure

proton pump inhibitors (PPIs):

irreversibly binds to H+/K+ pumps → prevents movement of H+ ions from parietal cells to stomach → temporarily blocks stomach acid secretion

• any drug ending in -prazole

• treats GERD, ulcers, esophagitis etc.