Lecture 2Sodium channelOutside cell inside is K and HChannel opens na comes in cellBlockers: local anesthetics, antiarythmics, anti epilecptics (seizures)LA (local anesthetics)

End in caineEster (one i)

Hyrdophillic and lipophilicStarted with procaineCocaine only vasoconstricting LA (all others vasodilate)

Constricting helped reduce bleeding, dilation helps wash away LA so more has to be usedCountered with constrictor (norepinephrine on alpha receptors)Concentrates epinephrine, norepinephrine, and dopamine by inhibiting reuptake

Plasma metabolism (esterases), low toxicity, some allergiesamide (two i)

hydro and lipophilic (longer acting than esters)started with lidocainestable in hospitalhepatic metabolism, rare allergies, more toxicity

AntiarrhythimicPacemaker AP5 phases

Na in, k out, ca in/k out, k out, Ca inNa blockers on phase 0 (QRS depolarization)Antiarrythmic classifiedI na channel blocker (ventricular arrhythmia)

A phase 0 block med, phase 3 block (k out repolarization inhibited)Affects depolarization and repolarizationTorsade de pointesLots of points on ekgMg by IV Quinidine, procainamide, disopyramide

Quinidine-atropine like (anticholinergic, dilated pupils), cinchonism (blurred vision, tinnitus, headache, digoxin levels, N&V, arrhythmia (fast), bronchodilating less urination, (less used than before)

ProcainamideMetabolized to class III (NAPA) which blocks K channel with original blocking na channelUsed for (WPW wofl Parkinson white syndrome)

Bundle of kent and bundle of his tachycardiaB phase 0 block (little), phase 3 stimulate (k out stimulated slightly)

Lidocaine, mexiletine (oral lidocaine)C phase 0 block most, phase 3 no effect (known as clean)

Flecainide Not as used because did not improve mortality

II beta blocker (type 1, ach receptor, dilates)III k channel blockerIV ca channel blockerV vagus booster (slows down heart)

AntiepilepticsGABA is brakeNMDA is acceleratorNA and CA are wires controlling everythingStop seizure (increase GABA or decrease NMDA)Na block= membrane stabilization (so no more depolarization)

Type I vaugh WilliamsCa block= inhibit release of NeurotransmitterCarbamazepine

NA blockerTricyclical (similar to antidepressants)

Many of the same ADRH receptor block= sedationm-receptor block= dry mouth (also in nticholinergicv/atropine like drugs, prevents people from talking)na channel block= arrhythmiak channel block= arrhythmiaalpha r block=hypertension (vasodilation, postural hypotension, slow get up5ht (serotonin)= weight gain

3a4 inducerPhenytoin blocks na and CA

Gum hyperplasia, megablastic anemia (folate deficiency) peripheral neuropathy, skin rash, hirsutiastism, facial feautres, CNS symptomsLiver can be saturated (zero order kinetics) (no fixed half life)

Ethanol, heparin, Aspirin, theophylline, phenytoin

Chlorida channels (GABA receptor)Reduce a cell acitivity (hyperpolarize)

Open K to let them outOpen cl to let them in

GABA receptors open cl channelsBenzoapamines (sleeping pills) (body produces endozepines)

Alpha receptor of GABA receptor, need GABA to workChange gaba bindingSedative, hypnotic, amnesiac, muscle tone decrease, antiepileptic, no analgesiaEnd with zolam,/zepamShort acting, TOMB (triazolam for anesthesia)Intermediate Letal (lorazepam phase II metabolism)Long acting valiumZaleplon, zolpidem, zopiclone ultra short acting hypnotic, sleeping pills (chem similar but

not a benza)Flumazenil is an antagonist for benza overdose

Can induce seizures, and panic attacksMetabolized quicker than benza

Carbolines block channel (increase fear)Gaba agonists

Benzo, barbituates, propofol, alcoholBarbituate and propofol bind beta subunits, don’t need gaba, no analgesiaBarbituates: anesthesia (thiopental lethal injection, release histamine); antiepileptic (phenobarbital )Propofanol ultra short acting barbiturate

Vigabatrin (vigorous gaba transaminase inhibitor)Stimulate Gaba levels more depolarization, antiepileptic

TiagabinGaba uptake inhibitor, increase gaba antiepilepsy

GabapentinNot an agonist, not good antiseizureReduce ca influx inhibiting neurotransmit release and activy

BacalaflenGaba b (presynaptic) Reduce transmitter release by same mechanism