Antiarrhythmic & Antihypertensive Drugs

Front 1

name some risk groups for arrhythmias

Back 1

occur in 25% of patients treated w/digitalis, 50% of anesthetized patients, >80% of patients w/acute MI

Front 2

which cells in the heart have action potentials with a straight phase 0? how about a sloped phase 0?

Back 2

straight phase 0: fast tissue --> ventricular and atrial myocytes, His Purkinje. sloped phase 0: slow tissue --> SA node and AV node

Front 3

which has a higher MDP (maximum depolarized potential): fast tissue or slow tissue?

Back 3

slow tissue --> MDP is set by IRK and GIRK

Front 4

what determines the intrinsic pacemaking activity of the SA and AV node cells?

Back 4

they have If (funny) channels that are open in phase 4 (DRK turn off), a few Ca channels also help.

Front 5

what is the effect of sympathetic stimulation on slow tissue?

Back 5

increase If and Ca, decrease DRK activity via beta-1 receptors --> increase phase 4 slope, decreases threshold, increase firing rate. Also, increased ca channel activity increases conduction velocity.

Front 6

what is the effect of parasympathetic stimulation on slow tissue?

Back 6

decrease If and Ca, increase DRK and GIRK activity via M2 receptors --> decrease phase 4 slope, decrease MDP, increase threshold, decrease firing rate. Also, decreased Ca channel activitydecreases conduction velocity.

Front 7

after an MI, there will be slow conduction in "fast" tissue (ischemic). what is the physiological basis for this?

Back 7

1. inactivation of Na channels --> slow phase 0 closure. 2. closure of gap junction channels

Front 8

what can cause abnormal pacemaking in fast ischemic tissue?

Back 8

slow depolarization of phase 4 --> abnormal activation of Na channels and If channels --> this can cause ectopic beats/pacemaking

Front 9

what is the physiological basis for refractory periods?

Back 9

Na and Ca channels are inactivated --> cell is depolarized and action potentials can't be fired.

Front 10

what characterizes escape beats?

Back 10

occur LATE, terminate a pause, bradycardia, vagal tone is a key regular

Front 11

what characterizes the enhanced automaticity of latent pacemakers?

Back 11

faster than the SA node, ectopic beats that occur EARLY

Front 12

what characterizes abnormal automaticity?

Back 12

tissue injury, myocytes acquire automaticity and ectopic beats occur, probably due to depolarization

Front 13

what is triggered activity?

Back 13

spontaneous beats triggered by an action potential. are either early afterdepolarizations (EADs) or delayed afterdepolarizations (DADs)

Front 14

what characterizes 1st degree AV block

Back 14

PR interval >.2 sec

Front 15

what are the 2 types of 2nd degree AV block? what differentiates them?

Back 15

mobitz I/wenckebach: PR increases. mobitz II/non-wenckebach: PR is constant.

Front 16

what characterizes 3rd-degree AV block?

Back 16

P and QRS are independent

Front 17

what pharmacological treatments treat heart block?

Back 17

NONE! 2nd and 3rd degree blocks may be treated w/ventricular pacemaker

Front 18

what is the basic definition of reentry?

Back 18

a single impulse excites more than once --> will lead to excessive activation

Front 19

what are the 3 conditions that must be met for reentry to occur?

Back 19

1. non-homogeneous impulse propagation 2. unidirectional block 3. slow conduction, allows normal tissue to recover from refractory period

Front 20

what are the 3 ways to interrupt a reentry circuit?

Back 20

increase refractory periods of reentered tissue (drugs), decrease cellular conduction velocity (drugs), surgery

Front 21

what two things are therapeutic approaches in the treatment of arrhythmias designed to do?

Back 21

reduce ectopic pacemaking and prevent impulse reentry

Front 22

how do drugs reduce ectopic pacemaking?

Back 22

reduce slope of diastolic depolarization (phase 4), increase firing threshold (make it more positive), make the MDP more negative

Front 23

how do drugs help prevent impulse reentry?

Back 23

modify abnormal impulse conduction by slowing conduction through certain regions or increasing the refractory period of some cells

Front 24

what are class I antiaarhythmic drugs?

Back 24

Na channel blockers

Front 25

what are class II antiarrhythmic drugs?

Back 25

beta-adrenergic blockers

Front 26

what is the physiology behind Na channel blockers? (which 4 effects do Na channels have on ventricular action potentials?)

Back 26

1. inhibit Na channels in FAST tissue --> raise threshold + slow abnormal phase 4 + increase relative refractory period + slows upstroke of phase 0 --> allow normal pacemakers to set pace --> reduces ectopy

Front 27

what problem is associated w/Na channels?

Back 27

slows conduction --> could slow it too much, which could lead to other arrhythmias!

Front 28

name some class Ia drugs

Back 28

quinidine, procainamide, disopyramide

Front 29

what characterizes class Ia drugs?

Back 29

MODERATE level of Na channel block, increase AP duration due to inhibition of DRK channels. used primarily to treat reentry arrhythmias

Front 30

name some class Ib drugs

Back 30

lidocaine, phenyotin, tocainide, mexilitine

Front 31

what characterizes class Ib drugs?

Back 31

MILD Na channel block, preferential block of Na channels in damaged fast tissue, shorten or don't change AP duration. used for reentry arrhythmias following MI

Front 32

name some class Ic drugs.

Back 32

flecainide, propafenone

Front 33

what characterizes class Ic drugs?

Back 33

POTENT Na channel block. pro-arrhythmic, risk of sudden cardiac death. rarely used.

Front 34

name some class II antiarrhtyhmics

Back 34

propranolol, acebutolol, esmolol, metropolol, timolol

Front 35

how do class II antiarrhythmics work?

Back 35

inhibit beta1-AR mediated stimulation of Ca channels and If channels in SLOW tissue --> slow pacemaking of slow tissue, reduce ectopy of slow tissue, interrupts reentry in slow tissue. also affect ischemic FAST tissue --> raise threshold and increase rel refractory period

Front 36

what are class III antiarrhythmics?

Back 36

DRK channel blockers

Front 37

name some class III drugs

Back 37

amiodarone, sotalol, bretylium

Front 38

how do class III drugs work?

Back 38

delay phase 3 of fast and slow tissue (block DRK channels) --> increase AP duration and increase ARP duration

Front 39

what are class IV antiarrhythmics?

Back 39

Ca channel blockers

Front 40

name some class IV drugs

Back 40

verapamil, diltiazem

Front 41

how do class IV antiarrhythmics work?

Back 41

slow phase 4 and phase 0 of slow tissue --> raise threshold, prolong ERP, slow conduction of slow tissue --> slow pacemaking of slow tissue --> decrease ectopy of slow tissue, interrupt reentry

Front 42

what explains why class IV antiarrhythmics may cause TACHYcardia?

Back 42

also cause vasodilation and lower blood pressure --> can cause REFLEX tachycardia

Front 43

what does adenosine do?

Back 43

activates GIRK channels via A1 receptors, inhibits Ca channels and funny channels --> causes ASYSTOLE and COMPLETE AV BLOCK

Front 44

does adenosine block ventricular or atrial arrhythmias?

Back 44

ATRIAL arrhythmias only.

Front 45

when is adenosine indicated?

Back 45

to interrupt reentry in slow tissue. to diagnose atrial v. ventricular arrhythmia. (need to have resuscitation equipment on hand)

Front 46

what does digoxin do?

Back 46

increases contractility (used to treat HF), increases vagal tone (used to treat arrhythmia)

Front 47

what is the most common cardiovascular disease?

Back 47

hypertension

Front 48

at what blood pressure does HTN-related organ damage start to occur?

Back 48

140/90

Front 49

what are the 4 sites of blood pressure control?

Back 49

venules (capacitance vessels), arterioles (resistance vessels), heart (pump output), and kidneys (regulate blood volume)

Front 50

what regulates blood pressurein the short-term?

Back 50

baroreceptor reflexes (autonomic nerves), humoral mechanisms (renin-angiotensin-aldosterone system), and local hormones (NO dilates vessels, endothelin-1 constricts)

Front 51

what regulates blood pressure in the long-term?

Back 51

the renal response. decreased pressure leads to increased reabsorption of salt and water, also increases renin production --> all of this will lead to volume retention

Front 52

what are the 4 classes of antihypertensive drugs?

Back 52

diuretics, sympathoplegics, vasodilators, anti-angiotensin drugs

Front 53

what do diuretics do?

Back 53

increase salt excretion, reduce blood volume

Front 54

what do sympathoplegic drugs do?

Back 54

reduce peripheral vascular resistance, inhibit cardiac function, increase venous pooling

Front 55

what do vasodilators do?

Back 55

relax vascular smooth muscle, dilate resistance vessels, increase capacitance

Front 56

what do anti-angiotensin drugs do?

Back 56

reduce peripheral vascular resistance, potentially blood volume

Front 57

what non-pharmacologic change can help you decrease your blood pressure?

Back 57

decrease salt intake (also lose weight and stuff)

Front 58

mechanism of diuretics

Back 58

decrease Na+ stores, some also have direct vasodilating effects

Front 59

how much do diuretics lower blood pressure?

Back 59

10-15 mmHg

Front 60

what class of drugs are methyldopa and clonidine? where do they work?

Back 60

sympathoplegic drugs. act on vasomotor area in the medulla --> attenuate sympathetic influence on the heart

Front 61

what class of drugs are guanethidine and reserpine? where do they work?

Back 61

sympathoplegic drugs. work at sympathetic presynaptic nerve terminals to interfere w/neuroepinephrine release/storage.

Front 62

in terms of HTN, what class of drugs are beta and alpha1 antagonists (propranolol, metoprolol, nadolol, prazosin, terazosin, doxazocin)? where do they work?

Back 62

sympathoplegic drugs. work at sympathetic POSTsynaptic nerve terminals.

Front 63

name some oral vasodilators

Back 63

hydralazine, minoxidil, CCBs

Front 64

name some parenteral vasodilators

Back 64

nitroprusside, diazoxide, fenoldopam (used in hypertensive emergencies), CCBs

Front 65

how do you use hydralazine?

Back 65

resistance develops, so use it in combination for outpatient management of HTN

Front 66

how does minoxidil work?

Back 66

opens K+ channels --> hyperpolarizes cells --> decreases Ca2+ entry ---> vasodilates

Front 67

what is a side effect of monixidil? is it ever beneficial?

Back 67

hirsutism. marketed as rogaine for male-pattern baldness.

Front 68

which one is a stronger pressor: angiotensin ii or norepinephrine?

Back 68

angiotensin ii (by about 40x)

Front 69

what do ACE inhibitors do?

Back 69

inhibit angiotensin-converting enzyme --> decrease angiotensin II and decrease inactivation of bradykinin (which promotes vasodilation)

Front 70

captopril is an example of what type of drug?

Back 70

ACE inhibitors

Front 71

do ACE inhibitors cause tachycardia?

Back 71

no.

Front 72

do ACE inhibitors affect vascular resistance?

Back 72

yes.

Front 73

what's a side effect with ACE inhibitors?

Back 73

dry cough. also severe hypotension in patients at risk.

Front 74

what cascade is begun with AT1 receptor activation?

Back 74

IP3 and DAG --> elevates intracellular Ca2+, activates PKC and --> stimulate aldosterone synthesis --> promotes Na+ and water retention

Front 75

name two ARBs

Back 75

losartan, valsartan and all the other -sartans

Front 76

which is more selective: ARBs or ACE inhibitors?

Back 76

ARBs - don't act on bradykinin (not associated w/dry cough or angioedema)