drugs and the heart

Question 1

DIAGRAM mechanisms regulating heart rate

Answer 1

SA node- If (funny) channels START depolarisation, but most of depolarisation due to first transient Ca2+ channels, then long lasting channels- thus Ca drives HR iK channels then start repolarisation, and process begins again

Question 2

effects of SNS/PNS on HR

Answer 2

SNS increases cAMP, hence If and Ica open more PNS decrease cAMP, hence Ik open more

Question 3

DIAGRAM mechanisms regulating contractility

Answer 3

depolarisation causes Ca2+ entry, activating RYR, channel, causing Ca2+ efflux from SR- 75% contraction due to Ca2+ from SR, 25% from outside some Ca2+ goes back into SR via ATP, but most goes via Ca Na exchanger, which is maintained by NaK pump

Question 4

mechanisms regulating heart O2 and supply

Answer 4

O2 increased by coronary blood flow/O2 content demand increased by HR, contractility, PRELOAD AND AFTERLOAD (heart needs to work harder as has to deal with more blood/TPR

Question 5

how drugs effect HR and contractility

Answer 5

beta blockers reduce If/Ica, calcium anatagonists lower Ica, Ivabradine lowers (If) B blcokers decrease contractility, Ca2+ lowers Ica

Question 6

types of calcium anatagonists

Answer 6

rate slowing are effective on heart and VCSM- eg phenylalkylamiles like Verapamil and benzothiazepines non-rate slowing have potent VCSM actions, but NO on heart eg dihydropiridines- causes vasodilation= reflex tachycardia thus ONLY rate slowing used for heart

Question 7

drugs affecting heart O2 demand/supply

Answer 7

organic nitrates (NO) increase sFC enzymes, which catalyses GTP into cGMP= relaxation of vessels= more coronary blood flow K+ channel openers= more hyperpolarisation= more difficult to contract= more coronary blood flow both also lower preload (venodilation) and afterload (vasodilation)

Question 8

treatment of stable angina and what is it

Answer 8

heart no receiving blood upon EXERTION due to atherosclerosis use beta blockers/Ca2+ (affects ability to exercise as can’t contract)- if combination doesn’t work, use nitrates, ivabradine or nicorandil (K+ opener)

Question 9

beta blocker side effects

Answer 9

beta 2 blockage reduce vasodilation as they are DILATING receptors- increases TPR= heart needs to work faster= CO reduced as well= heart failure worsened bradycardia cold extremities (less B2 vasodilation in extermities)

Question 10

how to stop beta blocker side effects

Answer 10

Pindolol is non-selective- has some ISA, so stimulates beta 2 a bit mixed blocker eg Carvedilol- alpha 1 blockage can decrease TPR

Question 11

who should not take beta blockers

Answer 11

asthmatics (dilates bronchioles) and diabetics (less glycogenolysis, as SNS helps with more glucose production)

Question 12

side effects of Ca2+ blockers and comparison to beta blockers

Answer 12

verapamil causes bradycardia (Ca2+ block) and constipation (gut Ca2+ channels= less motility) dihydropyridines- has vasdilatory effects= ankle oedema (more fluid goes to dilated vessels in ankle, headaches (blood in head), and palpitations (response of SNS to vasodilation) SAFER than beta blockers

Question 13

explain rhythm disturbances, types and major risks

Answer 13

arrhythmias (too fast) and dysrhythmias (abnormal)- increases likelihood of blood clotting, which can cause stroke either supraventricular (above ventricles ie atria) or ventricular arrhythmias

Question 14

DIAGRAM Vaughan Williams classification

Answer 14

use different anti-arrhythmic drugs based on which part of ventricular contraction is affected class 1- drugs reducing depolarisation ie Na+ blockage class 2- beta adrenergic blockage ie generalised inhibitory effect on contraction class 3- prolonged repolarisation class 4- Ca2+ blockage (during plateau)

Question 15

is Vaughan classification important

Answer 15

limited clinical significance

Question 16

how adenosine works

Answer 16

acts on adenosine receptors- binds to A1 receptors, inhibing adenylate cyclase= lower cAMP, affecting SA and AV= less chronotropy also effects A2 receptors VCSM, INCREASING cAMP= relaxing VCSM

Question 17

uses of adenosine+ why better for this than verampamil

Answer 17

for supraventricular tachyarrhytmias- short acting (30s), so safer

Question 18

how verampamil works+ use

Answer 18

blocks Ca2+ channels, decreasing ability to depolarise at ONLY SA node, increasing time heart has to have normal rhythm used for atrial arrhytmias

Question 19

DIAGRAM how amiodarone works and what problem it stops

Answer 19

normally AP moves down branch and 2, which cancel out when getting to 3- if branch 2 blocked due to damaged tissue eg after heart attack, impulses don’t cancel out, and can reenter via branch 2 (other 2), causing jerky contractions (another depolarisation) thus amiodarone causes K+ blockage= prolonging repolarisation phase= less likely and impulse reenters to cause depolarisation occurs again

Question 20

use and side effect of amiodarone

Answer 20

used for supra and ventricular arrhythmias- less safe then adenosine as longer acting

Question 21

digoxin (cardiac glycosides)

Answer 21

stimulates vagus nerve= less HR as longer refractory period NAK pump inhibited, so less Ca2+ moves out= greater contraction: thus slower and greater contractions

Question 22

uses and side effects of digoxin

Answer 22

atrial fibrillation/flutter can lead to dysrhythmias- also if someone has hypokalemia eg due to diuretics, not good to give digoxin, as digoxin competes with K+ for NaK pump- if less K+ like in hypokalemia, digoxin more potent= toxic