drugs and the heart Flashcards
DIAGRAM mechanisms regulating heart rate
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
effects of SNS/PNS on HR
SNS increases cAMP, hence If and Ica open more PNS decrease cAMP, hence Ik open more
DIAGRAM mechanisms regulating contractility
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
mechanisms regulating heart O2 and supply
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
how drugs effect HR and contractility
beta blockers reduce If/Ica, calcium anatagonists lower Ica, Ivabradine lowers (If) B blcokers decrease contractility, Ca2+ lowers Ica
types of calcium anatagonists
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
drugs affecting heart O2 demand/supply
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)
treatment of stable angina and what is it
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)
beta blocker side effects
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)
how to stop beta blocker side effects
Pindolol is non-selective- has some ISA, so stimulates beta 2 a bit mixed blocker eg Carvedilol- alpha 1 blockage can decrease TPR
who should not take beta blockers
asthmatics (dilates bronchioles) and diabetics (less glycogenolysis, as SNS helps with more glucose production)
side effects of Ca2+ blockers and comparison to beta blockers
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
explain rhythm disturbances, types and major risks
arrhythmias (too fast) and dysrhythmias (abnormal)- increases likelihood of blood clotting, which can cause stroke either supraventricular (above ventricles ie atria) or ventricular arrhythmias
DIAGRAM Vaughan Williams classification
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)
is Vaughan classification important
limited clinical significance
how adenosine works
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
uses of adenosine+ why better for this than verampamil
for supraventricular tachyarrhytmias- short acting (30s), so safer
how verampamil works+ use
blocks Ca2+ channels, decreasing ability to depolarise at ONLY SA node, increasing time heart has to have normal rhythm used for atrial arrhytmias
DIAGRAM how amiodarone works and what problem it stops
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
use and side effect of amiodarone
used for supra and ventricular arrhythmias- less safe then adenosine as longer acting
digoxin (cardiac glycosides)
stimulates vagus nerve= less HR as longer refractory period NAK pump inhibited, so less Ca2+ moves out= greater contraction: thus slower and greater contractions
uses and side effects of digoxin
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
