drugs and the heart Flashcards by Stephanie Dunn

what are If channels?

hyperpolarisation-activated cyclic nucleotide gated channels
“funny channels”
predominantly Na channel

How well did you know this?

Not at all

Perfectly

what are Ica (t or l) channels

transient T-type Ca channel or long-lasting L-type

mediate fast calcium influx

How well did you know this?

Not at all

Perfectly

what does the SNS do in terms of these channels?

inc. cAMP

this inc. If and Ica

How well did you know this?

Not at all

Perfectly

what does PNS do in terms of these channels?

dec. cAMP

this inc. If

How well did you know this?

Not at all

Perfectly

what do beta-1 adrenergic stimulation activate?

activated adenylate cyclase
creates cAMP
this activated PKA
PKA then has 2 actions

How well did you know this?

Not at all

Perfectly

what are the 2 actions of PKA then?

phosphorylates proteins in myofibril
induces CICR in SR by stimulating Ca influx into SR
most Ca is from CICR

How well did you know this?

Not at all

Perfectly

what mediates removal of Ca from cells?

PMCA (ATPase Ca channel)

- NCX (Na/Ca exchanger)

How well did you know this?

Not at all

Perfectly

what is the primary determinant of myocardial oxygen?

myocyte contraction

How well did you know this?

Not at all

Perfectly

what influences contraction?

inc. HR = inc. contractions
inc. afterload/contractility = inc. force of contractions
inc. preload = small inc. force of contractions

How well did you know this?

Not at all

Perfectly

what 3 classes of drugs have an effect on the HR?

beta blcokers: dec. If and Ica
Ca antagonists: dec. Ica
Icabradine: dec. If

How well did you know this?

Not at all

Perfectly

how do these drugs reduce the HR?

by prolonging the extent of the depolarisation

dec. SNS drive

How well did you know this?

Not at all

Perfectly

what are the 2 classes of drugs that have an effect on contractility?

beta blockers: dec. contractility - reduce phosphorylation and cross bridge formation
Ca antagonists: dec. Ica - stops further entry of Ca into myofibrils

How well did you know this?

Not at all

Perfectly

what are the 2 classes of Ca antagonists?

rate slowing - cardiac and VSM: phenylalkylamines (Verapamil) and benzothiazepines (Diltazem)
non rate slowing - VSM (more potent): dihydropyridines (Amlodipine)

How well did you know this?

Not at all

Perfectly

even though non-rate slowing have no effect on the heart, how do they cause tachycardia?

they cause a lot of vasodilation and can lead to a reflex tachycardia

How well did you know this?

Not at all

Perfectly

what are the classes of drugs that have an effect on myocardial oxygen supply/demand?

organic nitrates (directly supply NO, inc. cGMP which stimulates K+ channel opening and relaxation directly)
potassium channel openers (stimulates hyperpolarisation)

How well did you know this?

Not at all

Perfectly

what does these drugs do?

stimulates hyperpolarisation (ability of coronary arteries to contract is impaired)

what effect do these drugs have on preload and afterload? How?

drugs dec. preload and afterload (demand) and inc. oxygen supply (inc. blood flow)

vasodilation = dec, afterload as less TPR
venodilation = dec. preload

what is angina caused by?

angina is classic mismatch b/ myocardial supply and demand

what classes of drugs are used in angina treatment?

beta blocker or CCA: background treatment
nitrate: symptomatic treatment (i.e. exercise)
K channel openers

what are the side effects of beta blockers?

cardiac failure worsening (beta 1)
bradycardia (beta 1)
bronchoconstriction (beta 2)
hypoglycaemia (beta 2)
cold extremities

what are the side effects of rate limiting calcium channel blockers? e.g. Verapmil

bradycardia and AV block (heart Ca channels blocked)

- constipation (gut Ca channels blocked)

what are the side effects of non-rate limiting calcium channel blockers? e.g. Dihydropyridines

ankle oedema (vasodilation so more capillary pressure in extremities)
headache/flushing (vasodilation)
palpitations (reflex SNS adrenergic activation due to vasodilation)

what are the side effects of potassium channel openers and nitrates?

ankle oedema (vasodilation, capillary pressure in extremeities)
headache/flushing (vasodilation)

what are the aims of treatment in rhythm disturbances?

reduce sudden death

- alleviate symptoms

what is the simple classification of rhythm disturbances?

based on site of origin - supraventricular e.g. amiodarone, verapmil - ventricular e.g. flecainide, lidocaine - comples (supra and ventricular) e.g. disopyramide

Describe the Vaughan Williams Classification of antiarrhythmic drugs

Class 1: Na+ channel blockers Class 2: beta blockers Class 3: K channel blockade (prolong repolarisation) Class 4: Ca channel blockade

why is this classification of limited significance?

due to significance of cross overs in rhythm disturbances

what is the MoA of adenosine (selective anti-arrhythmics)?

- activates A1 receptors in SA and AV nodes - Gi protein activation to reduce AC conversion of ATP to cAMP - dec. cAMO - dec. ionotropic and chronotropic effect

describe facts of adenosine

- IV given - targets SVT - short action so safer than Verapmil - class V anti-arrhythmic

what are the uses of verapamil?

reduces ventricular responsiveness to atrial arrhythmias

what is the MoA of verapamil?

- blocks VGCC and so depresses SA firing and subsequent AV node conduction - Class 4 anti-arrhythmic

what are the uses of amiodarone?

- SVT and VT

what is the MoA of amiodarone?

complex but probably involving multiple ion channel block | prolongs hyperpolarisation which reduces chance of re entry

what are the adverse effects of amiodarone?

- accumulation in body - skin rashes (photosensitive) - hypo/hyperthryroidism - pulmonary fibrosis

what is the MoA of digoxin?

- inhibits Na/K ATPase - inc. intraceullar Na - reversal of Na/Ca exchanger - Na effluxed and Ca influx - inc. intraceullar Ca - this lengthens class IV are of ventricular muscle graph so lower chronicity - but inc. ionotropic effect as more Ca inside cell

what is the other MoA of digoxin?

central vagal stimulation --> inc. refractory period and reduced rate of conduction through AVN

what are the uses of digoxin?

- atrial fibrillation and flutter lead to rapid ventricular rate - this impairs ventricular filling and reduces CO - digoxin via vagal stimulation reduces conduction within AVM so fewer impulses get to ventricles - slows down ventricular tachyarrhyth,ia

what are the side effects of digoxin?

dysrhythmias e.g. AV conduction block

what happens if digoxin is co-administered with diuretics?

- get hypokalaemia - can lower threshold for digoxin toxicity - digoxin is a K receptor antagonist - low blood potassium means less competition, so effects of digoxin are enhanced