Drugs and the heart Flashcards
Recall the ion channels that influence heart rate
If (VGSC)
It (VGCC)
Il(VGCC)
Ik(VGPC)
Recall the roles of the sodium and calcium channels in depolarisation
If kickstarts depolarisation by allowing Na+ to move into cell
It (transient) begins to propagate AP
Il (long-lasting) produces the real upstrike of the AP
How does the SNS affect ion channels in the heart?
Linked to cAMP to increase opening of VGSCs and VGCCs
How does the PNS affect ion channels in the heart?
Increases Ik opening to prolong repolarisation
Describe the effect of beta-receptor activation on cardiac myocytes
PKA activated –>
- Contractility increase
- Reduced Ca++ reuptake into SR
What is the target of ivabradine?
If channel
Recall the 2 classes of calcium antagonists and their comparative tissue specificities
Rate-slowing: cardiac and SMC effects
Non-rate slowing: Just SMC, and more powerful on SMCs that rate-slowers
What is the main risk associated with non rate-slowing calcium antagonists?
Reflex antagonists: profound vasodilation leads to overstimulation of baroreceptors
Recall 2 classes of drug that act as rate-slowing calcium-antagonists
Phenylalkylamines
Benzothiapenes
Give an example of a non rate-slowing calcium antagonist
Amlodipine
What classes of drug can act as influencers on myocardial oxygen supply/ demand?
Organic nitrates
K+ channel openers
How do organic nitrates decrease the work burden of the heart?
NO –> more GTP converted to cGMP –> vasodilation
Describe the effects of vasodilation and venodilation on cardiac work
Vasodilation –> decreased AFTERload
Venodilation –> decreased PREload
What are organic nitrates/ K+ channel-openers most frequently used to treat?
Angina
Describe the instructions for administration of organic nitrate drugs
These are short acting, and so are used as opportunistic symptomatic relief
In which group of people are K+-channel-openers most frequently prescribed and why?
Asthmatics
Contra-indicted for beta-blockers
Systematically address the possible side-effects of a beta-blocker
Beta-1 side-effects: slow heart, care not to ppt heart block
Beta-2 SEs: bronchoconstriction (caution asthmatics), hypoglycaemia (caution: diabetics), cold extremities (caution, raynaud’s)
What sort of drug is verapamil?
Calcium channel antagonist
Recall 3 possible side effects of calcium channel antagonists
ABC:
AV block
Bradycardia
Constipation
Recall and justify 3 possible side effects of dihydropiridenes
Ankle oedema (vasodilation puts pressure on capillaries) Headache/ flushing (vasodilation) Palpitations (Ca++ channel interference)
What sort of drugs are dihydropiridenes?
Calcium channel antagonists
Recall the possible classifications of arrhythmias
Supraventricular
Ventricular
Complex
What tissue is affected by a supraventricular arrhythmia?
Atria/ nodal tissue
Recall 2 drugs implicated in supraventricular arrhythmia
Amiodarone
Verapamil
Recall 2 drugs implicated in ventricular arrhythmia
Lidocaine
Flecainide
Recall a drug implicated in complex arrhythmia
Disopyramide
Recall the Vaughan Williams classification of arrhtyhmia
I = SODIUM channel blockade II = BETA-adrenergic blockade III = Prolonged repolarisation (VGPC BLOCKADE) IV = CALCIUM channel blockade
Recall the method of administration of adenosine
IV
Why is adenosine generally seen as safer than verapamil?
Short-lived action so less concerned about long-term SEs
Recall the twofold mechanism of action of adenosine
- Effect on SMCs in heart and vasculature = stimulation of cAMP to increase RELAXATIOn
- Effect on NODAL tissue = REDUCES cAMP –> decreased ICa opening, increased Ik opening
What sort of arrythmia is verapamil particularly useful for treating?
Atrial arrhythmias - it reduces the ventricular response
What sort of arrythmia is amiodarone particularly useful for treating?
Re-entry rhythms caused by tissue block
Describe how a re-entry rhythm might arise
Normally if 2 APs coming down purkinje fibres meet at apex they cancel each other out + ensure the Aps continue up both sides.
In re-entry, goes back up and re-activates tissue to cause consistent contraction of ventricular muscle
What effect needs to be produced in the heart to combat reentry rhythms?
Prolonging of repolarisation so that tissue hit by re-entering AP is not depolarised again
How does amiodarone treat re-entry rhythms?
Blocks multiple ion channels to prolong repolarisation
Why has amiodarone got so many side effects? Recall some of these
Really long t1/2:
Skin rashes
Hypo/hyperthyroidism
Pulmonary fibrosis
What sort of drug is digoxin? Summarise its mechanism of action
Anti-arrhythmic:
Blocks Na+/K+ATPase
Recall the 2 sites of action of digoxin
Ventricles (improves contraction) Vagus nerve (increases refractory period)
Why is digoxin used for AF? (2 reasons)
- Improves ventricular filling
2. Combats ventricular tachycardia
When should you NOT give digoxin and why?
In hypokalaemia:
Digoxin competes with K+
