Drugs and the heart Flashcards
What are the ‘funny’ channels in the heart? - I f channels
Hyperpolarization activated cyclic nucleotide gated channels - switch on during hyperpolarised states and utilise cyclic AMP and drive sodium entry to initiate depolarisation. On their own they do not produce enough to complete depolarissation, but it starts it
What is the predominant channel that drives depolarisation in Heart rate
Calcium channels - transient t type calcium channels or long lasting l type
What channels repolarise the cells controlling heart rate
-potassium channels
What is phase 4 in heart rate regulation
Spontaneous depolarization that triggers an action potential
Mechanism regulating heart contractility - describe the steps
- signal promotes calcium entry
- calcium activates RyR receptor
- 25% of calcium comes from outside, 75% from sarcoplastic reticulum - calcium promotes troponin binding and causing contraction
- repolarisation via sodium exchanging for calcium to export calcium out of cell and sodium potassium atpase maintains sodium levels in cell
What mechanisms increase the myocardial oxygen demand
An increase in: heart rate preload afterload contractility
What are factors that can increase the myocardial oxygen supply
Increase in:
Coronary blood flow
Arterial O2 content
What drugs mainly effect rate of heart
Beta blockers and
What beta blockers effect on the heart rate
Sympathetic NS increases nodal activity, and therefore affects funny current and ca2+ channels
Therefore a beta blocker will stop the sympathetic NS therefore decrease If and Ica
Calcium antagonist effect on heart rate
Block Ca2+ therefore slow heart down
What affect ivabradine on heart rate
Block funny current therefore decreasing heart rate as spacing out the time between each depolarisation starting
What affect beta blockers and calcium channel blockers on contractility
decrease calcium entry therefore decrease contractility
What are the different types of calcium antagonists
there are two classes - rate slowing that have cardiac and smooth muscle actions and non rate slowing that only have smooth muscle actions, but these are more potent
What are examples of rate slowing drugs
Phenylalkylamines eg verapamil
Benzothiazepines eg diltiazem
What are examples of non rate slowing drugs
Dihydropyridines eg amlodipine
What effect do organic nitrates and potassium channel openers have on the heart and how does it do this?
It increases cyclic GMP therefore causing smooth muscle relaxation and hyperpolarisation (due to potassium efflux) of the cells making it harder to contract. K+ channel openers mainly just cause potassium efflux causing hyperpolarisation of the cell
What two different effects of nitrates and potassium channel openers influence preload and afterload? What is a consequence of this?
It causes vasodilation therefore decreasing afterload
Venodilate causing a decrease in preload
Therefore a decrease in myocardial oxygen demand
What is a stable angina
A cardiac stitch where the heart doesn’t receive enough oxygen during exercise causing pain
What is the first line treatment of a stable angina? What is the problem of this treatment
Beta blockers or calcium channel blocker by reducing HR and contractility but make it harder to exercise as less response to sympathetic stimuli and therefore less Ca2+ influx
beta blocker side effects
It can worsen heart failure as it makes your tissues less able to match CO to tissue needs, which is already a problem in heart failure.
It also increases vascular resistance by blocking dilating of vessels. This will make HF even worse as have to work harder to push blood around the body
Also causes bradycardia, and if a patient has conduction problems then this will be even worse
What are examples of beta blockers used on the heart
Pindolol - an equal affinity for beta1 and beta 2 receptors with intrinsic sympathetic activity
Carvediol that causes an alpha 1 blockade causing additional vasodilator properties (alpha 1, beta 1 and 2)
What kind of patients can you NOT use beta blockers for and why
Asthmastics and diabetics
They block B2 receptors in lungs therefore make asthma attacks worse
It also interferes with liver control of glucose and masks hyperglycaemia effects
What is a common side effect of beta blockers that really bothers patients
Cold extremities (also a worsening peripheral artery disease) due to a loss of beta 2 receptor mediated cutaneous vasodilation in extremities therefore no blood in extremities
Side effects of calcium channel blocker
they are ‘safer’ than beta blockers but they can cause bradycardia and constipation (can affect people from taking a drug)
What are side effects of dihydropyridines
Ankle oedema due to vasodilation meaning more blood in capillaries causing fluid coming out
Headache/flushing due to vasodilation
Palpitations due to reflex tachycardia due to vasodilation of vessels
What are the different arrythmias simply classified between
Supreventricular - above the ventricles
Ventricular
Complex ( a mix of both supra and ventricular)
What is the vaughn williams classification
A classification of anti arrhythmic drugs: seperating the drugs into:
Class 1- sodium channel blockers
Class 2 - beta adrenergic blockade
Class 3 - prologation of repolarisation (membrane stabilisation mainly due to potassium channel blockade)
Class 4 - calcium channel blockade
What drugs are used to treat supraventricular arrythmias and how does it do this?
Adenosine, binding to adenosine receptors having an inhibitory effect on adenylate cyclase and therefore inhibiting cyclic AMP therefore decrease funny current therefore reducing depolarisation via AV node
(less importantly also has effect on SM and promote relaxation)
How does verapamil work
Block Ca2+ channels therefore decreasing ability to depolarisation therefore causing a longer time between the depolarisations therefore increases chances of normal rhythm starting
How does amiderone work
Blocks re-entry arrhythmias
This is done by a potassium channel blockade therefore prolonging the repolarisation state
What is a reentry rhythm
Where areas of damaged or dead tissue due to heart attack etc that causes a signal for a heart to contract coming back up the heart to cause a contraction instead of going as it would do, down the heart and cause contraction down the heart
What are the effects of digoxin/.
Decrease stroke risk by inhibiting the Na K ATPase pump
Digoxin also increases refractory period and reduces rate of conduction through the AV node, therefore more time between heart contractions
What effect does digoxin have on inotropy
Blocks Na K ATPase therefore blocking Na+ movement into the cell. This means that Na+ can’t be exchanged for Ca2+ successfully therefore more Ca2+ in cardiac muscle as it can’t move out. Therefore making cardiac muscle contractions more powerful.
When is digoxin used
In AF and Atrial flutter particularly when worry about stroke
Side effects of digoxin
Dysrhythmias due to AV conduction block
What can make digoxin toxicity threshold worse therefore make effects worse and why
Hypokalaemias eg due to diuretic use due the digoxin binding to the potassium binding site. Potassium competes with digoxin for this site, and if K+ levels decrease then more digoxin binds to the target so has a more powerful effect
