Flashcards in Drugs and the Cardiovascular System – The Heart Deck (57)
What is the major store of calcium within the cardiomyocyte?
Channels associated with initiating a heart rate
ICa Long lasting
Role of If channels
Associated with cAMP
Are hyperpolarisation activated cyclic nucleotide gated channels which tend to let in sodium during hyperpolarised times
Role of 2 calcium channels
Main drivers behind depolarisation
Role of Ik
The heart has two signalling pathways that are involved in elevating the level of two intracellular second messengers. What are these second messengers?
Ca2+ and cAMP
Which plasma membrane proteins allow calcium to enter the cell in response to depolarisation?
What happens to the calcium once it has passes into the cell viathis channel?
It binds to ryanodine receptors on the sarcoplasmic reticulum and cause calcium release from the SR
How does the calcium stimulate contraction?
It binds to troponin on the thin filament
What are the different ways in which calcium is removed from the myoplasm after it has stimulated contraction? Which method is responsible for the majority of calcium removal?
Plasma membrane calcium ATPase
SERCA2a (sarcoendoplasmic reticulum calcium ATPase) –responsible for >70% of calcium removal
What features of contraction is SERCA2a responsible for and why?
Rate of calcium removal and so it’s responsible for the rate of cardiac muscle relaxation
Size of calcium store, which affects the contractility of the subsequent beat
What are beta adrenoceptors coupled with?
Adenylate cyclase – it increases cAMP, which is important in the opening of the If channel to begin depolarisation
How does the parasympathetic nervous system affect heart rate and contractility?
It is negatively coupled with adenylate cyclase
What are the determinants of myocardial oxygen supply?
Arterial oxygen content
Coronary blood flow
What are the determinents of myocardial oxygen demand?
What effect do beta-blockers and calcium channel blockers have on the channels responsible for the SA node action potential?
Beta-blockers decrease If and calcium channel activity
Calcium channel blockers only decrease calcium channel activity
These 2 affect both HR and contractility
Name a drug that decreases If activity.
Ivabradine (blocks the If channel)
What effect does Ivabradine have on contractility?
It has no effect on contractility because it doesn’t affect the calcium channels
What are the two types of calcium channel blocker?
Rate slowing - cardiac and smooth muscle effects
Non-rate slowing - only really potent in smooth muscle
What is a consequence of non-rate slowing calcium channel blockers?
Reflex tachycardia (baroreceptor reflex)
How do organic nitrates cause vasodilation in coronary vasculature?
Organic nitrates are substrates for nitric oxide production
The NO then diffuses into the smooth muscle and causes smooth muscle relaxation by activating guanylate cyclase
They are often given in angina patients before they exercise
How do potassium channel openers work?
They open the potassium channels and hyperpolarise the vascular smooth muscle so that it is less likely to contract
How do vasodilation and venodilation of nitrates and potassium channel openers reduce myocardial oxygen demand?
They reduce the pressure against which the heart is pumping (reduce afterload) and it also causes reduce venous return to the heart (reduced preload) meaning that contractility is decreased
As these drugs reduce the myocardial oxygen demand, what condition can they all be used to treat?
State some unwanted effects of beta-blockers.
Hypoglycaemia in diabetics on insulin
Cold extremities (because of beta-2 blockade)
Last 4 not examined
Under what circumstance must caution be taken when giving beta-blockers?
Cardiac failure – because they reduce heart rate and contractility it can have catastrophic consequences in cardiac failure patients
Reduced CO and increased vascular resistance
What are the side effects of verapamil?
Bradycardia and AV block
What are the side effects of dihydropyridines?
Ankle oedema - due to vasodilation
Headaches/flushing - due to vasodilation in brain
Palpitations- reflex tachycardia
What is a simple classification of arrhythmias?
Based on its point of origin
Supraventricular, Ventricular and Complex