pharmacology Flashcards
what are fast action potentials?
- present in atrial and ventricular muscle cells
- eg purkinje fibres
- In the diagram, the plateau phase is present
- Sodium dependent
what are slow action potentials?
- present in sinoatrial node, the normal pacemaker and atrioventricular node – this is the normal route of action potential conduction between atria and ventricles
- In phase 4, there is a gradual depolarization, this is known as the pacemaker potential
- Calcium dependent
what happens in phase 4 in ventricular cardiac muscle cells?
- period between action potentials (diastolic potential)
- There is a constanat movment of K+ ions out of the cel, resulting in a negative membrane potential of -90mV. Ion concentration across the membrane is mainained by the NA/K ATPase – if this is inhibited by digoxin, the cell will depolarize slightly
what happens in phase 0 in ventricular cardiac muscle cells?
- action potential is stimulated by impulses from the SA node
- involves rapid activation of voltage-activated Na+ channels at a threshold potential, generating an Na+ conductanced and an inward, depolarising Na+ current that drives Vm towards the Na+ equilibrium potential
what happens in phase 1 in ventricular cardiac muscle cells?
- K+ efflux is dominant
- most evident in cells which has a prominent plateau phase, such as purkinje fibres and epicardial ventricular fibres
what happens in phase 2 in ventricular cardiac muscle cells?
- influx of Ca+ is balanced by efflux of K+ - the plateau will last as long as this persists
- influx of Ca+ vis voltage-activated Ca2+ channels (lL-type)
- Ik1 channels open slow
- Ical increases duration of plateau
- drugs that block certain v potassium channels increase duration of ventricular action potentials - not good
what happens in phase 3 in ventricular cardiac muscle cells?
- efflux of K+ is dominant
- Ica slowly decreases due to the inactivation of Ltype Ca+ channels
how does the slow response differ from the fast response in the nodal tissues of the heart?
- Vm between action potential s(phase 4 ) is unsteady gradually shifting with a slope in the depolarising direction (pacemaker potential)
- slope steepness in the SA node sets action potential interval and thus heart rate
- upstroke (phase 0 ) is far less steep and is due to the opening of Ltype Ca2+ channels that mediate Ical
- there is no distinct steady plateau (phase 2 ) but instead a more gradual repolarisation (phae 3 ) caused by the opening of delayed rectifier K+ channels mediating Ik
what happens in phase 4?
- an effflux of K+
- reduce influx of Ca2+
- Na+ is increased, generating the pacemaker potential
what increases the intracellular conc of cycline AMP (cAMP)?
- coupling through Gs protein alpha subunit stimulates adenylyl cyclase to increase the intracellular conc of cAMP
what does signalling though Gs, B1-adrenoceptor activation cause?
- increased SA node action potential frequency and heart rate (positive chronotropic effect) due to:
1. an increase in the slope of phase 4 depolarisation by inhanced If and Ical
2. a reduction in the threshold for AP initiation by enhanced Ical
what are the impacts of sympathetic on cardiac rate and force?
- higher contractility because more Ca+ comes into the cell during plateau = enhanced CICR
- higher conduction velocity in AV node
- increase in automaticity
- decrease in duration of systole (due to increased uptake of Ca2+ into the sarcoplasmic reticulum)
- increased activity of the NAKATPase
- increased mass of cardiac muscle
parasympathetic: how does coupling through G1 protein work?
- via alpha subunit inhibits adenylyl cyclase and reduces cAMP
- via beta/gamma subunit dimer opens specific potassium channels
what does signalling through G1, M2 muscarininc recrptor activation cause?
- decreased SA node action potential frequency and heart rate due to
- a decrease in the slope in phase 4 depolarisation by reduced If and Ical
- an increase in the threshold for AP initation by reduced hyperpolarisation during phase 4 via GIRKs
what happens if you block HCN channels?
- a decrease in the slope of the pacemaker potential and a reduce in heart rate
summarise excitation contraction coupling in cardiac muscle relaxation
- repolarisation in phase 3 to phase 4
- voltage-activated l-type Ca channels return to closed state
- Ca influx ceases. Ca efflux occurs by the NA/Ca exchanger
- Ca release from the sacroplasmic reticulum ceases
- Ca dissociates form troponin C
- cross bridge between actin myosin break resulting in relaxation
what converts cAMP into 5’AMP?
phosphodiesterase enzyme (PDE)
what are catecholamines? (B-adrenoceptor ligands on the heart)
- dobutamine
- adrenaline
- noradrenaline
- they increase force, rate, cardiac output, O2 consumption
- they decrease cardiac efficiency
- can cause disturbances in cardiac rhythm
what are the effects of b-adrenoceptor agonists upon the heart?
- adrenaline = reverse cardiac arrest, anaphylactic shock
- dobutamine = heart failure,
what are the effects of B-adrenoceptor ligands upon the heart? (antagonists)
- thye may block B-adrenoceptors non-selectvely (propreanol) or selectively (atenolol)
- may be non-selective and a partial agonist (alprenolol)
- pharmacodynamic effects . of non selective blockers:
- at rest = little effect on anything
- during exercise, rate force and CO are depressed
- cornonary vessel diameter reduced
what are the clinical uses of B-adrenoceptor antagonists (CVS actions only)?
- treatment of disturbances of cardiac rhythm - B blockers decrease excessive sympathetic drive and healp to restore normal sinus rhythm
- angina treatment
- heart failure treatment-
- hypertension treatment
what are the adverse effects of B-blockers (As a class)?
- bronchospasm
- cardiac failure
- bradycardia
- hypoglycaemia
- fatigue
- cold extremities
what are the effects of non-selective muscarinic ACh receptor antagonist upon the heart?
- atropine = increases HR
- first line treatment in bradycardia, esp in MI
- used in anticholinesterase poisoning
what is digoxin?
- a cardiac glycoside that increases contracility of the heart
- binds to the a-subunit of NA/K ATPase in competition with K+