Pharmacology - drugs modifying cardiac rate and force Flashcards
What does coupling through Gs protein activities eating ardently cyclase to increase (CAMP) cause?
Increased HR
Increased force
Increased conduction velocity in the AV node
Increased automaticity (more chance for spontaneous beats)
Increased activity of Na+/K+-ATPase pump (important for repolarisation)
Increase mass of cardiac muscle
Decreased duration of systole
Decreased cardiac efficiency (O2 consumption increasing disproportionately with increasing work)
What is a positive lusitropic effect?
decreased duration of systole
What does coupling through Gi protein, inhibiting adenylyl cyclase, decreasing (CAMP) and opening K+ channels (GIRK) cause?
Decreased HR
Descreaed contractility
Decreased conduction through AV node
What might parasympathetic stimulation cause?
Parasympathetic stimulation may cause arrhythmias to occur in the atria
Describe vagal manoeuvres? What might they do?
Increase parasympathetic output and may be used in atrial tachycardia (atrial flutters, AF)
What 2 vagal manoeuvres might you get?
Valsalva manoeuvre - activates aortic baroreceptors
Massage of bifurcation of carotid artery - stimulates carotid sinus baroreceptors
The pacemaker potential is modulated by a depolarising funny current, what mediated this current?
Channels that are activated by:
Hyperpolarisation Cycle AMP (HCN channels)
What does hyperpolarisation following the action potential activate?
Hyperpolarization following the action potential activates cation selective HCN channels in the SA node facilitating a slow, phase 4, depolarization (the pacemaker potential)
What does block of the HCN channels do?
Decreases the slope of the pacemaker potential and reduces the heart rate
What drug is a selective blocker of HCN channels that is used to slow the heart rate?
Ivabradine
What is Ivabradine used in commonly?
Angina (a condition where coronary artery diseases reduces the blood supply to cardiac muscle - slower HR thus reduces O2 consumption)
Describe the steps in the excitation contraction coupling in cardiac muscle? (In phase 2)
(cross bridge formation of cardiac cells)
- Ventricular AP
- Opening of voltage gated Ca2+ channels (mainly L type) during phase 2 of AP
- Ca2+ influx into the cytoplasm
- Ca2+ induced release from the SR (CICR)
- Ca2+ binds to troponin C and shifts tropomyosin out of the actin cleft
- Cross bridge formation between actin and myosin resulting in contraction via sliding filament mechanism
Describe the steps in Excitation Contraction Coupling in Cardiac Muscle Relaxation?
(cross bridge relaxation of cardiac cells)
- Repolarization in phase 3 to phase 4
- Voltage-activated L-type Ca2+ channels close
- Ca2+ influx ceases. Ca2+ efflux occurs by the Na+/Ca2+ exchanger 1 (NCX1) a plasma membrane ATPase (not illustrated) is less important
- Ca2+ release from the sarcoplasmic reticulum ceases. Active sequestration via Ca2+-ATPase (SERCA) of Ca2+ from the cytoplasm now dominates
- Ca2+ dissociates from troponin C
- Cross bridges between actin and myosin break resulting in relaxation
Name some beta adrenoceptor agonists?
Adrenaline, dobutamine noradrenaline
What are some of the pharmacodynamic effects of beta adrenoceptor agonists?
Increased force, rate and cardiac output, and O2 consumption
Decreased cardiac efficiency ( O2 consumption increased more than cardiac work)
They can also cause disturbances in cardiac rhythm
What are the clinical uses of Adrenaline?
Alpha and beta agonist
Given in cardiac arrest and anaphylactic shock
Describe how adrenaline works on beta 1, 2 and alpha 1 receptors?
B1 = positive inotropic and chronotropic actions B2 = dilation of coronary arteries A1 = redistribution of blood flow to the heart (constricts blood vessels in the skin, mucosa and abdomen)
Describe dobutamine?
Selective for B adrenoceptors
Used in acute HF
Can cause less tachycardia than others B1 adrenoceptors
Describe beta adrenoceptor antagonists?
Can get non selective or selective
Describe non selective blockers?
Example propranolol
Cause little effect at rest
During exercise or stress cause significant depression in force, rate and CO
Coronary vessel diameter marginally reduced.
What are some clinical uses of Beta adrenoceptor antagonists?
Treat arrhythmias
- BB decreases excessive sympathetic drive and help restore normal sinus rhythm
- AF and SVT
- BB delay conduction through the AV node and help restore normal sinus rhythm
Treat angina
Treat HF (compensated + low dose0
Treat hypertension (no longer first line)
What are some side effects of beta blockers as a class?
Bronchospasm (due to block of airway smooth muscle B2 adrenoceptors) - can be a problem in asthma
Aggravation of cardiac failure - okay in low dose compensated
Bradycardia
Hypoglycaemia
Fatigue
Cold extremities
Describe the Effect of Non-Selective Muscarinic ACh Receptor Antagonists Upon The Heart
Increased HR in normal subjects at low doses
Give an example of a non selective muscarinic ACh receptor antagonist?
Atropine
