cardiovascular pharmacology Flashcards
Lignocaine
Describe the MOA of lignocaine on the heart
● Class IB antiarrhythmic drug
● Blocks activated and inactivated Na channels
● Greater effects on cells with longer action potentials i.e. ventricular and purkinje
fibres.
● Does not prolong the action potential
What are the adverse effects of lignocaine?
CNS: dizziness, anorexia, nausea vomiting, tinnitus, slurred speech, paresthesias
CVS: bradycardia, cardiovascular collapse, hypotension
Allergy
Flecainide
What is the mechanism of action of flecainide?
● Class IC antiarrhythmic drug
● Na channel blockade
● Inhibits the fast upstroke of the action potential
● Minimal effect on the action potential duration
What are the pharmacokinetics of flecainide?
● Well absorbed orally
● Half life 20 hours
● Peak plasma levels at 3 hours
● 30% excreted unchanged
● The rest metabolised by the liver
In which patients is flecainide contraindicated?
Those with hypotension and LV dysfunction
Propranolol
Describe the pharmacodynamics and clinical effects of propranolol
● Beta blocker - competitive, non selective blocker at B1 and B2 receptors
● CVS: decreases BP and HR, negatively chronotropic and inoptropic. Decreases
the effect of catecholamines.
● Inhibits the peripheral conversion of T4 to T3 making it useful in thyrotoxicosis
● Propranolol also has some activity as a sodium channel blocker
What are the adverse effects of propranolol?
● CVS: bradycardia, hypotension, worsening of CCF, QRS widening, arrhythmias in
toxicity
● CNS: sedation, depression, abnormal dreams, depression
● Resp: worsening asthma/COPD
● Decreased exercise tolerance, decreased libido, can mask symptoms of
hypoglycaemia
Describe the pharmacokinetics of metoprolol
● Given oral or IV
● Well absorbed, but bioavailability is 50% due to 1st pass effect (usually give half
the dose IV)
● Large Vd
● Half life 3-4 hours so BD dosing
● Liver metabolism
How is metoprolol different from propranolol?
● Metoprolol is B1 specific and propranolol is not
● Metoprolol has no action on sodium channels
Describe the pharmacodynamics of sotalol
● Non selective beta blocker, class II
● Also has Class III action, prolongs the plateau phase
What are the main side effects of sotalol?
● Proarrhythmic - especially QTc prolongation and torsades
● Can exacerbate CCF and asthma
● Can cause AV blockade
What drugs interact with sotalol to prolong the QT?
● Other drugs which prolong QTc = phenothiazines, such as chlorpromazine
● Macrolide antibiotics -azithromycin, erythromycin
● Some antidepressants, such as amitriptyline
● Drugs which cause hypokalaemia - like frusemide and other diuretics
● Drugs which depress the myocardium
● Calcium channel blockers that can increase refractory time
What antiarrhythmic class does amiodarone belong to?
Class III, but also has effects from class I, II and IV.
What are the effects of amiodarone on the heart?
● Increases the action potential duration due to blockade of K current
● Prolongs the QT interval
● Also blocks inactivated Na channels
● Weak adrenergic and Ca channel blocker
● Decreases automaticity
In what arrhythmias is amiodarone used?
● Atrial and ventricular tachyarrhythmias, such as
● Atrial fibrillation
● Ventricular tachycardia
● Ventricular fibrillation
● SVT (re-entrant or accessory)
What acute and chronic adverse effects can amiodarone cause?
Acute
● Arrhythmias: Bradycardia, heart block, torsades (rarely)
● Hypotension
Chronic
● Pulmonary fibrosis
● Abnormal LFTs and hepatitis
● Skin deposits leading to photodermatitis and grey-blue discolouration
● Corneal microdeposits
● Hypo or hyperthyroidism in both acute and chronic
What are some important drug interactions with amiodarone?
● Warfarin - increased anticoagulant effect via decreased warfarin metabolism
● Digoxin - risk of digoxin toxicity by increasing the plasma concentration
● Increased cardiac effects of other antiarrhythmic medications due to overlapping
MOAs (procainamide, flecainide, beta blockers)
● Increases the plasma concentration of phenytoin
Describe the MOA of calcium channel blockers
● Blocks voltage gated Ca channels
● Reduces the frequency of opening when depolarised
● Resulting in decreased calcium current, decreased calcium influx
● Causes vascular smooth muscle relaxation (therefore reducing afterload) - this
effect is greater in dihydropyridines
● Effects on the heart include decreased SA firing, decreased AV nodal conduction,
decreased contractility and cardiac output
● Verapamil and diltiazem also have a non specific anti-adrenergic effect
What are the toxic effects of calcium channel blockers?
● Minor: flushing, dizziness, nausea, constipation, peripheral oedema
● CVS - bradycardia, AV block, hypotension, heart failure, cardiac arrest
What are the indications for verapamil?
Angina, hypertension, atrial arrhythmias
What medications can be used to treat verapamil toxicity?
● IV calcium
● High does insulin euglycaemic therapy
What is adenosine and how does it work?
● A naturally occurring nucleoside
● Blocks the AV conduction by hyperpolarising the AV node, causes increased
refractory period
● Does this by activating inward rectifying K channels and suppression of calcium
dependent action potentials
● This interrupts the re-entry pathway through the AV node
What are the indications of adenosine?
Conversion of paroxysmal SVT to sinus rhythm
What are the pharmacokinetics of adenosine?
● Short half life of around 10 secs, duration of action 30 seconds
● Metabolised rapidly by adenosine deaminase in endothelial and red cells
● Must be given by rapid IV bolus through a proximal cannula with a good flush