S3 Cardiac Arrhythmia Drugs Flashcards
what are arrhythmias
heart condition with disturbances in :
Pacemaker impulse formation (SAN)
Contraction impulse formation (bundle of his)
this results in insufficient contraction to maintain CO
resting potential is created by the distribution of ions across the membrane such as Na, Ca, K and maintained by ion channels and exchangers
Describe the mechanisms of drugs that act on the fast cardiac AP (ventricles)
Drugs blocking the Na channels slow conduction in phase 0 (red), AP same duration
Beta blockers decrease phase 4 depolarization
drugs blocking K+ channels increase AP duration
drugs blocking Ca channels affect plateau phase and decrease phase 4 depol
Describe the mechanisms of drugs that act on the slow cardiac AP ( SAN and AVN)
Ca channel blockers reduce slope
Beta blockers reduce initial sloping phase and affect automaticity
how can arrhythmias form ?
abnormal impulse generation -
ectopic focus - AP arises from sites other than the SAN
Delayed or early after depolarisation
abnormal conduction -
conduction block of impulse from atria to ventricles
reentry - movement around a blocked area
wolf parkinson white (WPW) syndrome ( movement of impulses down AVN then back up pathway
area of infarct can lead to tachycardia
describe the action of drugs to treat arrhythmias
in the case of abnormal generation, we want to decrease the phase 4 slope (funny current) so its harder to generate a rhythm E.g Ca channel blocker or bisopralol or we can raise the threshold
in the case of abnormal conduction, we want to decrease conduction velocity (VG Na channels) and increase refractory period to prolong AP so cell cannot be re-excited
what are the different classes of drugs used to treat arrhythmias
CLASS - Action - Drugs
1a - moderate phase 0 (Na blockers)- quinidine, procainamide, disopyramide
1b - no change in phase 0 - lidocaine, mexiletine
1c- marked phase 0 - flecainide, propafenone
2 - beta-adrenergic blockers - propranolol, bisoprolol, metoprolol, esmolol
3- prolong repolarization (K blocker) - Amiodarone, Sotalol
4- Ca channel blockers - verapamil, diltiazem
describe class 1a drugs
absorption and elimination ; oral or IV
effects on heart : decrease conduction (decrease phase 0 (Na+) of the ap)
increase refractory period (increase APD (K+) and increase Na inactivation)
decrease automaticity (decrease slope of phase 4, fast potentials)
increase threshold (Na+)
quinidine is anticholinergic (atropine like action) to speed AV conduction
ECG ; increase QRS and QT
uses : quinidine : maintain sinus rhytms in atrial fibrillation
procainamide : treatment of ventricular arrhytmias
side effects : hypotension, dizziness, proarrythmia
describe class 1b drugs
effects on heart ; increase threshold decrease phase 0 conduction in fast beating or ischaemic tissue ECG ; increased QRD Uses : ventricular tachycardia side effects ; dizziness
describe class 1c drugs
effects on heart
decrease phase 0 conduction
decrease automaticity (increase threshold)
increase APD and refractory period
ECG; increase PR and QRS
Uses; used for supraventricular arrhythmias and ventricular contractions
wpw syndrome
side effects - proarrhythmia and sudden death with chronic use
describe class 2 drugs
effects on heart
increase APD ( action potential duration)
decreased phase 4 depol
ECG ; increased PR and decrease HR
uses ; treating sinus, CD tachycardia, protect ventricles from high atrial rates
side effects; bronchospasm, hypotension
describe class 3 drug amiodarone
amiodarone :
effects on heart ; increase refractory drug and APD
increase threshold
ecg ; increased pr and qrs
uses ; arrythmia , wpw
side effects; pulmonary fibrosis and hepatic injury
may need to reduce the dose of digoxin and monitor warfarin more closely
describe class 3 drug sotalol
effects on heart ; increased APD, slow phase 4
ecg ; increase QT, slow HR
uses ; ventricular tachycardia
side effects ; proarrhythmia , fatigue
describe class 4 drugs
effects on heart slow av conduction increased refractory period ecg ; increased PR uses ; control ventricles during supraventricular tachycardia side effects ; asystole or reduced CO
what is the mechanism for adenosine ?
natural nucleoside that binds A1 receptors and activates K+ currents in AV and SA node, decreases APD
effects on heart ; slow AV conduction
uses ; convert hypotension
what is the mechanism for Vernakalant ?
blocks atrial specific K+ channels
effects on heart ; slow atrial conduction
Uses ; Convert AF to sinus rhythm
what is the mechanism for Ivabradine ?
blocks funny current
slows sinus node
reduce sinus tachycardia
what is the mechanism for digoxin (cardiac glycosides)
effects on heart ; enhances vagal activity, slows AV conduction
uses ; to reduce ventricular rates in AF
what is the mechanism for Atropine ?
mechanism ; selective muscarinic antagonist
effects on heart ; block vagal activity to speed AV conduction
uses treat vagal bradycardia
which drugs can be used in AF
bisoprolol, verapamil, diltiazem, sotalol, felcainide with bisoprolol, amiodarone
should flecainide be used alone in atrial flutter
no give AV nodal blocking drugs to reduce ventricular rates in flutter
best drug for treatment WPW
flecainide, amiodarone
which drugs could be used in re-entrant SVT ?
adenosine and verapamil ( block AVN conduction, acute), bisoprolol ( block AVN chronic)
which drugs for ectopic beats
bisoprolol
which drugs to treat sinus tachycardia
ivabradine ( blocks SAN conduction)
where is cholesterol made and what is it used for ?
some obtained from diet but most synthesised in liver. Essential component of membranes (modulates fluidity). Precursor of steroid hormones
what is the pro - atherogenic effects of Ox- LDL
inhibits macrophage motility. induces T cell activation, enhances platelet aggregation
what are some examples of lipid lowering drugs ?
statins - simvastatin
fibrates - fenofibrate
Nicotinic acid/niacin
cholesterol lipase inhibitors - ezetimibe
describe the mechanism of statins ?
inhibit cholestrol synthesis in hepatocytes ( by inhibiting HMG - CoA reductase)
increase clearance of LDL, decrease the production of VLDL
Adverse drug reactions ADRS - increase transaminase levels , myopathy (of muscles)
used to prevent CVD
describe the mechanism of fibric acid derivatives
ampipathic carboxylic acids
PPARa agonist - increases production of lipoprotein lipase which reduces tryglyceride production
uses ; adjunctive to therapy diet
contraindication ; renal disease
describe the mechanism of nicotinic acid
reduces VLDL and increases HDL at high doses
Lipid lowering effect by inhibition of lipoprotein synthesis
adverse effects ; ithching, headache, activation of peptic ulcer
contraindications liver disease
describe the mechanism of ezetimibe
selectively inhibits intestinal cholesterol absorption
decreased intestinal delivery of cholesterol to the liver
increased expression of hepatic LDL receptors
ezetimibe circulates enterohepatically
ADRS : headache, abdominal pain
describe combination therapy for cholesterol
shall improve triglyceride, LDL, HDL levels
but is associated with increased risk for myopathy and rhabdomyolysis
describe what PCSK9 inhibitors
LDL receptor becomes internalised and inhibited by PCSK9 this draws more cholesterol but of circulation
offer atorvastatin 20 mg for the primary prevention of CVD
start statin treatment in people with CVD with atorvastatin80 mg
aim for > 40% reduction in non-HDL cholesterol, if this is not achieved may need to adapt lifestyle and diet
