Arrthymia: therapies, Drugs for irregular heart rhythms Flashcards
What is an arrhythmia?
- A deviation from the “normal” rhythm of the heart.
- (Sinus arrhythmia)
- Tachycardias: supraventricular arrhythmia, Ventricular arrhythmia
- (Bradycardias(Heart block))
Features of the resting membrane potential
- Inside the cell is a net negative charge relative to the outside:
- Due to uneven distribution of ions across the cell membrane.
- Dependant on the sodium-potassium ATPase pump (needs energy)
Vaughan-Williams classification drugs of antiarrhythmics
- IA: Quinidine, Procainamide, Dispyramide
- IB: Lidocaine, mexiletine, tocainide
- IC: Flecainide, propafenone
- II: Atenolol
- III: Amidarone, bretylium, sotalol
- IV: Diltiazem, verapamil
- V: Digoxin
Vaughan-Williams class I features
- Membrane-stabilising agents: decrease the amplitude (size of action potential)
- Reduces velocity of conduction/excitability
- Act on “Fast” sodium channel responsible for phase 0: present in “Non-nodal” cells
- Divided into Ia, Ib and Ic agents.
- Show use dependence (i.e. More effective at higher HR)
What is the agent mainly used in class I antiarrhythmics?
Flecainide
- Strong Na+ channel blockade
- prolongs ERP (effective refractory period)
Vaughan-Williams class II features
Beta blockers: atenolol, bisoprolol, propanolol
- Acts via Beta1 receptors to block sympathetic stimulation of the heart: prolongs phase 4 depolarisation, shortens phase 2
- Now first line for atrial fibrillation (Bisoprolol)
Vaughan-Williams class III features
Amiodarone, bretylium, sotalol
- Increase action potential duration
- Prolong repolarisation in phase 3
- Prolongs ERP
- Used for dysrhythmias that are difficult to treat
- Life-threatening ventricular tachycardia or fibrillation, atrial fibrillation or flutter: resistant to other drugs
- Sustained ventricular tachycardia
Features of Amidarone
- Used for VT (ventricular tachycardia) and occasionally in supraventricular tachycardia
- Many interactions with other drugs: particularly digoxin
- Because of tissue effects has striking side effect profile: thyroid, pulmonary fibrosis, Slate-grey pigmentation, corneal deposits, LFT abnormalities
Vaughan-Williams class IV features
Verapamil, Diltiazem
- Calcium channel blockers: bind to Lcard type voltage gated Ca channels
- Depress phase 4 depolarisation in SA and AV nodes: slows the heart rate
- Shorten phase 2 plateau phase (reduce contractility)
- Show use dependence
- Used for paroxysmal supraventricular tachycardia; rate control for atrial fibrillation and flutter.
Vaughan-Williams class V features
Other antiarrhythmics
- Digoxin, adenosine
- Have properties of several classes and are not placed into one particular class.
Features of Digoxin
- Cardiac glycoside
- Inhibits the sodium-potassium ATPase pump
- Increases vagal tone through: slows SA/AV node conduction
- Complex effect on the cardiac action potential: reduces the refractory period in myocardium
- Increases Ca2+ concentration intracellular: positive inotropic effect
What are indications for Digoxin?
Atrial dysrhythmias
- AF
- Atrial flutter
- (SVT)
Heart failure
Features of Digoxin toxicity
- Nausea and vomiting
- Xanthopsia!
- Bradycardia
- Tachycardia
- Arrhythmias: VT and VF
Signs of digoxin toxicity
- ‘Reverse tick’ appearance of ST segment in lateral leads
- Confusion
- Irregular pulse
What is Digoxin toxicity treatment?
- Stop digoxin: but long half life
- If levels very high and risk of significant arrhythmia: give Digiband
- Digoxin toxicity is more serious if potassium levels are low
What is Digiband?
- Digoxin immune antibody
- Binds with digoxin, forming complex molecules
- Excreted in urine
Features of Adenosine
- Slows/blocks conduction through the AV node
- Used to convert paroxysmal supraventricular tachycardia to sinus rhythm
- Very short half-life
- Only administered as fast IV push
- May cause asystole for a few seconds
- Other side effects minimal
What are side effects of antiarrhythmias?
- ALL antiarrhythmias can cause arrhythmias.
- Learn about one drug from each of the VW classifications (including betablocker, verapamil)
- Learn about digoxin and amiodarone
What are indications for anticoagulation?
- Atrial fibrillation: risk of stroke, peripheral emboli
- Thrombus in AF
Cardiovascular indications for anticoagulation
- Metallic heart valves
- DVT/PE: treatment, prophylaxis
What are characteristics of the “ideal” anticoagulant?
- Oral
- No need for monitoring
- No interaction with food or drugs
- Given once or twice a day/fixed dose irrespective of body weight/age.
- As effective as warfarin
- Safer than warfarin
Examples of oral anticoagulants
- Warfarin: vitamin K antagonist
- Dabigatran: direct thrombin inhibitor
- Rivaroxaban, Apixaban, Edoxaban- direct Xa inhibitors
Know about inhibition of factors II, VII, IX and X
On powerpoint
Monitoring warfarin therapy: What is normal INR (international normalised ratio)?
- Normal INR is 1
- Therapeutic INR is normally 2.5 - 4.0 depending on the clinical indication.
Adverse effects of warfarin therapy
- Bleeding (dose related)
- Interaction with multiple other drugs
- Pregnancy: teratogenic (chondrodysplasia), Retroplacental bleeding and foetal intracerebral bleeding
- Avoid in first and third trimesters
What are drugs that increase warfarin activity?
- Aspirin, Sulfonamides: decrease binding to albumin
- Cimetidine, Erythromycin: inhibit degradation
- Antibiotics (oral): decrease synthesis of clotting factors
Drug interaction with warfarin: drugs that promote bleeding
- Aspirin: inhibition of platelets
- Heparin antimetabolites: inhibition of clotting factors
Drug interaction with warfarin: drugs that decrease warfarin activity
- Barbiturates, Phenytoin: induction of metabolising enzymes (cytochrome P450)
- Vitamin K : promote clotting factor synthesis
- Cholestyramine: reduced absorption
How is warfarin metabolised?
It is metabolised by Cytochrome P450 pathway.
- So it interacts with drugs such as macrolide antibiotics, antfungals, anti-epileptic drugs
Inhibitors of Cytochrome p450
- Omeprazole
- Disulfiram
- Erythromycin
- Valproate
- Isoniazid
- Ciprofloxacin and Cimetidine
- Ethanol (acutely)
- Sulphonamides
Inducers of cytochrome p450
- Alcohol (chronic use)
- Barbiturates
- Carbamazepine
- Phenytoin
- Rifampicin
- Sulphonylureas
Monitoring warfarin therapy methods
- Regular INR
- Watch if therapy altered
- Patient education
- Alcohol intake
