CVS Drugs 41 to 50
What anti arrhythmic drugs can be used in the management of atrial fibrillation?
Beta-antagonists (class 2); calcium-antagonists (class 4); flecainide (class 1c); amiodarone (class 3); digoxin (unclassified); magnesium
What are the mechanisms of action of amiodarone?
Blocks Na, K, Ca channels; blocks beta adrenoreceptors; prolongs AV conduction; decreases automaticity; decreases automaticity of purkinje fibres
Prompt: what are the cellular mechanisms
Has actions on both rate and rhythm!
What are some important drug interactions with amiodarone?
warfarin (increased anticoagulant effect by inhibiting metabolism); digoxin ( increases plasma concentration leading to toxicity); increased cardiac effects of other antiarrhythmic agents; phenytoin ( increased plasma concentration)
Pass: at least 2
Describe the mechanism of action of lignocaine on the heart.
Blocks activated & inactivated Na channels; greater effect on ischaemic tissue; no vagal effects. Class 1 B antiarraythmic action.
Pass: Na channel block and Class 1B
Describe the adverse effects of lignocaine.
CNS: dizzy, anorexia, N&V, tinnitus, tremor, visual disturbance, paraesthesia, slurred speech seizure, resp depression
CVS: bradycardia, CVS collapse, uncommon proarrhythmia; can get SA arrest, impaired conduction may worsen/ precipitate pre existing CCF; decreased BP from myocardial depression
GI as above
Pass: CNS & Cardiac with at least x 3 example total
What are the features of digoxin toxicity?
G-I: anorexia, nausea, vomiting diarrhoea
CNS: visual disturbances, confusion, nightmares, agitation, drowsiness
Cardiac: features of bradycardia (progressing AV block, slow AF) and increased automaticity (VEBS and bigeminy, SVT with AV block, VT/VF)
Needs to recognise GI/CNS/Cardiac, as well as examples of bradycardia and inc. automaticity to pass
What factors might predispose patients towards digoxin toxicity?
Prompt: are there any interactions?
Hypokalaemia, hypercalcaemia, hypomagnesaemia
Renal impairment, hypothyroidism, Other drugs
Amiodarone, calcium channel blockers, potassium depleting drugs
Bold (with at least one example of each) to pass
What are the principal effects of adenosine on cardiac conduction?
Inhibits AV nodal conduction
Describe the pharmacokinetics of adenosine.
Rapidly metabolised. By red cells and endothelial cells
Very short elimination half-life (seconds)
What are the clinical implications of this pharmacokinetic profile?
Therefore must be given by rapid IV bolus. Side effects are short lived. No prolonged action to keep patient out of the arrhythmia. (Proximal IV site as preference).
Name some indications and contraindications to its use.
Indication: supraventricular tachycardia; diagnostic Contraindications: AV block, sick sinus, acute asthma, lack of consent
Pass: SVT and 1 CI.
List some drugs used in hypertensive emergencies.
GTN , nifedipine , diazoxide , hydrallazine , nitroprusside , esmolol , labetalol
Pass: At least 3
Tell us about the pharmacokinetics of Na nitroprusside.
IV administration, onset minutes, peak effect minutes,
1/2 life 2 minutes (thiocyanate 3 days), duration of action 1-
10 minutes, elimination-RBC’s to cyanide, liver to thiocyanate, renally excreted
Pass: Drugs 2/4 Bold
What are the potential toxicities of Na nitroprusside?
Cyanide toxicity – hypotension , metabolic acidosis , pink skin , tachypnoea decreased reflexes , dilated pupils , coma
Thiocyanate toxicity – ataxia , blurred vision , headache , nausea , vomiting , tinnitus, SOB, delirium, unconsciousness
Pass: Both bolded categories and 1 example of each.
What are the effects of Ca channel blockers on smooth muscle?
(Prompt: tissue level)
Relax smooth muscle esp vascular smooth muscle
Arterioles more sensitive than veins
Does effect bronchiolar GIT and uterine
By what mechanisms do Ca channel blockers control angina?
Decrease myocardial contractility
Decrease oxygen demand
Decrease afterload by relaxing vascular smooth muscle
Verapamil/ diltiazem have a non-specific antiadrenergic effect and decrease heart rate
Relieve and prevent coronary artery spasm
Why is verapamil more efficacious than dihydropyridines in the treatment of arrhythmias?
Blockade of L-channels more marked in tissues that fire frequently
More marked effects on tissues that depend on Ca channels for activation, SA & AV nodes
More marked on tissues with tissues less polarised at rest
What is the adrenoreceptor selectivity of noradrenaline?
Prompt: What receptors does it act on?
alpha1 = alpha2; Beta1 >> Beta2
alpha 1: post-synaptic effector cells, especially smooth muscle
alpha 2: presynaptic nerve terminals, platelets, lipocytes, smooth muscle
beta 1: post synaptic effector cells, especially heart, lipocytes, brain
Pass: All 3 bold
Describe the cardiovascular effects of infused noradrenaline.
Increases peripheral vascular resistance
Increases SBP and DBP
Pass: 2 of 3 bolded
What are the mechanisms of action of FRUSEMIDE?
=> decreased reabsorption of NaCl
increased prostaglandin synthesis
=> a) inhibition of salt transport in thick ascending limb
=> b) increased renal blood flow, decreased pulmonary congestion, decreased LV filling pressures
What are the toxic effects of FRUSEMIDE?
• decreased K metabolic alkalosis
• Allergy – rash, eosinophilia, interstitial nephritis
4+ to pass – must include decr K & one non-electrolyte
Describe the pharmacokinetics of metoprolol.
- Oral or IV
- Volume of distribution – large
- Half life – 3-4 hours
- Metabolised in liver
- Bioavailability 50% due to 1st pass effect
- Oral & IV & 1st pass
- OR 3/5
How does metoprolol differ from propanolol in its action at beta receptors?
- Beta 1 – full agonist
- Beta 2 – 50-100 fold less potent
- Beta 1 selective
How do Beta blockers control hypertension?
- Negative inotropic and chronotropic effects
- Slow AV node conduction
- Anatagonises release of renin/not fully understood
- Negative inotropic & chronotropic effect
How does heparin act?
- Heparin binds endogenous antithrombin and enhances its activity.
- Antithrombin inhibits factors IIa, IXa and Xa by complexing with them and inducing a conformational change.
- Bold to pass
How may heparin be administered?
- IV vs SC
- Continuously (following bolus) vs intermittent
- Therapeutic vs prophylactically
- Bold to pass
What are the potential adverse effects of heparin?
- Heparin-induced thrombocytopaenia
- Mineralocorticoid deficiency
- Bold +1 to pass
What are the advantages of low molecular weight heparins compared to unfractionated heparin?
- Have equal efficacy
- Increased SC bioavailability
- Require less frequent dosing
- Less monitoring
- Shorter chain heparin with less effect on thrombin (IIa)
- Demonstrates understanding