Cardiac Pharmacology Flashcards
What are the effects of angiotensin converting enzyme (ACE) inhibitors?
Balanced vasodilation Reduce aldosterone release Reduced glomerular capillary pressure Prevent angiotensin II mediated myocardial fibrosis and remodelling Anti-adrenergic effects Reduce vasopressin release Reduce endothelin release
What is aldosterone escape?
Despite adequate ACE inhibition, aldosterone levels may increase due to the stimulation of aldosterone release from the adrenal cortex by other mechanisms
How do you block aldosterone escape?
Aldosterone antagonism eg: Spironolactone
What are the targets of drug therapy in congestive heart failure?
- Counteracting oedema and effusions
- Counteracting neuro-endocrine activation
- Counteracting vasoconstriction
- Improving cardiac output
- Counteracting high sympathetic drive
What drugs can you use to counteract Odense and effusions?
Diuretics - furosemide
Furosemide
Loop diuretic
Oral administration for daily use
IV Administration for emergency (also venodilator when given IV)
Once patient is stable titrate does to effect
Ask owners to monitor response by monitoring respiratory rate
Side effects: pre-renal azotaemia, hypokalaemia
Should not be used on its own in the long term - ACE inhibitor
What do you need to monitor in patients on furosemide?
Urea and creatinine
K+, Na+, Cl-
When is furosemide contraindicated?
Renal failure
Why might diuretic resistance occur?
GI tract oedema
Furosemide resistance - tubular hypertrophy
Concurrent NSAID therapy
What should you do if diuretic resistance is occurring?
Increase dose of furosemide - 3 mg/kg TID max dose
Introduce other diuretics
- Torasemide - very potent but high risk of AKI
- Spironolactone
- Amiloride / hydrochlorothiazide
- Hydroflumethiazide / Spironolactone
Spironolactone
Weak potassium sparing diuretic
Aldosterone antagonist
(prilactone)
Significantly increases survival in CHF
Hydrochlorothiazide
Thiazide diuretic that acts on the DCT
Amiloride
K+ sparing diuretic acts on the PCT
Where are diuretics definitely contraindicated?
Pericardial effusion - patients have low blood pressure due to cardiac tamponade
How else can you treat effusions?
Thoracocentesis to drain pleural effusion
- obtain a sample for testing
Abdominocentesis - only in patients with serve respiratory compromise as protein rich exudate
What drugs can you use to counteract neuro-endocrine activation?
Angiotensin converting enzyme inhibitors
Aldosterone antagonists - Spironolactone
What are the effects of ACE inhibitors?
Balance vasodilators Reduces cardiac remodelling Reduces aldosterone release Reduces sympathetic activation Reduces vasopressin release Reduces endothelin release Increases the vasodilators bradykinin and prostaglandin Reduces the risk of glumerular hypertension
What are the benefits of ace inhibitors?
Increased quality of life and survival time
Slows down progression to DCM
Reduces wall thickness in HCM
Name the 4 ace inhibitors used in practice.
Benazepril
Enalapril
Ramipril - highest levels in the tissues
Imidapril - liquid preparation
What ace inhibitors are licensed?
Dog - all 4
Cat - none! Benazepril is licensed in for CKD so use this under the cascade
What are the side effects of ace inhibitors?
Hypotension Renal impairment Hyperkalaemia Anorexia Diarrhoea Vomiting Cough
When are ace inhibitors contraindicated?
Hypotension animals on high doses of furosemide
Aortic stenosis - aortic outflow tract obstruction
What drug combinations are indicated to prevent aldosterone escape and Hyperkalaemia?
Spironolactone + furosemide + ace inhibitors
How can you unload the failing heart?
Arteriodilators
Venodilators
Mixed vasodilators
What do arteriodilators do to unload the heart?
Redistribute the blood to the periphery, reducing mean arterial blood pressure and reducing afterload on the heart
Name some pure arteriodilators.
Amlodipine
Hydralazine
ACE inhibitors - Benazepril etc
Pimobendan - mixed venodilator
When are arteriodilators useful / indicated?
Mitral valve disease
Reduce regurgitant flow
Reduce afterload
Increase forwards stroke volume
How do venodilators work to unload the failing heart?
Diverts the blood away from the cardiopulmonary circuit
Eg: IV furosemide
What are mixed vasodilators?
Ace inhibitors
Pimobendan (also a major positive inotrope)
What category of drugs increase contractility?
Positive inotropes - calcium sensitiser
Pimobendan
Sensitises the cardiac myocyte to calcium - positive inotrope
Balanced venodilator - reduces myocardial work load
Reduced risk of arrhythmias compared to other PDE inhibitors that increase intra-cellular calcium concentrations
Given orally in a palatable tablet - must give 1 hour before feeding
What is the best protocol for dogs with DCM?
Pimobendan + diuretics + ace inhibitors + digoxin
How can you counteract sympathetic drive?
Digoxin
Beta blockers
When are beta blockers contraindicated?
Uncontrolled congestive heart failure
Poor contractility
What are the effects of digoxin?
Negative chronic rope
Weak positive inotrope
Reduces sympathetic tone and increases vagal tone
= slows the rate of depolarisation through the AV node
Digoxin
Liquid elixir has between absorption than tablets
Effects are seen in 6-8 hours
Takes 5 days for plasma levels to reach a steady state
What monitoring is required with the use of digoxin?
Check the drug level after 7 days of treatment
Aim for low end of therapeutic range
What are the side effects of digoxin?
Borborygmi Depression Anorexia Vomiting and diarrhoea Cardiac arrhythmias
What patients are at a greater risk of digitoxicity?
Thin Obese Ascites Hypoproteinaemia Hypothyroidism Impaired renal function Dobermann Hypoxia / acidosis Hypokalaemia
How can you prevent digitoxicity?
Start at a low dose
Dose to body surface area
Never use loading dose
Always check serum levels after 7 days
If ventricular rate is still to high add in another drug - eg: diltiazem for AF
What is the optimal treatment for CHF?
Furosemide Benazepril / ace inhibitor Pimobendan Spironolactone (SPAF)
Which anti-arrhythmic drug should you use to treat ventricular tachycardia long term?
Mexiletine
Class 1b anti-arrhythmic - Na+ channel inhibitor
Which drugs should you combine to achieve the best control in atrial fibrillation?
Treat underlying CHF - due to atrial stretch in small animals
Digoxin and diltiazem = chemical cardioversion
+/- Beta blockers (never in CHF)
How should you treat sick sinus syndrome?
Propantheline, pheylpropylamine
= parasympatheticolyics
How can ventricular tachycardia be treated?
First - Lidocaine IV then CRI - class 1b
Esmolol / Sotalol (beta blocker - class 2 anti-arrhythmic) - Sotalol also has class 3 actions Mexilitine (Na channel blocker - class 1 anti-arrhythmic) Amiodarone (class 1, 2 and 3 (K+ channel blocker) actions)
How should you treat supra ventricular tachycardia caused by high vagal tone?
Vagal manoeuvres
Verapamil / Diltiazem (Ca2+ channel blocker)
Esmolol (beta blocker)
How should you treat supraventricular arrhythmias?
Diltiazem - class 4 anti-arrhythmic - calcium channel blocker Digoxin - class 5 anti-arrhythmic - cardiac glycoside
How should you treat pulmonary hypertension?
Slidenafil - PDE inhibitor - vasodilator
Pimobendan - PDE inhibitor - venodilator
Anti coagulation therapy
What nutraceuticals and dietary modifications can you make in CHF?
Omega 3
Taurine - cats with DCM
Reduce Na+ in diet
How can you suppress a cough?
Opioids - codeine and butorphanol
What is a beneficial drug in pre-clinical mitral valve disease?
Pimobendan
Can delay onset of CHF by 15 months
What is the action of class 1 anti-arrhythmic?
Block Na+ channels
1a (intermediate Na+ channel blockers) - quinidine
1b (fast Na+ channel blockers) - lidocaine, mexilitine
1c (slow Na+ channel blockers) - encainide
What are class 2 anti-arrhythmics?
Beta blockers
Propanolol, Esmolol, atenolol, Sotalol (but mostly class 3)
What are class 3 anti-arrhythmias?
K+ channel blockers
Amoiodarone - also has class 1 and 2 actions Sotalol - also a beta blocker class 2
What are class 4 anti-arrhythmic drugs?
Calcium channel blockers
Diltiazem
Verapamil
What are class 5 anti-arrhythmics?
Direct nodal inhibition
Digoxin
Adenosine
How should you treat preclinical HCM?
Beta blockers - atenolol, Propanolol, emsomolol
- reduce LVOT and SAM
- slows heart rate and improves diastolic function
- CI in CHF
Pimobendan - Ca channel blocker
Benazepril - ace inhibitor
Diltiazem - positive lusiotrope = improves diastolic filling
There is no evidence that any drug slows down the progression to CHF
How should you treat clinical HCM?
Furosemide
Benazepril
Clopidogrel and aspirin
How should you manage a case of dysponea due to life threatening oedema in a cat?
Oxygen cage in a darkened room
Administer furosemide IV if a catheter can be placed, if not IM
Sedation with methadone if very anxious
Drain pleural effusion
How can you screen for HCM?
Annual screening by echo in breeding cats
Pro BNP on blood or pleural effusion in CHF cases only
How should you manage feline DCM?
Furosemide Benazepril Pimobendan Digoxin Taurine
Warmth
Humorous oxygen
Drain pleural effusion
How should you treat feline aortic thromboembolism?
Methadone - pain Aspirin Clopidogrel Low molecular weight heparin Physio
Treatment for CHF: Spironolactone, Benazepril, Pimobendan, furosemide
What drug is particularly useful in HOCM? When there is a left ventricular outflow tract obstruction
Atenolol - decreases heart rate and increases diastolic filling time
Diltiazem
Class 4 anti-arrhythmic
Calcium channel blocker
Negative chronotrope - achieves best rate control on AF with digoxin
Works quicker than digoxin which takes around a week to work
When are beta blockers contraindicated?
Uncontrolled CHF
- sympathetic tone is maintaining cardiac output
Diltiazem acts quicker in AF and is well tolerated
How can you treat supraventricular tachycardia due to an accessory pathway? (Wolff-Parkinson-White syndrome)
Ablate accessory pathway
Identified by delta waves on the ECG, notched QRS
What criteria should you use to decide to treat ventricular tachycardia?
Multiform
Patient haemodynamically compromised
HR rate over 200
R on T phenomemnon - high risk of progressing to V fib
What should you give only if IV lidocaine does not resolve ventricular tachycardia?
IV Amiodarone
Need to premedicate with steroids and anti-histamines first
How should you treat a bradyarrhythmia?
Rule out Hyperkalaemia / hypothyroidism
Atropine response test - if vagally mediated, HR will double in 30-40 mins
Anti-cholinergics - atropine, propantheline
Beta agonists - terbutaline (beta 2)
Xanthine derivatives - theophylline, aminothylline, etamiphyline
Pacemaker
How should you initially treat hypertension?
Amlodipine - calcium channel blocker with just vascular effects
How can you protect the kidneys in hypertension?
Ace inhibitors - benazepril
- reduce the GFR
Angiotensin II receptor blockers - Telmisartan
How can you prevent FATE in cats?
Low dose aspirin
Clopidogrel - FAT cat study - more effective at prevention
Low molecular weight Heparin (don’t need to monitor clotting time)
How should you treat pulmonary thromboembolism?
O2 therapy
Clopidogrel
Aspirin
Low molecular weight heparin
How should you treat lungworm?
Fenbendazole (panacur)
Milbemycin oxime (Milbemax)
Moxidectin (with imidacloprid in advocate) - repeat in 30days
Prednisolone - if pulmonary haemorrhage or very severe burden
How can you prevent lungworm?
Moxidectin or milbemycin q 4w
