VPH 300 Cardiovascular system

Name the 4 groups of positive inotropic drugs and name an example of each.

Cardiac glycosides (i.e. Digoxin)
Methylxanthines (i.e. Theophylline)
Catecholamines (i.e. Adrenaline)
Inodilators (i.e. Pimobendan)

Name the 3 types of vasodilators.

1. Afterload reducers (arteriodilators)
2. Preload reducers (venodilators)
3. Dual effect (preload & after load reducers)

Vasodilators reduce what in the treatment of CHF?

Cardiac load

Name the 3 types of dual effect vasodilators and an example of each.

Alpha blockers (i.e. Prasozin)
Angiotensin-converting enzyme (ACE) inhibitors (i.e. Benazepril)
Calcium-channel blocking drugs (i.e. Amlodipine/Diltiazem)

Example of an afterload reducer vasodilator?

Hydralazine

Example of an preload reducer vasodilator?

Nitrates (nitroglycerine)

How do afterload reducers help treat congestive heart failure (MOA)?

Reduce blood flow impedance (i.e. aortic flow & pressure)
Increase forward stroke volume
Decrease myocardial O2 demand
Decrease regurgitant flow in i.e. mitral valve insufficiency

What vasodilator drug decreases regurgitant flow caused by valvular insufficiencies to treat CHF?

Afterload reducers, i.e. hydralazine

How do preload reducers help treat congestive heart failure (MOA)?

Dilate systemic veins → reduce venous return → reduce LV filling pressure → reduce preload

Name 4 catecholamines which are used in the treatment of hypotension.

Adrenaline
Isoproterenol
Dopamine
Dobutamine

Administration of catecholamines in the treatment of hypotension?

I/V (due to short half-life)
Single bolus/continuous infusion

T/F: Dobutamine is used in the treatment of hypotension in shock AND improving renal perfusion in renal failure.

False, dopamine (dobutamine has no effect on kidney)

Catecholamines: side effects?

Arrthymogenic esp. in conditions of hypoxia or acidosis

Catecholamines should not be administered with what general anaesthetic agent and why?

Halothane (sensitises the heart to catecholamines)

Catecholamine administration is contra-indicated if what other positive inotropic drug is currently prescribed to a patient?

Cardiac glycosides

What are the 2 most important vasodilator drugs used in the treatment of cardiac failure and other forms of cardiac insufficiency?

ACE inhibitors (i.e. Benazepril)
Ca-channel blockers (i.e. Amlodipine, diltiazem)

Define inodilator.

Agent with inotropic effects that also causes vasodilation, leadings to decreased systemic and/or pulmonary vascular resistance
(INOTROPY + VASODILATION)

Give an example of an inodilator.

Pimobendan

Pimobendan: MOA?

Positive inotrope via Ca sensitisation of cardiac muscle (via inhibition of phosphodiesterase III and increase sensitivity to intracellular Ca)
+ Peripheral vasodilator (arterial & venous)

Pimobendan: Clinical indications?

1. Dog with CHF (dilated cardiomyopathy/DCM)
2. Dog with chronic mitral valve insufficiency

T/F: Greater survival times are observed in CHF dogs treated with ACE inhibitors and furosemide vs. those of dogs treated with pimobendan.

FALSE, greater survival times seen with treatment with pimobendan

ACE inhibitors: list the different classes and drugs in each.

Class 1: Captopril
Class 2: Enalapril / Benazepril
Class 3: Lisinopril

Explain how heart failure stimulates the RAA axis and results in the production of angiotensin II.

Heart failure: decreased renal perfusion → renin release
Renin acts on angiotensinogen → angiotensin I
ACE (angiotensin-converting enzyme) acts on angiotensin I → angiotensin II

Effects of angiotensin II?

Potent vasoconstrictor
Aldosterone release (Na reabsorption, water retention)
ADH release (water reabsorption in collecting ducts)

How does high angiotensin II increase preload?

Fluid retention and reabsorption due to ADH & aldosterone

How does high angiotensin II increase afterload?

Vasoconstrictor effects

How do ACE inhibitors decrease afterload and preload to treat CHF?

Reduce angiotensin II concentrations
- Vasodilation = decrease afterload
- Diuresis (less ADH, aldosterone) = decrease fluid retention = decrease preload

Anti-hypertensive effects of ACE inhibitors are potentiated by what?

Low-Na diet

ACE inhibitors: MOA?

Heart failure: ↓ renal perfusion, ∴ renin release
Angiotensin I + ACE → angiotensin II
- Potent vasoconstrictor
- Aldosterone release: Na reabsorption & water retention
- ADH release: Water reabsorption in collecting ducts

ACE inhibitors: reduce amount of angiotensin II
∴ Vasodilation → decrease bp/afterload
∴ Diuresis → decrease fluid retention/preload

ACE inhibitors: Clinical uses?

Congestive heart failure

ACE inhibitors are usually administered concurrently with which other 2 drugs in the treatment of CHF?

Furosemide
Diuretics

ACE inhibitors: side effects?

Hypotension
Azotemia
Increased risk of hyperkalaemia
Increased risk of kidney failure (if pre-existing renal disease)

Calcium channel blockers: MOA?

Suppresses Ca2+ influx through plasma membrane channels in cardiac tissues/vascular smooth muscle
∴ Decrease intracellular Ca2+ concentrations
= Decreased contractility
= Vasodilation
= Lower myocardial O2 demand
= Slow AV demand
= Lower impedance to LV ejection

Name the 2 most commonly used calcium channel blocker drugs?

Amlodipine
Diltiazem

Calcium channel blockers: Clinical indications?

Diltiazem: hypertrophic cardiomyopathy in cats

What drug is used to specifically treat hypertrophic cardiomyopathy in cats?

Diltiazem (Ca-channel blocker)

Example of anti-arrhythmic drug in Class IA?

Quinidine

Example of anti-arrhythmic drug in Class IB?

Lignocaine

Class I of anti-arrhythmic drugs: MOA?

Blocks fast inward sodium currents of myocardial cells
IA: Quinidine
IB: Lignocaine

Class II of anti-arrhythmic drugs: MOA? Example?

Block β-adrenoreceptors
i.e. Propanolol

Class III of anti-arrhythmic drugs: MOA? Example?

Block K channel = prolong repol and extend refractor periods
i.e. Amiodarone

Class IV of anti-arrhythmic drugs: MOA? Example?

Block Ca channel
i.e. Amlodipine, diltiazem

Quinidine is used to treat what in horses?

Atrial fibrillation

Treatment procedure of using quinidine in horses to treat atrial fibrillation?

Test dose: 20 mg/kg dissolved in water by stomach tube (to test sensitivity to SE)
Starting next day: 20 mg/kg dissolved in water every 2 hrs until rhythm returns to sinus rhythm
Once arrthymia stops: Continue treatment for 2-3 days at 20 mg/kg twice daily
DO ECG BEFORE EACH ADMINISTRATION TO SEE IF SINUS RHYTHM PRESENT
- Oral dose safer
- Urgent treatment? Can give I/V as infusion + I/V fluids simultaneously to overcome hypotensive effects