Pharmacological Options in Heart Failure
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Pharmacological Options in Heart Failure
Pharmacology heart failure
Vet Med - Module 10
The main endogenous control of the cardiovascular system comes from the ... nervous system?
In the heart, the sympathetic nervous system is mediated through ... receptors?
What effect does sympathetic stimulation have on the heart?
It increases HR and the force of contraction
What effect does stimulation of sympathetic alpha and beta receptors have on blood vessels?
Alpha - constriction
Beta - dilation
Define the following a) ionotrophy b) chronotrophy c) lustiopy
a) force of contraction
b) speed of contraction
c) diastolic relaxation of ventricles
Define heart failure
Heart failure is when the cardiovascular system is no longer able to pump enough blood to maintain sufficient perfusion
What class of drugs are used to stimulate the heart?
What is the mechanism of action of sympathomimetics?
They are B1-agonists that stimulate adenylate cyclase via a G-protein which increases cAMP, increases Ca
and increases contraction.
What are the endogenous sympathomimetics?
Why are catecholamines only used for resuscitation?
As they are not selective and stimulate both alpha and beta receptors which results in vasoconstriction, increased HR and pro-arrhythmic effects.
What is the name of the synthetic B1-agonist?
Why must dobutamine be given IV?
As it has a short half life
What happens to the efficacy of dobutamine with use?
The efficacy is lost with use as dobutamine downregualtes B-receptors
Dobutamine is a potent positive inotrope/chronotrope/lusitrope?
What is a diuretic?
A diuretic is a substance that promotes the production of urine i.e. increases excretion of water and electrolytes
List the different classes of diuretics
Loop, 'potassium sparing', thiazides, osmotic, cardbonic anhydrase inhibitors
What are diuretics used to treat?
They are used to treat and control systemic oedema e.g. from cardiac, hepatic and renal disease
What is the difference between high and low ceiling diuretics?
High ceiling diuretics will increase the levels of urine outflow to high levels, whereas low ceiling diuretics have a limit to how much diuresis you can trigger despite an increase in the dose given
Where are loop diuretics secreted into and where do they act?
They are secreted into the PCT and act on the ascending limb of the loop of henle
What is the mechanism of action of the loop diuretics?
They inhibit the Na
carrier in the lumenal membrane by combining with the Cl
site causing loss of these ions and water in the urine
Loop diuretics also induce ... synthesis which increases renal blood flow through vasodilation?
What is the most common loop diuretic used in veterinary medicine?
Are loop diuretics high or low ceiling diuretics?
How fast is the onset of action of the loop diuretics?
Rapid - 10-20 mins IV, 1-5hrs PO
How long do the loop diuretics last?
List some of the side effects of loop diuretics
Dehydration, pre-renal azotaemia, electrolyte disturbances, ototoxicity
Where are the thiazides secreted into and where do they act?
They are secreted into the PCT and act in the DCT
What is the mechanism of action of the thiazides?
They block Na
reabsorption causing loss of electrolytes and water in urine
What is the potency of the thiazides?
What happens to the thiazides if renal blood flow is low?
They are ineffective
Do thiazides last shorter or longer than furosemide?
True or false: thiazides have good oral absorption?
What are the side effects of thiazides?
Same as furosemide, alkalosis, insulin resistance
What are the two types of 'potassium sparing' diuretics?
Amiloride and spironolactone
What is the mechanism of action of amiloride?
It blocks the lumenal Na
Is amiloride a strong or weak diuretic?
Why is amiloride used as a diuretic if it is weak?
It is commonly used with other diuretics to reduce hypokalaemia
What is the mechanism of action of spironolactone?
It is a competitive aldosterone antagonist
Is spironolactone a strong or weak diuretic?
Why is spironolactone used?
To reduce hypokalaemia and to counter 'aldosterone escape'
What is the normal action of aldosterone?
Aldosterone acts on distal tubules/collecting ducts to increase reabsorption of ions and water, resulting in water retention, increased BP and increased blood volume
What is the aim of vasodilators?
To decrease the preload and after load to reduce the cardiac workload of the failing heart
List the main classes of vasodilators
Calcium channel blockers, alpha
adrenoreceptor antagonists, nitrates and angiotensin inhibitors
What is the mechanism of action of calcium channel blockers?
Block L-type calcium channels
What is the mechanism of action of alpha
They cause vasodilation (alpha
receptors normally cause vasoconstriction)
What is the mechanism of action of nitrates?
Nitrates act as donors of nitric oxide to mimic the natural endogenous system
What is a side effect of nitrates?
Why must you wear gloves when administering nitrates?
As they are very lipophilic so well absorbed into the skin and will have a rapid effect
What is the natural stimulus for NO production?
Shearing forces of blood as it flows past endothelial cells
What is the mechanism of action of ACE inhibitors?
They block the active site of the enzyme ACE where angiotensin I is converted into angiotensin II
List the effects of ACE inhibitors
Arteriolar and venodilation
Decreased plasma aldosterone
and water excretion
Enhanced bradykinin vasodilation
List some of the side effects of ACE inhibitors
hypotension, renal impairment, hyperkalaemia, (anorexia, diarrhoea, vomiting, cough)
In what form are ACE inhibitors administered?
How are ACE inhibitors eliminated?
Does food increase or decrease the bioavailability of ACE inhibitors?
Decreases - they should be given on an empty stomach
What is the mechanism of action of Telmisartan?
Competitive antagonist of the AT1 receptor
What is Telmisartan used for?
Decreased BP, decreased proteinuria
What are the side effects of Telmisartan?
hypotension, decreased RBC count
What is aldosterone escape?
Aldosterone escape is when there is still elevated levels of aldosterone in heart failure despite using an ACE inhibitor
What can cause aldosterone escape?
Incomplete ACE inhibition or other factors e.g. angiotensin II is not the only stimulus for the production of aldosterone
What other drug is given with inhibitors of angiotensin II to counteract aldosterone escape?
What are inodilators?
Drugs that combine a positive inotrope with a vasodilator
What effect do inodilators have on a) cardiac muscle cells b) vascular smooth muscle cells?
a) B1 agonists stimulate adenylate cyclase and PDE III inhibitors prevent breakdown of cAMP, increasing cAMP, increasing Ca
and increasing contraction.
b) Inhibition of myosin kinase which results in decreased contraction and a vasodilatory effect
What are the two types of inotropes?
Bipyridine compounds and Pimobedan (calcium sensitisers)
What is the mechanism of action of bipyridine compounds?
PDE III inhibitors
What is the mechanism of action of pimobedan (calcium sensitisers)?
Sensitises myocardium to Ca
i.e. it causes an increase in the force of contraction of the heart without an increase in intracellular Ca
levels. Also a PDE III inhibitor.
Which is less arrhythmogenic: bipyridine compounds or pimobedan?