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MODULE 10 - Cardiovascular System > PHARMACOLOGY - Pharmacological Treatment of Heart Failure > Flashcards

PHARMACOLOGY - Pharmacological Treatment of Heart Failure Flashcards

1
Q

Which adrenergic receptor in the heart tissue is predominately controlled by the sympathetic nervous system?

A

β1 adrenergic receptors

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2
Q

Which adrenergic receptor in the vascular smooth muscle is predominately controlled by the sympathetic nervous system?

A

Most of the vasculature is controlled by α adrenergic receptors for vasoconstriction, however the vasculature supplying the skeletal muscle have β2 adrenergic receptors for vasodilation

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3
Q

Why is the vasculature supplying skeletal muscle predominantly controlled by β2 adrenergic receptors rather than α adrenergic receptors?

A

The sympathetic nervous system will stimulate β2 adrenergic receptors to stimulate vasodilation of the vasculature to increase the blood supply to skeletal muscle

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4
Q

Which cholinergic receptor in the heart tissue is predominately controlled by the parasympathetic nervous system?

A

M2 cholinergic receptors

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5
Q

Which cholinergic receptor in the vasculature is predominately controlled by the parasympathetic nervous system?

A

The vasculature receives minimal input from the parasympathetic nervous system

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6
Q

How does the effects of increased cAMP differ between cardiac muscle cells and vascular smooth muscle cells?

A

In cardiac muscle cells, an increase in cAMP promotes calcium influx, which enhances contractility. In vascular smooth muscle, increased cAMP inhibits the contractile pathway of vascular smooth muscle and thus promotes vasodilation

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7
Q

What is an ionotrope?

A

An ionotrope is a substance which alters the force of muscular contraction

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8
Q

What is a chronotrope?

A

A chronotrope is a substance which alters the speed of muscular contraction

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9
Q

What is a lusitrope?

A

A lusitrope is a substance which alters the diastolic relaxation of the ventricles

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10
Q

What are the four classifications of drugs used in the treatment of heart failure?

A

Sympathomimetics
Diuretics
Vasodilators
Inodilators

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11
Q

What is the mechanism of action of sympathomimetics?

A

Sympathomimetics are β1 agonists which bind to β1 receptors on cardiac muscle which stimulates adenylate cyclase, increasing cAMP and the influx of calcium into the cell, increasing myocardial contractility

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12
Q

List two examples of sympathomimetics

A

Catecholamines
Dobutamine

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13
Q

Why should catecholamines only be used for resuscitation?

A

Catecholamines will bind to both α and β adrenergic receptors which will lead to major side effects so should only be used in emergency resuscitation

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14
Q

When is the use of dobutamine indicated?

A

The use of dobutamine is indicated when the patient is in life-threatening heart failure with severely impaired systolic function

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15
Q

Why should dobutamine only be used for three days?

A

Dobutamine should only be used for three days as excessive stimulation of the β1 receptors by dobutamine can cause the receptors to internalise within the cardiac muscle cell

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16
Q

How should dobutamine be administered? Why is this?

A

Dobutamine can only be administered by intravenous (IV) infusion due to its short half life

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17
Q

What are diuretics?

A

Diuretics are substances which promote urine production

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18
Q

Why are diuretics used when treating heart failure?

A

Diuretics are useful when treating heart failure as they promote urine production which reduces fluid overload in the body which would increase preload and normally increase cardiac workload

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19
Q

What are high ceiling diuretics?

A

High ceiling diuretics are diuretics with have a high capacity to cause diuresis (promote urine production)

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20
Q

What are low ceiling diuretics?

A

Low ceiling diuretics are diuretics with have a low capacity to cause diuresis (promote urine production)

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21
Q

When would the use of diuretics be contraindicated when treating patients with heart failure?

A

The use of diuretics would be contraindicated if the patient has cardiac tamponade

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22
Q

What are the four classifications of diuretic drugs?

A

Loop diuretics
Thiazides
K+ sparing diuretics
Osmotic diuretics

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23
Q

What is the mechanism of action for loop diuretics?

A

Loop diuretics inhibit the reabsorption of sodium and water through inhibiting the Na+/K+/2Cl- co-transporter on the lumenal membrane of the thick ascending loop of Henle

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24
Q

Why are loop diuretics classifed as high ceiling diuretics?

A

Loop diuretics can increase sodium excretion from around 1% to a range of 15 - 25%

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25
Q

Give an example of a loop diuretic drug

A

Furosemide

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26
Q

(T/F) Furosemide has a rapid onset and short duration of action

A

FALSE. Furosemide has a rapid onset and a long duration of action

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27
Q

What are the four possible side affects of Furosemide?

A

Dehydration
Pre-renal azotaemia
Electrolyte disturbances
Ototoxicity

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28
Q

How can the risk of ototoxicity due to Furosemide be reduced?

A

The risk of ototoxicity can be reduced through slow infusion or divided doses of Furosemide

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29
Q

What is the mechanism of action for thiazides?

A

Thiazides inhibit sodium and water reabsorption through inhibiting the Na+/Cl- co-transporter on the lumenal membrane of the distal convoluted tubule (DCT)

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30
Q

Give an example of a thiazide drug

A

Hydrochlorothiazide

31
Q

(T/F) Hydrochlorothiazide has a slower onset but longer duration of action than Furosemide

A

TRUE.

32
Q

What are the five possible side effects of thiazides?

A

Dehydration
Pre-renal azotaemia
Electrolyte disturbances
Alkalosis
Insulin resistance

33
Q

Why do loop diuretics and thiazides require renal prostaglandin production to carry out more efficient diuresis?

A

Renal prostaglandin has a vasodilatory effect which will increase the blood flow to the kidneys which will allow loop diuretics and thiazides to have an optimal diuretic effect

34
Q

Which drug can reduce the effect of diuretics and why?

A

NSAIDS can reduce the effects of diuretics as NSAIDS inhibit the production of prostaglandins, which would usually have a vasodilatory effect and increase blood flow to the kidneys to allow diuretics to have an optimal effect

35
Q

Give two examples of K+ sparing diuretics

A

Amiloride
Spironolactone

36
Q

What is the mechanism of action for amiloride?

A

K+ sparing diuretics inhibit the Na+ transporter on the lumenal membrane of the collecting duct, inhibiting sodium reabsorption while indirectly decreasing K+ loss

37
Q

What is the mechanism of action for spironolactone?

A

Spironolactone is an aldosterone inhibitor. Inhibiting the action of aldosterone inhibits the reabsorption of sodium and water at the distal tubules and collecting duct by the renin-angiotensin aldosterone system

38
Q

What are the possible side effects of spironolactone in cats?

A

Skin reactions

39
Q

What is the mechanism of action of osmotic diuretics?

A

Osmotic diuretics inhibit water reabsorption in the proximal convoluted tubule, the thin descending loop of Henle and the collecting duct

40
Q

Give an example of an osmotic diuretic

A

Mannitol

41
Q

Why are vasodilators used when treating heart failure?

A

Vasodilators are useful when treating heart failure as they dilate blood vessels which reduces vascular resistance and afterload which would normally increase cardiac workload. Vasodilation also increases the blood flow to the tissues and tissue perfusion

42
Q

What are the four classifications of vasodilator drugs?

A

L-type calcium channel blockers
α1 adrenoreceptor antagonists
Nitrovasodilators (nitrates)
Angiotensin inhibitors

43
Q

What is the mechanism of action for L-type calcium channel blockers?

A

L-type calcium channel blockers block L-type voltage-gated calcium channels on vascular smooth muscle cells, inhibiting the influx of calcium and thus contraction and vasoconstriction, promoting vasodilation

44
Q

Give an example of a calcium channel blocker

A

Amlodipine

45
Q

When is the use of amlodipine indicated?

A

The use of amlodipine is indicated as both a anti-hypertensive drug and a vasodilator drug in the treatment of heart failure

46
Q

What is the bioavailability of amlodipine?

A

The bioavailability of amlodipine is 90%

47
Q

What is the mechanism of action for α1 adrenoreceptor antagonists?

A

α1 adrenoreceptor antagonists inhibit α1 adrenoreceptors and thus decrease sympathetic stimulation, inhibiting vasoconstriction, thus promoting vasodilation

48
Q

Give an example of a α1 adrenoreceptor antagonist

A

Prazosin

49
Q

When is the use of prazosin indicated?

A

Prazosin is mainly used as an anti-hypertensive drug

50
Q

What is the half life (t1/2) of prazosin?

A

3 - 4 hours

51
Q

What is the mechanism by which patients can develop tolerance to prazosin?

A

Tolerance to prazosin can occur due to the internalisation of the α1 adrenoreceptors into the vascular smooth muscle cells

52
Q

What are the two possible side effects of prazosin?

A

Hypotension
Syncope

53
Q

What is the mechanism of action for nitrovasodilators (nitrates)?

A

Nitrovasodilators (nitrates) mimic endogenous processes through releasing nitric oxide into the body. Nitric oxide will activate the enzyme guanylate cyclase which will increase the production of cGMP which will relax vascular smooth muscle leading to vasodilation

54
Q

What is the potential side effect of nitrovasodilators (nitrates)?

A

Hypotension

55
Q

Why should you always wear gloves when administering nitrovasodilators (nitrates)?

A

Nitrovasodilators (nitrates) and very lipophilic drugs which are administered in the form of an ointment which can be absorbed into your skin and cause hypotension if gloves are not worn

56
Q

What are the two classifications of angiotensin inhibitors?

A

ACE inhibitors
Angiotensin II AT1 receptor antagonists

57
Q

What is the mechanism of action of ACE inhibitors?

A

ACE inhibitors inhibit the angiotensin covering enzyme (ACE) which converts angiotensin I into angiotensin II. The inhibition of angiotensin II production promotes vasodilation as angiotensin II is a potent vasoconstrictor

58
Q

How do ACE inhibitors also inhibit sodium and water reabsorption?

A

The inhibition of angiotensin II production prevents the secretion of aldosterone in the renin-angiotensin aldosterone system which will inhibits reabsorption of sodium and subsequently water

59
Q

How do ACE inhibitors enhance bradykinin vasodilation?

A

ACE inhibitors inhibit angiotensin covering enzyme (ACE) which would usually break down bradykinin which is a vasodilator

60
Q

How do ACE inhibitors affect kidney function?

A

ACE inhibitors cause vasodilation and thus decrease the blood pressure in the blood vessels in the glomerulus, enhancing kidney function

61
Q

ACE inhibitors are pro-drugs. What does this mean?

A

Pro-drugs are drugs administered in their inactive form but are activated by endogenous metabolic processes within the body

62
Q

Why should ACE inhibitors always be given on an empty stomach?

A

Food can reduce the bioavailability of ACE inhibitors

63
Q

What are the three potential side effects of ACE inhibitors?

A

Hypotension
Renal impairment
Hyperkalaemia

64
Q

What is the mechanism of action of angiotensin II AT1 receptor antagonists?

A

Angiotensin II AT1 receptor antagonists inhibit the binding of angiotensin II to their AT1 receptors, promoting vasodilation through inhibiting angiotensin II binding

65
Q

What is the only angiotensin II AT1 receptor antagonist licensed in veterinary medicine?

A

Telmisartan

66
Q

When is the use of telmisartan indicated?

A

Telmisartan is used as an anti-hypertensive drug and used to treat patients with proteinuria

67
Q

Which species is telmisartan licensed for?

A

Cats

68
Q

What is the mechanism of action of inodilators?

A

Inodilators inhibit phosphodiesterase III (PDE III) in cardiac and vascular smooth muscle cells. PDE III would usually break down cAMP so through inhibiting the action of this enzyme, cAMP production will increase. Increased cAMP in cardiac muscle cells will increase the influx of calcium into the cell, increasing myocardial contractility. In vascular smooth muscle cells, increase cAMP will inhibit the contraction pathway and thus promote vasodilation

69
Q

List two examples of inodilators

A

Amrinone
Milrinone

Bypyridine

70
Q

Why is the use of amrinone and milrinone contraindicated in veterinary medicine?

A

Amrinone and milrinone can cause ventricular arrhythmias and chord tendinae rupture

71
Q

Which drug can be used as an inodilator in veterinary medicine?

A

Pimobendan

72
Q

What is the mechanism of action for pimobendan?

A

Pimobendan increases the sensitivity of cardiac muscle cells to calcium and thus promotes myocardial contractility, it also inhibits PDE III in vascular smooth muscle cells to promote vasodilation

73
Q

Why should pimobendan always be given on an empty stomach?

A

Food can reduce the bioavailability of pimobendan

74
Q

What are the three other functions of pimobendan?

A

Inhibits phosphodiesterase V (PDE V) in the lungs
Antiplatelet effects
Positive lusitrophic effect

MODULE 10 - Cardiovascular System (16 decks)

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