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CHAPTER 1: Clinical Pathology: Clinical chemistry > Pharmacology-(i)Cardiovascular drugs > Flashcards

Pharmacology-(i)Cardiovascular drugs Flashcards

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1
Q

What is the mechanism of action of furosemide?(3)

A
  • Blocks reabsorption of chloride in the loop of Henle
  • Increases urinary excretion of sodium, chloride, calcium, magnesium, and potassium
  • Mild venodilator, shifting fluid from pulmonary to systemic circulation
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2
Q

What are the indications of furosemide?(4)

A
  • Congestive heart failure
  • Pulmonary oedema, pleural effusion, ascites
  • Oliguric renal failure(increases urine flow)
  • Hypercalcaemia
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3
Q

What are the side effects of furosemide?(4)

A

-dehydration
-prerenal azotaemia
-hypokalaemia
-hypochloremic metabolic acidosis
NOTE: Cats more more sensitive to adverse effects

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4
Q

What is the mechanism of action of spironolactone?(3)

A

Aldosterone antagonist
-Moderatre diuretic effect
-Acts in distal renal tubule and collecting duct
Indirectly leads to a decrease in K+ loss
Check pic 3

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5
Q

Give 2 indications of spironolactone.

A

-Second-line diuretic
-Ascites due to portal hypertension
Can be used in combination with hydrochlorthiazide

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6
Q

Give two side effects of spironolactone.

A
  • Hyperkalaemia

- Gastrointestinal upset(uncommon)

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7
Q

Give the mechanism of action of thiazide diuretics.(4)

A
  • Weak diuretic
  • Blocks sodium and chloride reabsorption in the distal tubule
  • Increases calcium reabsorption
  • Decreases potassium and magnesium absorption
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8
Q

Give an indication of thiazide diuretics(1).

A

-Management of ascites and oedema; used in combination with spironolactone

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9
Q

Give the side effects of thiazide diuretics(4).

A

-Mild hypokalaemia, hypomagnesaemia, hypochloraemic metabolic alkalosis, hyponatraemia; contraindicated with hypercalcaemia

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10
Q

List important pharmacokinetic features involved in the metabolism/excretion of angiotensin-converting enzyme inhibitors as a vasodilator.
Give two examples of ACE inhibitors.

A

e.gEnalapril, benazepril
-Metabolised by liver to active drugs(enalaprilat or benazeprilat)
Enalaprilat excreted in urine; benazeprilat excreted in urine and bile.

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11
Q

What is the mechanism of action?

A
  • Blocks ACE(lungs and vascular endothelium). Prevents the conversion of angiotensin I to angiotensin II.
  • An arterial and venous dilator
    (1) Decreases total peripheral and pulmonary vascular resistance
    (2) Decreases sytemic blood pressure
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12
Q

What are the indications of ACE inhibitors?(3)

A

a. Congestive heart failure
(1) Afterload reduction
(2) Shifts blood from pulmonary to venous circulation

b. Hypertension
c. Protein-losing nephropathy
(1) Decreases glomerular protein loss
(2) May decrease mesangial cell proliferation and glomerular fibrosis.

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13
Q

What are the side effects of ACE inhibitors?

A
  • GI upset
  • hypotension
  • prerenal azotaemia
  • hyperkalaemia(uncommon)
  • contraindicated in dehydration
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14
Q

What is the function of amlodipine?

A

-Calcium channel blocker that is used as a vasodilator not an arrhythmic

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15
Q

What is the mechanism of action of amlodipine(2)?

A
  • Greatest effect on vascular smooth muscle. Peripheral arteriolar vasodilator
  • Little effect on automaticity, conduction velocity of the atrioventricular(AV) ot sinoatrial nodes(SA) or myocardial contractility.
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16
Q

Indications of amlodipine(1)

A

-Hypertension

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17
Q

Side effects of amlodipine

A
  • Negative inotrpic effects

- hypotension(reflex tachycardia)

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18
Q

What is the function of nitroglycerin?

A
  • Venodilator
  • Donor of nitric oxide
  • Reduces preload via pulmonary vein dilation. Shifts from pulmonary to venous system.
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19
Q

What is the indication of nitroglycerin?

A

-Congestive heart failure(ointment or patch)

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20
Q

What are the side effects of nitroglycerin?

A
  • Hypotension
  • Irritation at site pf application
  • Tolerance with continued therapy
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21
Q

What is the mechanism of action of hydralazine?(4)

A
  • Potent arterial vasodilator
  • Direct action on vascular smooth muscle to decrease contractility by modification of calcium metabolism.
  • Decreases systemic vascular resistance
  • Decreases afterload
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22
Q

What are the indications of hydralazine?(2)

A
  • Congestive heart failure

- Severe or refractory hypertension

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23
Q

What are the side effects of hydralazine?

A
  • Hypotension
  • Reflex tachycardia
  • GI upset
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24
Q

What is the mechanism of action of prazosin?(3)

A
  • alpha-1 adrenergic antagonist
  • Balanced vasodilator
  • Reduces preload and afterload
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25
Q

What are the indications of prazosin?

A
  • Congestive heart failure

- Refractory hypertension

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26
Q

What are the side effects of prazosin?

A

-GI upset, syncope(first dose effect), development of drug tolerance

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27
Q

What is the shared mechanism of action of class I antiarrhythmics? Give some examples.

A

e. g. lidocaine, quinidine, procainamide, mexiletine
1. Shared mechanisms of action
- Membrane stabilisers
- Inhibit fast sodium channels
- Inhibit the rate of spontaneous depolarisation

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28
Q

What are the indications and pharmacokinetic features of lidocaine?

A

-Drug of choice to treat life-threatening ventricular arrhythmias-not effective orally owing to significant first-pass hepatic metabolism, intravenous(IV) administration only
NOTE: Little or no effect on SA or AN nodes or atrial muscle

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29
Q

What are the side effects of lidocaine?

A

-Vomiting, central nervous system(CNS) signs(ataxia, depression, nystagmus, seizures; treat with diazepam). Use with caution in patients with hepatic failure; cats are more sensitive to CNS side effects(lower doses used)

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30
Q

What are the additional mechanisms of procainamide?

A

(1) Prolongs refractory period in both the atria and ventricles
(2) Decreases myocardial excitability
(3) Anticholinergic effects

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31
Q

What are the indications of procainamide?

A

Used IV for lidocaine-refractory ventricular arrhythmias

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32
Q

What are the side effects and contraindications of procainamide?

A

GI upset, do not use with second- or third- degree AV block, drug-induced arrhythmias, may cause hypotension with rapid IV administration; contraindicated in myasthenia gravis

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33
Q

What are the indications of mexiletine?

A

-Oral drug of choice for ventricular arrhythmias in dogs

NOTE: Oral analogue of lidocaine

34
Q

What are the side effects and contraindications of mexiletine?

A

-GI upset.

Do not use with second- and third- degree AV block

35
Q

What is the mechanism of action of quinidine?

A

It prolongs the duration of the action potential and refractory period in both the atria and ventricles. Like procainamide, also has anticholinergic effects.

36
Q

What are the indications of quinidine?(3)

A

(1) Atrial fibrillation
(a) Direct effect on atrial muscle
(b) Anticholinergic effect prolongs atrial refractory period
(c) Converts atrial fibrillation to normal sinus rhythm in horses
(2) Refractory supraventricular tachycardias
(3) Ventricular arrhythmias

37
Q

What are the side effects of quinidine?(4)

A

-GI upset, hypotension, worsening of congestive heart failure, AV block

38
Q

What are the contraindications of quinidine?(2)

A

-Digoxin toxicity, myasthenia gravis

39
Q

What is the mechanism of action of beta blockers(class II antiarrhythmics)?

A

Adrenergic receptor antagonists

  • Decrease sinus heart rate
  • Increase the refractory period of the AV node
  • Decrease myocardial oxygen demad
  • Decrease cardiac inotropy
40
Q

What is the mechanism of propanolol?

A

-Nonselective beta-adrenergic antagonist: both beta-1 and beta-2 receptor blockade

41
Q

What are the indications of propanolol?(3)

A
  • Supraventricular arrhythmias
  • Ventricular arrhythmias
  • Hypertrophic and thyrotoxic heart disease
42
Q

What are the side effects of propanolol?

A
  • Negative inotropic effect
  • bradycardia
  • hypotension
  • decresed hepatic blood flow(decreases clearance of lidocaine)
  • beta-2 blockade(hypoglycaemia, hepatic receptors, bronchoconstriction, bronchial receptos)
43
Q

What are the contraindications of propanolol?

A

-Overt heart failure, sinus bradycardia, asthma

44
Q

What is the mechanism of action of atenolol, metoprolol, esmolol?(2)

A
  • beta-1 adrenergic selective receptor anatagonists

- decreases the risk of bronchospasm

45
Q

What are the indications of atenolol, metoprolol, esmolol?(4)

A
  • Supraventricular arrhythmias
  • Atenolol drug of choice for feline arrhythmias
  • Hypertrophic and thyrotoxic heart disease
  • Esmolol used IV only(short half life)
46
Q

What are the side effects of atenolol, metoprolol, esmolol?(4)

A
  • Negative inotropic effect
  • Hypotension
  • Lethargy
  • Diarrhea
47
Q

What is the mechanism of action of class III antiarrhythmics?(2)

A
  • Block potassium channels
    a. Prolong the refractory period
    b. Increase the duration of the action potential
  • Greatest effects in Purkinje fibers and ventricular muscle
48
Q

What is the mechanism of action of sotalol?(2)

A
  • Combination of class II and class III antiarrhythmics
    (1) Nonselective beta adrenergic receptor anatgonist
    (2) Block potassium channels
49
Q

What are the indications of sotalol?(1)

A

-Refractory ventricular arrhythmias; boxer arrhythmias

50
Q

What are the side effects of sotalol?(5)

A
  • Drug-drug interactions
  • Negative inotropy
  • Proarrhythmic, bronchotive inotropy
  • Proarrhythmic, bronchospasm
  • GI upset
51
Q

What are the contraindications of sotalol?

A
  • Asthma

- Sinus bradycardia, second- or third- degree heart block

52
Q

What is the mechanism of action of amiodarone?(4)

A

a. (1)Structural analogue of thyroid hormone
(2) Inhibits alpha and beta receptors(nonselective, noncompetitive)
(3) Inhibits sodium and calcium channels
(4) Prolongs action potential duration and refractory period

53
Q

What are the indications of amiodarone?

A

Reserved for refractory ventricular tachycardia

54
Q

What are the side effects of amiodarone?(3)

A

Many drug interactions, GI upset, neutropenia, hepatotoxicity

55
Q

What are the contraindications of amiodarone?

A

-Second- and third- degree AV block, bradyarrhythmias

56
Q

What is the mechanism of action of calcium channel blockers(class IV antiarrhythmics)?

A

a. Block influx of calcium through slow calcium channels during plateau of action potentials
b. Slow SA and AV node conduction
c. Decrease vascular smooth muscle contractility. Systemic and coronary vasodilation
d. Decrease myocardial contractility(negative inotropy)

57
Q

What is the mechanism of action of diltiazem?

A
  • Slows AV conduction velocity and prolongs refractory period(rarely affects SA node conduction)
  • Minimal effect on cardiac contractility
  • Mild peripheral vasodilation
58
Q

What are the indications of diltiazem?(2)

A
  • Supraventricular tachyarrhythmias(atrial fibrillation)

- Hypertrophic cardiomyopathy(cats)

59
Q

What are the side effects of diltiazem?(4)

A

-Bradycardia(dogs)
-GI upset(cats)-
-hypotension
arrhythmias

60
Q

What are the contraindications of diltiazem?(4)

A
  • Potentiate the negative inotropic and chronotropic effects of beta-adrenergic antagonists
  • severe hypotension
  • sick sinus syndrome
  • second- or third- degree AV block
61
Q

What is the mechanism of action of verapamil?(3)

A
  • Pronouned effect on AV node
    (1) Increased refractory period
    (2) Decreased automaticity and AV conduction
  • Clinically significant negative inotropy
  • Decreased peipheral vascular resistance
62
Q

What are the indications of verapamil?

A

-Supraventricular tachyarrhythmias

63
Q

What are the side effects of verapamil?

A
  • Increased blood lecels of digoxin and theophylline
  • hypotension(resulting from systemic vasodilation)
  • heart block
64
Q

Give two examples of adrenergic agonists.

A
  • Dobutamine

- Dopamine

65
Q

What is the mechanism of action of dobutamine?(2)

A

a. Synthetic catecholamine

b. Direct beta-1 agonist with mild beta-2 and alpha-1 adrenergic effects

66
Q

What is the function of dobutamine?(2)

A
  • Increases myocardial contractility and output

- Minimal effects on systemic blood pressure or heart rate

67
Q

What are the indications of dobutamine?

A

-Cardiogenic shock; intended for short term use(48 to 72 hours)

68
Q

What are the side effects of dobutamine?(3)

A

-Beta-1 receptor desensitisation occurs with prolonged use, ectopic beats, increased heart rate or blood pressure

69
Q

What is the mechanism of action of dopamine?

A

a. Endogenous catecholamine that acts on alpha and beta adrenergic receptors and dopamine receptors
b. Positive inotrope; stimulation of cardiac beta-1 receptors

70
Q

What are the effects of dopamine with increasing doses(from low dose to moderate to high dose)?

A

(1) Low dose(2 ug/kg/min):stimulates dopaminergic receptors to increase mesenteric, coronary and renal blood flow.
(2) Moderate dose(5 ug/kg/min):cardiac beta-1 adrenergic stimulation, producing increased cardiac output with minimal effect in peripheral vasculature
(3) High dose(>10ug/kg/min): stimulates alpha-adrenergic receptors producing peripheral vasoconstriction and increased blood pressure

71
Q

What are the indications of of dopamine?(2)

A
  • refractory hypertension

- acute renal failure

72
Q

What are the side effects of dopamine?(3)

A
  • Tachycardia
  • arrhythmias
  • increased myocardial oxygen demand
73
Q

What are the contraindications of dopamine?(3)

A
  • Pheochromocytoma
  • ventricular fibrillation
  • uncorrected tachyarrhythmia
74
Q

What is the mechanism of action of digoxin?(3)

A
  • Mild positive inotrope. Inhibits Na+/K+ ATPase pump, promoting Na+/Ca2+ exchange and increasing intracellular calcium concentration.
  • Slows rapid ventricular rates; increases parasympathetic tone
  • Neurohumoral modulation. Reduces plasma levels of norepinephrine, aldosterone, renin
75
Q

WHat are the indications of digoxin?(2)

A
  • Congestive heart failure(decreased contractility)-dilated cardiomyopathy or valvular disease
  • Supraventricular tachycardua(atrial fibrillation)
76
Q

What are the side effects of digoxin?(4)

A

1.Digoxin toxicity(narrow theraputic range)
Therapeutic drug monitoring recommended
2.Extracardia: GI upset, muscle weaknessm depression, disorientation
3.Cardiac: partial or complete heart block, ventricular arrhythmias
4.Many drug interactions

77
Q

(i) Give two examples of phosphodiesterase inhibitors.

(ii) What is the mechanism of action of phosphodiesterase inhibitors?

A

(i)Pimobendan, amirinone(milrinone)

(ii)
1/Positive inotropes or vasodilators
2.Inhibit phosphodiesterase type III(cardiac specific phosphodiesterase)
a.Increased intracellular cAMP
b.Increased myocardial contractility
3.Arteriodilation anf venodilation(both pulomanry and systemic vasculature)
4.Potentiate adrenergic signal transduction
a.Increases myocardial cobtractility(positive inotrope)
b.Increases myocardial relaxation
5.Enhanced cardiac contractility without increased myocardial oxygen consumption

78
Q

What are the additional mechanisms of pimobendan?(2)

A

a. Potentiates adrenergic signal transduction(positive inotrope; increases myocardial relaxation)
b. Enhanced cardiac contractility without increased myocardial oxygen consumption

79
Q

What are the indications of pimobendan?(3)

A
  • Congestive heart failure
  • Dilated cardiomyopathy
  • Valvular disease
80
Q

What are the side effects of pimobendan?(2)

A
  • Arrhythmias

- Mild GI upset

81
Q

What are the indications of amrinone, milrinone?(2)

A

a.Congestive heart failure(decreased contractility).Dilated cardiomyopathy or valvular disease
b.Arterial hypertension
NOTE:Milrinone is 10-20 times more potent.

82
Q

What are the side effects of amrinone, milrinone?(5)

A
  • Arrhythmias
  • GI upset
  • thrombocytopenia
  • hepatotoxicity
  • fever

CHAPTER 1: Clinical Pathology: Clinical chemistry (11 decks)

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