Cardiovascular Drugs (Veterinary Pharmacology)

Cardiovascular Drugs
(Veterinary Pharmacology)
dr. Dian Nugrahenny, M.Biomed.

Dr. drg. Nur Permatasari, MS.
Basic Anatomy and Physiology
Functions of cardiovascular system:

Delivery of oxygen, nutrients, and hormones to the various
parts of the body
Transports waste products to the appropriate waste
removal system
© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.

Component of Cardiovascular
System
 Cardiac
 Blood vessels
 Blood
Guyton Textbook of Medical Physiology, 11th ed.

Basic Anatomy and Physiology

Cardiac sympathetic and
parasympathetic nerves

Possible mechanisms for influencing
heart function
Lüllmann et al. 2000. Color Atlas of Pharmacology, 2nd ed. Thieme.

Processes in
myocardial
contraction
and
relaxation
Lüllmann et al. 2000. Color Atlas of

Pharmacology, 2nd ed. Thieme.
Cardiovascular Diseases
Heart failure Hypertension
Arrhythmia
Cardiomyopathy Thromboembolism
Congestive Heart Failure
 Inadequate tissue perfusion from a failing pump, volume overload
 Major causes: hypertension, myocardial infarction
Right Heart Failure Left Heart

Predominant: Sign: Failure
venous congestion Predominant:
Subcutaneous Symptom
edema Dyspnea,
Abdominal effusion
orthopnea, cough
(pulmonary edema)
(ascites)
Hepatomegaly
Splenomegaly
Drugs for Heart Failure
3D:
VasoDilators:
 Venodilators
 Arteriolar dilators
Diuretics
Digitalis
Vasodilators
Venodilators: Reduces preload by trapping blood in the venous
circulation
Arteriolar dilators: Reduces afterload by reducing arterial
resistance
Potensial side
effect:
hypotension
Lüllmann et al. 2000. Color Atlas of

Pharmacology, 2nd ed. Thieme.
Nitrates
• Drugs: nitroglycerin,
ISDN, ISMN.
• As NO donors.
• The effect is more

pronounced in
venous than in
arterial beds.
Ca2+-Channel
Blocker (CCB)
Inhibit the influx of Ca2+
ions without affecting
inward Na+ or outward K+
currents to a significant
degree.
Nifedipine Inhibition of cardiac functions by

VERAPAMIL
Verapamil used as an antiarrhythmic drug

Renin-Angiotensin-Aldosterone System
(RAAS)
ACE
Inhibitor:
enalapril,
benazapril,
imidapril
Action of Angiotensin II
reabsorption Adrenal cortex

Other Vasodilators
 Hydralazine:
 Dilate arterioles
 Treats hypertension
 Less postural hypotension
 Minoxidil:
 Dilate arterioles
 For severe hypertension
 Diazoxide:
 Given i.v. causes prominent arteriolar dilation
 For hypertensive crises
 Can be used in the management of insulin-secreting pancreatic tumors.
 Nitroprusside sodium:
 Dilate venous and arterioles
 Given i.v. for hypertensive crises
Diuretics
 Drugs with a direct renal action.
 Augment urine excretion (diuresis) by inhibiting the
reabsorption of NaCl and water.
 Indications:
1. Mobilization of edemas: increase renal excretion of Na+
and H2O.
2. Antihypertensive therapy: decrease peripheral
resistance.
3. Therapy of congestive heart failure: decrease peripheral
resistance, cure symptoms of venous congestion.
Adverse effects of diuretics
Massive use of diuretics entails a hazard of adverse effects:

The decrease in blood volume can lead to hypotension and
collapse;
Blood viscosity rises due to the increase in erythro- and
thrombocyte concentration, bringing an increased risk of
intravascular coagulation or thrombosis.
Action of diuretics
1. Thiazides (e.g. HCT): act in the
intermediate segment of distal tubules.
2. Loop diuretics (e.g. furosemide): act in the
thick portion of the ascending limb of
Henle’s loop.
3. K+-sparing diuretics (e.g. spironolactone):
an aldosterone antagonist, act in the distal
portion of the distal tubule and the
proximal part of the collecting ducts.
Digitalis, cardiac glycosides
 In severe cases of myocardial insufficiency, digitalis may
be added to augment cardiac force (positive inotrope)
and to relieve the symptoms of insufficiency.
 Digoxin is a weak positive inotrope.
 Very narrow therapeutic index.
 Very long half-life, about 30 hours in dog and 20 hours in
cat.
 Digoxin has many drug interactions: diuretics,verapamil,
amiodarone, etc.
Digitalis inhibits Na+/K+-ATPases activity. Na+ utilizes Na+/Ca2+ exchange
mechanism to enable Na+ to exit the cell, in return Ca 2+ enters the cells.
The increase of cytosolic Ca2+ promotes a positive inotropic response.
Adverse effects of digitalis
 Dysrhythmias
 Toxicity – very narrow therapeutic index – hypokalemia makes
it easier for toxicity to occur
 Nausea, vomiting
 Disturbances of
color vision
 Fatigue
Therapy of intoxication of digitalis
 Administration of K+, which reduces binding of digoxin,
but may impair AV-conduction.
 Administration of antiarrhythmics, such as phenytoin or

lidocaine.
 Oral administration of colestyramine for binding and

preventing absorption of digitoxin present in the
intestines (enterohepatic cycle).
 Injection of antibody fragments (Fab) that bind and

inactivate digitoxin and digoxin.
Beta-blocker
By blocking cardiac β-receptors, cardiac work can no longer
be augmented above basal levels.
This effect is utilized

prophylactically in
angina pectoris to
prevent myocardial
stress that could
trigger an ischemic
attack.
β-Blockers also
serve to lower
cardiac rate.
Agonist Antagonist
Cardiac Arrhythmias
 Autonomic nervous system disorders
 Altered ionic permeability of cardiac membranes

 Factors: trauma; hypoxia; infection; metabolic disease;
drugs and toxins
 Intrinsic cardiovascular disease

Cardiac impulse generation and
conduction
AARDs: General Mechanisms of
Action
 Change gating properties of cardiac ion channels
(Na+, Ca2+, K+) directly
 Change neuromodulatory control of cardiac ion

channel opening/closing
Classification of AARDs
a) Variables for normal tissue models in ventricular tissue. b) Variables for SA and AV nodal
tissue only. c) Also has type II β-blocking actions. d) Classification controversial. e) Not clinically
manifest. f) Also has sodium, calcium, and β-blocking actions.
Hemostasis and Thrombosis
C. SECONDARY HEMOSTASIS
latelets
adhesion
ADP, adenosine diphosphate; t-PA, tissue type plasminogen activator

Hemostasis and Thrombosis
Parenteral anticoagulants
Heparin
Administered by injection
Helps inactivate thrombin, factor Xa and others
*Prophylaxis of venous thrombosis
Half-life is short
Therapeutic uses
 Pregnancy – if needed
 Open heart surgery
 Deep Vein Thrombosis
 Acute MI
Adverse reactions
 Bleeding
 Thrombocytopenia – heparin induced
 Hypersensitivity
 Must monitor aPTT (activated partial thromboplastin
time)
Oral anticoagulants
Warfarin
Act as “false” vitamin K and prevent regeneration of active
vitamin K from vitamin K epoxide, hence the synthesis of
vitamin K-dependent clotting factors.
Vitamin K promotes activation of factors II, VII, IX, and X.
Peak effects take several days.

Therapeutic uses
 Long-term prophylaxis of thrombosis
 Must monitor PT (prothrombin time)/INR (international
normalized ratio, contains a correction factor for PT)
Adverse reactions
 Warfarin has many drug interactions

 Hemorrhage
 Vitamin K can be given in case of overdose
Antiplatelet drugs
Aspirin
Prevention of thrombosis in arteries
Suppresses platelet aggregation due to inhibition of
thromboxan (TXA2) synthesis
Indications: prophylaxis of MI, prevent reinfarction in
patients with acute MI, prevent stroke
Low dose - no greater than 325 mg/day
Adverse effects: GI bleeding, bronchoconstriction
Hypertension
 Primary (essential): 90%

 Secondary
 Virtually no symptoms
 Treatment is usually life-long
 Consequences of hypertension: heart disease, kidney
disease, blindness, stroke
Pharmacologic Therapy
Sites of action: 4. Vascular smooth
1.Brainstem muscle
2.Sympathetic Ganglia – used 5. Renal tubules
for emergencies  Angiotensin-
3.Terminal of adrenergic nerves converting enzyme
 Beta 1 receptors on the  Angiotensin II
heart receptors
 Alpha 1 – adrenergic
6. Calcium antagonist
receptors on blood vessels
Initial drug therapy choices
DiPiro et al. 2005. Pharmacotherapy: A Pathophysiologic Approach, 6th ed. The McGraw-Hill Companies, Inc.
Compelling indications
Treatment of Chronic Hypertension in
Pregnancy
Semangat belajar!!! 

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Cardiovascular Drugs

dr. Dian Nugrahenny, M.Biomed.

Functions of cardiovascular system:

© 2004 by Thomson Delmar Learning, a part of the Thomson Corporation.

Guyton Textbook of Medical Physiology, 11th ed.

Guyton Textbook of Medical Physiology, 11th ed.

Guyton Textbook of Medical Physiology, 11th ed.

Lüllmann et al. 2000. Color Atlas of Pharmacology, 2nd ed. Thieme.

Lüllmann et al. 2000. Color Atlas of

Heart failure Hypertension

Right Heart Failure Left Heart

Lüllmann et al. 2000. Color Atlas of

• The effect is more

Nifedipine Inhibition of cardiac functions by

Verapamil used as an antiarrhythmic drug

reabsorption Adrenal cortex

Massive use of diuretics entails a hazard of adverse effects:

 Administration of antiarrhythmics, such as phenytoin or

 Oral administration of colestyramine for binding and

 Injection of antibody fragments (Fab) that bind and

This effect is utilized

 Autonomic nervous system disorders

 Altered ionic permeability of cardiac membranes

drugs and toxins

 Intrinsic cardiovascular disease

 Change neuromodulatory control of cardiac ion

ADP, adenosine diphosphate; t-PA, tissue type plasminogen activator

Vitamin K promotes activation of factors II, VII, IX, and X.

Peak effects take several days.

 Warfarin has many drug interactions

 Primary (essential): 90%

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