Cardiovascular Drugs

Dr Ian Oberholzer
UNAM 2023
 The Circulatory System

Two primary functions:

A. Delivery of oxygen, nutrients, hormones, electrolytes
etc. to the cells
B. Remove carbon dioxide and other metabolic waste

There are two major divisions

1. Pulmonary circulation: delivers blood to the lungs
2. Systemic circulation: delivers blood to all other
tissues

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 Regulation of Blood pressure
BP = CO x TPR
BP – Blood Pressure
CO – Cardiac Output
PVR – Peripheral Vascular Resistance
CO = HR x SV
HR – Heart Rate
SV – Stroke Volume

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 Hypertension
Hypertension is defined as an elevated blood pressure
(above 140/90 mmHg, normal reading being 120/80
mmHg)

Hypertension is an important risk factor for the future

development of cardiovascular disease

The risk of cardiovascular disease doubles for every

20/10 mmHg rise in blood pressure
Stroke and myocardial infarctions are the most
important complications that are seen
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 Regulation of Blood Pressure
Cardiac Output
 Controlled by the stroke volume and the heart rate
Heart Rate: controlled primarily by the ANS
 Heart rate is increased by the sympathetic nervous system
through the action on Beta 1 receptors on the heart
 Heart rate is decreased by parasympathetic nervous system
through M2 receptors on the heart.
Stroke volume: this is determined by 3 factors
 Myocardial contractility: controlled by the degree of cardiac
dilation
 Afterload: arteriole pressure that the left ventricle must
overcome
 Preload: amount of tension applied to the muscle prior to
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Systems that regulate Blood Pressure
Autonomic Nervous System
 Stimulation of the sympathetic nervous system leads to an
increase in BP through the binding of norepinephrine on
beta 1 receptors on the heart
 Stimulation of the parasympathetic nervous system leads
to a decrease in BP through the binding of acetylcholine
on M2 receptors on the heart.
RAAS
 The Renin-Angiotensin-Aldosterone System regulates BP,
blood volume, fluid and electrolyte balance.
The Kidneys
 The kidneys regulate blood volume and fluid through the
input of hormones and various other systems such as the
6 RAAS
 RAA System

TOTAL PERIPHERAL
CARDIAC OUTPUT
RESISTANCE
 Actions of Angiotensin II
The most prominent actions are vasoconstriction and aldosterone
release
Vasoconstriction:
 ANG II is a powerful vasoconstrictor of arterioles (less of veins).
 It works by causing contraction of vascular smooth muscle by
binding directly to the vascular smooth muscle.
 Indirect vasoconstriction is caused by stimulation of the sympathetic
nervous system
Release of Aldosterone:
 ANG II acts on the adrenal cortex to promote synthesis and secretion
of aldosterone
Alteration of cardiac and vascular structure:
 ANG II can cause hypertrophy and remodeling of the cardiac muscle
 ANG II is thought to be responsible for increasing the thickness of
blood vessel walls
 Actions of Aldosterone

Causes of retention of sodium and excretion of

potassium and hydrogen
 Sodium retention leads to water retention as well which in
turn leads to an increase to blood volume and BP
Activate Sympathetic Nervous System which leads to an
increase in BP
Causes cardiac remodeling
Drugs Acting on RAAS
PHARMACOLOGY
• Pharmacological class / examples
Class

Role (clinical) • Drug of choice ; Alternative,

• Type A, B, C, D, and E
Adverse effects

Mechanism: • Action(s) of the drug

• Unique AADME
11 Pharmacokinetics
 Angiotensin-Converting Enzyme Inhibitors

Examples: Perindopril, Captopril, Ramipril, Enalapril

MOA: Inhibit ACE which inhibits the production of ANG II
and aldosterone
 Vasodilation
 Reduction in CO
 Reduced Blood volume
 Prevent or reverse pathological changes in the heart and blood
vessels mediated by ANG II and aldosterone
Indications:
 Hypertension: reduces BP
 HF, acute myocardial infarction, left ventricular dysfunction
prevents and reverses cardiac hypertrophy and remodeling
 Diabetic and Non-diabetic nephropathy: reduced glomerular
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filtration pressure - Glomerular disease
 ACE i's cont’d…
Adverse effects
 Hyperkalemia
 Fetal kidney injury
 Persistent dry cough
 Angioedema
 Contraindicated in patients with bilateral renal artery
stenosis
Pharmacokinetics
 All ACEi’s are given orally except enalaprilat
 Captopril has the shortest half life (given 2-3 times a
day)
 All ACE inhibitors are prodrugs except lisinopril
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 Excreted via the kidneys
 Angiotensin Receptor Blockers

Examples: Losartan, Irbesartan, Valsartan, Telmisartan

MOA: block access of ANG II to its receptors in blood vessels,
the adrenal glands and all other tissue
 Vasodilation
 Reduction in CO
 Reduced Blood volume
 Prevent or reverse pathological changes in the heart and blood vessels
mediated by ANG II and aldosterone
Indications:
 Hypertension: reduces BP
 HR, acute myocardial infarction, left ventricular dysfunction:
prevents and reverses cardiac hypertrophy and remodeling
 Diabetic and non-diabetic nephropathy: reduced glomerular filtration

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pressure
 Stroke Prevention in patients with hypertension and LV dysfunction
 ARBs cont’d…

Adverse effects
 Hyperkalemia
 Fetal kidney injury
 Angioedema
 Contraindicated in patients with bilateral renal artery
stenosis
Pharmacokinetics
 All ARBs are given orally
 Excreted via the kidneys

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 Direct Renin Inhibitor
Example: Aliskiren
MOA: Binds tightly to Renin and inhibits the cleavage
of Angiotensinogen to ANG I
 Prevents ANG II and aldosterone production
Indications
 Hypertension
Pharmacokinetics:
 Orally bioavailability is low (2.5%)
 Half life of 24 hours
Adverse Effects:
 Generally well tolerated but at higher doses can cause
diarrhoea
16  Contraindicated in pregnancy
 Aldosterone Antagonists
Example: Eplerenone and Spironolactone
MOA: Inhibits the actions of aldosterone (Eplerenone
is more selective to aldosterone receptors)
 Excretion of sodium and water
Indications
 Hypertension
 Heart Failure
Pharmacokinetics:
 Administered orally
Adverse Effects:
 Gynecomastia
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 END

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