L4 VASOACTIVE DRUGS - DR - Yagub S Saleh

Anbar Medical College THE VASCULAR SYSTEM Dr.
Yagub S Saleh
Dep. of Pharmacology 2023-2024
VASOACTIVE DRUGS
 Vasoconstrictor drugs
 Vasodilator drugs
Vasoconstrictor drugs
 Direct acting:
 Alpha1 adrenoceptor agonists
 Indirect acting:
 Drugs that release noradrenalin from sympathetic nerve terminals or inhibit its
reuptake
 Some eicosanoids :
 Thromboxane A2
 Peptides:
 Endothelin, angiotensin and antidiuretic hormone
 Ergot alkaloids:
 Sumatriptan acting through 5-HT type 2 receptor
Clinical uses of vasoconstrictor drugs
1. Local applications (nasal decongestion)
2. Coadministration with local anaesthetics
3. Adrenaline in anaphylactic shock and in cardiac arrest
4. Antidiuretic hormone to stop bleeding from oesophageal varices in patients with portal
hypertension caused by liver disease
Vasodilators drugs
Vasodilators action:
 Increase local tissue blood flow
 Reduce arterial pressure
 Reduce central venous pressure
Net effects are
 Reduction of cardiac pre-load (reduced filling pressure)
 Reduction of after-load (reduced vascular resistance)
The net result is reduction of cardiac work
AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 1

Anbar Medical College THE VASCULAR SYSTEM Dr. Yagub S Saleh
Calcium Antagonists
Block directly voltage-dependent calcium channels & cause generalised arterial vasodilation.
Individual agents exhibit distinct patterns
Nifedipine: act preferentially on vascular smooth muscle.(rapidly acting ). It causes reflex

tachycardia as a result of lowering the blood pressure, hypotension, ankle oedema, headache &
constipation. Caution should be taken in ischaemic pain. Use with b-blocker and diuretics
Amlodipine: Similar to nifedipine except much longer t 1/2 (40h) permitting the same benefits
as the longest-acting formulations of nifedipine without requiring a special formulation.
Verapamil: acts mainly on the heart. It causes Hypotension, myocardial depression,

constipation &dependent oedema
Diltiazem: is intermediate in specificity. It causes Hypotension, dizziness, flushing

&bradycardia

Potassium Channel Activators

Relax smooth muscle by selectively increasing the membrane permeability to K+ causing
hyperpolarisation
Minoxidil
1. Very potent and long-acting vasodilator
2. Causes marked salt and water retention (usually prescribed with a loop diuretic)
3. Reflex tachycardia (a β-adrenoceptor antagonist prevents it)
4. Also it causes hirsutism
Diazoxide
Diabetogenic, fluid retention (oedema, usea diuretic)
Drugs that act via cyclic nucleotides and enzymes by increasing cAMP or cGMP
Nitric oxide (NO), nitrates and the natriuretic peptides act through cGMP
Dopamin increases cAMP by activating adenylate cyclase
Nitroprusside (i.v.)
 Yields NO, acts equally on arterial and venous smooth muscle
 t1/2 is only few minutes, it must be given as a continuous infusion with careful monitoring
to avoid hypotension.
Usage:
 In intensive care units for hypertensive crises
 To produce controlled hypotension during surgery
Phosphodiesterase inhibitors
Methylxanthines: Theophylline
Exert their main effects on extravascular smooth muscle
Papaverine
Vasodilator of blood vessels (cerebral and coronary vasodilator)
Sildenafil (Viagra) inhibits the breakdown of cGMP. Increases penile erection

Vasodilators with unknown mechanism of action

A. Hydralazine
It appears to have multiple, direct effects on the vascular smooth muscle.
 First, hydralazine causes smooth muscle hyperpolarization quite likely through the
opening of K+-channels.
 It also may inhibit IP3-induced release of calcium from the smooth muscle sarcoplasmic
reticulum. This calcium combines with calmodulin to activate myosin light chain kinase,
which induces contraction.
 Finally, hydralazine stimulates the formation of nitric oxide by the vascular endothelium,
leading to cGMP-mediated vasodilation.
Acts mainly on arteries and arterioles causing a fall in BP accompanied by reflex tachycardia.
Side Effects: headaches, flushing and tachycardia. Genetic polymorphism in pharmacokinetics
slow acetylators---systemic lupus erythematosus like syndrome
Usage: severe hypertension
B. Ethanol
Dilates cutaneous vessels – familiar flush
Antagonists of sympathetic vasoconstriction

Selective α1-adrenoceptor antagonists (e.g., prazosin, terazosin, doxazosin)
Non-selective (α1 & α2) antagonists (e.g., phentolamine, phenoxybenzamine).
Side effects
 Dizziness, orthostatic hypotension (due to loss of reflex vasoconstriction upon standing),
 Nasal congestion (due to dilation of nasal mucosal arterioles)
 Headache, and reflex tachycardia (especially with non-selective alpha-blockers).
 Fluid retention.
Alpha blockers have not been shown to be beneficial in heart failure or angina, and should not be
used in these conditions.
The renin-angiotensin system
 ACEI- angiotensin-converting enzyme inhibitors (captopril, enalapril, ramipril,…)

 Angiotensin II receptor subtype1 antagonists (AT1) (losartan, valsartan,
candesartan…)
Centrally Acting Sympatholytics
 Clonidine
 α-methyldopa

Endothelin Receptor Antagonists

Endothelin-1 (ET-1) is produced by the vascular endothelium. It is a very potent vasoconstrictor
that binds to smooth muscle endothelin receptors, of which there are two subtypes: ETA and
ETB receptors.
ET-1 in the heart causes SR release of calcium, which increases contractility. ET-1 also
increases heart rate.
One endothelin receptor antagonist has been approved. Bosentan, a non-selective ET-1 receptor
antagonist (blocks ETA and ETB receptors) is currently used in the treatment of pulmonary
hypertension.
Renin Inhibitors
Aliskiren is a renin inhibitor that was approved for the treatment of hypertension by the U.S.
FDA in 2007
Clinical uses of vasoactive drugs:

1. Hypertension
2. Cardiac failure
3. Angina pectoris
4. Raynaud´s disease

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Anbar Medical College THE VASCULAR SYSTEM Dr.

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 1

Individual agents exhibit distinct patterns

Nifedipine: act preferentially on vascular smooth muscle.(rapidly acting ). It causes reflex

Verapamil: acts mainly on the heart. It causes Hypotension, myocardial depression,

Diltiazem: is intermediate in specificity. It causes Hypotension, dizziness, flushing

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 2

Potassium Channel Activators

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 3

Vasodilators with unknown mechanism of action

Antagonists of sympathetic vasoconstriction

The renin-angiotensin system

 ACEI- angiotensin-converting enzyme inhibitors (captopril, enalapril, ramipril,…)

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 4

Endothelin Receptor Antagonists

Clinical uses of vasoactive drugs:

AnbarMedical College -- Dr.Yagub S Saleh 2023-2024 Page 5

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