pharmacology lectures

1. Directly Acting
Vasodilators

2. Directly Acting Vasodilators
Classification
A-According to route of adminstration
1-Oral Vasodilators
Hydralazine
Minoxidil
2-Parenteral Vasodilators
Sodium Nitroprusside
Diazoxide Fenoldopam
3-Oral & Parenteral Vasodilators
Calcium Channel Blockers

3. Drugs Used Parenterally are for hypertensive
emergencies
Among these only Na Nitroprusside is both Arteriolar
and Venous Dilators while all the others are arterial
dilators

4. Vasodilator
Decreased PVR
Decreased BP
Activation of Renin-Angiotensin-System Activation of BaroreceptorSympathetic System
Increased Renin Release Increased HR, FOC
Angitensinogen__Angiotensin-1 Increased C O -------- Increased B.P
Angiotensin-2 Reflex Tachycardia
prevented by Beta-Blockers
Increased Aldosterone
Increased Na+ & Water
Retension
Increased Blood Volume
Increased B.P

5. So Vasodilators tend to:
1. Increase BP back to high levels by
a) Increasing Renin Release
b) Increasing Sympathetic outflow through the
baroreceptor reflex
2. Cause Reflex Tachycardia (Again increased reflex
sympathetic activity

6. Other Common Features
1. Most can cause Palpitations and can precipitate
angina and arrythmias due to the increased
sympathetic activity (However these effects are less
or absent with Calcium Channel Blockers due to their
depressant effects on the heart)

7. 2. They also cause headache and flushing due to the
vasodilatation
3. They may also cause salt and water retention
(Increased Renin and aldosterone) and thus edema
4. They do not cause postural Hypotension because
sympathetic reflexes are intact

8. Common Use: Hypertension
By causing vasodilatation they decrease PVR.
Not used alone because of the
compensatory mechanisms causing
various adverse effects
Used with Beta Blockers to decrease the
effects on heart due to reflex increase in
sympathetic activity
And used with diuretics to decrease the
plasma volume increased due to
retention of Na and increased renin and
aldosterone

9. Hydralazine
Given orally, Metabolised by Acetylation
Mechanism of Action
Not clear; It may involve generation of NO and
stimulation of cGMP
Uses
Hypertension
CCF (Decreases Afterload)

11. Adverse Effects of Hydralazine
All the common adverse effects:
(Extension of pharmacological effects)
Tachycardia, palpitations leading to angina and arrythmias
Hypotension
Headache and flushing

12. Distinctive Adverse Effect( immunological)
Mechanism is unknown
1-SLE like syndrome—high doses or slow
acetylators—arthralgia, myalgia, skin rashes and
fever
2-Illness resemble Serum Sickness
Haemolytic Anaemia
Vasculititis
Glomerulonrphritis
3—Pyridoxine responsive polyneuropathy
Other adverse Effects
Anorexia, nausea, sweating

13. Minoxidil
Orally given and converted into
active form in body---Minoxidil
Sulfate, Only dilates arerioles

14. Mechanism of Action
 It is a Potassium Channel opener
 Relaxation of vascular smooth muscle by
activation of ATP-Modulated K+ Channels.
 By opening K+ Channels----- increased K+
Efflux This results in hyperpolarisation and
stabilizes the membrane at its resting
potential------ Relaxation of vascular smooth
muscle
------- Vasodilation ------ decreased PVR
-------decreased B.P

15. Uses:
 Hypertension
Severe, life threatening,drug resistant
 Alopecia
Used to stimulate hair growth in male pattern baldness (Topical
therapy)

16. Mechanism of increase hair
growth
 Exact is unknown but may involve;
a.Increase microcirculation around hair follicles.
b.Direct stimulation of resting hair follicles.
c.Alteration of androgen effect on genetically hair follicles.

17. Adverse Effect
Oedema
Reflex tachycardia
Hypotension
Rashes , Steven Johnson’s syndrome
Glucose intolerance
Thrombocytopenia
Distinctive Adverse Effect
Hirsutism (Hence used for baldness)

18. Diazoxide
Given Parenterally, arteriolar dilator
Structural similarity to Thiazide diuretics but no diuresis
Mechanism of Action
Potassium channel Opener like Minoxidil

19. Distinctive Adverse Effects
 Extensive Hypotension
 Hyperglycemia (Inhibits insulin
release from pancreas by opening
potassium channels in the Beta
cells of pancreas and hence used
in treatment of insulinoma
 Gout
 Hirsutism
 Pain & necrosis on extavasation

20. Uses
 Hypertensive crisis
 Hyperinsulinaemia
 Eclampsia
 Alopecia
 Preterm labour

21. Sodium Nitroprusside
Parenterally Administered; Arterial and Venous Dilator
Mechanism of Action
It causes release of Nitric oxide that activates guanylyl
cyclase or it may directly stimulate the enzyme to
increase cGMP which relaxes vascular smooth muscle

22. Uses
Hypertensive Emergencies
Heart Failure
Distinctive Adverse Effects
Cyanide Poisoning: Nitroprusside is a complex of iron,
cyanide and a nitroso group and is rapidly
metabolized by uptake into RBCs with liberation of
cyanide

23. Most of the cyanide is converted into thiocyanate which is less toxic
and slowly excreted through kidneys
 Accumulation of cyanide causes: Metabolic acidosis, arrythmias,
excessive hypotension and death
Treatment: Give sodium thiosulfate to convert to thiocyanate or give
hydrxocobalamin that forms non toxic cyanocobalamin

24. Thiocyanate may accumulate and cause
weakness, disorientation, psychosis,
muscle spasms, and convulsions and
hypothyroidism
Na Nitroprusside may also cause
Methemoglobinemia delayed
hypothyroidism.

25. Fenoldopam
New Parenteral arteriolar dilator
Mechanism of Action
D1 receptor agonist resulting in dilatation of peripheral
arteries and natriuresis
Distinctive Adverse Effect
Increases Intraocular pressure and thus avoided in
glaucoma