1. Pharmacology
        1.4. Cardiovascular drugs
1.4.2. Peripheral vasodilators

Peripheral vasodilators

- Nitric oxide and nitrovasodilators

[Ref: SH(H)2:p359-374]

 

Used to treat HTN, hypertensive crisis, and facilitate forward LV stroke volume

Nitric oxide (NO)

Physiological effect of NO

CVS

Regulation of systemic and pulmonary vascular resistance

Autoregulation of local circulation
* Endothelium-derived relaxing factor (EDRF)

Resp

Bronchodilation

V/Q matching

Platelets

Inhibits platelet activation

Nervous system

Neurotransmitter
* Excitatory in the CNS

May play a role in pain

Immune function

(???)

Effects of increased/decreased NO

Decreased NO
Increased NO

Clinical use

NO has been used clinically as an inhaled gas for treatment of pulmonary hypertension

May be useful in treatment of ARDS

Toxicity

Sodium nitroprusside (SNP)

Direct-acting, nonselective peripheral vasodilator
--> Relaxation of arterial and venous vascular smooth muscles

Mechanism of action

NB:

One of the cyanide ions may also react with MetHb to form cyanomethaemoglobin (non-toxic)

Actions of SNP

CVS

Direct venous and arterial vasodilation
--> Decrease in systemic BP

Cardiac output tend to increase due to reflex tachycardia and decreased systemic vascular resistance
* Despite decreased venous return secondary to venodilation

Possible coronary steal effect

CNS

Increased cerebral blood flow and blood volume
--> Increased ICP

Resp

Controlled hypotension could lead to decreased PaO2
--> Hypoxic pulmonary vasoconstriction

Platelet aggregation

Increased NO
--> Increased intracellular cGMP
--> Inhibition of platelet aggregation

Infusion rate of SNP > 3 microgram/kg/min
--> Increased bleeding time

Clinical use

Toxicity

Cyanide toxicity
Treatment of cyanide toxicity
Thiocyanate toxicity

Rare because thiocyanate is 100-fold less toxic than cyanide

Signs include:
* Hyperreflexia
* Confusion
* Psychosis

Methaemoglobinaemia

Requires doses of SNP exceeding 10mg/kg
--> Unlikely in clinical practice

Phototoxicity

After solution is prepared, must protect from light by aluminum foil
--> Can break down in vitro and form cyanide

Administration and dosage

Nitroglycerin

Organic nitrate

 

Action

Mechanism of action

Effects on organ systems

CVS

Clinical uses

Angina pectoris

Acute and chronic, due to atherosclerosis or coronary artery vasospasm
* Reduces myocardial oxygen requirement by reducing preload (mainly) and afterload
* May also stop vasospasm

Acute coronary syndrome

IV administration of nitroglycerin...

Other conditions

Route of administration

NB:

Absorbed by PVC, thus GTN infusion requires special tubing

Pharmacokinetics

Elimination half-time of 1.5 min

Large volume of distribution

Complications

Methaemoglobinaemia
Tolerance

Side-effects

Other drugs

 

Dipyridamole

 

Diazoxide

Side effects of diazoxide

 

Adenosine

Mechanism of action

Stimulation of potassium channels in supraventricular tissues
--> Hyperpolarisation of atrial myocytes
--> Decrease in diastolic depolarisation (phase 4) of the pacemaker cells in SA node

Ventricular myocytes do not have adenosine-sensitive potassium channels

Clinical use

Treatment of paroxysmal SVT and narrow complex tachyardia
Controlled hypotension

 

 

 

 

 

 



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