Vasodilators and Antihypertensives Flashcards
What will a drug that increases smooth muscle intracellular cAMP or intracellular cGMP cause?
Vasodilatation
What do clonidine and methyldopa do? What are their side effects?
- alpha 2 agonists
- both have minimal alpha 1 agonist action
- clonidine
- can be given via epidural or subarachnoid route, can reduce post-op opioid requirements
- diuresis via inhibition of ADH release
- inhibits insulin release
- rebound hypertension following abrupt cessation
- methyldopa - given orally or (rarely) IV
- sedation, positive direct Coombs test in 10-20% of cases
What is dexmedetomidine?
A more selective alpha 2 agonist
What is the MOA of ganglion blocking agents?
- non-depolarizing competitive antagonist at ganglion type nicotinic receptor of autonomic ganglia
- inhibits sympathetic input to peripheral vasculature
- vasodilation
What are the SEs of ganglion blocking agents?
- associated histamine release
- SEs mainly due to parasympathetic antagonism
- prev. used in treating hypertension and inducing peri-operative hypotension (eg trimetaphan)
What is the MOA of adrenergic neurone blocking agents?
- enters adrenergic neurone via uptake 1 noradrenaline pathway
- displaces noradrenaline and prevents further norad release
- decreases alpha 1 receptor stimulation
- vasodilation
How is guanethidine given?
Orally or IV
What are the SEs of adrenergic neurone blocking agents?
- diarrhoea
- postural hypotension
- commonly used to manage chronic pain
Where does hydralazine act?
- mainly on arterioles
- bioavailability affected by acetylator status
What are the SEs of hydralazine?
- reflex tachycardia
- fluid retention
- increased cerebral blood flow
- nausea and vomiting
- long term oral use can cause a lupus like syndrome
How does hydralazine work?
A directly acting vasodilator, producing NO which acts on G-protein coupled receptors activated guanylate cyclase and increasing intracellular cGMP levels to cause vasodilation.
Produces vasodilation of both arterial and venous vessels.
Arterial vasodilation reduces SVR while venous vasodilation increases venous capacitance and reduces preload.
How does dose affect how nitrates work?
- lower doses act on veins
- higher doses act on arterioles
- GTN is highly lipid-soluble so can be given via the transdermal route
What are the SEs of nitrates?
Headache, flushing, postural hypotension and tachycardia
How does nitrate tolerance occur?
Due to depletion of sulphyldryl groups
Can nitrates cause methaemoglobinaemia?
Yes
How do nitrates like GTN and isosorbide mononitrate work?
They produce vasodilation of primarily venous vessels. This increases venous capacitance and reduces preload.
What is sodium nitroprusside? (SNP)
A directly acting vasodilator (produces NO which acts on G protein coupled receptors, activating guanylate cyclase and increasing intracellular cGMP levels to cause vasodilation)
How is SNP given and where does it act?
- given only parenterally
- rapid onset and offset
- acts on arterioles and venules
- increases ICP but autoregulation maintained
- activates renin/angiotensin system and increases plasma catecholamines which can cause rebound hypertension if stopped abruptly
- hypoxic pulmonary vasoconstriction can be inhibited causing shunt
What are the SEs of SNP?
- reacts with oxyHb in RBCs to form cyanide, nitric oxide and methaemoglobin
- high infusion rates can cause cyanide accumulation
- methaemoglobin can react with cyanide to form cyanmethaemoglobin
What is the MOA of calcium channel blockers?
- blocks L-type Ca2+ channels and reduces Ca2+ entry into cells
- causes vasodilation, reduces myocardial contractility, reduced propagation of cardiac depolarization
What is the MOA of thiazide diuretics?
- high dose
- inhibits sodium and chloride ion reabsorption in distal tubule of kideny
- low dose
- activates potassium channels which cause hyperpolarization and relaxation
