anti-hypertensives Flashcards
Clonidine presentation and uses
Available as 25-300mcg tablets and as a colourless solution for injection containing 150mcg/mL.
Transdermal patch is also available but takes 48 hours to reach therapeutic levels.
Used in the treatment of HTN, chronic and acute pain, suppression of symptoms of opioid withdrawal and sedation
Clonidine Mechanism of action
Stimulates alpha 2 receptors in the lateral reticular nucleus resulting in reduced central sympathetic outflow and alpha 2 receptors in the spinal cord where they augment endogenous opioid release and modulate noradrenergic pathways.
MAC is reduced (sedation increased) by stimulation of postsynaptic alpha 2 receptors centrally.
Clonidine effects
CVS: Causes a prolonged fall in BP. CO is maintained despite bradycardia. PR interval is lengthened, AV node conduction depressed and BRR sensitised. Effects on vascular system complex as any vasoconstriction induced by alpha 2b receptors is offset by decreased SNS stimulation. Stablizes CVS response to surgical stimuli.
CNS - produces sedation and a reduction of up to 50% of MAC. Anxiolytic at low doses. Anxiogenic at high doses
Analgesia - provides analgesia with no respiratory depression. Acts synergistically with opioids.
Renal - causes diuresis
Endocrine - stress response to surgery is inhibited
Clonidine kinetics
Clonidine is rapidly and almost completely absorbed orally.
Low protein binding. Vd 2.1L/Kg.
Elimination half life long at 9-18 hours. 50% excreted unchanged in urine therefore dose should be reduced in renal impairment
Sodium Nitroprusside uses
Usually administered as a low dose infusion for hypertensive emergencies
Sodium Nitroprusside mechanism of action
Vasodilates both arteries and veins by production of nitric oxide. Activates the enzyme guanylate cyclase leading to increased levels of intracellular cGMP. This causes vascular smooth muscle relaxation.
Sodium Nitroprusside effects
CVS - Arterial vasodilation = decreased systemic vascular resistance. Venous vasodilation increases the venous capacitance and reduces preload. Cardiac output maintained by reflex tachycardia.
Resp - May inhibit HPV
CNS - ICP increased due to cerebral vasodilation and increased cerebral blood flow.
Sodium Nitroprusside kinetics
Not absorbed orally. short t1/2. Duration of action less than 10 min.
Sodium Nitroprusside toxicity
Metabolism is complication but causes cyanide ions to be formed. these can cause toxicity
Nitric oxide MOA and use
Vasodilator. Synthesised in endothelial cells from amino acid L-arginine. Diffuses in to pre-capillary arterioles where it activates guanylyl cyclase and increases cGMP –> vascular smooth muscle relaxation.
Inhaled NO uses for severe pulmonary HTN and acute right heart dysfunction
GTN presentation
Aerosol spray delivering 400mcg per metered dose
Tablets containing 300-600mcg - both used PRN sublingually.
Modified release tablets containing also available (either buccal or swallowed)
Transdermal patch (5-15mg/24 hours)
GTN uses
used in the treatment and prophylaxis of angina, in LV failure associated with myocardial infarction and following cardiac surgery
GTN mechanism of action
Vasodilates veins by the production of nitric oxide. Activates guanylate cyclase leading to increased cGMP. Causes vascular smooth muscle relaxation
GTN effects
CVS - GTN produces vasodilation predominantly of the capacitance vessels (veins) - in contrast to SNP. This decreases venous return, preload and wall tension. Leads to decreased oxygen demand and increased coronary blood flow. Postural hypotension may occur. Coronary artery flow may be increased directly by coronary vasodilation. Tolerance occurs quickly however a daily drug free period of a few hours will prevent this
CNS - Increase in intracranial pressure and headache resulting from cerebral vasodilation may occur
GI - relaxes GI sphincters and sphincter of oddi
GTN kinetics
Rapidly absorbed from sublingual mucosa and GI tract although latter is subject to extensive first pass metabolism resulting in oral bioavailability less than 5%.
Sublingual effects seen within 3 min and last 30-60min.
Nifedipine presentation and uses
Capsules containing 5-10mg (sublingual) or oral 10-60mg. Onset of action 15-20min after oral .
Used in prophylaxis and treatment of angina, hypertension and raynauds syndrome
Nifedipine effects
Reduces tone in peripheral and coronary arteries resulting in reduced systemic vascular resistance, decreased BP and increased coronary artery blood flow
Nifedipine kinetics
Bioavailability of 60% due to first pass metabolism
Highly protein bound (95%) and elimination half life five hours.
Excreted inactive in urine
Amlodipine
Dihydropryidine derivative that is available only for oral administration (5 to 10mg). Elimination half life is 30 to 40 hours.
Hydralazine presentation and uses
Available as 25-50mg tablets and as 20mg powder for reconstitution.
Used orally in the control of chronic hypertension and chronic heart failure. Used IV in acute HTN associated with pre-eclampsia at 10-20mg
Hydralazine MOA
Uncertain mechanism but involves activation of guanylate cyclase and an increase in cGMP. Decreases intracellular calcium and causes vasodilation
Hydralazine effects
CVS - reduces arteriolar tone and SVR. Capacitance vessels (veins) are less affected. Reflex tachycardia and increase CO occur (can be antagonised by b blocker).
CNS - cerebral blood flow decreases due to vasodilation
GI - N + V common
Miscellaneous - peripheral neuropathy and blood dyscrasia. Long term therapy can cause lupus
Cilazparil use
ACE inhibitor. Prodrug metabolized to active metabolite cilazaprilat.
Used for the treatment of hypertension and heart failure, especially in the presence of diabetic nephropathy
Cilazapril MOA
ACE inhibitor. Competes with angiontensin 1 for binding at angiotensin converting enzyme. This leads to decreased angiotensin 2 and the effects of the drug lead from this. i.e decreased AT2 = decreased aldosterone, decreased vasoconstriction
Cilazapril kinetics
Generally well absorbed 50-70%.
Metabolised by liver esterases to active drug. Eliminated by the kidneys.
Excreted renally therefore dose adjustment needed in renal failure
Enalapril
Prodrug hydrolysed in the liver to active compound enalprilat. Half life 4-8 hours but increases in chronic use.
Losartan presentation and uses
Angiotensin 2 receptor blocking agent.
Available as 25-50mg tablets and in combination with hydrochlorothiazide. Used in the treatment of HTN where dry cough is a side effect of ACEI.
Losartan MOA
Specific AT2 receptor blocker at all sites within the body. Therefore inhibits all effects of AT2 including contraction of smooth muscle, thirst, ADH release, aldosterone secretion
Losartan effects
Similar to ACEI except does not block the breakdown of bradykinin so don’t get the cough associated with ACEI.
Losartan Kinetics
Bioavailability of 30% due to extensive first pass metabolism. Highly protein bound (99%).
Less than 10% excreted in inactive form in the urine
