PT10

Name the two types of direct acting vasodilators?

Calcium channel blockers, potassium channel opener

What is mechanism of hydralazine?

Unknown

What is the main hypertensive mechanism of CCBS?

Block L type voltage gated calcium influx in vascular smoot muscle, decrease TPR

Which CCBs work at vascular smooth muscle?

1,4-dihydropyrdines

Example of 1,4-dihydropyrdines?

Nifedipine, amlodipine

What is the common indication for intermediate CCBs?

Antianginal, anti-arrhythmic

Which CCBs work at intermediate specificity ?

Benzothiazepines

Example of a Benzothiazepines?

Diltiazem

What is the common indications for cardiac CCBs?

Anti-arrhythmic

Which CCBs work at cardiac muscle?

phenylalkylamines

Example of phenylalkylamines?

Verapamil

When are CCBs first line?

Over 55, African/ Caribbean origin

What is the difference between the 2 main vascular selective dihydropyridines?

Nifedipine fast acting, amlodipine slow acting

How do potassium channels control membrane potential?

In smooth muscle, when the muscle is depolarised can leak out potassium to get membrane hyperpolarisation, shutting down voltage gated calcium channels leading to vasorelaxation

What is potassium channels regulation linked to?

Intracellular ATP, linked to cell metabolism, higher cytosolic ATP keeps K channels closed

What are potassium channel activators mode of antihypertensive action?

Membrane hyperpolarisation, closure of L type VACCs, vasorelaxation

How many parts in the potassium channel made up of?

2 parts

How many subunits does the potassium channel have?

4 and a sulfonylurea that has nuclear binding areas which sense ADP

Name examples of potassium channel blockers?

Minoxidil

What are the indications for minoxidil?

Severe resistant hypertension

What are the adverse effects of minoxidil?

Reflex tachycardia, fluid retention, diabetes, hirsutism

What is the systemic effects of hydralazine?

Dilation of arteries and arterioles, decrease of TPR

What are the indications for hydralazine?

Severe hypertension in pregnancy, heart failure in patients of AC origin

Why may some people have low sensitivity to hydralazine?

Polymorphism in the liver enzyme involved in N-acetylation

What are the adverse effects of hydralazine?

Lupus, tachycardia, palpitations, hypotension and peripheral oedema

What are drugs that work on the sympathetic nervous system?

Beta Blockers, alpha 1 antagonists

What are the central acting drugs?

alpha 2 agonists, imidazoline agonists, ganglion blockers, adrenergic neuron blockers

Name some of the common beta blockers?

Atenolol, metoprolol, propranolol

What is the antihypertensive mechanism of beta blockers?

Block B1 adrenoceptors in the heart and kidney, preventing relax tachycardia and renin release

What are the addition benefits with nebivolol?

B1 selective, stimulates NO release in vascular endothelium

What are the addition benefits with pindolol?

B1 selective partial agonist at low sympathetic activity

What are the addition benefits with carvedilol?

Non selective B blocker, a1 antagonism

What are the therapeutic indications of beta blockers?

Resistant hypertension, severe hypertension in pregnancy

Adverse effects of beta blockers?

Bronchoconstriction, reduced hypoglycaemia awareness, bradycardia, negative inotropic effect in the heart, fatigue, cold, erectile dysfunction

What is the mechanism of anti-hypertension of alpha 1 blockers?

Inhibition of post synaptic a1 adrenoceptors, causing arterial dilation reducing TPR ad reduced pre load, less reflex tachycardia

What are the therapeutic uses of alpha blockers?

Severe resistant hypertension

What are the adverse effects of alpha blockers?

First dose hypotension, dizziness, fatigue

Name the common alpha 1 selective blockers?

Doxazosin, Prazosin

Name the a2 adrenoceptor agonists?

Clonidine used in the treatment of insomnia and opioid withdrawal and a-methyldopa can get rebound hypertension on withdrawal, reduction of sympathetic outflow

Name the I1 receptor agonists?

Moxonidine

What is moxonidine indictaed for?

Mild to moderate essential hypertension when other medication cannot be used,

Where does moxonidine work?

rostral ventro-lateral pressor and ventromedial depressor areas of the medula oblongata, reduction of sympathetic outflow

What are the adverse effects of central acting drugs?

Can cause respiratory depression via acting on respiratory centre in medulla, activating pre synaptic a2 adrenoceptors

What are the therapeutic uses of moxonidine?

Resistant hypertension

What are the therapeutic uses of a-methyldopa?

Severe hypertension in pregnancy

What are the therapeutic uses of clonidine?

rarely used in hypertension, migraine, insomnia, opioid withdrawal

What are the adverse effects of the central acting hypertensives?

Rebound hypertension, dry mouth, sedation and drowsiness (less moxonidine) respiratory (clonidine), immune haemolytic (anaemia with methyldopa), liver toxicity (hepatitis methyldopa)

Name the ganglion blockers

Trimetaphan

Describe the characteristics of Trimpetaphan?

Competitive N Ach receptor antagonist, sulphonium compound, does not cross BBB, both para/symph systems

Adverse effects of trimethaphan?

Largely obsolete as a antihypertensive, cause reflex tachycardia, postural hypotension, cycloplegia

Name the adrenergic neuron blocking drugs

Guanethidine, reserpine

What is Guanethidine mechanism?

Taken up by MET and VMAT depleting vesicles of NA in synapse, meaning less sympathetic affect

What is the reserpine mechanism?

Taken up by NET, irreversibly inhibits VMAT preventing NA in vesicles, blocking

What are the therapeutic uses of guanethidine?

In hypertensive crisis IV

What are the therapeutic us es of reserpine?

Clinically obsolete, used in combination with diuretics in developing countries