SNS antagonists Flashcards
what do alpha 2 receptors do to NE release?
- there are pre-synaptic alpha 2 receptors
- alpha 2 receptors have a -ve feedback on NE release
what do alpha 1 receptors do?
vasoconstriction
relaxation of GIT
what do alpha 2 receptors do
inhibition of NT release,
contraction of VSMC,
CNS
what do beta 1 receptors do?
cardiac stimulation,
relaxation of GIT,
renin release
what do beta 2 receptors do?
bronchodilation,
vasodilation,
relaxation of VSMC,
hepatic glycenolysis
what do beta 3 receptors do?
lipolysis
name a non selective (alpha 1 and beta 1) adrenoreceptor ANTAGONIST
labetol
name an alpha 1 and beta 2 ANTAGONIST
phentolamine
name an alpha 1 antagonist
prazosin
name a beta 1 and 2 selective antagonist
propanolol
name a beta 1 selective anatagonist
atenolol
what is hypertension?
- underlying cause rarely diagnosed
- defined as DAMP > 90mmHg
- BP as 140/90mmHg or higher
what are the main elements that control hypertension?
- blood volume
- CO
- TPR
what are the 4 different targets for anti-hypertensives?
- SNS nerves that release vasoconstrictor molecules
- kidney and heart
- arterioles - control/determine TPR
- CNS - determine BP set point, regulate some systems involved in BP control
what are the targets of beta-adrenoceptor antagonists?
- CNS: to reduce sympathetic tone
- Heart (beta 1): reduce ionotropic and chronotropic effect
- kidneys (beta 1): reduce renin prodiction
what are the unwanted effects of beta-adrenoreceptor antagonists?
- bronchoconstriction
- cardiac failure
- hypoglycaemia (beta blockers may mask symptoms, non selective also block hepatic glycogenolysis)
- fatigue (reduced CO)
- cold extremities (loss of beta receptor mediated vasodilation)
- bad dreams
what is propanolol? what does it cause?
- beta 1 and beta 2 selective
- in subject at rest = very little effect
- during exercise can reduce HR, CO and ABP
- as non-selective, produces all typical adverse effects
what is atenolol? what does it do?
- beta 1 selective
- antagonises effects of NE on heart but affects any organ with beta 1
- less effect on airways than non-selective but not safe with asthmatic
- selectivity is concentration dependent (too much and becomes non-selective)
what is labetalol? what does it do?
- alpha 1 and beta 1 dual-action antagonist
- lowers BP via reduction in TPR
- induces reduction in HR or CO –> wanes with chronic use
what is the problem with alpha-adrenoreceptor?
- fall in arterial pressure (as alpha receptors are main mediators of TPR)
- problem with postural hypotension
- as there is a fall in TPR, you get reflex tachycardia
what is phetolamine and what does it cause?
- non selective alpha-antagonist
- causes vasodilation and fall in BP
- but simultaneous blockade of alpha 2 receptors tends to inc. NE release
- this enhances reflex tachycardia
- inc. GIT motility and diarrhoea common
- no longer clinically used
what is prazosin and what does it cause?
- alpha 1 antagonist
- causes vasodilation, fall in BP
- less reflex tachycardia as don’t block alpha 2 receptors to inc. NE release
- dramatic hypotenive effect
- causes a modest dec. in LDL and inc. in HDL = GOOD
how is methyldopa an antihypertensive medication?
- methyldopa taken up by noradrenergic neurones
- methyldopa is decarboxylated and hydroxylated to form alpha-methyl-NA (false NT)
- methyldopa not broken down within neuron
- accumulates in larger quantities than NA
- displaces NA from vesicles
what’s the MoA?
- less active than NA on alpha-1 receptors (less effective in causing vasoconstriction)
- more active on presynaptic alpha 2 receptors (more -ve feedback on NE release)
- minor effects on CNS
what are the benefits of methyldopa?
- renal and CNS blood flow maintained –> used in pt with renal insufficiency or CNS disease
- recommended in hypertensive pregnant women –> no adverse effects on foetus
what are the adverse effects of methyldopa?
- dry mouth
- sedation
- orthostatic hypotension
- male sexual dysfunction
what is the main cause of arrythmias?
- myocardial ischaemia
what is propanolol?
- non selective beta antagonist class II drug
- reduces mortality of pt with MI
- partially successful in arrhythmias that occur during exercise/mental stress
what is angina?
pain that occurs when the O2 supply to myocardium is insufficient for its needs
where does the pain spread in angina?
- spreads down dermatome T1 in chest, arm, and neck
- bought on by exertion of excitement
what are the types of angina?
- stable: pain on exertion - due to fixed narrowing of coronary vessels
- unstable: pain with less exertion and with pain at rest - thrombus but without complete occlusion of artery
- variable: occurs at rest, caused by coronary artery spams, ass/ w. atheromatous disease
how do beta adrenoreceptor antagonists reduce myocardial demand?
- by decreasing ionotropic and chronotropic effect
- at low doses does not affect bronchial SM, systolic BP
- reduces oxygen demand whilst maintaining effort
what are the adverse effects of beta-adrenoceptor antagonist’s?
- fatigue
- insomia
- dizziness
- sexual dysfunction
- bronchospasm
- bradycardia
- heart block
- hypotension
what is glaucoma caused by?
- poor drainage of aqueous humour
- can permanently damage optic nerve
describe the production of aqueous humour
- produced by blood vessels in ciliary body via actions of carbonic anhydrase
- production is indirectly related to BP
describe the flow of aqueous humour
posterior chamber –> through pupil to anterior chamber –> trabecular meshword and into veins and canal of Schlemm
what beta adrenoceptor antagonists are used in glaucoma treatment? what do they do?
- non selective block of beta 1 and 2
- timolol maleate, corteolol hydrocholride
- reduce rate of aqueous humour formation by blocking receptors on ciliary body
