Adrenoreceptor Antagonists Flashcards
A1 receptor activation causes
Vascular smooth muscle conraction
Bladder contractino
INtestinal relaxation
Glycogenolysis
DEcreased insulin + glucagon secretion
A1 recepto works how?
Gq protein coupled receptor- binding activates phospholipase C
Phospholipase C causes the breakdown of PIP2 to DAG + IP3
IP3 binds to receptors on the SR to trigger calcium ion release
Calcium binds to calmodulin, activating myosin light chain kinase
THis phosphorylates myosin light chains causing activation to allow actin binding + contraction
What happens when a2 receptors are activated
Gi coupled. ie activation inhibits adenylyl cyclase, decrease in intracellular calcium ions
What effects does stimulation of a2 have?
Reduced NA release
Vasodilation
vasoconstriction of veins
PLatelet aggregation
intestinal relaxation
B adrenoreceptors are all what type?
Gs protein coupled
B1 adrenoreceptor activation effects
Increases HR + positive inotropy
INcreased renin secretion
Lipolysis
B2 adrenoreceptor activation causes?
Smooth muscle relaxation (vascular, bronchiolar and intestinal)
Glycogenolysis + increases insulin/glucagon secretion
B3 receptor activation causes?
Lipolysis and thermogenesis
Examples of selective a1 antagonists?
Pazosin
Doxazosin
Terazosinh
WHat are selective a1 antagonists used for?
HTN
Phaeochromocytoma
ccf
Prevent vasoconstrictive effects of NA, causing a fall in SVR without a reflect tachycadia
Can help CO due to reduced afterload
RElaxes bladder muscle
Side effects of selective a1 antagonists
Severe post. hypotension
SYncope
Dizziness
Peeing more
What is phentolamine?
Short acting competitive antagonist of a1 and a2 receptors (3 times more affinity for a1)
IV
Treats hyertensive crises due to excessive sympathetic activity (or phaeo removal eg)Sid
Side effects of phentolamine?
Nasal congestion (bv in nose vasodilate)
Sulphites can cause bronchospasm in asthmatics
Raises insulin levels so can cause hypolgycaemia
What is phenoxybenzamine?
Longer acting alpha blocer with more affintiy for a1 receptors
Can be oral or IV
Pre op phaeo
Irreversible blockade of receptors-half life is 24 hours but effects last until new receptors are produced
NOn selective B blocker examples?
Carvedilol, labetolol, pindolol, propranolol, timolol
Selective B1 recetpor antagonism
Atenolol, metoprolol, esmolol, nebivolol
B blocker physiological effects
Negative inotropy and chronotropy
Reduces sa node automaticity
Decreases AV conduction
Increases time in diastole increasing oxygen supply to the myocardium
INdications for B blockers
IHD- post MI
Arrhythmias
Thyrotoxicoisis
ANxiety
Migraine prophylaxis
Glaucoma
S/E of B blockers
Reduced peripheral circulation and cool extremities
CAn cause bronchospasm in susceptible indiciduals
Masks hypoglycaemia
Increased uterine tone
Esmolol properties
Cardioselective
Fast onset and offset
can also be given as an infusion
Labetolol MOA
Selectively antagonises a1 and B adrenoreceptors
1:3 A:B when given orally
1:7 A:B when given IV
Pharmacokinetics og labetolol
SIg. first pass effect
50% protein bound
Metabolised in liver
(made of 4 isomers)
Indications for labetolol?
Anti HTN especially in pregnancy
What is a phaeochromocytoma and what does it produce
Tumour of the chromaffin cells in the adrenal medulla or other paraganglia of the SNS
COmmonly produces either:
-NA- causing severe HTN refractory to treatment
-ADrenaline or dopamine, causing episodic symptoms
