Adrenoreceptor Antagonists

Question 1

A1 receptor activation causes

Answer 1

Vascular smooth muscle conraction
Bladder contractino
INtestinal relaxation
Glycogenolysis
DEcreased insulin + glucagon secretion

Question 2

A1 recepto works how?

Answer 2

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

Question 3

What happens when a2 receptors are activated

Answer 3

Gi coupled. ie activation inhibits adenylyl cyclase, decrease in intracellular calcium ions

Question 4

What effects does stimulation of a2 have?

Answer 4

Reduced NA release
Vasodilation
vasoconstriction of veins
PLatelet aggregation
intestinal relaxation

Question 5

B adrenoreceptors are all what type?

Answer 5

Gs protein coupled

Question 6

B1 adrenoreceptor activation effects

Answer 6

Increases HR + positive inotropy
INcreased renin secretion
Lipolysis

Question 7

B2 adrenoreceptor activation causes?

Answer 7

Smooth muscle relaxation (vascular, bronchiolar and intestinal)
Glycogenolysis + increases insulin/glucagon secretion

Question 8

B3 receptor activation causes?

Answer 8

Lipolysis and thermogenesis

Question 9

Examples of selective a1 antagonists?

Answer 9

Pazosin
Doxazosin
Terazosinh

Question 10

WHat are selective a1 antagonists used for?

Answer 10

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

Question 11

Side effects of selective a1 antagonists

Answer 11

Severe post. hypotension
SYncope
Dizziness
Peeing more

Question 12

What is phentolamine?

Answer 12

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

Question 13

Side effects of phentolamine?

Answer 13

Nasal congestion (bv in nose vasodilate)
Sulphites can cause bronchospasm in asthmatics
Raises insulin levels so can cause hypolgycaemia

Question 14

What is phenoxybenzamine?

Answer 14

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

Question 15

NOn selective B blocker examples?

Answer 15

Carvedilol, labetolol, pindolol, propranolol, timolol

Question 16

Selective B1 recetpor antagonism

Answer 16

Atenolol, metoprolol, esmolol, nebivolol

Question 17

B blocker physiological effects

Answer 17

Negative inotropy and chronotropy
Reduces sa node automaticity
Decreases AV conduction
Increases time in diastole increasing oxygen supply to the myocardium

Question 18

INdications for B blockers

Answer 18

IHD- post MI
Arrhythmias
Thyrotoxicoisis
ANxiety
Migraine prophylaxis
Glaucoma

Question 19

S/E of B blockers

Answer 19

Reduced peripheral circulation and cool extremities
CAn cause bronchospasm in susceptible indiciduals
Masks hypoglycaemia
Increased uterine tone

Question 20

Esmolol properties

Answer 20

Cardioselective
Fast onset and offset
can also be given as an infusion

Question 21

Labetolol MOA

Answer 21

Selectively antagonises a1 and B adrenoreceptors
1:3 A:B when given orally
1:7 A:B when given IV

Question 22

Pharmacokinetics og labetolol

Answer 22

SIg. first pass effect
50% protein bound
Metabolised in liver
(made of 4 isomers)

Question 23

Indications for labetolol?

Answer 23

Anti HTN especially in pregnancy

Question 24

What is a phaeochromocytoma and what does it produce

Answer 24

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