9 - SNS Antagonists Flashcards
Outline what the adrenoceptor subtypes do
a1 - vasoconstriction, relaxation of GIT
a2 - inhibition of NT release, contraction of vascular smooth muscle, CNS actions
b1 - increased cardiac rate and force, relaxation of GIT, renin release from kidney
b2 - bronchodilation, vasodilation, relaxation of visceral smooth muscle , hepatic glycogenolysis
b3 - lipolysis
List the adrenoceptor subtypes and selective drugs for each
Non - selective (a1 + b1) - carvedilol
a1 + a2 - phentolamine
a1 - prazosin
b1 + b2 - propanolol
b1 - atenolol
List the 4 clinical uses of SNS antagonists
- Hypertension
- Arrhythmias
- Angina
- Glaucoma
Outline the treatment of hypertension using SNS antagonists
BP = CO x TPR
Hypertension is > 140/90 lying down
Main contributors are blood volume, CO and vascular tone
Therefore main targets are heart and kidney (b1), sympathetic nerves that release NorA (b1/b2), CNS (b1/b2)
How do beta blockers work?
They decrease HR and FOC. They also decrease renin secretion and therefore ATII as ATII is a potent vasoconstrictor and increases aldosterone production (which increases sodium reuptake)
N.B. Blockade of he facilitatory effects of presynaptic b adrenoceptors on noradrenaline release may also contribute to the antihypertensive effect
Name the types and give examples of beta blockers
Non-selective b1 + b2 propranolol
Cardio-selective b1 atenolol, pindolol
Mixed b-a b1+b2, a carvedilol (additional vasodilator properties)
Other: Nebivolol b1; also potentiates NO
Sotalol b1+b2; also inhibits K+ channels
What are some side effects of beta blockers
Bronchoconstriction - Asthma/COPD
Cardiac failure - need some sympathetic drive to heart
Hypoglycaemia - masks the symptoms of hypoglycaemia + inhibits glycogenolysis
Fatigue - decreased cardiac output and muscle perfusion
Cold extremities - loss of beta receptor mediated vasodilation in cutaneous vessels
Bad Dreams
N.B. Cardio-selective agents have less side effects than non-selective ones.
Describe the transduction systems of the two alpha adrenoceptors
a1 - Gq linked -(PLC-PIP2)- IP3+DAG (Ca2+ + PKC)
Postsynaptic on vascular smooth muscle
a2 - Gi linked - presynaptic autoreceptors inhibiting NorA release
Outline the properties and reduced clinical usage of alpha blockers
a1 - Prazosin - antihypertensive but is less powerful and only used as adjunctive treatment
Non-selective - Phentolamine - used to treat pheochromocytoma (tumour in adrenal medulla that produces A)
Why does a2 receptor blockade reduce the effectiveness of Phentolamine?
a2 receptor blocked
negative feedback inhibited
more NorA secreted
competitively competes w/Phentolamine
Why does baroreceptor firing reduce the effectiveness of Phentolamine?
Baroreceptor firing provides a homeostatic response to a change in BP through increased sympathetic stimulation
Outline the properties and reduced clinical usage of methyldopa
a2 agonist
Not metabolised very well by MOA
Used as an antihypertensive (very powerful)
- kidney disease
- cerebrovascular disease
Side effects - hypotension, profoundly dry mouth
Outline the treatment of arrhythmias using SNS antagonists
Arrhythmias are usually caused by damage to the heart, myocardial ischemias
Increased sympathetic drive precipitates arrhythmias, AV conductance is dependent on sympathetic activity, if heart is not efficiently filling up and ejecting blood, speeding up will make this worse
Outline the treatment of angina using SNS antagonists
Starts as stable angina (matched)
“heart stitch”
Nearly always caused by atherosclerosis
Stable - pain on exertion, increased demand on heart
Unstable - pain w/ less and less exertion, risk of infarction*
Variable- occurs at rest, coronary artery spasm
*platelet fibrin thrombus associated w/ a ruptured atheromatous plaque but w/out complete occlusion of the vessel.
b1 selective agents (metoprolol) reduce HR and contractile activity w/out affecting bronchial smooth muscle
N.B. BBs impair ability to exercise
Outline the treatment of glaucoma using SNS antagonists
b1 receptors coupled to carbonic anhydrase (which produces aqueous humour) so inhibition of b1 receptor stops production of bicarbonate ions
