SNS antagonists Flashcards
What is the function of a1, a2, b1, b2, b3?
a1 - vasoconstriction, relaxation of the GIT
a2 - inhibition of transmitter release, contraction of vascular smooth muscle, CNS actions. (negative feedback role - tend to inhibit sympathetic function)
b1 - increased cardiac rate and force, relaxation of GIT, renin release from kidney
b2 - bronchodilaiton, vasodilation, relaxation of visceral smooth muscle, hepatic glycogenolysis
b3 - lipolysis
Describe the a2 receptor?
Negative feedback receptor found on the presynaptic neurone. When activated they inhibit neurotransmitter release. They decrease the amount of NA released into the synapse; used to make sure the effect doesn’t last for too long.
List some adrenoceptor antagonists?
Mixed blocker: (a1+b1) carvedilol Non-selective: Class selective but not subtype selective (a1+a2) phentolamine (b1+b2) propranolol Subtype selective: e.g b1-selective or a1-selective (a1) Prazosin (b1) Atenolol
Describe hypertension and the SNS antagonists
Physiology: BP = CO x TPR (usually TPR that causes hypertension). The main contributors to BP are blood volume, cardiac output and vascular tone.
Hypertension is defined as consistently being above 140/90 mmHg
See notes for risks - HF & MI, stroke, KD
Beta-blockers: predominately block b1
Heart - decrease CO (reducing HR and contractility). Blocks b1
Sympathetic nerves - that release the vasoconstrictor molecule. Blockts b1/b2
Kidney - blood volume/vasoconstrictor. Target the renin angiotensin aldosterone system. Blocks b1
Arterioles - determine PR
CNS - determines BP set point and regulates some systems involved in BP control and autonomic NS. Blocks b1/b2
See lectures
Beta blockers have been superceded by ACE inhibitors, calcium channel blockers and diuretics due to the large side effect profile of beta blockers
What are some examples of beta blockers?
Propanolol: equal affinity for b1+b2 receptors
Atenolol: more selective for b1 receptors
Carvediol: mixed b and a blocker (b1,b2 & a1). Tha a1 blockage gives extra vasodilator properties
Nebivolol: b1 + potentates NO
Sotalol: b1 + b2 + inhibits K+ channels
What are the negative side effect profile of beta blockers?
Bronchoconstriction - Asthma/COPD (even selective agents can bind to b2 to some extent)
Cardiac failure - need some sympathetic drive to the heart especially for heart failure
Hypoglycemia - for diabetics they know they are having a diabetic episode from sympathetic effects e.g tremors. Beta blockers can block those symptoms so they don’t know they are having an episode. They block glycogenolysis and gluconeogenesis
Fatigue - decreased CO and muscle perfusion (based off b2)
Cold extremities - loss of beta receptor mediated vasodilation in cutaneous vessels
Bad dreams
What is the advantage of atenolol over propranolol?
b1 selective so it is ‘cardioselective’ you lose all the negative b2 side effects. E.g bronchoconstriction is the lungs which is a b2 mediated effect
In practice this may not always work.
What advantages does carvedilol have over propanolol and atenolol?
b1 - heart and kidney
a1 - vasoconstriction
Carvedilol targets more receptors so more effects of reducing blood pressure
Briefly describe a1 and a2 receptors?
a1 - g-protein linked, postsynaptic membrane on vascular smooth muscle, PLC linked
a2 - g-protein linked, presynaptic autoreceptors inhibiting NA release
Clinical pharmacology:
Non-selective a-blocker: Phentolamine - used to treat phaechromocytoma-induced hypertension
a1 specific blocker: prazosin inhibit the vasoconstrictor activity of NA
What are the side effects of phentolamine?
Non-selective a-blocker - GI side effects, constipation
Why do a2 receptors and baroreceptors reduce the effectiveness of phentolamine?
Block a1 receptor - good prevents vasoconstriction
Block a2 receptor - bad prevents the negative feedback effect of NA so more NA is released into the synapse. NA competes with the phentolamine - out competing
Reduced blood pressure –> affects the baroreceptor reduced firing so the CO increases and SV.
Reduces the effects of phentolamine. This is bad if hypertension is associated with heart problems
What is a false transmitter?
It replaces the endogenous transmitter. Methyldopa replaces dopa in the synthesis of NA. The final product is methylNA which is less active at adrenoceptors. It is not metabolised by MAO and is more likely to accumulate and displace NA in the vesicle.
It is better agonist on a2 receptors than NA so it decreases the sympathetic nerve release of NA. Enhancing the negative feedback first.
They don’t great to a1, b1 and b2
What are the main uses of methyldopa?
Improves blood flow - effective anti-hypertensive.
Used in renal - treats kidney disease
CNS - cerebrovascular disease
What are the side of effects methyldopa?
Affects the salivary gland - dry mouth
Postural hypotension - because they are so good at what they do
Describe arrhythmias
Abnormal or ireegular heart beats - 350,000 deaths in the US alone mainly caused by myocardial ischaemia. CO falls because blood flow is suboptimal in the heart.
b1 - increase sympathetic drive to the heart - so the precipitate arrhythmias. Beta blockers slow the heart rate giving more time for the heart to fill effectively with blood for increased CO.
b1 - conductance dependent on sympathetic activity
