Pharmacology 9 - SNS antagonists Flashcards
List the functions of a1 adrenoreceptors
- Vasoconstriction
- Relaxation of GIT
List the functions of a2 adrenoreceptors
- Inhibition of transmitter release
- Contraction of vascular smooth muscle
- CNS actions
List the functions of B1 adrenoceptors
- Increased cardiac rate and force
- Relaxation of GIT
- Renin release from kidney
List the functions of B2 adrenoceptors
- Bronchodilation
- Vasodilation
- Relaxation of visceral smooth muscle
- Hepatic glycogenolysis
List the functions of B3 adrenoceptors
Lipolysis
List the adrenoceptor antagonist drugs
- Non-selective drugs, eg. Carvedilol (a1 and B1)
- Non-selective alpha eg. phentolamine (a1 and a2)
- Prazosin (a1)
- Non-selective beta eg. propanolol (B1 and B2)
- Atenolol (B1)
List the tissue targets for anti-hypertensive drugs
- The heart - cardiac output
- Sympathetic nerves (which release noradrenaline)
- The kidney (blood volume and vasoconstriction)
- Arterioles
How are beta blockers useful in hypertension treatment?
- B1 blockers block the heart
- B1/B2 block nerves that release noradrenaline
- B1 blocks kidney
- B1/2 blocks CNS control of blood pressure
- Decreased heart rate, force of contraction and cardiac output
- Decreased renin and angiotensin II (vasoconstrictor and increases aldosterone production)
List the beta blockers that could be used in blood pressure treatment
- Non-selective (eg.propanolol)
- B1 selective (atenolol)
- Mixed B-a blockers (carvediolol - alpha 1 blockade gives additional vasodilator properties)
Others
- Nebidolol (also potentiates NO - vasdilator)
- Sotalol (inhibits potassium channels)
List the side effects of beta blockers
- Bronchoconstriction (important in asthma and COPD)
- Cardiac failure
- Hypoglycaemia (masks the symptoms of hypoglycaemia and inhibits glycogen breakdown)
- Fatigue (decreased muscle perfusion and CO)
- Cold extremities (loss of B-receptor mediated vasodilation)
- Bad dreams
What is the advantage of atenolol over propanolol?
- Atenolol is beta 1 selective, so therefore is less likely to cause the more serious side effects
- Eg. asthmatics bronchoconstriction and diabetics hypoglycaemia
What is the advantage of carvedilol over atenolol and propanolol?
- Lowers blood pressure by reducing peripheral resistance
- This is by blocking constriction of arterioles
List the uses of alpha blockers
- No selective a-blocker (phentolamie) treats phaechromocytoma-induced hypertension
- a1 specific blockers (prazosin) inhibits vasoconstrictor activity of NE
- Modest blood pressure lowering effects
Why do alpha 2 receptors and baroreceptors reduce the effectiveness of phentolamine?
- If phentolamine is non-selective it will block the alpha 2 receptor as well as alpha 1, reducing negative feedback so there is increased noradrenaline release
- Low baroreceptor firing rate as blood pressure decreases reduces the vagus nerve stimulation, therefore increasing the cardiac output and stroke volume via increased sympathetic stimulation.
What is methyldopa?
- A false transmitter that produces a-methylnoradrenaline rather then noradrenaline
- Alpha methylnoradrenaline is released into the synapse, it is selective for alpha 2 receptors, the main effect is therefore negative feedback to noradrenaline release
- It is not broken down by MAO, so the concentration gradient is reduced and therefore a-methylnoradrenaline remains in the synapse and acts for longer periods of time than noradrenaline
List the functions of methyldopa
- Improved blood flow
- Anti-hypertensive
- Useful when hypertension is contributing towards kidney disease and cerebrovascular disease
How are adrenoceptors important in arrhythmias?
- Increase sympathetic drive to the heart precipitates arrhythmias (B1)
- AV conductance is dependent on sympathetic activity (B1)
What drug is used to treat arrhythmias?
Propanolol
List the types of angina
- Stable (pain on exertion due to narrowing of the coronary vessels)
- Unstable (pain with less and less exertion until there is pain at rest)
- Variable (occurs at rest caused by coronary artery spasm)
How can beta blockers be used in angina treatment?
- Reduce heart rate and myocardial contractile activity (without affecting bronchial smooth muscle at low doses)
- Reduces oxygen demand while maintaining the same degree of effort
- Uses beta 1-selective agents such as metoprolol
How are beta blockers useful in glaucoma treatment?
- Ciliary body endothelial cells produce aqueous humour via beta 1 receptors and carbonic anydrase
- Therefore, production of aqueous humour decreases when the beta 1 receptors are blocked
What does hypertension contribute towards?
- Most important risk factor for stroke (50% ischaemic stroke)
- Risk factor for heart failure (25% of cases, 70% in the elderly), MI, and kidney disease
List the main contributors to hypertension
- Blood volume
- Cardiac output
- Vascular tone
Which receptors can be blocked on the presynaptic neuron to reduce hypertension?
- Beta receptors on the presynaptic nerves increase noradrenaline release
- Useful in the fight or flight response (as they are more sensitive to adrenaline)
Which type of receptors are alpha 1?
- Gq-linked
- Increase calcium influx and as a result contraction
List the side effects of alpha blockers
Increased GI motility, causing diarrhoea
List the side effects of methyldopa
- Hypotension as it is so effective
- Causes a profound dry mouth (as it blocks saliva production)
Define arrhythmia
Any kind of abnormal or irregular heart beat
