Download Pharmacology 6 – SNS Antagonists

Pharmacology 6 – SNS Antagonists
Anil Chopra
1. Name common examples of non-selective and selective SNS antagonists and what
are they clinically used for.
2. How do SNS antagonists produce their anti-hypertensive effects and what are
their side effects.
3. Compare the effects produced by selective and non-selective antagonists, name
examples of each drug.
4. What other beneficial effects does Prazosin have which is increasing its popularity
as an anti-hypertensive.
5. Describe the actions of the false transmitter methyldopa and what are its clinical
uses and side effects.
6. How can SNS antagonist drugs be used to treat arrhythmias and angina.
7. What is glaucoma and how is the aqueous humor formed in the eye.
8. Describe how SNS agonists and antagonists can be used in the treatment of
glaucoma. What other drugs can be used to treat glaucoma and by what
mechanisms do they work.
Sympathetic nervous system antagonists target both post-synaptic and pre-synaptic
receptors.
Types of Adrenoceptors
 α1- Vasoconstriction, Relaxation of GIT, salivary secretion.
 α2 - Inhibition of transmitter release, contraction of vascular SM, CNS actions.
 β1- Increased cardiac rate and force, relaxation of GIT.
 β2- Bronchodilation, vasodilation, relaxation of visceral smooth muscle, hepatic
glycogenolysis
 β3- Lipolysis
Names
 Non-selective: (α1+ β1) Labetalol
 α1+ α2 : Phentolamine
 α1: Prazosin
 β1 + b2: Propranolol
 β1: Atenolol
 False transmitter: methyldopa
Usage
 Hypertension:
o A sign rather than disease
o Sustained diastolic pressure over 90mmHg
o Elements that contribute to hypertension
 High blood volume
 Increase cardiac output
 Peripheral Vascular tone
o Sites for Antihypertensives
 Sympathetic nerves
 Kidney (regulation of blood volume)
and renin release.



Heart
Arterioles(peripheral
resistance vessels)
CNS (determinants of blood
pressure)
 Cardiac Arrhythmias
o Abnormal or irregular heart
beats
o Caused by myocardial ischaemia
o Increases in sympathetic tone can
precipitate or aggravate cardiac arrhythmias.
o Propanolol is a particularly effective drug.
 Angina
o Pain, that occurs when the oxygen supply to the myocardium is insufficient for
its needs.
o Pain distribution - chest, arm, neck.
o β-blockers effect drugs.
 Modify Plasma Lipid levels
o α1 antagonists are particularly useful at changing the ratio of LDLs and
HDLs.
 Glaucoma
o Characterized by increase in intraocular pressure.
o Caused by poor drainage of the aqueous humour.
o If untreated, it permanently damages the optic nerve, blindness.
o Non-selective β-antagonists are effective as they reduce the rate of
aqueous humor formation.
Mode of Action
β Blockers
Labetolol
- Blocks both β1 and α1 receptors.
- Lowers blood pressure by lowering peripheral resistance
- Does not change heart rate or cardiac output.
Propanolol
- Non- selective (β1 and β2) – the first β-blocker.
- Causes little change at rest (only really has an effect when exercising /stress)
Atenolol
- Cardioselective i.e. Targets specifically β1 receptors
- Antagonises noradrenaline on heart mainly
- Other organs affected – kidney.
- Not appropriate for asthmatics
- Slight effect on airways.
α Blockers
Phentolamine
- Non selective for α adrenoceptors i.e. blocks α1 and α2 receptors.
- Cause vasodilation and fall in blood pressure – principal target is α1 receptor.
- Blockade of α2 receptors produces side effect.
- Increases Gastro-intestinal tract motility.
- No longer used
Prazoin
- Highly selective for α1 receptors in peripheral resistance vessels
- Vasodilation and reduction of peripheral resistance in peripheral vessels.
- Cardiac output also decreases because of fall in venous pressure.
- Less tachycardia (no α2 action)
- Hypotension is dramatic.
- α1 antagonists cause a slight increase in HDL and lower LDL.
False Transmitter
Methyldopa
- Taken up by adrenergic neurones
- Decarboxylated and hydroxylated to form false transmitter, a-methyl-norepinephrine.
- It is not metabolised by monoamine oxidase and so accumulates in the neurone,
displacing noradrenaline.
- When it is released it has little effect on α1 receptors, but a large effect on α2.
Side effects
β adrenoceptor antagonists
 Bronchoconstriction (β2 receptors also on bronchial smooth muscle)
 Cardiac Failure (patients with heart disease need the sympathetic tone)
 Hypoglycaemia – do not give β2 antagonists to diabetics (block of β2 receptors in
the heart it stops the palpitations before hypoglycaemic attack and liver it stops
the breakdown of glycogen to glucose).
 Fatigue
 Cold extremities
 Bad Dreams
α Adrenoceptor Antagonists
 Reflex tachycardia.
 Postural hypotension
Generally non- selective
- cause a fall in arterial pressure
- common side effect is postural hypotension
- Cardiac output and heart rate increases (reflex response to fall in arterial pressure)
- Blood flow to cutaneous and splanchnic vascular beds increases but the vascular
smooth muscle itself is not affected.
Methyldopa
- Dry mouth
- Sedation
- Orthostatic hypotension.
- Male sexual dysfunction