SNS Antagonists Flashcards
What do alpha 1 receptors generally do?
Vasoconstriction, relaxation of GIT
What do alpha 2 receptors generally do?
Inhibit transmitter release, contraction of vascular smooth muscle, CNS actions
What do beta 1 receptors generally do?
Increase cardiac rate and force, relaxation of GIT, renin release from kidney
What do beta 2 receptors generally do?
Bronchodilation, vasodilation, relaxation of visceral smooth muscle, hepatic glycogenolysis
What do beta 3 receptors generally do?
Lipolysis
Give an example of a totally non-selective adrenoceptor antagonist?
Carvedilol
Give an example of an alpha adrenoceptor antagonist?
Phentolamine
Give an example of an alpha 1 adrenoceptor antagonist
Prazosin
Give an example of a beta adrenoceptor antagonist?
Propanolol
Give an example of a beta 1 adrenoceptor antagonist?
Atenolol
What is hypertension defined as?
Blood pressure consistently above 140/90mmHg when sitting or lying down as an average 30 year old male
What is the single most important risk factor for stroke, myocardial infarction and chronic kidney disease
Hypertension
What are the main contributors to hypertension?
Blood volume
Cardiac output
Vascular tone
Where are the tissue targets for antihypertensive drugs
The heart Sympathetic nerves that release NA Kidney - blood vol and vasoconstriction Arterioles - determine TPR CNS - determines BP set point and regulates some systems involved in blood pressure control and autonomic NS
What do beta blockers target
Beta 1 receptors on:
Heart, Sympathetic nerves, Kidney, CNS control of BP
Beta 2 receptors on:
Sympathetic nerves and CNS
What do beta blockers do in the heart?
Decrease HR and force of contraction leading to a decrease in CO. The heart does not have to work as hard - reduced BP
How do beta blockers work in the heart
Beta receptors positively coupled with adenylate cyclase, leading to ATP -> cAMP -> PKA. Block the beta receptor so decrease PKA
What do beta blockers do in the kidney?
Block sympathetic nerve receptors so decrease renin production, leading to a decrease in angiotensin II release. Loss the vasoconstriction effect and aldosterone production increases
What will a blockade of the facilitatory effects of presynaptic nerve terminals beta adrenoceptors do?
decrease NA secretion
Noradrenaline causes vasoconstriction
What are examples of beta blockers?
Propanolol Carvedilol Atenolol Nebicolol Sotalol
What does propanolol have affinity to?
Equal affinity for beta 1 and beta 2 receptors
What does carvedilol have affinity to?
It is a mixed beta and alpha receptor
What are the cardioselective beta blockers?
Beta 1 selective agents eg atenolol and pindelol
Never totally selective to one receptor, there is always some affinity to the others too
What other effect does the beta blocker nebivolol have?
Also potentiates NO
selective to b1
What other effect does the beta blocker Sotalol have?
Aso inhibits K+ channels
It is also non selective so has affinity to beta 1 and 2
Side effects of beta blockers?
Bronchoconstriction - dont give to asthmatics and COPD
Cardiac failure - needs some sympathetic drive to the heart
Hypoglycemia - mask the symptoms of hypoglycemia/inhibit glycogen breakdown
Fatigue - decrease cardiac output and muscle perfusion
Cold extremities - loss of b receptor mediated vasodilation in cutaneous vessels
Bad dreams
What is the advantage of atenolol over propanolol?
Atenolol is more b1 specific so it won’t affect the liver and lungs as much as they are b2 driven - asthmatics and diabetics
What are beta 2 liberated responses in lungs and liver
Lungs - dilate airways
Liver - liberate glucose
What advantage does carvediol have over atenolol and propranolol?
It targets a1 too making a more powerful hypotensive effect due to vasodilator properties so decrease TPR (more side effects too)
What protein receptor is linked to a1 receptors? what else are a1 receptors linked to?
Gq linked and PLC and calcium influx
What is the effect of a2 receptors and why?
linked to AC which decreases PKA and cAMP due to it being linked to the inhibitory G protein Gi
When is a non selective alpha blocker used?
To treat phaechromocytoma induced hypertension (tumour in adrenal medulla that pumps out adrenaline)
What is an example of a non selective alpha blocker?
phentolamine
When is an alpha 1 specific blocker used?
Inhibit the vasoconstrictor activity of NE - which has modest blood pressure lowering effects and is only used as adjunctive treatment
What is an example of an alpha 1 specific blocker?
Prazosin
What are side effects of phentolamine
GI - increase in function leading to diarrhoea
Why do alpha 2 receptors reduce the effectiveness of phentolamine?
Alpha 2 receptors blocked, reduce negative feedback, so more NA released in synapse which makes competitive reaction between NA and phentolamine and its ability to block
Why do baroreceptors reduce the effectiveness of phentolamine?
If interfere with vasculature - dilate blood vessels and baroreceptor responses fall, lose vagus nerve activity therefore increases sympathetic activity, so SV increases
Give an example of a false transmitter
Methyldopa
What does methyldopa replace
DOPA in the noradrenaline pathway leading to the formation of alpha methyl noradrenaline
What is the difference between alpha methyl noradrenaline and noradrenaline?
Less active with beta/alpha 1 receptors and more selective to alpha 2 - more neg feedback effect. Also not well metabolised by MAO - so more likely to accumulate and displace NA in the vesicle
Why is alpha methyl noradrenaline not being metabolised by MAO relevant and useful?
It accumulates in larger quantites than NA therefore can displace NA from vesicles
Method of action of methyldopa
- Less active than NA on a1-receptors – less effective in causing vasoconstriction.
- More active on presynaptic a2-receptors – more negative feedback on NE release.
- Some minor effects on CNS – stimulates vasopressor centre.
Methyldopa side effects
Salivary glands - dry mouth
Blood vessels - causes so much hypotension (even tho thats what you want) that it can be limiting
What is the main cause of arrhythmias?
Myocardial ischemia (damage to heart tissue itself)
What can exacerbate the problem of a arrhythmia?
Increased sympathetic activity so you want to normlaly slow the heart down
Why are beta blockers usually used to treat arrhythmias?
b1 drives heart rate and contraction
What drug generally used for arrhythmias?
Propranolol
What are the characteristics of a stable angina?
Pain on exertion. Increased demand on the heart. There is still enough blood flow at rest to match tissue demand
What is a stable angina due to?
Fixed narrowing of the coronary vessels eg atheroma
What are the characteristics of an unstable angina?
Pain with less and less exertion, culminating with pain at rest
What is an unstable angina due to?
Platelet-fibrin thrombus associated with a ruptured atheromatous plaque, but without complete occlusion of the vessel. There is risk of infarction
What are the characteristics of a variable angina
Occurs at rest
What is a variable angina?
Coronary artery spasm - associated with atheromatous disease
How can beta blockers be used to treat an angina?
At low doses the b1 selective agents eg metoprolol reduce HR and myocardial contractile activity without affecting bronchial smooth muscle. This reduces oxygen demand whilst maintaining the same degree of effort
What is a glaucoma characterized by?
Increased intraocular pressure
What is a glaucoma caused by?
Poor drainage of the aqueous humour
What happens if a glaucoma is left untreated?
It permanently damages the optic nerve leading to blindness
How do beta blockers treat glaucoma?
b1 receptors are coupled with carbonic anhydrase. If block b1 then stop the carbonic anhydrase making bicarbonate ions that contribute to the ciliary body making aqueous humour
