SNS Antagonists Flashcards
What are alpha1 receptors involved in
Vasconstriction
Relaxation of the GIT
What are alpha2 receptors involved in
Inhibition of transmitter release
Contraction of vascular smooth muscle
CNS actions
What are beta1 receptors involved in
Increased cardiac rate and force
Relaxation of GIT
Renin release from the kidney
What are beta2 receptors involved in
Bronchodilation
Vasodilation
Relaxation of visceral smooth muscle
Hepatic glycogenolysis
What are beta3 receptors involved
Lipolysis
What is the mechanism of SNS synaptic transmission
- norepinephrine
- Release of norepinephrine into synaptic cleft
- alpha1 receptor stimulation
- alpha2-mediated negative feedback
Describe carvedilol targets
Mixed alpha1 and beta1 - non-selective
alpha1 blockade gives additional vasodilator properties
Which receptors does phentolamine target
alpha1 and alpha2
Which receptors does prazosin target
alpha1
Which receptors does propanalol target
non-selective
beta1 and beta2 receptors
equal affinity for both
Which receptors does atenolol target
beta1 selective
How is blood pressure calculated
BP = cardiac output x total peripheral resistance
What is hypertension defined as
Blood pressure is consistently above 140/90
Describe the pathophysiology of hypertension
Important risk factor for stroke, causes about 50% of ischaemic strokes
Accounts for 25% of heart failure cases, increasing to ~70%
Major risk factor for MI and chronic kidney disease
The goal of therapy is to reduce mortality from cardiovascular or renal events
What are the main contributors to blood pressure
Blood volume
Cardiac output
Vascular tone
What are the targets for anti hypertensives
The heart (cardiac output) Sympathetic nerves (release the vasoconstrictor noradrenaline) Kidney (blood volume/vasoconstriction) Arterioles (determine peripheral resistance) CNS (determines blood pressure set point and regulates some systems involved in Blood pressure control & autonomic NS)
What are the targets of beta blockers
heart - b1 (reduce rate and CO)
Sympathetic nerves - b1 + b2
Kidney - b1 (reduce renin production)
CNS - b1/b2 (reduce sympathetic tone)
Why can beta blockers be used to treat hypertension
Reduction in heart rate and - , leading to a reduction in CO
The heart does not have to work as hard and the BP decreases
Reduction in renin and angiotensin II release - vasodilation
Blockade of the facilitatory effects of presynaptic β-adrenoceptors on noradrenaline release may also contribute to the antihypertensive effect.
What are the targets and effects of nebivolol
beta1
Potentiates NO
What are the targets and effects of sotalol
beta1 and beta2
Inhibits potassium channels
What are the unwanted effects of beta blockers
Bronchoconstriction (bad for asthma/COPD)
Cardiac failure
Hypoglycaemia (masks symptoms of hypoglycaemia and inhibit glycogen breakdown)
Fatigue (due to reduction in CO and muscle perfusion)
Cold extremities (loss of beta receptor mediated vasodilation in cutaneous vessels)
Bad dreams
What is the advantage of atenolol over propanolol
Atenolol is b1 selective, avoiding some unwanted side effects
Less effects on the airways
What is the advantage of carvedilol over atenolol and propranolol
Beta-mediated effects on the heart and kidney but also vasodilation from blockage of vasoconstriction in arterioles
Compare alpha1 to alpha2 receptors
a1 - Gq linked (stim), pathway involves DAG and IP3, postsynaptic on vascular smooth muscle
a2 - Gi linked, pathway involves cAMP and PKA, presynaptic auto receptors inhibiting NE release
Describe phentolamine
Non-selective alpha-blocker
Used to treat phaechromocytoma-induced hypertension
Describe prazosin
alpha1 specific blocker
Inhibits the vasoconstrictor activity of NE
Have modest blood pressure lowering effects
Only used as adjunctive treatment
How do non-selective alpha blockers lower blood pressure
Vasodilation to reduce arterial pressure
What are the unwanted effects of non-selective alpha blockers
Postural hypotension
CO and heart rate increases as a reflex to low arterial pressure
Increased blood flow through cutaneous and splanchnic beds
Blockade of alpha2 increases NA release, enhancing the reflex tachycardia
Increased GIT motility -> diarrhoea
Compares phentolamine to prazosin
Less tachycardia from prazosin than non-selective antagonists since they do not increase noradrenaline release from nerve terminals (no a2 actions)
Baroreceptor firing rate decreases -> increases sympathetic activity
Describe methyldopa
Antihypertensive
- Taken up by noradrenergic neurons
- Decarboxylated and hydroxylated to form the false transmitter a-methyl-noradrenaline
- Taken into the pre-synaptic neurone
- Not de-aminated by MAO
- Accumulates in larger quantities and displaces NA from synaptic vesicles
What are the effects of methyldopa
Improved blood flow
Anti-hypertensive
Stimulates vasopressor center in the brainstem to inhibit sympathetic outflow
What are the side effects of methyldopa
Dry mouth
Sedation
Orthostatic hypotension
Male sexual dysfunction
Why are SNS antagonists used for treating arrhythmias
An increase in sympathetic drive to the heart via b1 can precipitate or aggravate arrhythmias
After MI there is an increase in sympathetic tone
AV conductance also depends on sympathetic activity
Refractory period of the AV node is increased by beta-adrenoceptor antagonists. interfering with AV conduction in tachycardias and slowing ventricular rate
How may propranolol be used for arrhythmias
non-selective b-antagonists so reduces mortality of patients with MI
Particularly successful in arrhythmias that occur during exercise or mental stress
What is stable angina
Stable-pain on exertion. Increased demand on the heart and is due to fixed narrowing of the coronary vessels e.g. atheroma
What is unstable angina
Unstable-pain with less and less exertion, culminating with pain at rest.
Platelet-fibrin thrombus associated with a ruptured atheromatous plaque, but without complete occlusion of the vessel.
Risk of infarction.
What is variable angina
Occurs at rest
caused by coronary artery spasm
Associated with atheromatous disease
What is angina
Pain that occurs when the oxygen supply to the myocardium is insufficient for its needs.
Pain distribution - chest, arm , neck.
Brought on by exertion or excitement.
How is angina treated using SNS antagonists
Metoprolol (b-selective) at low doses will reduce heart rate and myocardial contractile activity without affecting bronchial smooth muscle
Reduces oxygen demand whilst maintaining the same degree of effort
What is glaucoma
Characterised by an increase in intraocular pressure
Caused by poor drainage of the aqueous humour
If untreated, it permanently damages the optic nerve, blindness
Describe intraocular fluid drainage
Produced by blood vessels in ciliary body via the actions of carbonic anhydrase.
Flows into posterior chamber, through the pupil to anterior chamber.
Drains into trabecular network and into the veins and canal of Schlemm.
