SNS Antagonists Flashcards by Alexandra Chan

What are alpha1 receptors involved in

Vasconstriction

Relaxation of the GIT

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What are alpha2 receptors involved in

Inhibition of transmitter release
Contraction of vascular smooth muscle
CNS actions

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What are beta1 receptors involved in

Increased cardiac rate and force
Relaxation of GIT
Renin release from the kidney

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What are beta2 receptors involved in

Bronchodilation
Vasodilation
Relaxation of visceral smooth muscle
Hepatic glycogenolysis

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What are beta3 receptors involved

Lipolysis

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What is the mechanism of SNS synaptic transmission

norepinephrine
Release of norepinephrine into synaptic cleft
alpha1 receptor stimulation
alpha2-mediated negative feedback

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Describe carvedilol targets

Mixed alpha1 and beta1 - non-selective

alpha1 blockade gives additional vasodilator properties

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Which receptors does phentolamine target

alpha1 and alpha2

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Which receptors does prazosin target

alpha1

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Which receptors does propanalol target

non-selective
beta1 and beta2 receptors
equal affinity for both

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Which receptors does atenolol target

beta1 selective

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How is blood pressure calculated

BP = cardiac output x total peripheral resistance

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What is hypertension defined as

Blood pressure is consistently above 140/90

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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

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What are the main contributors to blood pressure

Blood volume
Cardiac output
Vascular tone

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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 &amp; autonomic NS)

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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 1. Taken up by noradrenergic neurons 2. Decarboxylated and hydroxylated to form the false transmitter a-methyl-noradrenaline 3. Taken into the pre-synaptic neurone 4. Not de-aminated by MAO 5. 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.