SNS Antagonists

Question 1

The function of the a1 adrenoceptor subtype

Answer 1

Vasoconstriction, relaxation of the GIT

(Inhibitory effect of on the gut during fight or flight - divert function to other areas)

Question 2

The function of the a2 adrenoceptor subtype

Answer 2

Inhibition of transmitter release, contraction of vascular smooth muscle, CNS action

(inhibit sympathetic activity)

Question 3

The function of the b1 adrenoceptor subtype

Answer 3

Increased cardiac rate and force, relaxation of the GIT and renin release from the kidney

Question 4

The function of the b2 adrenoceptor subtype

Answer 4

Bronchodilation, vasodilation, relaxation of the visceral smooth muscle and hepatic glycogenolysis

Question 5

The function of the b3 adrenoceptor subtype

Answer 5

Lipolysis

Question 6

Other than uptake 1 receptors, how are the actions of transmitters modulated

Answer 6

A2 receptor on the presynaptic neuron

Switches off the effect of the NA being released, this means that the effect of NA on the postsynaptic neurone is fast and not prolonged

Question 7

Example of a non-selective (a1 +b1) antagonist

Answer 7

Carvedilol

Question 8

Example of a non-selective alpha antagonist (a1 +a2)

Answer 8

Phentolamine

Question 9

Example of a selective a1 antagonist

Answer 9

Prazosin

Question 10

Example of a non-selective beta antagonist (b1 +b2)

Answer 10

Propranolol

Question 11

Example of a selective b1 antagonist

Answer 11

atenolol

Question 12

What are some of the clinical uses of adrenoceptor antagonists

Answer 12

Treatment of hypertension, arrhythmias, angina and glaucoma

Question 13

Describe the pathophysiology of hypertension (BP, RISK )

Answer 13

> Consistently being over 140/90mmHg

Important risk factor for:

stroke (50% of ischaemic stroke)

25% of heart failure (70% in elderly)

MI and chronic kidney disease

Question 14

What is the ultimate goal of hypertension therapy

Answer 14

Reduce the mortality from cardiovascular or renal events

Question 15

What are the target tissues for antihypertensive drugs

Answer 15

Heart = affect CO

Kidney = blood volume/ vasoconstriction (renin and aldosterone)

Arterioles = peripheral resistance

Question 16

What tissues can beta blockers target in relation to hypertension

Answer 16

B1 = heart, kidney

B1/2 = sympathetic nerves releasing vasoconstrictor NA, CNS (blood pressure control)

Question 17

Describe the mechanisms of beta-blockers

Answer 17

Decrease heart rate and force of contraction = decrease CO = Decrease BP

Block b1 in the kidneys (activated via sympathetic activation) = Decrease renin = Less Angiotensin 2 (a potent vasoconstrictor) and aldosterone (decrease BP and volume)

Question 18

Actions of Nebivolol

Answer 18

Targets b1 receptors

Potentiates the action of NO (Relax)

Question 19

Actions of Sotalol

Answer 19

Targets both b1 and b2 receptors

Inhibits K+ channels (interferes with ell hyperpolarisation)

Question 20

Groups of people who should be cautious with beta-blockers (5)

Answer 20

Asthma/COPD = causes bronchoconstriction

Cardiac failure = Need sympathetic drive in order to match blood/tissue demand

Hypoglycemia = bb block the symptoms of hypoglycaemia (sweating, palpitations, tremors) non-selective beta-blockers can affect the b2 receptors which are involved in glucose release from the liver

Fatigue = decrease in CO and muscle perfusion

Cold extremities = loss of b2 receptor-mediated vasodilation in cutaneous vessels

Question 21

What is the advantage of atenolol over propranolol

Answer 21

Propranolol = non-selective beta-blocker

Atenolol = selective b1 blocker

Atenolol (cardio-selective drug) antagonises the effect of NA on the heart but will affect other areas such as the kidney with b1 receptors.

Less effect on airways than non-selective drugs but still not safe for asthmatics (liver/bronchioles)

Question 22

What advantage does carvedilol have over atenolol and propranolol

Answer 22

Dual acting b1 and a1 antagonist (4:1)

> Lowers BP by reducing peripheral resistance

> Induces a change in heart rate/CO but wanes with chronic use

Question 23

Compare the blockade of a1 and a2 receptors

Answer 23

a1 receptors = Gq-linked = postsynaptic receptor is on vascular smooth muscle

a2 receptors = Gi-linked = presynaptic autoreceptors inhibit NE release