Lecture 38 - Pharmacology of the autonomic nervous system

Question 1

what does the ANS regulate?

Answer 1

Contraction and relaxation of smooth muscle
All exocrine and some endocrine secretions
The heartbeat
Certain steps in intermediary metabolism

Question 2

what are cholinergic receptors?

Answer 2

Cholinergic receptors respond to the neurotransmitter acetylcholine (ACh)

2 types of aCh receptors - muscarine and nicotine

Question 3

what are nicotinic receptors?

Answer 3

are located postsynaptically in all autonomic ganglia and at the neuromuscular junction (see muscle & nerve lectures).
At these junctions nicotinic receptors function as the excitatory receptor for the postsynaptic cell.

Question 4

Nicotinic ACh receptor

Answer 4

fast acting molecular switch
An oligomeric protein composed of
an extracellular ligand binding domain
a gated, membrane spanning pore

gate opened by binding of neurotransmitter released from nerve terminal - conformational change

Question 5

muscarinic receptors

Answer 5

located postsynaptically at the parasympathetic neuroeffector junction.
increase or decrease activity of effector cells
also located postsynaptically at the neuroeffector junction of sympathetic fibres in sweat glands, where they increase sweating.
endothelial cells of blood vessels.

Question 6

types of Muscarinic receptors

Answer 6

All are G-protein coupled receptors
Ligand binding induces a conformational change that causes the receptor to interact with a specific G-protein
M1, M3 and M5 receptors are coupled to the activation of phospholipase C (producing inositol triphosphate and DAG as the second messengers)
M2 and M4 subtypes are negatively coupled to adenylyl cyclase leading to reduction of cAMP formation

Question 7

Clinical uses of muscarinic antagonists

Answer 7

Treatment of sinus bradycardia: i.v. atropine
To dilate the pupil: tropicamide eye drops
Prevent motion sickness: hyoscine, oral or transdermal
Asthma: ipratropium by inhalation
Relaxation of GI smooth muscle: hyoscine (oral/IV)
Urge incontinence: relaxation of bladder detrusor – oxybutynin, tolterodine, solifenacin

Question 8

side effects of muscarinic antagonists

Answer 8

Dry mouth
Blurred Vision
Constipation
Urinary retention
Cognitive impairment

Question 9

Noradrenergic transmission

Answer 9

Noradrenaline and adrenaline are catcholamines synthesised from tyrosine

Sympathetic nerve terminals account for all of the noradrenaline in peripheral tissues

Heart, spleen, vas deferens and some blood vessels are rich in NA

Question 10

Classification of adrenergic receptors

2 types-  and ß

Answer 10

alpha - Noradrenaline > adrenaline > isoprenaline

Beta - Isoprenaline > adrenaline > noradrenaline

all are G-protein coupled receptors

Question 11

alpha - 1 receptor activation causes…

Answer 11

Vasoconstriction
Relaxation of GI smooth muscle
Salivary secretion
Hepatic glycogenolysis

Question 12

Alpha 2 receptor activation causes…

Answer 12

Inhibition of transmitter release (inc NA and Ach release from autonomic nerves)
Platelet aggregation
Contraction of vascular smooth muscle
Inhibition of insulin release

Question 13

selective alpha 1 agonists

Answer 13

Phenylephrine and oxymetazoline (topical decongestant)

Question 14

Selective alpha 2 agonists

Answer 14

Clonidine, alpha-methylnoradrenaline- reduce blood pressure

Question 15

beta 1 receptor activation

Answer 15

increase cardiac rate and force

Question 16

Beta 2 receptor activation

Answer 16

bronchodilaiton, vasodilation, relaxation of visceral smooth muscle, hepatic glycogenolysis, muscle tremor

Question 17

Beta 3 adrenoreceptor activation

Answer 17

lipolysis

Question 18

Selective B1 agonists

Answer 18

Dobutamine- increased cardiac contraction

Question 19

Selective B2 agonists

Answer 19

Salbutamol, terbutaline, salmeterol- used for bronchodilator action in asthma

Ritodrine – premature labour

Question 20

Selective B3 agonists

Answer 20

Under development for obesity control

Question 21

Beta-adrenoreceptor antagonists (Beta-Blockers)

Answer 21

Propanolol blocks 1 and 2 adrenoreceptors equally (non-selective)
Atenolol, Bisoprolol are selective for Beta- 1 receptors (cardioselective)
Some other drugs also have partial agonist activity
Activities on cardiovascular system and bronchial smooth muscle and are slight during rest

Question 22

Main uses of Beta-adrenoreceptor antagonists

Answer 22

Hypertension
Angina pectoris
Cardiac dysrhythmias
Following myocardial infarction

Question 23

Side effects of Beta-adrenoreceptor antagonists

Answer 23

Cold extremities
Insomnia,(lipophilic)
Bronchoconstriction- important in asthmatics (non-selective)
Cardiac failure (acute decompensated)
Bradycardia
Hypoglycaemia – (non-selective in diabetics)
Fatigue