Drugs and the Peripheral nervous system L11

Question 1

where is noradrenaline released

Answer 1

released by postganglionic fibres and the sympathetic nervous system

Question 2

how is noradrenaline synthesised

Answer 2

enzyme tyrosine hydroxylase converts tyrosine into DOPA
enzyme DOPA carboxylase converts DOPA to dopamine
enzyme dopamine B-hydroxylase converts dopamine to noradrenaline

Question 3

how is NA stored

Answer 3

in vesicles

Question 4

how is NA released

Answer 4

exocytosis

Question 5

what types of receptors does NA interact with

Answer 5

Alpha or Beta Noradrenergic receptors

Question 6

how is NA action terminated

Answer 6

it is reuptook by transporter and either
1. recycled into vesicles
2. broken down by monoamine oxidase into amines

Question 7

describe alpha 1,2 noradrenergic receptors
- where are they found
- what type of receptors are they
- what kind of response do they have

Answer 7

1. located on effector tissue of sympathetic nervous system
2. G protein or metabotropic
3. slow response

Question 8

describe beta 1,2 and 3 noradrenergic receptors
- where are they found
- what type of receptors are they
- what kind of response do they have

Answer 8

1. located on effector tissue of sympathetic nervous system
2. G protein or metabotropic
3. slow response

Question 9

what parts of sympathetic nervous system will A1 receptors effect

Answer 9

1. Pupils dilate(radial muscle contracts)
2. Blood vessels to visceral organs & skin constrict
3. Brain activity general alertness

Question 10

what parts of sympathetic nervous system will A2 receptors effect

Answer 10

A2 receptors found on presynaptic neurone not effector tissue
- acts as a negative feedback system
- when NA (ACh or other neurotransmitters) binds to them, they inhibit release of further NA dampening down effect of sympathetic NS

Question 11

what are A2 auto-receptors and heteroreceptors

Answer 11

1. autoreceptors
   - only sensitive to the neurotransmitters or hormones released by the neuron on which the autoreceptor sits
2. heteroreceptor
   - receptor regulating the synthesis and/or the release of mediators other than its own ligand

Question 12

what part of the sympathetic nervous system do B1 receptors effect

Answer 12

1. Heart rate increases (and force of contraction)

Question 13

what part of the sympathetic nervous system do B2 receptors effect

Answer 13

1. Airways in lungs dilate (bronchodilation)
2. Lens of eye adjust for far vision (ciliary muscle relax)
3. Blood vessels to limb muscles dilate

Question 14

what part of the sympathetic nervous system do B3 receptors effect

Answer 14

1. Increase lipolysis (breakdown of triglycerides to fatty acids)

Question 15

give 5 examples of noradrenergic agonists

Answer 15

1. adrenaline
2. clonidine
3. dobutamine
4. salbutamol
5. Clenbuterol

Question 16

describe agonist effects of adrenaline

Answer 16

acts on all the noradrenergic receptors
destroyed in gut so has to be injection
- when given locally, it can prolong and isolate local anaesthesia
- mediates vasoconstriction when bound to A1
- when given intramusically, can treat anaphylactic shock
- mediates cardiac stimulation when bound to B1
- mediated bronchiol smooth muscle relaxation when bound to B2

Question 17

describe agonist effects of Clonidine

Answer 17

acts on A2 receptors
- it decrease NA release dampen down overall sympathetic system so is used to treat hypertension
- involve a central effect (nucleus tractus solitarius) which results in decrease sympathetic outflow.
- Also used to treat withdrawal symptoms in morphine withdrawal (inhibits central NA release which drives withdrawal symptoms)

Question 18

describe agonist effects of dobutamine

Answer 18

acts on B1 receptor
- increased cardiac rate and force so used to treat heart failure

Question 19

describe agonist effects of salbutamol

Answer 19

acts on B2 receptors
Used to treat asthma.
beta 2 – mediated bronchiol smooth muscle relaxation:

Question 20

describe agonist effects of Clenbuterol

Answer 20

acts on B2 and 3 receptors
B2: bronchodilation- treat asthma
B3: lipolysis/increased metabolism- Increases muscle bulk in athletes/body builders/livestock

Question 21

give examples of Noradrenergic antagonists

Answer 21

1. prazosin
2. Tamsulson
3. Propranolol
4. Atenolol
5. Timolol

Question 22

describe antagonist effects of prazosin

Answer 22

acts on A1 receptors
- A1 – antagonism: vasodilation and decreased vascular resistance treat hypertension
- Side effects: orthostatic or postural hypotension due to some loss in sympathetic reflex

Question 23

describe antagonist effects of Tamsulson

Answer 23

acts on A1
- A1 – antagonism: relaxation of smooth muscle in bladder neck, ease of urinary flow treats urination problems in prostate hyperplasia
- Side effects: orthostatic or postural hypotension due to some loss in sympathetic reflex

Question 24

describe antagonist effects of propanol

Answer 24

acts on B1 and 2
B1: Used to treat hypertension and angina
Blocking B1 receptors decreases cardiac output and also decreases oxygen demand.
B2: blocking B2 receptors causes bronchoconstriction. Therefore contra-indicative in asthmatics .

Question 25

describe antagonist effects of Atenolol

Answer 25

acts on B1 - Used to treat hypertension and angina Blocking B1 decreases cardiac output and also decreases oxygen demand. - Side effect: can cause rebound hypertension/ angina on abrupt withdrawal probably due to B1 receptor supersensitivity

Question 26

describe antagonist effects of Timolol

Answer 26

acts on B2 receptors - Used to treat glaucoma, antagonism of B2– receptors cause ciliary contraction, and decreased intraocular pressure

Question 27

where are Potential sites of drug action on NA neurotransmission

Answer 27

Synthesis Storage Release Receptors Uptake Metabolism

Question 28

how can synthesis of NA be targeted

Answer 28

1. give a false substrate such as methlyDOPA - DOPA carboxylase converts this to MeDA which is converted to MeNA - this outcompetes normally NA synthesis. as it uses the same enzymes, less enzyme available to

Question 29

how can synthesis of NA be targeted what is it used to treat

Answer 29

1. give a false substrate such as methlyDOPA - DOPA carboxylase converts this to MeDA which is converted to MeNA - this outcompetes normally NA synthesis. as it uses the same enzymes, less enzyme available to synthesise NA so less is made so sympathetic system is inhibited - Used in the treatment of hypertension

Question 30

how can storage be targeted what is it used to treat

Answer 30

Reserpine disrupts storage of NA in synaptic vesicles - Overall decrease in NA neurotransmission Used to treat hypertension

Question 31

how can release be targeted what is it used to treat

Answer 31

NA release is subject to autoinhibitory control via presynaptic A2 -autoreceptor clonidine (A2-agonist) causes inhibition of NA release Overall decrease in NA neurotransmission Used to treat hypertension

Question 32

how can uptake be targeted what is it used to treat

Answer 32

NA uptake can be blocked by NA reuptake inhibitors This will prolong the action of NA in the synapse - desipramine tricyclic antidepressants - reboxetine selective noradrenaline reuptake inhibitors - treat depression

Question 33

how can metabolism be targeted what is it used to treat

Answer 33

After reuptake NA is metabolised by the enzymes monoamine oxidase (MAO), and catecholamine transferase (COMT) - By blocking these enzymes the amount of NA available for release is increased. - tranylcypramine blocks MAO and allows more NA to be recycled so increases NA neurotransmission.

Question 34

what else does monoamine oxidase (MAO), and catecholamine transferase (COMT) block

Answer 34

block the metabolism of dietary amines (e.g. commonly found in cheese, marmite) and amines found in popular cold remedies. - Accumulation of dietary amines can have a sympathomimetic effect and result in hypertension