Pharmacology Hyp2

Question 1

What is the main neurotransmitter in the sympathetic NS and what does it do?

Answer 1

Noradrenaline

Involved in fight or flight

Question 2

What is the rate limiting step in noradrenaline synthesis?

Answer 2

Tyrosine hydroxylase

Question 3

What is VMAT and what does it do?

Answer 3

Vesicular Monoamine Transporter
Powered by transvesicular proton gradient
Lots of protons in vesicles

Question 4

What is uptake 1, termination of the adrenergic signal?

Answer 4

Noradrenaline uptake
Terminates signal in periphery using noradrenaline transporter
75% repacked into vesicles by VMAT

Question 5

What is uptake 2, termination of the adrenergic signal?

Answer 5

Noradrenaline mechanism
Remaining 25% is uptaken by non- neuronal cells
By extraneuronal monamine transport (EMT)

Question 6

Which enzymes metabolise noradrenaline?

Answer 6

By two intracellular enzymes 
Monoamine oxidase (MAO) which is bound to the surface of mitochondria 
Catechol- O- methyl transferase (COMT)

Question 7

Name the five types of adrenergic receptors:

Answer 7

a adrenergic:
a1 and a2
B adrenergic:
B1, B2, B3

Question 8

Where is the a1 adrenergic receptor found and what does it do?

Answer 8

Found in the smooth muscle and it a Gq G- protein

It increases PLC, IP3 and increases the intracellular Ca2+ conc and therefore increases contraction

Question 9

Where is the a2 adrenergic receptor found and what does it do?

Answer 9

Found in the presynaptic and its a Gi G-protein

It decreases the activation of adenylate cyclase and decreases in cAMP

Question 10

Where is the B1 adrenergic receptor found and what does it do?

Answer 10

Found in the heart and is a Gs G- protein

Increases inactivation of adenylate cyclase and increases in cAMP and increases intracellular signalling pathway

Question 11

Where is the B2 adrenergic receptor found and what does it do?

Answer 11

Found in the smooth muscle and is a Gs G- protein

Increases inactivation of adenylate cyclase and increases in cAMP and increases intracellular signalling pathway

Question 12

Where is the B3 adrenergic receptor found and what does it do?

Answer 12

Found in the fat tissue and is a Gs G- protein

Increases inactivation of adenylate cyclase and increases in cAMP and increases intracellular signalling pathway

Question 13

Which adrenergic receptors work on the blood vessels and what effect do they have?

Answer 13

a1, a2 and B2
a= constriction
B2= dilation

Question 14

Which adrenergic receptors work on the heart and what effect do they have?

Answer 14

B1, they increase contraction

Question 15

Which adrenergic receptors work on the bronchi and what effect do they have?

Answer 15

a1= increase in contraction
B2= relaxation

Question 16

Which adrenergic receptors work on the kidneys and what effect do they have?

Answer 16

a1 and a2= vasoconstriction

B1 and B2= renin release

Question 17

Which adrenergic receptors work on the adipocytes and what effect do they have?

Answer 17

a2= inhibition of lipolysis 
B= lipolysis

Question 18

How is the a1 receptor involved in smooth muscle constriction?

Answer 18

Noradrenaline binding leads to activation of Phospholipase , which catalyses PIP2 to form DAG AND IP3. IP3 opens Ca2+ channels on sarcoplasmic reticulum and therefore increases cytoplasmic concentration of Ca2+ ions

Question 19

How is the a2 receptor involved in the negative feedback loop?

Answer 19

Noradrenaline binding to Gi which inactivates adenylate cyclase, this decreases CAMP levels and activates protein kinase A
Location is important for consequence

Question 20

How is B1 receptor in the cardiac muscle involved in cardiac contraction?

Answer 20

Increases cytoplasmic Ca2+ concetration

Question 21

How is B2 receptors stimulate bronchodilation?

Answer 21

Inactivation of myosin light chain kinase, which switches off myosin and decrease in force being produced so relaxed

Question 22

Give five classes of drugs that were/ are used to inhibit an adrenergic synapse and therefore noradrenaline:

Answer 22

1. Noradrenaline synthesis inhibitors
2. vMAT inhibitors
3. Noradrenaline release inhibitors
4. Inhibition of noradrenaline uptake
5. Inhibition of noradrenaline metabolism

Question 23

Give an example of noradrenaline synthesis inhibitors and how are they used?

Answer 23

Metyrosine
Inhibits tyrosine hydroxylase
Originally used to treat hypertension but not specific

Question 24

Give an example of vMAT inhibitors and how are they used?

Answer 24

Reserpine

Originally used to treat hypertension but non specific, acted on all noradrenaline

Question 25

Give an example of noradrenaline release inhibitors and how are they used?

Answer 25

Guanethidine
Internalised during uptake stage with noradrenaline
Concentrated in transmitter vesicles
Decrease in noradrenaline content in vesicles
Non specific

Question 26

How do inhibitors of noradrenaline uptake work?

Answer 26

Bind and block reuptake transporter

Question 27

Give an example of noradrenaline metabolism inhibitors and how are they used?

Answer 27

Pheneizine and iproniazid
Irreversible MAO inhibitors
Used to treat depression

Question 28

What is a diuretic?

Answer 28

Anything that promotes the formation of urine by the kidney

e.g caffeine, alcohol

Question 29

How do diuretics work?

Answer 29

In the kidney by inhibiting the reabsorption of ions (mainly Na+) which gives a higher osmolarity in the kidney tubule and hence more excretion of water

Question 30

Give five classes of diuretics and an example of each:

Answer 30

1. Thiazides e.g bendroflumethiazide
2. Loop diuretics e.g. furosemide
3. Potassium sparing diuretics e.g. amiloride, aldosterone antagonists
4. Carbonic anhydrase inhibitors- no longer used
5. Osmotic diuretics e.g mannitol but not used in the treatment of hypertension

Question 31

What occurs in the proximal tubule?

Answer 31

Reabsorption of most of the solutes and water occurs there
60-70% of water and Na+ reabsorbed here, 98% of glucose
Na+ is reabsorbed via the Na+-H+ exchanger so H+ ions are excreted
Bicarbonate ions are absorbed to regulate pH
Carbonic anyhdrase inhibitors act here to have their diuretic effect by providing the H+ ions

Question 32

What occurs in the loop of Henle?

Answer 32

Water is reabsorbed in the descending loop
Na+ and Cl- is reabsorbed in the ascending loop
Loop diuretics act at the ascending loop of Henle. by inhibiting the Na+, K+, Cl- (NKCC2) co-transporter
The inner medulla has high osmolarity which allows Na+ in so K+ and Cl- up its gradient

Question 33

What occurs in the distal tubule?

Answer 33

Na+ and Cl- is reabsorbed
Thiazide diuretics act at the distal tubule
Inhibit the Na+, Cl- co transporter

Question 34

What occurs in the collecting ducts?

Answer 34

Water is reabsorbed under the control of hormones, ADH (antidiretic hormone vasopressin) and aldosterone
Potassium sparing diuretics act here