Pharmacology Hyp2 Flashcards
What is the main neurotransmitter in the sympathetic NS and what does it do?
Noradrenaline
Involved in fight or flight
What is the rate limiting step in noradrenaline synthesis?
Tyrosine hydroxylase
What is VMAT and what does it do?
Vesicular Monoamine Transporter
Powered by transvesicular proton gradient
Lots of protons in vesicles
What is uptake 1, termination of the adrenergic signal?
Noradrenaline uptake
Terminates signal in periphery using noradrenaline transporter
75% repacked into vesicles by VMAT
What is uptake 2, termination of the adrenergic signal?
Noradrenaline mechanism
Remaining 25% is uptaken by non- neuronal cells
By extraneuronal monamine transport (EMT)
Which enzymes metabolise noradrenaline?
By two intracellular enzymes Monoamine oxidase (MAO) which is bound to the surface of mitochondria Catechol- O- methyl transferase (COMT)
Name the five types of adrenergic receptors:
a adrenergic:
a1 and a2
B adrenergic:
B1, B2, B3
Where is the a1 adrenergic receptor found and what does it do?
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
Where is the a2 adrenergic receptor found and what does it do?
Found in the presynaptic and its a Gi G-protein
It decreases the activation of adenylate cyclase and decreases in cAMP
Where is the B1 adrenergic receptor found and what does it do?
Found in the heart and is a Gs G- protein
Increases inactivation of adenylate cyclase and increases in cAMP and increases intracellular signalling pathway
Where is the B2 adrenergic receptor found and what does it do?
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
Where is the B3 adrenergic receptor found and what does it do?
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
Which adrenergic receptors work on the blood vessels and what effect do they have?
a1, a2 and B2
a= constriction
B2= dilation
Which adrenergic receptors work on the heart and what effect do they have?
B1, they increase contraction
Which adrenergic receptors work on the bronchi and what effect do they have?
a1= increase in contraction B2= relaxation
Which adrenergic receptors work on the kidneys and what effect do they have?
a1 and a2= vasoconstriction
B1 and B2= renin release
Which adrenergic receptors work on the adipocytes and what effect do they have?
a2= inhibition of lipolysis B= lipolysis
How is the a1 receptor involved in smooth muscle constriction?
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
How is the a2 receptor involved in the negative feedback loop?
Noradrenaline binding to Gi which inactivates adenylate cyclase, this decreases CAMP levels and activates protein kinase A
Location is important for consequence
How is B1 receptor in the cardiac muscle involved in cardiac contraction?
Increases cytoplasmic Ca2+ concetration
How is B2 receptors stimulate bronchodilation?
Inactivation of myosin light chain kinase, which switches off myosin and decrease in force being produced so relaxed
Give five classes of drugs that were/ are used to inhibit an adrenergic synapse and therefore noradrenaline:
- Noradrenaline synthesis inhibitors
- vMAT inhibitors
- Noradrenaline release inhibitors
- Inhibition of noradrenaline uptake
- Inhibition of noradrenaline metabolism
Give an example of noradrenaline synthesis inhibitors and how are they used?
Metyrosine
Inhibits tyrosine hydroxylase
Originally used to treat hypertension but not specific
Give an example of vMAT inhibitors and how are they used?
Reserpine
Originally used to treat hypertension but non specific, acted on all noradrenaline
Give an example of noradrenaline release inhibitors and how are they used?
Guanethidine
Internalised during uptake stage with noradrenaline
Concentrated in transmitter vesicles
Decrease in noradrenaline content in vesicles
Non specific
How do inhibitors of noradrenaline uptake work?
Bind and block reuptake transporter
Give an example of noradrenaline metabolism inhibitors and how are they used?
Pheneizine and iproniazid
Irreversible MAO inhibitors
Used to treat depression
What is a diuretic?
Anything that promotes the formation of urine by the kidney
e.g caffeine, alcohol
How do diuretics work?
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
Give five classes of diuretics and an example of each:
- Thiazides e.g bendroflumethiazide
- Loop diuretics e.g. furosemide
- Potassium sparing diuretics e.g. amiloride, aldosterone antagonists
- Carbonic anhydrase inhibitors- no longer used
- Osmotic diuretics e.g mannitol but not used in the treatment of hypertension
What occurs in the proximal tubule?
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
What occurs in the loop of Henle?
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
What occurs in the distal tubule?
Na+ and Cl- is reabsorbed
Thiazide diuretics act at the distal tubule
Inhibit the Na+, Cl- co transporter
What occurs in the collecting ducts?
Water is reabsorbed under the control of hormones, ADH (antidiretic hormone vasopressin) and aldosterone
Potassium sparing diuretics act here
