Chemistry Hyp2 Flashcards
How do Thiazide diuretics work?
Act on Na+/Cl- symporter in distal convoluted tubule
Compete for chlorine binding site
Inhibit reabsorption of sodium leading to diuresis without changing the pH of the urine
What is common between all diuretics?
Sulfonamides
Name three types of diuretics:
Carbonic anyhdrade inhibitors
Thiazides
Loop diuretics
How were carbonic anhydrase inhibitors developed?
Sufonilamide was first developed as an antibiotic and a side effect was diuresis
How do carbonic anhydrase inhibitors work and what are they used for?
Normal acidification of urine achieved by secretion of H+ ions by tubular cells in the kidney
H+ ions provided by the action of carbonic anhydrase which catalyses the formation of carbonic acid by:
CO2 + H2O = H2CO3 = H+ + HCO3-
H+ are exchanged with Na+ in urine so inhibition leads to sodium loss through excretion
Now used for glaucoma as needs a high dose for hypertension
What are thiazide like diuretics and name two?
Contain saulfonamide moieties but don’t share the common ring structure
Chlorthalidone
Indapamide
How do loop diuretics work?
Work in the loop of Henle at Na+/K+/2Cl- symporter
Don’t work at Na+/Cl- sympoter
More effective diuretic
Name two loop diuretics:
Furosemide
Buthetanide
How important are the phenolic -OH groups on a catecholamine for adrenergic binding?
Very important, without the para OH, it significantly decreases Beta selectivity
Can change the meta OH group for a group that does H bonding
What substitution can be made to a catecholamine to increase a2 selectivity?
Add a methyl group to the chain
What evidence is shown that the B adrenoreceptor has a hydrophobic pocket whereas the a adrenoreceptor doesn’t?
The presence of a bulky N-alkyl group, such as isopropyl or butyl, is particularly good for β-adrenoceptor activity, shows there’s a pocket due to increase van Der walls, but when the same happened for a receptor, there was a loss in potency.
What is a modification to the B selectivity on the amine nitrogen?
Adding a polar functional group is placed at the end of the alkyl group, the situation changes. In particular, adding a phenol group to the end of a C2 alkyl chain results in a dramatic rise in activity
What three things do beta blockers do to work as anti hypertensives?
Reduce CO in the heart
Reduce renin production in the kidney
Act on the CNS to decrease activity in the sympathetic NS
Why can’t propanalol be used for asthmatics and what can be used instead?
It is a non selective B antagonist so works on B1 and B2, leading to contraction of bronchial smooth muscles, need only selective for B1 such as atenolol
