Drugs and enzymes

Question 1

Name three drugs that work by enzyme inhinition

Answer 1

statins
ACE inhibitors
Parkinson’s drugs

Question 2

What enzyme do statins inhibit?

Answer 2

the rate limiting step in the cholesterol synthesis pathway

HMG-CoA reductase inhibitors

Question 3

What substance does giving ACE inhibitors directly reduce the production of?

Answer 3

angiotensin 2

Question 4

What are the symptoms of parkinsons?

Answer 4

hypokinesia
tremor at rest
muscle rigidity
cognitive impairment

Question 5

What happens to the neurones in parkinsons

Answer 5

degeneration of dopaminergic neurones

Question 6

What are the different drugs that act on enzymes that can be used in parkinsons?

Answer 6

enzyme substrate L-DOPA
peripheral dopa decarboxylase inhibitor (carbidopa) - inhibits conversion of L-DOPA to dopamine outside the BBB
peripheral COMT inhibitor - inhibits conversion of L-DOPA to another product, so more L-DOPA for CNS
central COMT inhibitors - inhibits the conversion of dopamine to another substance in the brain, so more dopamine NT
MAOIs - prevents dopamine breakdown and increases dopamine availability

Question 7

what are the different types of transporters in the cell membrane?

Answer 7

antiporter
symporter
uniporter

Question 8

Give an example of a symporter

Answer 8

NKCC
transports Na,K and Cl into cells
furoseminde is a loop diuretic and acts by inhibiting NKCC
causes Na,K, Cl loss in urine

Question 9

Give four examples of ion channels in the body

Answer 9

ENaC
voltage gated calcium channels
voltage gated potassium channels
receptor mediated chloride channel

Question 10

What does ENaC do?

Answer 10

reabsorption of sodium and chloride ions in the collecting ducts of the kidney

Question 11

Which diuretic works at ENaC?

Answer 11

thiazide

Question 12

Where are voltage gated calcium channels found?

Answer 12

in the cell membrane of excitable cells eg muscle, glial cells and neurones

Question 13

What do voltage gated calcium channels do?

Answer 13

they are opened when an action potential depolarises the membrane and this causes calcium to enter the cell causing muscular contraction

Question 14

Give an example of a drug that works at voltage gated calcium channels and explain how it works

Answer 14

Amlodipine - it is angioselective; working on the heart muscle cells and smooth vascular muscle cells
It inhibits the contraction of both these types of muscle cells
causes vasodilation and prevents excessive constriction of coronary arteries
so lowers BP

Question 15

where are voltage gated sodium channels found and how do they work?

Answer 15

in excitable cells

an action potential opens the Na+ channels and Na+ enter, causing the voltage across the membrane to increase

Question 16

Give an example of a drug that works on voltage gated sodium channels and how does it work?

Answer 16

Lidocaine

blocks transmission of the action potential and blocks signalling in the heart, reducing arrhythmia

Question 17

What do potassium channels in the islets of langerhans do?

Answer 17

when glucose enters the islet of langerhans cells, the K+ channel closes, which causes Ca2+ to enter the cell stimulating exocytosis of vesicles containing insulin

Question 18

Which drugs act to block the potassium channels in islets of langerhans to stimulate insulin secretion?

Answer 18

repaglinide, nateglinide and sulfonylurea

Question 19

What type of channel is the GABA receptor?

Answer 19

A ligand gated ion channel

Question 20

Give an example of a drug class that works at the GABA A receptor

Answer 20

barbiturates - increase the permeability of the channel to chloride
as well as benzodiazepines

Question 21

Where are GABA A receptors found and what do they do there?

Answer 21

post synaptic

allow Cl- into the cell so cause hyperpolarisation

Question 22

Give examples of active ion transporters

Answer 22

NA/K ATPase

K/H ATPase

Question 23

what does the NA/K ATPase do?

Answer 23

pumps three Na+ out and 2 K+ ions in to create an electrochemical gradient across the cell membrane

Question 24

Name a drug that works at the Na/K ATPase and how it works

Answer 24

Digoxin
inhibits the Na/K ATPase mainly in the myocardium
used for atrial fibrillation, atrial flutter and heart failure
the inhibition causes increased intracellular Na and decreased activity of the Na/Ca exchanger, so increases intracellular calcium
this means the cardiac action potential is increased, so decreases the heart rate

Question 25

Where is the K/H ATPase found and how does it work?

Answer 25

stomach

exchanges K+ in the lumen for hydronium ions (H3O+) so acidifies the stomach and results in cleavage of pepsin

Question 26

Name a class of drugs that works at the K/H ATPase

Answer 26

proton pump inhibitors

Question 27

Give examples of irreversible enzyme inhibitors

Answer 27

organophosphates (inhibitor of cholinesterase)
omeprazole
aspirin (COX inhibitor)

Question 28

What are the effects of organophosphates?

Answer 28

twitching, severe weakness, paralysis, confusion, loss of reflexes, convulsions, coma, hypotension, bradycardia, salivation, defacation, urination

Question 29

Where in the cells are CYP enzymes found?

Answer 29

inner membrane of mitochondria

endoplasmic reticulum