drugs, enzymes and transporters Flashcards

1
Q

outline what enzyme inhibition of a drug target is and the 2 types.

A

a molecule that binds to the enzymes active site, inhibiting the substrate from binding and catalyzing the reaction

Two types:
- Irreversible inhibitors usually react with the enzyme and change it chemically (e.g. viacovalent bondformation).
- Reversible inhibitors bindnon-covalentlyand different types of inhibition are produced depending on whether these inhibitors bind to theenzyme, the enzyme-substrate complex, or both.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

statins are enzyme inhibitors, briefly explain how they work.

A

HMG-CoA reductase inhibitors

  • block the rate-limiting step in the cholesterol pathway
  • this reduces “bad” cholesterol
  • primary prevention of cardiovascular disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

angiotensin-converting enzyme (ACE) inhibitors are an example of an enzyme inhibitor drug, briefly explain how this works.

A

normal ACE function:
- converts angiotensin I to angiotensin II
- angiotensin II is a vasoconstrictor and stimulates aldosterone release
- this all increases blood pressure

effect of ACE inhibitors:
- block the conversion of angiotensin I to angiotensin II
- results in decreased vasoconstriction and aldosterone
- outcome - lower blood pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are the 3 main protein ports in cell membranes?

A
  • Uniporters: use energy from ATP to pull molecules in.
  • Symporters: use the movement in of one molecule to pull in another molecule against a concentration gradient.
  • Antiporters: one substance moves against its gradient, using energy from the second substance (mostly Na+, K+ or H+) moving down its gradient.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

list some locations of where ion channels are in the body.

A
  • epithelium (Sodium) – heart failure
  • Voltage-gated (Calcium, Sodium) – nerve, arrhythmia
  • Metabolic (Potassium) – diabetes
  • Receptor Activated (Chloride) - epilepsy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

describe epithelial channels and the drugs which block them.

A
  • sodium channels
  • apical membrane-bound
  • heterotrimmeris (2 sets of 3 proteins)
  • selectively permeable to Na+ ions
  • causes reabsorption of Na+ ions at nephrons
  • blocked by amiloride
  • thiazide targets Na and Cl cotransporter - less reabsorption
  • used as an anti-hypertensive
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what are amiloride and thaizide and how do they work?

A

amiloride - blocks epithelial sodium channel
thaizide - blocks Na Cl cotransporter

used as an anti-hypersensitve

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

describe what are voltage-gated calcium channels and the drugs used to inhibit them.

A
  • passive
  • found in membranes of excitable cells
  • at resting state they are usually closed
  • activated upon depolarisation
  • Ca+ enters cell resulting in activation of Ca-sensitive K channels, muscular contraction, excitation of neurons ect
  • amlopipine - angioselective Ca channel blocker
  • this inhibits contraction of cardiac and vascular smooth muscle cells
  • causes vasodilation and reduces peripheral resistance - lowering blood pressure
  • also prevents excessive constriction in coronary arteries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is amlodipine and how does it work?

A
  • blocks voltage gated calcium channels
  • amlopipine - angioselective Ca channel blocker
  • this inhibits contraction of cardiac and vascular smooth muscle cells
  • causes vasodilation and reduces peripheral resistance - lowering blood pressure
  • also prevents excessive constriction in coronary arteries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

describe and explain voltage-gated sodium channels and the drugs which inhibit them.

A
  • passive
  • conducts Na through plasma membrane
  • can either be voltage-gated or ligand-gated according to what activates them

in excitable cells they have 3 main states:
- closed
- open
- inactivated

  • action potential causes gates to open
  • Na flows in
  • lidocaine (anaesthetic) blocks transmission of the action potential
  • also blocks signalling in the heart, reducing arrhythmia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what is lidocaine and how does it work?

A
  • lidocaine (anaesthetic) blocks transmission of the action potential
  • also blocks signalling in the heart, reducing arrhythmia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

describe and explain voltage-gated potassium channels and the drugs which inhibit them.

A
  • passive
  • selective for K
  • 3 states: closed, open and inactivated
  • action potential allows the activation gates to open elicting a downstream effect
  • found in pancreas - regulate insulin
  • repaglinide, nateglinide and sulfonylurea
  • lower blood glucose conc
  • block K channels
  • allowing depolarisation to occur
  • when beta cell is depolarised - insulin is released
  • treatment for type 2 diabetes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

describe and explain receptor mediated chloride channels and the drugs which inhibit them.

A
  • passive
  • ligand-gated ion channels
  • ionotrophic receptors
  • open to allow ions to pass through the membrane in response to the binding of a ligand such as a neurotransmitter

GABA-A receptor
- GABA is an inhibitory ligand
- GABA-A is the receptor and is post-synaptic - opens Cl channel -and induces hyperpolarisation
- drugs can create greater activation of GABA-A - GABA - craeting further inhibition

barbiturates increases the permeability of the channel to chloride

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are repaglinide, nateglinide and sulfonylurea and how do they work?

A
  • repaglinide, nateglinide and sulfonylurea
  • lower blood glucose conc
  • block K channels
  • allowing depolarisation to occur
  • when beta cell is depolarised - insulin is released
  • treatment for type 2 diabetes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

name the passive transporter proteins.

A
  • receptor mediated - chloride
  • voltage gated - potassium
  • voltage gated - sodium
  • voltage gated - calcium
  • epithelial sodium channels
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

name the active transporter proteins.

A
  • sodium pump (Na/K ATP-ase)
  • proton pump (K / H ATP-ase)
17
Q

outline the sodium pump and drugs which act upon it.

A
  • pumps out 3 Na
  • pumps in 2 K
  • against conc gradient
  • It has antiporter-like activity (moves both molecules against their concentration gradients.

digoxin
- inhibits pump in myocardium
- used for atrial fibrilation, atrial flutter, and heart failure
- causes inc in intracellular Na
- dec in activity of Na-Ca exchanger - increases intracellular Ca
- legnthens cardiac action potential - decreased heart rate

18
Q

what is digoxin and how does it work?

A
  • inhibits pump in myocardium
  • used for atrial fibrilation, atrial flutter, and heart failure
  • causes inc in intracellular Na
  • dec in activity of Na-Ca exchanger - increases intracellular Ca
  • legnthens cardiac action potential - decreased heart rate
19
Q
A
  • heterodimeric protein
  • gastric hydrogen potassium ATPase or K/K ATPase - in stomach
  • responsible for acidification of the digestive enzyme pepsin

protein-pump inhibitors:
- omeprazole - inhibits acid secretion
- irreversabele
- largely superseded by H2-receptor antagonist

20
Q

give an example of an irreversable enzyme inhibitor.

A
  • omeprazole - proton pump inhibitor - enzyme
  • aspirin - COX inhibitor - enzyme
21
Q

outline the difference between tolerance and desensitization.

A

tolerance = a gradual reduction in the response to a drug after repeated use, requiring higher doses to achieve the same effect

desensitization = a rapid reduction in the receptor responsiveness following continuous or repeated exposure to a stimulus (drug or agonist)