drugs, enzymes and transporters Flashcards
outline what enzyme inhibition of a drug target is and the 2 types.
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.
statins are enzyme inhibitors, briefly explain how they work.
HMG-CoA reductase inhibitors
- block the rate-limiting step in the cholesterol pathway
- this reduces “bad” cholesterol
- primary prevention of cardiovascular disease
angiotensin-converting enzyme (ACE) inhibitors are an example of an enzyme inhibitor drug, briefly explain how this works.
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
what are the 3 main protein ports in cell membranes?
- 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.
list some locations of where ion channels are in the body.
- epithelium (Sodium) – heart failure
- Voltage-gated (Calcium, Sodium) – nerve, arrhythmia
- Metabolic (Potassium) – diabetes
- Receptor Activated (Chloride) - epilepsy
describe epithelial channels and the drugs which block them.
- 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
what are amiloride and thaizide and how do they work?
amiloride - blocks epithelial sodium channel
thaizide - blocks Na Cl cotransporter
used as an anti-hypersensitve
describe what are voltage-gated calcium channels and the drugs used to inhibit them.
- 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
what is amlodipine and how does it work?
- 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
describe and explain voltage-gated sodium channels and the drugs which inhibit them.
- 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
what is lidocaine and how does it work?
- lidocaine (anaesthetic) blocks transmission of the action potential
- also blocks signalling in the heart, reducing arrhythmia
describe and explain voltage-gated potassium channels and the drugs which inhibit them.
- 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
describe and explain receptor mediated chloride channels and the drugs which inhibit them.
- 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
what are repaglinide, nateglinide and sulfonylurea and how do they work?
- 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
name the passive transporter proteins.
- receptor mediated - chloride
- voltage gated - potassium
- voltage gated - sodium
- voltage gated - calcium
- epithelial sodium channels