Drugs and enzymes Flashcards
Name three drugs that work by enzyme inhinition
statins
ACE inhibitors
Parkinson’s drugs
What enzyme do statins inhibit?
the rate limiting step in the cholesterol synthesis pathway
HMG-CoA reductase inhibitors
What substance does giving ACE inhibitors directly reduce the production of?
angiotensin 2
What are the symptoms of parkinsons?
hypokinesia
tremor at rest
muscle rigidity
cognitive impairment
What happens to the neurones in parkinsons
degeneration of dopaminergic neurones
What are the different drugs that act on enzymes that can be used in parkinsons?
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
what are the different types of transporters in the cell membrane?
antiporter
symporter
uniporter
Give an example of a symporter
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
Give four examples of ion channels in the body
ENaC
voltage gated calcium channels
voltage gated potassium channels
receptor mediated chloride channel
What does ENaC do?
reabsorption of sodium and chloride ions in the collecting ducts of the kidney
Which diuretic works at ENaC?
thiazide
Where are voltage gated calcium channels found?
in the cell membrane of excitable cells eg muscle, glial cells and neurones
What do voltage gated calcium channels do?
they are opened when an action potential depolarises the membrane and this causes calcium to enter the cell causing muscular contraction
Give an example of a drug that works at voltage gated calcium channels and explain how it works
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
where are voltage gated sodium channels found and how do they work?
in excitable cells
an action potential opens the Na+ channels and Na+ enter, causing the voltage across the membrane to increase
Give an example of a drug that works on voltage gated sodium channels and how does it work?
Lidocaine
blocks transmission of the action potential and blocks signalling in the heart, reducing arrhythmia
What do potassium channels in the islets of langerhans do?
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
Which drugs act to block the potassium channels in islets of langerhans to stimulate insulin secretion?
repaglinide, nateglinide and sulfonylurea
What type of channel is the GABA receptor?
A ligand gated ion channel
Give an example of a drug class that works at the GABA A receptor
barbiturates - increase the permeability of the channel to chloride
as well as benzodiazepines
Where are GABA A receptors found and what do they do there?
post synaptic
allow Cl- into the cell so cause hyperpolarisation
Give examples of active ion transporters
NA/K ATPase
K/H ATPase
what does the NA/K ATPase do?
pumps three Na+ out and 2 K+ ions in to create an electrochemical gradient across the cell membrane
Name a drug that works at the Na/K ATPase and how it works
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
Where is the K/H ATPase found and how does it work?
stomach
exchanges K+ in the lumen for hydronium ions (H3O+) so acidifies the stomach and results in cleavage of pepsin
Name a class of drugs that works at the K/H ATPase
proton pump inhibitors
Give examples of irreversible enzyme inhibitors
organophosphates (inhibitor of cholinesterase)
omeprazole
aspirin (COX inhibitor)
What are the effects of organophosphates?
twitching, severe weakness, paralysis, confusion, loss of reflexes, convulsions, coma, hypotension, bradycardia, salivation, defacation, urination
Where in the cells are CYP enzymes found?
inner membrane of mitochondria
endoplasmic reticulum
