Lecture 13 - Enzymes and Alcohol Flashcards
Why are enzymes important in pharmacology?
Drug metabolism
Drug targets
Drug metabolism
– Enzymes remove drugs from body
– Changes their activity can
change individual drug
responses
Drug Metabolism: Alcohol (Ethanol)
Slow process
Alcohol Dehydrogenase (ADH)
Acetaldehyde (Aldehyde)
Aldehyde Dehydrogenase
Acetic Acid
Between Ethanol and Allyl alcohol will the enzyme metabolizes first preferentially?
Ethanol kM = 0.45
Allyl kM = 3.0
Ethanol
Low kM
High O affinity
Ethylene Glycol metabolism and toxicity
Alcohol dehydrogenase (ADH) Glycolaldehyde (Aldehyde) Aldehyde dehydrogenase (ALDH) Glycolic acid (Glycolate) Glyoxylic acid Oxalic Acid (toxic)
The process to get rid of ethylene glycol makes it
More poisonous
To make the patient better need to prevent the pathway
How do you prevent the pathway of ethylene glycol from happening?
Give alcohol ethanol
Prevent Alcohol dehydrogenase and Aldehyde dehydrogenase
Poison info centre if patient took too much ethylene glycol threshold INTERVENTION LEVEL
Symptoms
Drowsiness
Mild irritation
Exposure to self harm
Poison info centre if patient took too much ethylene glycol TREATMENT
Ethanol
Fomepizole (inhibitor of Alcohol dehydrogenase)
Approved treatment for antifreeze poisoning
How do drugs act?
Go in body
Bind (enzymes, Receptors)
Change process
Change physiology
Receptors 4 types
Forms channel across membrane (K pumps, Na pumps, Ca pumps)
Transmit signal across membrane (Choline receptor)
Membrane bound enzymes
Intracellular.
Receptors come in lots of
shapes and sizes
Enzyme
1 active site
Change S to P
Bind S
Receptor
Multiple bind sites
Unchange
Bind ligands
protein molecule that receives chemical signals from outside a cell
Enzyme Terminology
Substrate
Inhibitor
Receptor Terminology
Ligand
Agonist
Antagonist
Ligand
Molecule / drug that binds to receptor
Agonist
Binds to receptor as something changes
A chemical capable of activating a receptor to induce a response
Increase action of receptor
Antagonist
A drug blocks receptor and stops the effects of another drug or molecule
What is an agonist at GABAa receptor?
Alcohol
GABAA Receptor
Multiple binding sites
Membrane bound
Ligand gated Cl- channel
GABAA receptor main effects
Inhibitory
Turns down responses to other stimuli
GABAA Ligands (many things that bind)
Ethanol (Alcohol)
Benzodiazepines (sedatives)
Barbiturates (seadtives)
When ligand binds conformation changes and allows
Cl- ions
Alcohol and GABAA
Agonist binding opens Cl- channels allows Cl- into cell
Decrease activity in brain
Loss coordination, memory loss, slurred speech etc.
Effects of Alcohol and GABAA depends on
dose
Lower dose of Alcohol and GABAA
Loss inhibitions and relaxation
High dose of Alcohol and GABAA
Coma or death
The enzymes in alcohol dehydrogenase.
In dehydrogenase can’t process alcohol quick enough
Alcohol builds up
More Cl- ions in cell
Leads to death
In the case study our patient showed slurred speech, drowsiness and
eventually became unresponsive. How can you account for these
symptoms?
thylene glycol binds to GABAA receptor and causes similar symptoms as Alcohol.
