W4: Pharmacokinetics mechanism of drug-drug interaction Flashcards
One of the drug-drug interaction at the absorption phase is the _____.
Changes in pH
Some drugs are capable of changing the pH, disrupting the ____ of another drug
ionization
Drug-drug can also form _____ in the GIT to form insoluble complex for absorption.
complexes
Some drug affect intestinal ______. Higher_____, higher absorption rate.
blood flow
Bacterial flora can affect drug absorption by either _______ of drugs by metabolism or _____ in active form to be reabsorbed to liver.
can either inactive drugs or conjugates into active form
A type of drug that can be inactivated by bacterial flora is _______
Digoxin (medication for heart failure)
A type of drug that can be activated by bacterial flora is _______
Oral hormone contraceptives
Why is digoxin given with antibiotics? Is it safe?
Antibiotics kills the normal bacterial flora and this allows an increase in digoxin levels in the body.
Usually digoxin dose have to be reduced if given with antibiotics, otherwise it will lead to toxicity.
How will antibiotics affect oral hormone contraceptive? Consequences include?
Antibiotics kills the normal bacterial flora and oral hormone contraceptive won’t be activated. No effect will happen.
It might lead to unintended pregnancy because hormone regulation is normal.
How will drug-drug interaction be presented in distribution phase?
They will compete for plasma protein binding
How can two drugs fight for plasma protein binding?
They both bind at different degree hence the one with lower affinity will be displaced by another drug.
What are the two outcomes for drugs that fight for plasma protein binding?
The free drug (lower affinity for plasma protein) might cause:
- Increase in therapeutic effect due to increase distribution
- Toxicity if the free drug has a low therapeutic index
How can drug-drug interaction affect metabolism?
Drug can bind to lipid membrane of endoplasmic reticulum, which induce the microsomal cytochrome P450 enzymes (CYP450).
This can lead to competitive inhibit or induce metabolism of another drug.
What happens when drug A competitively induces metabolism of drug B?
It will lead to the increase in drug B metabolites and decrease the effect of drug.
What happens when drug C competitively inhibit metabolism of drug B?
It will lead to excessive drug B levels and toxicity. Emergence of side effects.
How can toxicity happen in competitively inducing metabolism?
A non toxic substance goes through metabolism to transform into its toxic metabolite.
Paracetamol’s metabolite , N-acetylbenzoqionone imine is toxic = paracetamol poisoning.
There is an ______ tolerance of drugs when competitively induced to metabolize.
Increase tolerance of drugs because there are increased levels of inactive metabolites
Factors affecting elimination of drug includes cardiac output, ________ and ________________.
- cardiac output
- lipid solubility
- glomerular filtration rate
If a drug goes through active tubular secretion (elimination), how can another drug affect this?
The other drug can competitively bind to the protein responsible for active transport, reducing the excretion rate and increases the concentration of the object drug.
- can lead to toxicity lorh
What is active tubular secretion?
When a drug relies on a protein transporter for elimination through the proximal tubules
What is object drug?
Object drug is the drug administered for an intended therapeutic effect that can be modified by another drug through drug interaction
What is precipitant drug?
The drug responsible for affecting the pharmacokinetics or pharmacodynamics of the object drug.
What is passive tubular reabsorption and what is it affected by?
The reabsorption of drug in the tubules regulated by concentration and lipid solubility.
which drug is easier to reabsorb? non-ionized or ionized drug ?
Non-ionized drugs are easier to be reabsorbed. In other words, ionized drugs are easier to be excreted .
Lithium is a positively charged element used to treat bipolar and depression. How can sodium bicarbonate interact with lithium?
Hint: elimination
Sodium bicarbonate can cause the urine to be alkaline which increases the clearance of lithium. A consequence of this is a decrease in lithium action in the body.
How can antacids affect the clearance of salicylates? Salicylate are salts of salicylic acid, use as analgesic agent for mild and moderate agents.
Antacids increases the pH of urine to increase clearance rate of salicylates and decrease its action.
In acidic urine, weakly acidic drugs will ______ excreted.
will not be excreted because it is non-ionized.
In acidic urine, weakly basic drugs will ______ excreted.
will be excreted because it is ionized.
In alkaline urine, weakly basic drugs will ______ excreted.
will not be excreted because it is non-ionized
In alkaline urine, weakly acidic drugs will ______ excreted.
will be excreted because it is ionized.
