Lecture 19 - drug interactions Flashcards
describe what a drug interaction is and the properties of a drug interaction.
a drug interaction is a pharmacological or clinical response to the administration of a drug combination differs from the known effects of the two agents when given alone.
object drug is the drug affected by the interaction and precipitant drug is the drug causing the interaction
it may be harmful causing toxicity and reduced efficacy or may be beneficial causing synergistic combinations, increased convenience, reduced toxicity and cost reduction
what are the causes of drug-drug interactions ?
True incidence difficult to determine
Data for drug-related hospital admissions do not separate out drug interactions, focus on adverse drug reactions
Most data are in the form of case reports
Patients receiving polypharmacy are at risk
Difficulty in assessing role of OTC and herbal drugs in drug interactions
what are two types of drug drug interactions?
pharmacokinetics is when one drug alters the level of another
and pharmacodynamic when there is no change in drug level. Activity of one drug is altered by another
describe the pharmacokinetics of how a drug is metabolised in the body
- site of absorption - drug absorbed into bloodstream by the GI tract
- Plasma protein binding - After absorption, the drug can bind to plasma proteins in the blood
- Site of metabolism: The liver is often the main site where drugs are metabolized or broken down into different chemicals
- Site of action: The drug reaches its target location in the body where it will exert its intended effect.
- Site of excretion/reabsorption: Finally, the drug or its metabolites are excreted from the body, commonly through the kidneys into the urine, or through the bile into the feces.
the free drug interacts with different sites of action
describe the pharmacokinetic interactions at the gastrointestinal tract
GI is the site of drug absorption.
Tetracycline can form insoluble complexes with metal ions such as iron, aluminium, and calcium.
As a result of these interactions, there is a loss of therapeutic effect of tetracycline,
what sit he interaction between quinolone antibiotics and antacids
there is alteration in absorption known which causes a process known as chelation.
Therefore, it sir recommended of the cheating drug such as antacids to be taken 4 hours before the antibiotics or 2 hours afters the antibiotic dose.
the graph indicates indicates that the absorption of moxifloxacin is significantly reduced when administered with Maalox
what is a drug drug interaction affecting adsorption
colestyramine which is a cholesterol reducing agent binds t warfarin, thyroxin and digoxin, causing reduced absorption and therapeutic effect.
how can stomach pH alter the absorption of a drug?
stomach pH can alter the absorption of the drug ketoconazole when taken with antacids or H2 antagonists
Ketoconazole absorption is pH dependent with highest absorption at low gastric pH
the dissolution of ketoconazole is decreased at pH>5
how can certain drugs can affect the absorption of other medications by altering gastrointestinal (GI) motility?
drugs increasing gastric emptying such as metoclopramide and domperidone decreases time for dissolution and absorption of drugs in the stomach eg digoxin and can lead to increased absorption of drug normally absorbed from the small intestine eg ciclosporin
nversely, drugs that decrease gastric emptying, such as opioid analgesics (e.g., morphine) and anticholinergics, can slow down GI motility, potentially leading to a decreased absorption of other drug
what is the drug interaction between digoxin ad quinidine ?
digoxin is sued of heart failure and quinidine for antiarrhythmics
Both medications bind to proteins within the body, but when used together, quinidine can displace digoxin from its protein binding sites. This displacement can lead to an increase in the levels of free digoxin in the bloodstream, as a result there can be increase in digoxin toxicity which manifests as arrhythmias, visual disturbances or Gi disturbances
outline the importance of hepatic metbaolism in the liver
Numerous drugs are enzymatically metabolised in the liver:
Phase 1 Metabolism
Oxidation
Reduction
Hydrolysis
cytochrome P450 groups; oxidation of drugs
what is the cytochrome P450 system ?
groups of enzymes that modify some drugs -substrates, can be turned off - act as inhibitors or can be enhanced ie inducers
discuss the metabolism of drugs by the CYP450 enzymes
Some drugs are metabolized by a single isozyme of CYP450. Examples include:
Desipramine metabolized by CYP2D6
Omeprazole metabolized by CYP2C19
Diclofenac metabolized by CYP2C19
Most drugs are metabolised by more than one isozyme e.g. imipramine (CYP2D6, CYP1A2, CYP2C19)
If co-administered with CYP450 inhibitor, some isozymes may compensate for inhibited isozyme
what are the substates and inhibitors of the CYP2C9 family?
substrates are sulfonylureas and S-warfarin
inhibitors are sulfamethoxazole, amiodarone, cimetidine, fluoxetine and fluxconazole
patients administered co-trimoxazole and sulfonylureas were 8 time more likely hospitalised due to hypoglycaemia
discuss the concept and of CYP450 induction
Inducers are a list of drugs that can increase cyp450 enzymes activity. such as rifampicin, carbamazepine, phenobarbital, phenytoin, nevirapine, pioglitazone and st johns wort.
The induction process has a gradual onset and offset because it involves increased DNA transcription and the synthesis of new CYP enzymes
Onset and offset
(Depends on t1/2 of inducer, time to make new CYP proteins, and rate of degradation of CYP proteins)
