Lec 19-Drug interactions Flashcards
What is a drug interaction
- An interactions occur when
- The effects of one drug are altered by the co-administration of another drug; herbal medicine; food drink or other environment chemical agent
What is a drug interaction
Effects of one drug are changed
- Presence/effects of another drug
- Herbal medicine
- Food or drink
- Environmental chemical agents
What might happen
- Additive or enhanced effect of one or more drugs
- Antagonism of the effect of one or more drugs
- Any other alteration in the effect of one or more drugs
- NB drug interactions vs ADR
- NB effect vs Clinical effect
More at risk patients
- Risk increases with number of drugs used
- ADR patients taking 6-10 drugs:7%
- ADR patients taking 16-20 drugs: 40% (rise largely attributed to drug infraction’s)
Risk groups of Polypharmacy
- Hepatic disease
- Renal disease
- Long term therapy for chronic disease
- Patients in intensive care
- Transplants patients
- Patients undergoing complicated surgery
- Those with more than 1 prescriber
Risk factor for drug interactions
- Number of drugs
- Extremes of age
- Chronic medical conditions
- Transplantation
- Critical illness
- Complex surgical procedures
Problem drugs
- Narrow therapeutic index (safety ratio): warfarin; phenytoin; Li; digoxin; theophylline
- Hepatic enzyme inducers: rifampicin; carbamazepine; phenytoin; phenobarbitone
- Hepatic enzyme Inhibitors: fluconazole; erythomycin; fluoxetine; cimetidine; ciprofloxacin; diltazem; verapamil
Inhibition
- Normal drug metabolism: normal levels of enzymes convert drugs into metabolites. Depending on the drug, these metabolites may be therapeutic, harmful or inactive
- Inhibitors and drug metabolism : inhibiting compounds block drug metabolism enzymes. Depending on the drug, inhibition can lead to reduced therapeutic effects or toxic buildup of unmetabolized compounds
Clinical consequences
- Therapeutic failure
- Toxicity
- Enhanced therapeutic effect
Pharmacodynamic interactions
- How a drug acts on the body
- Pharmacodynamic interactions include
- Agonists and antagonists same receptors
- Additive effects on a physiological systems
- Opposing effects on a physiological system
- Alterations in fluid/electrolyte balance
- Interference with transport mechanisms
Pharmacodynamic interaction examples
- Synergism (multiplication of effects more than additive) : progesterone and oestrogen; Alcohol and anti-depressants
- Additives: Multiple anti-HTN: ACEI’s and thiazide diuretics
- Antagonism: B-agonists and B-blocker; Anti-coagulants and vit K
Pharmacokinetics (kinesis is moving about)
-What the body does to a drug Interactions can affect: -Absorption-how drugs get to site -Distribution- how drugs get to site -Metabolism- how there removed -Excretion- how there removed
Pharmacokinetic stages
- Drug –> GI tract -(absorption) –> intravascular compartment (circulation) Extravascular compartment (tissue) —> effect
- Drug removed by metabolism/excretion at intravascular compartment
Absorption
- Rate of absorption will be affected by route of administration
- Intravenous= fast
- Oral; intramuscular; percutaneous= slower
Oral administration
- Drug absorbed from small intestine
- Cell membranes are lipid barriers between aqueous compartments of the body
- Rate of drug absorption determined by: lipid solubility; ionisation
Drug diffusion across a membrane
- Gasous cross membrane
- Hydrophobic molecules: benzene cross membrane
- Small polar molecules: ethanol, water- cross membrane
- Large polar molecules: glucose; don’t pass membranes
- Charged molecules: Don’t pass membranes
Intraction’s affecting absorption
Drugs can affect
-pH
-GI motility
-Chelation (chemical reaction between large multi ring structure and certain metals Ca2+ from antacids and tetracyclines )
Can alter
-Rate of absorption (MR will have the same amount of drug released but will have lower but longer time reducing toxicity)
-Amount absorbed (on a graph this is the area under the curve
Incidence
THEORETICAL:
CLINICALLY RELAVENT
