Week 2: Introduction to Drug Interactions Flashcards
Drug Interactions Pharmacokinetics Pharmacodynamics
Likelihood and significance of drug interactions
Increasing amount of drugs being taken will increase the likelihood of a drug interaction
Not all drugs interactions are clinically significant
Potential clinical significance
When a therapeutic combination could lead to an unexplained change or complication in the patients condition
What is a drug interaction?
An interaction is said to occur when the effects of one drug are changed by the presence of another drug, herbal medicine, food, drink, medical conditions or environmental chemical agent
What is the effect of a drug interaction?
Additive or increased exposure/effects of one or more drugs
Decreased exposure or effects of one or more drugs causing decreased effectiveness
Antagonism of the effects of one or more drugs
Clinically important drug interactions
Drugs with a narrow therapeutic index
Drugs with a steep dose-response curve
Drug-Disease interactions examples
Tricyclic antidepressant and history of postural hypotension
Long term use of NSAID for osteoarthritis and chronic renal failure
Anticholinergic drugs to prevent extrapyramidal side effects of antipsychotic drugs
Long term prescription of long half life benzodiazepine to treat insomnia, dementia or anxiety
Drug-Food and Drug-Herb interaction examples
Alterations of drug absorption
Grapefruit juice inhibits intestinal CYP3A4
Vitamin K and Warfarin
Herbal products with anticoagulant and anti platelet properties
What is pharmacokinetics?
The effects of the drug on the body
Absorption, distribution, metabolism and excretion
What is pharmacodynamics?
The effects of the body on the drug
e.g. receptor interactions
What is Cmax?
The maximum concentration of the drug in the bloodstream from a dose
What is Tmax?
The time it takes for the drug to reach Cmax
What is the half life?
The time it takes for half of the concentration within the bloodstream to clear from the body
What does area under the curve of a concentration time graph indicate?
The total exposure to the drug that the body receives `
What is absorption?
The routes of drug administration
Drug travels through the gut to liver to veins to heart to lungs to heart then to arterial circulation
The route of administration impacts the time for drug action to occur
What is distribution?
- 4 main compartments of the body
- Volume of distribution calculation
Movement of drug between compartments of body (blood/plasma, fat, extracellular fluid, intracellular fluid)
Free drug can move between bound drug is localized to that compartment to eventually reach equilibrium across all compartments
The Vd = total amount of drug in body/concentration of drug in plasma
What is metabolism?
- First pass metabolism
Metabolism of the drug often occurs in the liver
FIrst pass metabolism refers to oral drugs entering the liver before distribution therefore are metabolized before having an effect on the body thus a reduction in dose reaching the circulation occurs
What is a cytochrome p450 enzyme?
- Processes
- Phases
Metabolite within the liver to metabolis various forms of drugs
Processes include: Oxidation, Hydrolysis and Hydroxylation
The two phases are metabolism for drug activation and metabolism for drug excretion
What is excretion?
- Clearance formula
Irreversable removal of drug from body
Most drugs excreted by kidneys (nephron to collecting duct to urine)
Clearance = (Concentration of drug in urine x Rate urine produced) / Concentration of drug in plasma
What are the order of kinetics?
First order - Excretion rate dependent on plasma concentration
Zero order - Excretion rate independent of plasma concentration (metabolite to excrete)
What are the 4 pillars of Quality of Medicines (QUM)
Safety
Efficacy
Judiciousness
Appropriateness
Pharmacokinetic changes in elderly
Renal function often deteriorates - influences excretion
Measured by creatinine clearance
Pharmacodynamic changes in elderly
Altered sensitivity to drugs due to changes in drug receptors and target organ responses
Reduced physiological reserves and impairment of secondary compensatory mechanism predisposes to adverse effects
What is polypharmacy?
- Superpolypharmacy
Multiple drugs
Increased risk of drug interactions and adverse effects
Superpolypharmacy - +10 drugs
Can also occur by misdiagnosing symptoms as new disease when it is adverse effects of current medication
What is adherence?
- How is it maximised
The extent to which a person’s behaviour corresponds with agreed recommendations from health care provider
Maximise by building a therapeutic alliance with patient
What is hepatic impairment?
Acute or chronic liver dysfunction impairs patients ability to metabolize drugs and thus eliminate them
What are some factors that influence the action of drugs within the body?
The action of some drugs can be influenced by genetics, extreme heat (Queensland)
What are the 4 stages of prescribing and therapeutic decision making?
The 4 stages are information gathering, decision making, communication and review/monitor/follow up
What is teratogenic exposure?
Exogenous agent that can modify any embryonic of fetal functional or structural development
What factors affect the teratogenicity and placental transfer of a drug?
Gestational timing of dose (which trimester mother is in)
Size of dose/administration route
Lipophilicity
What proves a drug is a teratogen?
Produces deformities in >2-3% exposed mothers
Consistent pattern of deformities
Define Category A drugs for pregnant women
Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in frequency of malformation or other direct or indirect harmful effects on fetus
Define Category B1 drugs for pregnant women
Drugs which have been taken by only a limited number of pregnant women and women of child bearing age, without an increase in frequency of malformation or other direct or indirect harmful effects of fetus
Studies in animals have not shown evidence of an increased occurrence of fetal damage
Define Category B2 drugs for pregnant women
Drugs which have been taken by only a limited number of pregnant women and women of child bearing age without an increase in the frequency of malformation or other direct or indirect harmful effects of fetus
Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage
Define Category B3 drugs for pregnant women
Drugs which have been taken by only a limited number of pregnant women and women of child bearing age, without an increase in frequency of malformation or other direct or indirect harmful effects on the fetus
Studies in animals have shown evidence of an increased occurrence of fetal damage (significance in humans is uncertain)
Define Category C drugs for pregnant women
Drugs which have caused or may be suspected of causing harmful effects on fetus or neonate without causing malformations
These effects may be reversible
Define Category D drugs for pregnant women
Drugs which have caused, are suspected to have caused or may be expected to cause an increase incidence of fetal malformation or irreversible damage
These drugs may have adverse pharmacological effects
Define Category X drugs for pregnant women
Drugs which have such a high risk of causing permanent damage to fetus that they should not be used in pregnancy or when there is the possibility of pregnancy
