drug interactions Flashcards
define clearance (CL)
The rate of drug elimination/drug plasma conc
Efficiency of irreversible elimination of a drug from systemic circulation
what can drug interactions lead to
adverse drug reactions (ADRs)
3 guidelines for prescribers
avoid co prescribing drugs with clinically significant interactions
appropriately monitor patients taking interacting drugs
recognise drug interactions and take appropotate action
what are the 2 types of drug-drug interactions
pharmacokinetic and pharmacodynamic
define drug interaction
occurs when a substance alters the expected performance of a drug
define pharmacodynamic
occur when drugs have an effect on the same target or physiological stem
the effect the drug has on the human body
define pharmacokinetic
occur when a drug affects the pharmacokinetics ( absorption, distribution, metabolism or excretion) of another drug
what the body does with the drug (the disposition of a compound within an organism)
what are the 4 types of pharmacodynamic interactions
- synergistic
- antagonistic
- summation
- potentation
synergistic - work together
antagonistic - cancel each other out
what kind of drugs are less problematic
highly selective drugs
describe synergy
interaction of drugs such that the total effect is greater than the sum of the individual effects (1+1>2)
describe antagonism
an antagonist is a substance that acts against and blocks an action (2 drugs opposed to each other) (1+1=0)
describe summation
different drugs used together to have the same effect as a single drug would (1+1=1)
describe potentaion
enhancement of one drug by another so that the combined effect is greater than the sum of each one alone (1+1=1+1.5)
are drug interactions only positive
no
Drug interactions can be positive or negative.
3 risk factors for drug interactions
Narrow therapeutic index
Steep dose/response curve
Saturable metabolism
4 mechanism steps for pharmacokinetics
Absorption, Distribution, Metabolism, Excretion
what 4 things affect absoprtion
Motility
Acidity
Solubility
Complex formation
how does motility affect absoprtion
if the gut has slowed digestion, the drugs won’t work as well (oral contraceptive pill and antibiotics is the most common interaction)
how does acidity affect absoroption
pH and pKa interactions.
3 ways the drug can distribute
can go into the proteins, other tissues or the effect site
describe protein binding
If you give 2 highly protein bound drugs, they will make each other strong and increase their effect so you always make sure you know what drugs the patient has taken before giving them new drugs
what 4 things affect metabolism
CYP450
inhibition
induction
excretion
impact of CYP450
Haemoproteins
Metabolise many substrates – endogenous and exogenous
what is inhibition
Drug A blocks metabolism of drug B, leaving more free drug B in the plasma so it has an increased effect
what is induction
Drug C induced CYP450 isoenzyme leading to increased metabolism of drug D so it has a decreased effect
what is excretion
Renal
- pH dependant
- Weak bases – cleared faster if urine is acidic
- Weak acids – cleared faster if urine alkali
Billary (minor)
3 mechanisms for pharmacoydnamics
Receptor based
Signal transduction
Physiological systems
describe receptor based
Agonists
Partial agonists
Antagonists
Competitive
Non-competitive
describe signal based
its rare
describe physiological systems
Different drugs that effect different receptors, but in the same physiological system
2 drug interactions to be aware of
Warfarin – lots of interactions – enzyme induction
Acute kidney injury – NSAIDs, ACEi
