pharmocology 3 drug metabolism and interactions Flashcards
adverse drugs effects
Type A - pharmacological or toxic effect Type B - idiosyncrasy drug allergy
drugs with low therapeutic index
- anticoagulant i.e. warfarin
- aminoglycoside antibiotics i.e. gentamicin
- anticonvulsants i.e. phenytoin
high risk of going into toxic concentrations
adverse drug effect site of actions
1) localised
- asprin (mouth ulcers, GI irritation)
2) systemic
- majority of reactions
adverse drug effects time course
1) acute toxicity
- narcotics
- single intake/rapid onset
2) sub acute toxicity
- repeated exposure (hours/days)
- tetracycline i.e. rental impairment
3) chronic toxicity
- repeated exposure (months /years)
- chemical carcinogenesis
mechanisms of type A adverse effects
- for augmented
- exaggerated therapeutic responses
- secondary unwanted actions
- more predictable or anticipated effects
mechanisms of type B adverse effects
- pharmacologically unexpected unpredictable or idiosyncratic adverse reactions
- immunologic (allergic or anaphylactic)
- idiosyncratic (qualitively abnormal adverse reactions that occur in a given individual and whose mechanisms is not yet understood)
type A reactions what to look for
predictable mainly dictated by the dose given to the pt
- respiratory depression
cardiac toxicity
what pharmokinetics can be targeted fro adverse effects of the drugs
- absorption
- distribution
- metabolism
- excretion
when should antacids and iron preparation s be take
empty stomahc
decrease absorption by chelation
what may cause abnormal drug metaboliums
effect on CP450 drug metabolising enzyme (induction or inhibition)
disease (rental or hepatic dysfunction)
inherited factors either phase 1 oxidation or 2 conjugation
factors which affect renal excretion of drugs
1) kidney function
2) protein binding
3) urine pH
4) urine flow
renal excretion of drugs controlled by
1) glomerular filtration
2) tubular secretion
3) tubular reabsorption
type A vs B reaction
Pharmacologically predictable A yes B no dose dependan A yes B no Incidence and morbidity high A low B treatment decrease dose A B stop
drug allergy characteristics
- delay after initial exposure
- precipitated with small doses of drug
- does not resemble normal pharmacology
- classical symptoms of allergic response
drug allergy drug related factors
nature of the drug
degree of exposure
route of administration
cross sensitisation ie close structural chemical relationship with other drugs
drug allergy host related factors
age sex genetic factors diseases previous exposire
anaphylaxis mechansim
release of inflammatory mediators from mast cells to tissue oedema/damage
signs and symptoms of anaphylaxis
SOB lightheadedness confusion diarhoeaa skin rash/hives HR change
tx for anaphylaxis
adrenaline
antihistamine
steroids
B2 antagonist ie bronchodilator
drug drug interaction mechanisms and subdivisions
1) pharmaceutical
2) pharmacodynamic
3) pharmacokinetic
- absorption
- distribution
- metabolism
- excretion
how are drugs metabolised in the liver
CP450 enuzyme
drug drug interactions can either
Can lead to
1) no effect
2) beneficial effect
- eg using antagist and agonist together, produces an effect without the toxicity
3) toxic effect
CYP3A induction
induction of enzyme activity particularly cytochrome P450
- Requires synthesis of new enzymes
- leads to loss of efficacy in the same dose
what do enzyme inhibitors do with blood/drug conc levels
increase concentration of drug within blood levesl
enzyme inducers
reduce concentration of drug in blood levels
metabolised faster therefore leads to faster excreation
substrates which use cytochrome P3A
midazolam
what does erthromycin do
inhibitor
increases the effect of eg warfarin by inhibition of CP450
midazolam
inhibits CP3A
therefore increases the plasma concentration of teh drug
st johns wort
extract from flower
enhances metabolism of drugs
reduces plasma levels by inducing CYP3A
excessive dosage of LA effects
CNS stimulation by depressing inhibitory pathway
then CNS depression: leathargy , respiratory depression, unconcoisness,
effect of CYP3A4 and benzodiazepines
inhibition (increase plasma levels)
