M1 L4: Drug Reactions Flashcards
Adverse Drug Reactions
harmful or unintended responses from drug
side effects could be bad or okay - ADRs are very bad
2 causes of ADR
- iatrogenic
- error in prescribing, transcribing, dispensing, or administering drug - unexpected drug toxicity
- unintended drug response
2 types of ADR
- pharmacodynamic
- extension of therapeutic effect
- effects in non-target tissues or organs - non-pharmacodynamic
- unrelated to main drug action
- drug idiosyncrasy
- allergic reactions
- tolerance, addiction, and physical dependence
- teratogenesis (when mom takes something and it affects the baby)
- idiopathic drug reaction
2 types of ADR: Pharmacodynamic
- extension of therapeutic effect
- overdose - effects in non-target tissues or organs
- drug receptors exist in other tissues
7 types of ADR: non-pharmacodynamic
- unrelated to main drug reaction
- drug idiosyncrasy
- allergic reactions
- adverse biotransformation reactions
- tolerance, addiction, physical dependence
- teratogenesis
- idiopathic drug reaction
types of ADR mneumonic
A - Augmented: dose-related
B - Bizarre: non-dose related
C - Chronic: dose related and time related
D - Delayed: time related
E - end of use: withdrawal
F - failure: failure of therapy
Drug-Drug Interactions
effect one drug has in the presence of another
the more drugs a pt takes the more likely
can be beneficial which:
- increases effectiveness, decreases toxcicity
or the opposite and be harmful
risk factors for DDI
- age
- polypharmacy
- genetic factors
- drug properties
- pathological conditions
5 types of DDI
- addition
- synergistic
- antagonistic
- potentiation
- altered physiology
Potentiation can overlap with synergistic
Addition DDI
1+1=2
2 drugs bind to the same receptor to produce the same effect (sedation)
greater effect greater sedation
ex: 2 benzodiazepine drugs given together -> additive effect
Synergism DDI
1+1=3
2 drugs bind to diff receptors - increase sedative effect
2 do the same job
ex: barbiturate + alcohol = increased CNS depression
Antagonism DDI example
1+1=0
ex: naloxone inhibits the effects of morphine at the opioid receptor.
Potentiation
One drug does not elicit a response on its own but enhances the response of another drug.
Ex: penicillin + clavulanic acid = increased penicillin effect
(clavulanic acid: not an antibiotic, prevents antibiotic resistance in bacteria that secrete beta lactamase enzyme, inactivates most penicillin
Altered Physiology
ex: hydrochloro (HCT; diuretic) = increased digitalis toxicity
HCT - K+ excretion - hypokalemia
digitalis toxicity increased by hypokalemia
what is the link btwn DDI’s and pharmacokinetics
one drug alters ADME of another drug - alters concentration of drug - alters the drug response
DDI and absorption
drug rate may alter the rate and/or extent of absorption of another drug
Ca+ rich sources interfere with tetracycline antibiotics
laxatives enhance intestinal motility - decrease absorption of other drugs
anticholinergics delay rate of absorption
prokinetic drugs enhance rate of absorption
- Tetracycline - usually taken orally
- Calcium tends to combine tetracycline kelates (idk how to spell it) and be secreted together
- With tetracycline dairy products would cause the drug not to be absorbed
- Anticholinergic - tend to reduce motility of the intestine, they interfere with absorption
DDI and distribution
one drug may alter the distribution of another
ex: competition on the same protein binding sites in blood (sulphonamide displaces warfarin)
Anything to interfere with delivery will affect distribution of drug
Warfarin - is a oral anticoagulant to help the blood fluid without clotting
Sulphonamide - compete with warfarin
DDI and biotransformation
some drugs affect the activity of the cytochrome P450 (CYP) enzymes
- CYP’s are important in metabolism of many drugs, and endogenous substances
enzyme induction - increases CYP activity - increases rate of drug metabolism - decreases drug’s effect - decreases drug’s benefit
enzyme inhibition - decreases CYP activity - decreases rate of drug metabolism - increases drug effect - increases ADR
Takes care of metabolism of drugs
If you have liver disease or something that inhibits this, adverse effects will rise because the drug will not exit the body
Enzyme induction: some will stimulate the system, become too active and break down the drugs quickly
Enzyme inhibition: some drugs will inhibit the system, these drugs will accumulate and make adverse effects in the body
Ex of enzyme inducers
Barbiturates and anti-convulsant
phenytoin
carbamazepine
rifampicin
smoking
Ex of enzyme inhibitors
cimetidine
ciprofloxacin
erythromycin
fluoxetine
grapefruit
DDI and excretion
one drug may alter rate of excretion of another drug by the kidneys
(anything that affects kidneys affects excretion!)
enhancing excretion: diuretics increase amount of urine - increase excretion of other drugs
delaying excretion:
- probenecid competitively inhibit penicillin excretion - increase therapeutic effect (beneficial)
- NSAIDs competitively inhibit methotrexate excretion - increase toxicity (harmful)
Drug-Food Interactions (2)
- Grapefruit
- Decreases CYP 3A4 (this is the grapefruit enzyme inhibitor very important and metabolizes 50% of medications) and increases drug response
ex: calcium channel blockers - Tyramine-containing food
- tyramine: has sympathomimetic effect, is inactivated by MAO enzyme
- MAOI prevent tyramine inactivation - severe hypertension
ex: some types of cheese
