what are the 2 factors that affect the drug interaction consequence?
patient-related factors (ex: diet, genetics..)
administration - related factors (ex: route, dosage, order...)
when are drug interactions beneficial? harmful?
beneficial if therapeutic effects increase and toxicity or cost decrease
harmful if opposite
what are 5 consequences of drug interactions?
potentiation: drug B increases drug A
additive: total effect = drug A + B -> alcohol & anxiolytics (harmful)
synergistic: total effect > drugs A + B -> codeine + NSAIDs (beneficial)
antagonistic: drug B decreases drug A -> naloxone decreases heroin (beneficial)
unique: effect unrelated to A or B
what are chemical/physical interactions?
most common when drugs pre-combined in IV -> frequently form precipitate
most likely antagonist
risk of chemical interactions in body decreases cuz of body water dilution
no precipitate DOES NOT MEAN no interaction
what are kinetic interactions? what are 4 types?
response alteration via changes in bioavailability
absorption: gastric pH alterations, GI transit alterations, P-glycoprotein affinity/concentration
distribution: extracellular pH alterations, plasma protein affinity
metabolism: hepatic enzyme induction/inhibition
excretion: GF alterations, urine pH alterations, P-glycoprotein, tubular secretion transporters competition
what are CYP1A2 substrates, inducers and inhibitors?
clozapine, methadone
tobacco, carbamazepine
acyclovir, oral contraceptives
what are CYP2C9 substrates, inducers and inhibitors?
warfarin, diazepam
carbamazepine, st-john's worth
azaleas, isoniazid
what are CYP2C19 substrates, inducers and inhibitors?
clopidogrel, phenytoin
st-john's worth, phenytoin
cimetidine, isoniazid
what are CYP2D6 substrates, inducers and inhibitors?
codeine
not inducible
ritonavir, propanolol
what are CYP3A4 substrates, inducers and inhibitors?
immunosuppressants, anti-cancer, antibiotics...
carbamazepine, st john's worth
ritonavir, cyclosporine, grapefruit
what is dynamic interactions?
response alteration via changes in effective concentration -> amount of drug molecule contributing to physiological effects?
what are 2 interactions in dynamic?
1. receptor interactions
a. antagonism ex: warfarin + vitamin K
b. regulation/tolerance ex: alcohol abuse decreases GABA receptors
2.physiological interactions
ex: alcohol + cocaine = opposite physiological effect
what are food-drug interactions?
clinically significant but poorly researched
decreased drug response
metabolic interactions
absorption interactions
grapefruit juice -> inhibition of CYP3A4 -> increase drug bioavailability
what should be nursing clinical considerations of interactions (3)?
1. notice situations w/higher risk of interactions
2. minimize adverse effects of interactions (complete history, reduce Rx)
3. watch for timing of meal + drug intake (empty stomach is 1 hour before meal or 2 hours after)
what does right ward shift DRC mean? left ward shift?
lower drug response
higher drug response
what are ADRs?
adverse drug reactions: noxious, unintended, undesired effect occuring at normal dose
what are 5 ADRs?
Augmented -> dose dependent predicted from known pharmacology of drug -> hypoglycaemia insulin (most common)
Bizarre -> unpredictable, dose independent, rare, fatal -> anaphylaxis to penicillin (most common)
Chronic -> prolong treatment
Delayed -> after years of treatment
End of use -> withdrawal effect
what are examples of idiosyncratic toxicities?
SJS and TEN
what is hepatoxicity? what are examples of hepatotoxic drugs?
an acute or chronic liver injury secondary to drugs or herbal compounds.
liver enzymes convert drugs into toxic metabolites
frequent cause of acute liver failure
statins, anti seizure, antifungals, antimicrobials, acetaminophen
what is nursing advice for hepatoxicity?
frequent LFT -> look for increases AST or ALT (liver enzymes)
monitor liver injury Sx (jaundice)
educate patient
what are QT interval drugs? examples?
they prolong QT interval time, female risk > cuz already long QT
QT>470 sec -> increased dysrhythmias -> increased V fib
antidysrhythmic, antipsychotics, antidepressants, antimicrobials..
what are side effects?
Nearly unavoidable secondary drug effectsat therapeutic dosage• Usually Type A (Predictable & Dose-dependent)• Ex.: Gastric irritation from Aspirin• Ex.: Constipation from opioid analgesics
what are idiosyncratic effects?
Uncommon DR resulting from GeneticVariation• Usually Type B (Dose independent & Unrelated)• Ex.: G6PD Deficiency + Aspirin → RBC Hemolysis
what is toxicity?
Detrimental physiologic effects caused byexcessive drug dosage• Definines ANY SEVERE ADR regardless of dosage• Ex.: Coma from Morphine overdose• Ex.:Neutropenia from anticancer therapeutic dose
what are allergic reactions?
Aberrant and harmful immune responsetriggered by a drug• Example of idiosyncratic effect• Most severe AR caused by Penicillins
what is physical dependance?
Physiological adaptation to long-term drug effects• Ex.: Nasal congestion after using sprays• Ex.: Insomnia without sleeping pills
what is carcinogenic effect?
Ability of a drug to induce mutations leading to cancer development• Usually undocumented until many years post-marketing
what is addiction?
Addiction = Physical + Psychological Dependence
what is physiological dependence?
Intense motivational cravings to consume a drug• Ex.: Opioids; Nicotine dependence
what is teratogenic effect?
Ability of a drug to induce birth defects (Thalidomide!!)• Scrutinized and tested during new drug development
what are the nursing clinical considerations of ADR?
1. identifying ADRs
2. Minimizing ADRs
3. Patient advocacy + education
what are medication errors? is it common? give examples of errors
any preventable event that may cause inappropriate medication use or patient harm, while medication is in control of HCP
major cause of morbidity + mortality -> injures 1.5 M + kills 7000/year
wrong patient/drug/route/time/dose...
what are major causes of meds errors?
human factors: stress, knowledge deficit, drug preparation error
communication mistakes: illegible handwriting, oral order confusion
name confusion: Celebrex vs celexa / rifampin vs rifaximin
packaging mistakes
what are nursing clinical considerations of meds errors?
nurses = last line of defence -> no one can catch nurse mistake
minimize them
report them
why do we need to adjust dosages for pregnant women?
pregnancy physiological changes = increased BP -> increased GFR -> increased excretion
increased GI transit time -> increased absorption
can a teratogen always affect baby? are they major causes of birth defects?
no, there are windows of variability that vary per organ/drug/defect/fetus
minor cause of birth defects <1%
what are 3 types of teratogens? what are known teratogens?
fast-acting = easier to detect
slow acting = harder to detect
behavioural = impossible
alcohol, ACE inhibitors, sex hormones, anti seizure drugs, anticancer, thalidomide
what are drugs to avoid during breast feeding?
all drugs of abuse
anticancer/immunosuppressants
radioactive compounds
atenolol
lithium
what are drugs safe during breast feeding?
analgesia
anticoagulants
antidepressants
beta-blockers
glucocorticoids
what is patient-education advice for drugs + breast feeding?
administer immediately after or even during it
avoid Rx w/long T1/2 or sustained release formulations
what are considerations of infant drug administration?
kids NOT mini adults
organ immaturity -> infant drug sensitivity > adults
what are 5 major PK (kinetics) processes that neonates/infants have immaturity in?
absorption
protein binding
permeable BBB
hepatic metabolism
renal excretion
what are specific adverse effects in infants?
interference w/developmental process
ex: androgens, aspirin, chloramphenicol, glucocorticoids, promethazine, fluoroquinolone...
what are nursing pediatric considerations?
dosage
adherence promotion
what are elderly kinetic changes?
essentially everything decreases except body fat + gastric pH
kinetics similar to neonates
how does body water:fat ratio change affect drugs?
lipid soluble = more diluted
water soluble = more concentrated
what are nursing considerations for geriatrics?
minimize ADR
avoid these drugs: ibuprofen + aspirin, proton-pump inhibitors, benzodiazepines barbiturates, alpha-blockers
remember adherence promotion