Pharm 5 Flashcards
factors modifiying drug action
body size, age, routes of administration, psychological factors, pathological states, other drugs, tolerance
individual does wt formula
dose = bd wt/70 * average adult dose
individual dose BSA
Individual dose (BSA) = BSA (M2)/1.7 x average adult dose
young’s formula
Child dose =( age/age+12) x average adult dose (Young_s formula)
diling’s formula
Child dose = age/20 x average adult dose (Dilling_s formula)
tolerance
requirment of a higher dose of a drug to produce the effect
natural tolerance
if individual is inherently less sensitive to the drug
ex of natural tolerance
african ppl to hypertensives
acquired tolerance
repeated use of drug in an individual who was initially responsive,
results in less response
tolernace is seen more in
CNS depressants
tolerance need not develop equally to all effects of a drug, for example
tolerance develops to analgesic and euphoric actions of morphine but not to its constipating and mitotic actions
mechanisms of tolerance
pharmacokinetic/drug disposition tolerance,
pharmacodynamic/cellular tolerance
pharmacokinetic/drug disposition tolerance
the effective concentration of the durg at the active site is decreased, mostly by enhancement of drug elimination on cronic ues
eg of pharmacokinetic/drug disposition tolerance
barbiturates, carbamazepine
pharmacodynamic/cellular tolerance
drug action is reduced;
cells of target organ become less responsive;
may be due to downregulation of receptors, weakening of response effectuation or other compensatory homeostatic mechanisms
eg of pharmacodynamic/cellular tolerance
morphine,
barbiturate,
nitrates
cross tolerance
development of tolerance to pharmacologically related drugs
cross tolerance eg
alcoholics are relatively tolerant to barbiturates and general anesthetics
tachyphylaxis (acute tolerance)
literally means fast - protection
rapid development of tolerance, due to doses of a drug repeate in quick succession result in marked reduction in response
eg of tachyphylaxis
usually seen with indirectly acting drugs like
ephedrine,
tyramine,
amphetamine
how do these tachyphylactic drugs act
by releasing catecholamines in the body,
synthesis of which is unable to match release and as a result stores get depleted,
other mechanisms involved slow dissociation of drugs from its receptors,
internalization of receptors
receptor regulation
upregulation and down regulation
upregulation
prolonged deprivation of the agonist (by denervation or continued use of an antagonist or a drug which reduces input),
supersensitivity of the receptor as well as the effector system to the agonist
upregulation may occur due to
unmasking of receptors or their proliferations or accentuation of signal amplification by transducer
example of upregulation
sudden discontinuation of propranolol in angina pectoris -
down regulation
continued intense receptor stimulation causes desnesitization of refractoriness and the desired effect is not produced,
the receptor becomes less sensitive to the agonist
ex of downregulation
continuous use of beta 2 agonists in pateints with bronchial asthma
down regulation may occur due to
masking or internalization of the receptor,
decreased synthesis/increased destruction of the receptor
masking or internalization of the receptor
receptors become inaccessible to the agonists, refractoriness develops as well as fades quickly
decreased synthesis/increased destruction of the receptor
refractroiness develops over weeks or months and recedes slowly
therapeutic drug monitoring
measuring and monitoring of plasma concentration of a drug in a patient at different time intervals during treatment
when is therapeutic drug monitoring done
drugs whose therapeutic index is too low (toxic drugs) or whose therapeutic window is too narrow
drug concentration may vary from patient to patient due to
ogarnacijubetuc varuabkes – absirotuibm dustrubytion, and clearance (also half-life)
most TDM drugs work over a
small range
below the range the tdm drug
is not effective and the patient begins having symptoms again
above the range the tdm drug
produces toxicity
ex tdm drug
phenytoin (antiepileptic drug) plasma conc. Should be 10 - 20 ug/mL plasma
less than 10 ug phenytoin
failure of therapy
more than 20 ug phenytoin
toxicity – nystagmus, diplopia
Examples of drugs that need TDM
antiepileptics,
cardiac drugs,
antibiotics,
phychiatric drugs
antiepileptics
phenobarbital, phenytoin, valproic acid, arbamazepine, ethosuximide
cardiac drugs
digoxin,
quinidine,
procainamide
antibiotics
aminoglycosides (gentamicin, tobramycin, amikacin)
psychiatric drugs
lithium,
desipramine
adverse drug reactions
a response to a medicine used in humans or animals, which is noxious and unintended, including lack of efficacy, and which occurs at any dosage and can also result from overdose, misuse or abuse of a medicine
advers drug reactions are associated with
substantial morbidity and mortality
incidence of serious ADRs
6.70%
ards in hospital admissions
0.3 - 7 %
__.cause of death among hospitalized patients
4th to 6th
classification fo adr’s is based on
onset,
severity,
type
onset can be
acute,
subacute,
latent
acute occurse w/in
60 min
sub-acute
1 to 24hrs
latent
greater than 2 days
severity is classified into
mild, moderate, severe
mild
bothersome but requires no change in therapy
moderate
requires change in therapy,
additional treatment,
hospitalization
severe
disabling or life-threatening
severity
results in death, is life-threatening, requires hospitalization, prolongs hospitalization, causes disability, causes congenital anomalies, requires intervention to prevent permanent injury
Types of ADRs
A - augmented, B- bizzare, C -cumulative, D- delayed, E - end-of-use
type A -augmented
extension of pharmacological effect,
often predictable and dose dependent,
responsible for at least 2/3 of ADRs
type A eg
propranolol causes heart block,
anticholinergics cause dry mouth
type B - bizzarre
nature of reaction can’t be predicted,
idiosyncratic or immunologic reactions,
rare and unpredictable
Type B eg
chloramphenical and aplastic anemia
Type C - cumulative
associated with long-term use,
involve dose accumulation
Type C eg
phenacetin - interstitial nephritis,
antimalarials - ocular toxicity
Type D -delayed
delayed efects (dose independent)
Type D eg
carcinogenicity - immunosuppressants,
Teratogenicity - fetal hydantoin syndrome
Type E - End of use
associated with the withdrawl of a medicine,
Type E eg
insomnia anxiety and perceptual distrubances following the wothdrawal of benzodiazepines
Types of hypersensitivity
I-immediate or anaphyalactic (IgE),
II - cytotoxic antibody (IgG, IgM),
III - serum sickness/ag-ab complex (IgG, IgM),
IV- delayed hypersensitivity (cell mediated)
type I eg
anaphylaxis w/ penicillins
type II eg
methyldopa causes hemolytic anemia
type III eg
procainamide - induced lupus –>anti histone ab
type IV eg
contact dermatitis
common drugs causing ADRS
antibiotics, antineoplastics, anticoagulants, cardiovascular drugs, hypoglycemics, nsaid/analgesics, diagnostic agents, CNS drugs
Body systems commonly involved in ADR
hematologic, cns, dermatologic/allergic, metabolic, cardiovascular, gastrointestinal, renal/genitourinary, respiratory, sensory
ADR Risk Factors
age (children and elderly, multiple medications (polypharmacy),
altered physiology,
multiple co-morbid conditions,
inappropriate medication prescribing use or monitoring,
prior history of ADRs,
extent (dose) and duration of exposure,
genetic predisposition
Pharmacovigilance - ADR detection
subjective report , objective report, medication order screening, spontaneous reporting (most common), medication utilization review
subjective report
patient complaint
objective report
direct observation of event, abnormal findings (physical exam, laboratory test, diagnostic procedure)
medication order screening
abrupt medication discontinuation,
abrupt dosage reduction,
orders for “tracer” or “trigger” substances,
orders for special tests or serum drug concentrations
spontaneous reporting
most common
medication utilization review
computerized screening,
chart review and concurrent audits
Idiosyncracy
genetically determined abnormal reactivity to a drug/chemical,
also bizzare drug effects occure due to peculiariteis of an indifidual for no definate genotypic reason
idosyncracy eg
INH toxicity in slow/rapid acetylators,
G6PD deficiency
idiosyncracy for no genetic reasoning
barbiturates cause excitement and mental confusion in some individual
drug dependence
physical, psychological (withdrawl symptoms)
teratogenicity
thalidomide,
anticancer drugs,
androgens,
phenytoin
thalidomide
phocomelia
anticancer drugs
multiple defects,
fetal death
androgens
virilization,
limb esophageal cardiac defects
phenytoin
cleft lip/cleft palate
mutagenicity and carcinogenicity
anticancer drugs,
radioisotopes,
estrogen
mutagenicity is determined by
Ames test
Iatrogenesis
adverse effects or complications caused by or resulting from medical treatment or advice (drug-or-physician induced adverse effects)
iatrogenesis ex
steroid induced diabetes mellitus and osteoporosis,
drug-induced parkinsonism
tramadol induces
vomitting,
observed with oral, parenteral and continuous release preparations
contact dermatitis due to
Vit-K injury
clonidine induces
urticaria
teeth and nail discoloration due to
iron capsules
erythromycin induces
mobilliform rashes
s-amlodipine induces
pedal edema
heparin induces
contact dermatitis
dapsone induces
toxic epidermal cecrolysis
cotrimoxazole induces
fixed drug eruption
acetaminophen can cause
fixed drug reaction
