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Flashcards in Pharm 5 Deck (107)
1

factors modifiying drug action

body size,
age,
routes of administration,
psychological factors,
pathological states,
other drugs,
tolerance

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individual does wt formula

dose = bd wt/70 * average adult dose

3

individual dose BSA

Individual dose (BSA) = BSA (M2)/1.7 x average adult dose

4

young's formula

Child dose =( age/age+12) x average adult dose (Young_s formula)

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diling's formula

Child dose = age/20 x average adult dose (Dilling_s formula)

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tolerance

requirment of a higher dose of a drug to produce the effect

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natural tolerance

if individual is inherently less sensitive to the drug

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ex of natural tolerance

african ppl to hypertensives

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acquired tolerance

repeated use of drug in an individual who was initially responsive,
results in less response

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tolernace is seen more in

CNS depressants

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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

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mechanisms of tolerance

pharmacokinetic/drug disposition tolerance,
pharmacodynamic/cellular tolerance

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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

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eg of pharmacokinetic/drug disposition tolerance

barbiturates, carbamazepine

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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

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eg of pharmacodynamic/cellular tolerance

morphine,
barbiturate,
nitrates

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cross tolerance

development of tolerance to pharmacologically related drugs

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cross tolerance eg

alcoholics are relatively tolerant to barbiturates and general anesthetics

19

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

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eg of tachyphylaxis

usually seen with indirectly acting drugs like
ephedrine,
tyramine,
amphetamine

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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

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receptor regulation

upregulation and down regulation

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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

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upregulation may occur due to

unmasking of receptors or their proliferations or accentuation of signal amplification by transducer

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example of upregulation

sudden discontinuation of propranolol in angina pectoris -

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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

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ex of downregulation

continuous use of beta 2 agonists in pateints with bronchial asthma

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down regulation may occur due to

masking or internalization of the receptor,
decreased synthesis/increased destruction of the receptor

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masking or internalization of the receptor

receptors become inaccessible to the agonists, refractoriness develops as well as fades quickly

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decreased synthesis/increased destruction of the receptor

refractroiness develops over weeks or months and recedes slowly

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therapeutic drug monitoring

measuring and monitoring of plasma concentration of a drug in a patient at different time intervals during treatment

32

when is therapeutic drug monitoring done

drugs whose therapeutic index is too low (toxic drugs) or whose therapeutic window is too narrow

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drug concentration may vary from patient to patient due to

ogarnacijubetuc varuabkes -- absirotuibm dustrubytion, and clearance (also half-life)

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most TDM drugs work over a

small range

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below the range the tdm drug

is not effective and the patient begins having symptoms again

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above the range the tdm drug

produces toxicity

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ex tdm drug

phenytoin (antiepileptic drug) plasma conc. Should be 10 - 20 ug/mL plasma

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less than 10 ug phenytoin

failure of therapy

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more than 20 ug phenytoin

toxicity -- nystagmus, diplopia

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Examples of drugs that need TDM

antiepileptics,
cardiac drugs,
antibiotics,
phychiatric drugs

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antiepileptics

phenobarbital,
phenytoin,
valproic acid,
arbamazepine,
ethosuximide

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cardiac drugs

digoxin,
quinidine,
procainamide

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antibiotics

aminoglycosides (gentamicin, tobramycin, amikacin)

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psychiatric drugs

lithium,
desipramine

45

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

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advers drug reactions are associated with

substantial morbidity and mortality

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incidence of serious ADRs

6.70%

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ards in hospital admissions

0.3 - 7 %

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__.cause of death among hospitalized patients

4th to 6th

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classification fo adr's is based on

onset,
severity,
type

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onset can be

acute,
subacute,
latent

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acute occurse w/in

60 min

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sub-acute

1 to 24hrs

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latent

greater than 2 days

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severity is classified into

mild, moderate, severe

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mild

bothersome but requires no change in therapy

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moderate

requires change in therapy,
additional treatment,
hospitalization

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severe

disabling or life-threatening

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severity

results in death,
is life-threatening,
requires hospitalization,
prolongs hospitalization,
causes disability,
causes congenital anomalies,
requires intervention to prevent permanent injury

60

Types of ADRs

A - augmented,
B- bizzare,
C -cumulative,
D- delayed,
E - end-of-use

61

type A -augmented

extension of pharmacological effect,
often predictable and dose dependent,
responsible for at least 2/3 of ADRs

62

type A eg

propranolol causes heart block,
anticholinergics cause dry mouth

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type B - bizzarre

nature of reaction can't be predicted,
idiosyncratic or immunologic reactions,
rare and unpredictable

64

Type B eg

chloramphenical and aplastic anemia

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Type C - cumulative

associated with long-term use,
involve dose accumulation

66

Type C eg

phenacetin - interstitial nephritis,
antimalarials - ocular toxicity

67

Type D -delayed

delayed efects (dose independent)

68

Type D eg

carcinogenicity - immunosuppressants,
Teratogenicity - fetal hydantoin syndrome

69

Type E - End of use

associated with the withdrawl of a medicine,

70

Type E eg

insomnia anxiety and perceptual distrubances following the wothdrawal of benzodiazepines

71

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)

72

type I eg

anaphylaxis w/ penicillins

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type II eg

methyldopa causes hemolytic anemia

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type III eg

procainamide - induced lupus -->anti histone ab

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type IV eg

contact dermatitis

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common drugs causing ADRS

antibiotics,
antineoplastics,
anticoagulants,
cardiovascular drugs,
hypoglycemics,
nsaid/analgesics,
diagnostic agents,
CNS drugs

77

Body systems commonly involved in ADR

hematologic,
cns,
dermatologic/allergic,
metabolic,
cardiovascular,
gastrointestinal,
renal/genitourinary,
respiratory,
sensory

78

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

79

Pharmacovigilance - ADR detection

subjective report ,
objective report,
medication order screening,
spontaneous reporting (most common),
medication utilization review

80

subjective report

patient complaint

81

objective report

direct observation of event,
abnormal findings (physical exam, laboratory test, diagnostic procedure)

82

medication order screening

abrupt medication discontinuation,
abrupt dosage reduction,
orders for "tracer" or "trigger" substances,
orders for special tests or serum drug concentrations

83

spontaneous reporting

most common

84

medication utilization review

computerized screening,
chart review and concurrent audits

85

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

86

idosyncracy eg

INH toxicity in slow/rapid acetylators,
G6PD deficiency

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idiosyncracy for no genetic reasoning

barbiturates cause excitement and mental confusion in some individual

88

drug dependence

physical, psychological (withdrawl symptoms)

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teratogenicity

thalidomide,
anticancer drugs,
androgens,
phenytoin

90

thalidomide

phocomelia

91

anticancer drugs

multiple defects,
fetal death

92

androgens

virilization,
limb esophageal cardiac defects

93

phenytoin

cleft lip/cleft palate

94

mutagenicity and carcinogenicity

anticancer drugs,
radioisotopes,
estrogen

95

mutagenicity is determined by

Ames test

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Iatrogenesis

adverse effects or complications caused by or resulting from medical treatment or advice (drug-or-physician induced adverse effects)

97

iatrogenesis ex

steroid induced diabetes mellitus and osteoporosis,
drug-induced parkinsonism

98

tramadol induces

vomitting,
observed with oral, parenteral and continuous release preparations

99

contact dermatitis due to

Vit-K injury

100

clonidine induces

urticaria

101

teeth and nail discoloration due to

iron capsules

102

erythromycin induces

mobilliform rashes

103

s-amlodipine induces

pedal edema

104

heparin induces

contact dermatitis

105

dapsone induces

toxic epidermal cecrolysis

106

cotrimoxazole induces

fixed drug eruption

107

acetaminophen can cause

fixed drug reaction