ADR and ADE
Reasons for ADRs in elderly
Concomitant use of several meds Decreased drug ADME
Type C
Continuous
Type D
Delayed
True or False Children above 18 years old are may be at risk at developing REYE SYNDROME if given with ACETYLSALICYLIC ACID when infected with chicken pox or influenza
False, below 18 yrs old
X linked recessive → Primaquine , Sulfonamides, nitrofurantoin causes Hemolytic anemia
G6PD dificiency
2 types of hypersensitivity/ allergy
Humoral - Type I,II,III Cell-mediated - Type IV
Faulty oxidation, AR , Phenytoin toxicity increases in slow hydroxylators.
Hydroxylase polymorphism
True or False ADRs, including drug interactions, are common cause of admission to hospital in the elderly
True
True or False Children are often at risk of ADR's becoz their capacity to metabolize drugs are not fully developed
True
Type U
Unclassified
AD, required for Heme synthesis → Barbiturates , phenytoin , carbamazepine give rise to acute intermittent porphyria
Uroporphyrinogen synthetase enzyme deficiency
manifested effects are due to long exposure or how many years of treatment can be due to accumulation thus the effects are delayed includes: Carginogenicity, Teratogenicity,
delayed
use of a drug for non-therapeutic effect may lead to organ damage, addiction and disturbed patterns of behavior use of these drugs often occurs criminal penalty in addiction to the potential for physical, social and psychologic harm
drug abuse
Use of drug produces a state in which person believes that continuous use is necessary for state of well being ( psychic dependence) or to avoid withdrawal symptoms ( physical dependence. is the body's physical need, or addiction, to a specific agent. It is a state in which use of drugs for personal satisfaction often in the face of known risk to health.
drug dependance
dose (what factor affecting adr?)
drug-related
duration of therapy (what factor affecting adr?)
drug-related
inherent toxicity (what factor affecting adr?)
drug-related
pharmacodynamic properties (what factor affecting adr?)
drug-related
pharmacokinetic properties (what factor affecting adr?)
drug-related
Type E
end of use
results from sudden termination or abrupt discontinuation of drug includes: "Withdrawal Syndrome
end of use
Counterfeit medicines Underdosing of medications Drug interaction and incompatibilities Resistance Inappropriate use Manufacturing errors Patient tolerance Prior patient adherence
failure
Type F
failure
Type G
genotoxicity
Type H
hypersensitivity
immunologically mediated allergic responses occurs when sensitized individuals are re-exposed to same drug again generally occur even with smaller dose
hypersensitivity/ allergy
any adverse condition in a patient occuring as the result of treatment by a physician, surgeon, or other health professional, or especially infections acquired by the patient during the course of treatment
iatrogenic disease
genetically determined abnormal reactivity to a chemical certain bizaare drug effects due to pecularities of an individual for which no definite genotype has been described drug reacts in some unique features of an individual, not found in majority of the subjects, produces uncharacteristic reaction
idiosynerasy
appearance of a characteristic toxic effect of a drug in an individual at therapeutic doses implication is that the individual has low threshold due to increase sensitivity at low doses or failure to tolerate even a single dose of a drug
intolerance
(Severity) directly/ indirectly contributes to death
lethal
(Severity) requires treatment / change in treatment/ prolongation by at least 1 day , requires intensive treatment
moderate
Adr to drugs
most common cause of iatrogenic disease
capacity of a drug to cause genetic effects and cancer respectively take 10-14 years to develop
mutagenicity/ carcinogenicity
- are any agents that can induce or increase the frequency of mutation in an organism
mutagens
age (what factor affecting adr?)
patient-related
compliance with dosing regimen (what factor affecting adr?)
patient-related
concurrent disease (what factor affecting adr?)
patient-related
genetic influences (what factor affecting adr?)
patient-related
miscellaneous (what factor affecting adr?)
patient-related
previous adr experience (what factor affecting adr?)
patient-related
sex (what factor affecting adr?)
patient-related
total # of medications (what factor affecting adr?)
patient-related
Factors affecting adverse drug reaction
patient-related drug-related
drug or its metabolites induces a cell mediated immune response which on exposure to light produces a papular or eczematous contact dermatitis. - longer wavelength (320-400nm) UV-A
photoallergy
cutaneous reaction resulting from drug induced sensitization of the skin to UV radiation
photosensitivity
drugs or its metabolites accumulates in the skin, absorbs light and undergoes photochemical reaction resulting in local tissue damage, more common problem - shorter wavelength (290- 320nm) UV-B
phototoxicity
these are the indirect consequences of the primary action of the drug includes: superinfections, latent activation
secondary side effects
(Severity) potentially life threatening, cause permanent damage
severe
any unintended effects of pharmaceutical products occuring at a doses normally used by the patient which is related to the pharmacology action of the drug
side effects
Carisoprodol
skeletal muscle relaxant
capacity of a drug to cause fetal abnormalities when administered to a pregnant mother
teratogenecity
exaggerated form of side effects and a result of excessive pharmacological action of a drug due to overdosage and prolonged use predictable and dose-related extension effect of the therapeutic effect itself
toxicity/ toxic effects
teratogenecity category Aspirin, Phenytoin, Valproate, Carbamazepine, Lorazepam Methotrexate
Category D
teratogenecity category Estrogens, Isotretinoin, Ergometrine, Thalidomide
Category E
includes: hypersensitivity reaction, anaphylactic reaction, idiosyncratic reaction
bizarre
less common
bizarre
unpredictable adverse reacion
bizarre
are any chemical substance or mixture of a chemical substance which induce cancer or its incidence
carcinogens
associated with long-term use or chronic use of the drug thus related to the dose and duration treatment
continuous
biological characteristics can be predicted from the chemical structure of the drug or metabolite
continuous
paracetamol analgesics ethambutol
continuous
Adverse drug event
any event associated with the use of drug in humans, whether or not considered as drug-related
teratogenecity category Magesium sulfate injection, Thyroxine
Category A
Chloramphenicol/Ciprofloxacin Penicillin Aspirin
bizarre
STEPS INVOLVED IN ADR MONITORING
1. Identifying adverse drug reaction (ADR). 2. Assessing causality between drug and suspected reaction by using various algorithms. 3. Documentation of ADR in patient's medical records. 4. Reporting serious ADRs to pharmacovigilance centers /ADR regulating authorities
teratogenecity category Penicillin V, Amoxicillin, Cefaclor, Lidocaine, Erythrromycin Paracetamol
Category B
teratogenecity category Morphine, Codeine, Atropine, Thiopentene, Coeticosteroids Adrenaline, Bupivacaine
Category C
Detection of ADR
1. pre-marketing studies 2. post marketing surveillance 3. Under reporting 4. Communicating ADRs
Many drugs can be passed from mother to infant via breast milk
Amantadine Cyclophosphamide Cocaine Carisoprodol
Adverse drug event
Any injury caused by a medical treatment, not necessary due to an error
Faulty hydrolysis: AR, normal action of succinylcholine hydrolysis takes 5 min, here it takes 1-2 hours, results in prolonged respiratory failure
Atypical pseudocholinesterase
Type A
Augmented
an ADR that can easily be predicted from unknow pharmacology of the drug
Augmented
an extension of the pharmacologic effect
Augmented
beta-blockers loop diuretics antihistamine narcotics anti-cancer
Augmented
more common type of reaction
Augmented
preventable and reversible
Augmented
Type B
Bizarre
abnormal effects unrelated from drug's known pharmacological actions
Bizarre
(Severity) no treatment/ antidote/ prolongation of hospitalization does not affect day-to-day patient activities
Minor
Acute - within 60 minutes
Onset
Latent - > 2 days
Onset
Sub-acute - 1 to 24 hours
Onset
Sub-chronic - - occurs or persist in 1-3 months
Onset
chronic - occurs or persists in 3-6 months
Onset
4 ADR Classification
Onset Severity Chemical Reaction Other categories
2 types of drug dependence
Psychological dependence Physical dependence
adverse drug reaction
according to FDA, it is any adverse event occuring in the course of the use of drug in professional practice
adverse drug reaction
according to WHO, it is any noxious, unintended, and undesired effect of a drug which occurs at a dose used in humans
Adverse drug event
according to WHO, it is any untoward medical occurance
AR In fast acetylators → INH → Acetyl hydrazine results in Hepatotoxicity
acetylator status
Cyclophosphamide
antineoplastic
Amantadine
antiviral