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