Adverse Drug reactions Flashcards
Define Adverse Drug Reaction:
= response to a drug which is noxious and unintended, that occurs at doses normally used for prophylaxis, diagnosis or therapy of disease, of for modifications of psychological function
- different to side effect
Factors which contribute to Adverse drug reactions
- Age (children and elderly)
- Sex (Females more likely
- Genetics (genetic polymorphines)
- polypharmacy (drug interactions)
What is the role of therapeutic good administration (TGA) in regulation of medicines
= TGA are regulatory authority for therapeutic goods and maintains Australian Register of Therapeutic goods
- Assessment and monitoring of therapeutic goods in au’s - evaluate and regulate BEFORE they reach market - monitor AFTER they reach market - Decisions based on risk-benefit analysis
What is the process by which adverse reactions are reported to the TGA?
- Anyone can report to TGA website
- any adverse reaction of registered/ listed medicines, vaccine, medical devices should be reported regardless
What are the two categorises that adverse drug reactions are classed as?
- Type A-F based on augmented or bizarre (based on properties of drug)
- Augmented
- Bizarre
- Chronic
- Delayed
- End of use (withdrawal)
- Failure
- DoTS Classification (some don’t fit A-F)
- D = dose related?
- T = time related
- S = Susceptibility related
List the Characteristics, examples and management of:
Type A - Augmented
Characteristics
- common
- predictable
- related to pharmacological action of the drug
- dose related
Examples
- Digoxin toxicity
Management
- Reduce the dose or withhold the treatment
List the Characteristics, examples and management of:
Type B - Bizarre
Characteristics
- uncommon
- not related to pharmacological action of the drug
- unpredictable
- may be caused by genetic factor
Examples
- Immunoglogical reactions (allergies)
Management
- Withhold treatment and avoid in future
List the Characteristics, examples and management of:
Type C Chronic
Characteristics
- uncommon
- related to cumulative dose
Example
- Corticosteroid induced adrenal suppression
Management
- reduce dose or withhold treatment
List the Characteristics, examples and management of:
Type D - Delayed
Characteristics
- uncommon
- usually dose related
- occurs or becomes apparent after use of drug
Examples
- Teretogenesis (birth defects)
- Cancer
Treatment - irreversible
List the Characteristics, examples and management of:
Type E - withdrawal - End of use
Characteristics
- uncommon
- occurs soon after withdrawal of drug
Examples
- Opioid withdrawal
benzodiazepine withdrawal
Management
- reintroduce and withdraw slowly
List the Characteristics, examples and management of:
Type F Failure
Characteristics
- common
- dose related
- often caused by drug interactions
e.g
oral contraceptive failure
management
- increased dose
- consider effects of other therapy
Example of Type A
= Digoxin Toxicity
What is the MOA of Digoxin:
= slows HR and reduced AV node conduction
= increase forced of myocardial contraction
- inhibits sodium calcium pump
Define therapeutic index:
the dosage range in which the drug has the desired effect before effects become adverse, a high therapeutic index is desirable while a low TI means there is a narrow window between the dose that causes therapeutic effect and the dose at which adverse effects occur
Indications of Digoxin
- AF (first line)
- HF last line
What is the role of P-Glycoproteins in Digoxin toxicity
- Drugs that reduce digoxin elimination via inhabitation of P-glycoproteins, leading to increased concentration of drug:
- Amiodarone
- Verapamil
- Diltiazem
- Clarithromycin
- Omeprazole
Symptoms of Digoxin toxicity
- GI symptoms (nausea and anorexia)
- cardiac symptoms (dysrhythmias)
Prevention of digoxin toxicity:
- dose should be tailored according to
- renal function
- clinical response
- concentration monitoring
- caution with concomitant drugs causing hypothalamic
- Concentration monitoring
Treatment of digoxin toxicity:
- antidote = Digifab
What is an example of Type B adverse reaction
= Sulfonamide hypersensitivity (allergie)
Compare the two types of reactions in a Type B bizarre reaction
Type 1 - immediate
e. g. hay fever, penut allergy
- immediate or anaphylactic hypersensitivity
- body encounters antigen and produce IGE antibody against it
- cause inflammatory response
Type IV - Cell mediated or delayed
- delayed reaction - activation of adaptive immune system and t-cell involvement - infiltration of immune cells and release of cytokines
Example of Type C
= chronic administration of corticosteroids
MOA or corticosteroids
= exert Enti-inflammatory on airways and reduce airway hyperactivity
indications of corticosteroids
- asthma
- autoimmune or inflammatory disease
- COPD
Adverse reactions chronic use of corticosteroids:
- immunosuppression –> infection
- adrenal suppression
- hypertension
- cataracts
- inhibit growth in children
How does chronic inhaled corticosteroids lead to oral candidiasis
inhaled corticosteroids cause local anti-inflammatory and immunosuppressive effects to site of admin
how does chronic inhaled corticosteroid lead to adrenal suppression
- glucocorticoid release controlled by negative feedback loop involving hypothalamus and anterior pituitary
- admin of glucocorticoids reduces pt ability to synthesis corticosteroids due to supporession of feedback loop —> atrophy of adrenal glands
Example of Type D
= Thalidomide and teratogenesis
Teratogen ?
Teratogen = is an agent/factor which causes congenital malformations in the embryo or foetus, a process called teratogenesis
- E.g Agent orange - caused foetal defects - Warfarin: Foetal warfarin syndrome, foetal bleeding, spontaneous abortion - Isotretinoin: ear malfunctions, cleft palate, heart defects
What is the Thalidomide tragedy ?
Thalidomide was prescribed for morning sickness in pregnant women
- increase in phocomelia (seal limbs) in new bones - Discovered that therapeutic doses it produces virtually 100% malformed infants if taken first 3-6 weeks - withdrawal from market
Drugs for use with pregnancy ?
- most drugs will cross the placenta during pregnancy (potentially harm foetus)
- Category A, B1, B2, B3, C, D, X
- A - Drugs which taken by a large number of pregnant women and without increase in the frequency of malformations
- X - High risk causing permeant damage to foetus
- Category A, B1, B2, B3, C, D, X
Type E example
= End/withdrawal syndrome
What is physical dependence?
Physical dependence = occurs as a result of repeated administration of a drug and means that withdrawal, or use of antagonist of this drug causes adverse psychological effects (sweating, nausea, shivering, piloerection, muscle aches, tachycardia, increased BP)
- withdrawal effects can be experienced when administering an agonist e.g. heroin + Naloxone - withdrawal refers to the abrupt cessation of a drug where there is physical dependence result in adverse effects 0
Which drugs upon cessation may cause withdrawal symptoms?
- opioids - restlessness/ anxiety, runny nose, diarrhoea/vomiting, shivering, piloerection, hostility
- benzodiazepine - anxiety, dysphoria, irritability, insomnia, sweating, memories impairment, tremor, hallucinations
- Alcohol
How to manage withdrawal?
- Drugs withdrawn gradually and symptoms monitored (dose tapered)
- pharmacological interventions can be used for withdrawal due to illicit use e.g. method one and opioid withdrawal
- using benzodiazepine with a longer half life
Type F example
= Oral contraceptive failure
What is the role of cytochrome P450 enzymes metabolism
- Both pills are metabolised by CYP3A4 = metabolism of the pill by CYP450 reduces the plasma concentration of active drug
