ADRs and Clinical Study Flashcards
What are the Different Types of ADRs and their A-F classification?
- Type A: Augmented, dose related (usually resolved by reducing dose)
- Type B: Bizarre, unrelated to dose, includes hypersensitivity
- Type C: Chronic, dose and time related
- Type D: Delayed, time related
- Type E: End of use, related to drug withdrawal
- Type F: Failure, unexpected failure of therapy
Discuss Type A: Augmented, dose related (usually resolved by reducing dose)
- Predictable from known pharmacology
- 3 principal mechanisms
- exaggerated therapeutic response at target site
- desired pharmalogical effect but at another site
- impaired metabolism
- 3 principal mechanisms
Discuss Type B: Bizarre, unrelated to dose, includes hypersensitivity
- Unpredictable
- Severe reactions
- Causes:
- abnormal drug metabolism or receptors
- allergic reactions
Discuss Type C: Chronic, dose and time related
- Often due to adaptive changes at receptor or metabolism
- development of drug tolerance (e.g. opioids)
Discuss Type D: Delayed, time related
- Only acceptable if benefits outweigh risk (e.g. infertility in young person receiving cancer treatment)
Discuss Type E: End of use, related to drug withdrawal
- Rebound after abrupt discontinuation
Discuss Type F: Failure, unexpected failure of therapy
- Drug interactions
What are the reasons for paracetamol toxicity?
- Hepatotoxicity in overdose
- toxic metabolite formed if there is insufficient levels of glutathione
- Treatment: glutathione-like molecule NAC
- toxic metabolite formed if there is insufficient levels of glutathione
What are the reasons for Gray Baby Syndrome?
- Chloramphenicol
- Due to impaired glucoronisation in neonates
- Also due to impaired renal clearance
What are the symptoms of Gray Baby Syndrome?
- Abdominal distension
- Diarrhoea
- Vomiting
- Circulatory collapse and death
What are the reasons of Gasping Baby Syndrome?
- Benzyl alcohol
- Related to immaturity of glycine conjugation system resulting in accumulation of benzoic acid metabolite
What are the symptoms of Gasping Baby Syndrome?
- Metabolic acidosis
- Seizures
- Gasping
Define On-Target ADRs
Exaggerated drug response at the correct receptor site
Define Off-Target ADRs
Drug affects unintended target
Define Idiosyncratic
Unknown mechanism
Aspirin on-target ADRs
Prevents blood clotting as intended, but too much (GIT)
Aspirin off-target ADRs
Trough mechanism independent off blood clotting (e.g. bronchospasms in asthmatics)
Define Teratogens
An agent or factor which causes malformation of an embryo without affecting the mother
What are risk factors for ADRs?
- Pregnancy
- first trimester > most drug risk
- embryo most vulnerable to teratogens
- second and third trimester
- affects functional development or growth
- first trimester > most drug risk
- Food, Herbs & Other Medicines
- Foods may compete for ADME
- induce or inhibit metabolic enzymes
- K+ competes with digoxin for transporter sites
- Herbs acting via same mechanism increases drug effects and chance of toxicity
- Foods may compete for ADME
How are ADRs monitored in Australia?
- Reduce polypharmacy
- Simple medication regimens
- Educating patients
- Post marketing surveillance
Define Standard Deviation
Measure of how spread out measurements are around the mean
What are reasons for patient randomisation?
- Prevents ‘data-skewing’
- Eliminates bias
What are the typical designs of four phases in drug testing?
- Phase 1
- group of 3 patients
- used to learn ‘maximum tolerated dose’ of a drug
- is the drug safe?
- Phase 2
- Therapeutic activity screen
- Confirm dose-range is similar in most people
- How well does it work?
- Phase 3
- Experimental group vs. control group
- Randomisation, blinding
- Compare it with standard deviation
- Phase 4: Post marketing study
- After drug has been marketed
- Designed to monitor the effectiveness of the approved intervention
- Collect information abount adverse effects with widespread use
What is a placebo effect?
Beneficial effect produced by a placebo drug or treatment, due to patient’s belief in that treatment
Why is study blinding important?
- Patient may have preconceived notions about the benefits of therapy
- Patients try to get well
What is the importance of power analysis?
- Allows use to determine the sample size required to detect an effect of a given size with a given degree of confidence
- properly designed study, power expected >80%
