Adverse Drug Reactions and Monitoring Drug Therapy Flashcards
What is an adverse drug reaction?
an unwanted or harmful reaction experienced following the administration of a drug (or drug combination), suspected to be related to drug use
What are type A adverse drug reactions?
Augmented adverse drug reactions
- dose related
- largely predictable from known pharmacological/biochemical effects of a drug or its metabolites
- classified as pharmacological or biochemical
What are type B adverse drug reactions
Bizzare adverse drug reactions
- not dose related
- idiosyncratic and unpredictable
- often immunological in nature
What is an adverse drug event?
an untoward occurrence after exposure to a drug, that is not necessarily caused by the drug
(e.g. patient involved in RTA whilst on specific medication)
Describe the 2 types of pharmacological toxicity
- toxicity relating to the primary therapeutic effect of the drug but the dose is too high
- e.g. warfarin and bleeding - toxicity not relating to the primary therapeutic effect of the drug but still related to other pharmacological properties (i.e. off target effectd)
- beta blockers causing bronchoconstriction in asthmatics
- antipsychotics causing parkinsonism
- What is biochemical toxicity?
2. Describe 2 examples of biochemical toxicity
- tissue damage caused by the interraction of a drug/drug metabolite with cellular compoments
- toxic metabolite of paracetamol induces hepatic injury
cyclophosphamide causes haemorrhagic cystitis (as eliminated in the urine, thus causes cell damage in the bladder)
- Why do NSAIDs cause GI irritation?
2. What type of ADR is this?
- NSAIDs inhibit the production of prostaglandins
- prostaglandins are important in the stomach for the maintenance of the mucosal layer and to reduce acid secretion
- NSAIDs inhibit the production of prostaglandins
- Type A
Name 5 examples of Type A ADRs
- constipation with opioids
- sedation with antihistamines
- parkinsonism with dopamine antagonists
- hyperprolactinaemia associated with dopamine antagonists
- hepatic failure associated with paracetamol overdose
Which type of antibiotics should be avoided if a patient has a hx of allergic reaction to penicillin?
- penicillin
- cephalosporin
- beta lactams
- How should ADRs be reported?
2. What information should be recorded?
- reported to MHRA using yellow card scheme
- one piece of patient information
name(s) of suspected drug(s)
brief description of ADR
contact details of reporter
What is the result of a drug interraction of ACEi and NSAIDs?
AKI (both reduce renal blood flow by dilating the efferent arteriole (ACEi) and constricting the afferent arteriole (NSAIDs))
Name 10 CPY450 inhibitors
- sodium valproate
- ciprofloxacin
- sulfonamide
- cimetidine
- antifungals
- amiodarone
- isoniazid
- erythromycin
- clarythromycin
- grapefruit juice
Name 5 CYP450 Inducers
- carbamazepine
- rifampicin
- barbituates
- phenytoin
- st john’s wort
Name 4 important interractions relatinf to CPY450
- combined oral contraceptives and rifampicin
- warfarin and carbamazepine
- statins and clarythromycin
- warfarin and amiodarone
- What is pharmacodynamic variation?
2. What is pharmacokinetic variation?
- different drug concentrations at sites of action; occurs because of differences in absorption, distribution, metabolsim or excretion
- differences in responses to drugs at the same concentrations between individuals
- What are the 4 phenotypes of CPY2D6?
- What is the results of these different phenotypes?
- Which analgesic drug is affected by CPY2D6 phenotypes?
- ultrarapid metabolisers; extensive metabolisers; intermediate metabolisers; poor metabolisers
- patients who are poor metabolisers and ultrarapid metabolisers can have markedly altered responses to drugs that are CYP2D6 substrates
- coedine - CYP2D6 is responsible for metabolising coedine to morphine
- ultrarapid metabolisers have higher than expected morphine levels, with more side effects and shorter than expected duration of analgesia
which drugs is it important to consider TPMT activity before use?
azathioprine, mercaptopurine, tioguanine
- these drugs shouldn’t be given to people with absent TPMT activity
- Name 2 ways in which pregnancy can influence drug distribution?
- Why must lipophilic drugs be used with caution in pregnancy?
- decreased plasma albumin concentration
increased cardiac output → increased renal blood flow → increased renal elimination
describe reasons for poor adherence to drug treatment
- poor knowledge of the illness and the medication
- administration and dosage of the medication
- independent pausing, stopping or controlling of medication
- lack of competence in self management
- fear towards drugs
- media and others as a source of medication information
- diseases where poor control does not yet produce symptoms
- challenges with lifestyle changes
- replacing prescription drugs with self administered drugs
What tool can be used to assess a patient’s health literacy?
REALM-R list
- What is therapeutic drug monitoring?
2. Name 4 criteria for the use of therapeutic drug monitoring
- measurement of medication levels in body fluids (usually serum)
- absence of good clinical markers of drug effect
poor correlation between dose and clinical effect
narrow therapeutic window
good correlation between plasma drug concentration and clinical effect
Name examples of drugs which therapeutic drug monitoring is used for
- gentamycin
- vancomycin
- phenytoin
- carbamazepine
- ciclosporin
- tacrolimus
- methotrexate
- digoxin
- lithium
- theophylline
What are the legal requirement on a prescription?
- signed
- ink/indelible
- repeat once, only if repeatable
- dispensed within 6 months
- address of practitioner
- indicate if doctor/dentist/nurse/pharmacist
- date
- name and address of a patient
- age of patient if under 12
- dose in numbers and words if a CD
- What occurs in phase 1 trials?
2. What must be obtained before phase 1 trials can be performed?
- pharmacology of a candidate drug is tested in a small group of health volunteers (confirm safety)
- clinical trial applications - ensures sufficient preclinical research has been conducted to allow testing in humans to go ahead
- What is done in phase 2 trials?
2. What is the aim of phase 2 trials?
- examine the efficacy of a compound in volunteer patients who have the condition the drug is intended to treat
- to determine the most effective dose and method of delivery, the appropriate dosing interval and to reconfirm product safety
- What is done in phase 3 trials?
2. what is the aim of phase 3 trials?
- drug tested in a much larger patient population, across multiple international sites
- Aim is to reconfirm phase 2 findings in a larger population and to identify the best dosage regimen
What is required following phase 3 trials before a drug can be licensed?
a submission for marketing authorisations is made to the national regulatory authority (MHRA)
What is done in phase 4 trials?
post marketing studies/surveillance
