ADRs Flashcards
1
Q
Side effects
A
- Unintended secondary effects a medication (predictably) will cause
- May be harmless or serious
- If SE are serious enough to negate the beneficial effect of a medicine’s therapeutic action, it may be discontinued - the patient may stop taking it (poor compliance) or the prescriber might suggest an alternative plan
2
Q
What are side effects
A
- Drugs are intended to target specific areas and/or receptors - these seldom exist solitarily
- Targets are members of large groups of similar proteins (like a family of proteins eg (adrenergic, cholinergic, dopaminergic, opioid and histamine) with classes and subclasses
- When drugs bind to and act on unintended targets = side effects
- Salbutamol (a ß2 adrenoceptor agonist) targets ß2 receptors in the lung, but can also bind to ß1 receptors in the heart causing tachycardia – a side effect
- Verapamil can block calcium channels in the wall of the digestive system resulting in reduction in peristalsis, leading to constipation as a side effect.
3
Q
Hazardous SE
A
- Chemotherapy drugs target rapidly dividing cells by fragmenting DNA, cross-linking strands, blocking enzymes essential to DNA synthesis and/or paralysing the cells
- The main targets are rapidly dividing cancerous cells, but other cells (e.g. epithelial and white blood cells) receive ‘unwanted attention’
- SE include: Dry mouth, hair loss
- Gastro-intestinal disturbances * Neutropenia
4
Q
ADRs vs SEs
A
- DRs are undesired effects that occur with the normal use (within the recommended doses) of a drug. An ADR always describes a harmful/undesirable reaction
- SE can be harmful or beneficial e.g. SSRI for depression helping hot flushes, or amitryptiline helping mood and pain, or mirtazapine increasing appetite in thin depressed patient
- ADRs are always harmful=adverse, eg anaphylaxis, headaches, vomiting
4
Q
Costs of ADRs
A
- ADRs can seriously affect patients’ quality of life
- Can cause patients to lose confidence in the healthcare system.
- Contribute to increased costs of patient care and can lengthen hospital stays.
- May mimic disease, resulting in unnecessary investigations and delays in treatment.
- A cost of about £380 million a year to the NHS in England
5
Q
ADRs- probablities
A
- More common in patients who receive 10 or more different drugs during admission
- When less than 6 drugs are used, the risk of ADR is around 5%
- Increases to 40% if more than 15 drugs are used
- 1 in 7 inpatients experience ADR, and 50% could have been avoided!
- There can be serious ADRs with OTC and herbal drugs
6
Q
Classification of ADRs
A
- Type A – Augmented reaction
- Type B – Bizarre
- Type C – Chronic/Continuing
- Type D- Delayed
- Type E – End of Dose
7
Q
TYPE A ADR – AUGMENTED
A
- Extended effects of drug, normally documented e.g. in the BNF
- Usually dose-related (e.g. bleeding with warfarin or respiratory depression with opioids)
- Predictable, and usually recognised before marketing of drug
- Mortality low, and responds to dose reduction
- More likely in young, old and renal and liver impairment
- Type A reactions usually result from an exaggeration of a drug’s normal pharmacological actions when given at the usual therapeutic dose and dose dependent e.g. hypotension with CCBs, dry mouth with TCAs
8
Q
Mx of type A ADRs
A
- Reducing the dose of the drug
- Switching to an alternative drug (in same/other class)
- Stopping the drug altogether
- Record ADRs in medical notes
9
Q
TYPE B (Bizarre) REACTIONS
A
- Novel and unexpected from the known pharmacological actions of the drug
- Skin rashes with ABx
10
Q
Allergic Reaction- Type B
A
- Patient’s immune system identifies a drug as foreign
- Unpredictable response to a medication
- Makes up greater than 10% of all medication
reactions - Patient may become sensitized to the initial dose,
then repeated administration causes a severe allergic response - Medication acts as an antigen triggering the release of the body’s antibodies
- May be mild or severe
- Severe reaction e.g. anaphylactic reaction
- Mild reaction e.g. hives, rash, pruritus/itching
- Among the different classes of medications, antibiotics cause the highest incidence of allergic reactions
11
Q
Type B Reactions- Subtypes
A
- Type I – Anaphylaxis e.g penicillins
- Type II- cytotoxic/blood dyscrasias e.g. carbimazole
- Type III- immune complex-mediated (serum sickness) e.g. thiazides
- Type IV- T-cell mediated (rashes) e.g. penicillins
12
Q
Type B ADR Mx
A
- Prompt detection and rapid action
- Suspected drug to be withheld immediately
- Resuscitation measures and treatment as needed
- The drug should be stopped/alternative found
- Record in patient notes - should be easily visible to future prescribers
- Prescriber informed
13
Q
Characteristics of Type A & B
A
- Type A: Predictable,
Usually dose dependent, High morbidity,
Low mortality, Responds to dose reduction - Type B: Unpredictable, Rarely dose dependent, Low morbidity, High mortality, Responds to drug withdrawal
14
Q
Type D reactions
A
- Delayed reactions
- Carcinogenesis – e.g. Diethylstillbestrol/oestrogen during
pregnancy - vaginal carcinoma in daughter - Impaired fertility – e.g. Inadequate sperm counts from prior exposure to cytotoxics like cyclophosphamide
- Impaired foetal development – e.g. Spina bifida in the foetus after maternal exposure to sodium valproate in pregnancy.
15
Q
Type C ADR- Chronic/continuing
A
- Continued exposure tolerance e.g. Opioids
- Cumulative effects e.g. Methotrexate & liver
- Long term effects e.g. osteoporosis & steroids
16
Q
Type E- End of exposure
A
- Withdrawal effects after long term treatment
- Rebound responses e.g. SSRIs and benzodiazepines
17
Q
High Risk Groups for ADRs
A
- Age – very young and old
- Sex – female
- End organ failure – liver or renal impairment
- Polypharmacy
- Multimorbidity
- Genetic factors
18
Q
Drug interactions
A
- Drug interactions can occur between drugs+drugs or drugs+food
- Occurs when one medication modifies the action of another
- Common in people taking several medications
- One medication may potentiate or diminish the action of another or alter the way it is absorbed, metabolized or eliminated
- E.g. Warfarin and Amiodarone (half warfarin), levothyroxine and iron (levo first)
*
19
Q
Drug interaction- P450
A
- P450 enzyme in the liver metabolises drugs
- Some drugs can either increase or decrease P450 activity
(remember inhibitors and inducers from pharmacology lectures) - If P450 drugs activity is increased, some drugs are metabolised more quickly leading to decreased bioavailability
- If P450 is inhibited, some drugs are metabolised more slowly leading to increased bioavailability
20
Q
Types of drug interaction
A
- Additive effect
- Potentiation/synergistic effect
- Antagonistic effect
- Decreased or increased absorption
- Decreased or increased metabolism and excretion
21
Q
Why report ADRs
A
- Suspected ADR to any drug (therapeutic agent) should be reported to:
- The Medicines and Healthcare Products Regulatory Agency (MHRA)
- Why?
- To recognise unknown hazards
- To take adequate regulatory measures * To ensure safety of use of medicines
22
Q
How to report ADRs
A
- Yellow Card Scheme
- Electronic form at www.yellowcard.mhra.gov.uk
- Prepaid yellow cards via post
- Mobile app
- Some primary care software can do this directly through the system
- A freephone service is available in the UK for advice and information on suspected ADR - 0800 731 6789
23
Q
Yellow Card Scheme- when a new ADR is found
A
- MHRA will review how this medication is used, and the
cautions/warnings that prescribers and patients should be told about - Update information on SPC (Summary of Product Characteristics) and PIL (Patient Information Leaflets)
- If risks outweigh benefits, the drug can be withdrawn e.g. Rosuvastatin 80mg and rhabdomyolosis
- Black triangel denotes drugs closely monitored by MHRA e.g. new drugs
- All ADRs should be reported, even if it is not certain that the drug has caused it or if other drugs were given simaltaneously
