Intentional and Unintentional presentations Flashcards
What drugs can cause Gynaecomastia?
Spironolactone
Oestrogens
Methyldopa
Digoxin
What drugs can cause galactorrhea?
Antipsychotics Tricyclics Metoclopramide Oestrogens Methyldopa
What is the Criteria for diagnose of ADR?
Timing with drug treatment
Improvement after drug discontinued (dechallenge) or dose reduced (Type A dose related ADRs)
Worsening after rechallenge dose increase (Type A dose related ADRs)
Associated with high plasma drug concentrations (Type A dose related ADRs)
Reaction previously recognised as caused by a drug that the patient is exposed to
Illness that is commonly the result of an adverse drug reaction (e.g. postural hypotension, confusion)
Exclusion of other causes
How can adverse drug reaction be avoided?
Only prescribe when there is a clear indication
Use drug with most favourable risk-benefit
Check with patient for previous ADRs / Allergy
Careful patient education
Appropriate use of drug
Common and/or important adverse effects (look up in BNF or Summary of Product Characteristics (SPC)
Monitor therapy
Particular care in susceptible patients
How can drug reactions be classified?
Augmented Dose-related and predictable Avoidable insulin causing hypoglycaemia warfarin causing bleeding nitrates causing headaches
Bizarre (Idiosyncratic) not-dose related and not predictable Penicillin: anaphylaxis Halothane: hepatitis Chloramphenicol: agranulocytosis
Chronic treatment effects
Variable, occur with prolonged but not short duration treatment
osteoporosis with steroids
Steroid-induced Cushing’s syndrome
Phenothiazine-induced tardive dyskinesia
Fenfluramine(reduce weight)-induced pulmonary hypertension
Delayed effects
Variable, occur some time after discontinuation of treatment
Drug-induced fetal abnormalities
Drug-induced cancers (recipients or offspring)
Eg-squamous cell carcimoma
End-of-treatment
Variable, effects occur on withdrawal of a drug
Adrenocortical insufficiency after steroid treatment
Drug withdrawal seizures
Withdrawal reactions following paroxetine
What are the common adverse drug reaction?
NSAIDs
(GI complications, Cerebral haemorrhage, renal impairment, wheezing, rash)
Diuretics
Renal impairment, hypotension, electrolyte disturbances, gout
Warfarin
bleeding
ACE /AII inhibitors
Renal impairment, hypotension, electrolyte disturbances
Beta blockers
Bradycardia, heart block, hypotension, wheezing
Opiates
Constipation, vomiting, confusion, urinary retention
Digoxin
Toxicity,renal impairment
Prednisolone
GI complications, hyperglycaemia, osteoporotic fracture
Clopidogrel
GI bleeding
What is an adverse drug reaction?
response to a drug that is noxious and unintended and that occurs at doses normally used for prophylaxis, diagnosis, or treatment of disease or for modification of physiological function”*.
Definition has now been extended in the European Union to include abuse, medication error, and overdose.
*International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, www.ich.org/
most common cause of iatrogenic disease
can mimic common conditions
cause approximately 6.5% of all hospital admissions in the UK
9% definitely and 63% possibly avoidable
17% due to interactions
Mean length of stay 8 days
Total cost £466M
occur during 20% of hospital inpatient episodes
cause death in 0.01 - 0.1% of hospital inpatients
What are the problems with new drugs?
Lack of experience in special patient groups clinical trials Elderly Children Lactating women Pregnancy Multiple disease Polypharmacy
Lack of experience on adverse effects Exposure in about 1500 people only Short duration Unlikely to detect ADRs Less frequent than 1/500 With long latency
What are the onjectives of Pharmacovigilance?
Identify previously unrecognised hazards
Evaluate changes in risks and benefits
Take action to promote safer use
Provide optimal information to users
What is the yellow card scheme?
Means by which suspicions that an ADR has occurred may be collated
Voluntary - relies on co-operation of healthcare professionals.
Patients can only report side-effects
Purpose is early identification of previously unrecognised safety hazards
All drugs included - focus on:
Serious ADRs
Reactions in children
New drugs (black triangle)
Around 18,000 reports per year
Data from the scheme made available publicity on Yellow Card website as drug analysis prints.
What Potential regulatory action can be taken following a yellow card scheme?
Withdraw drug if risks exceed benefits (rare) Make changes to promote safer use Remove indication Add contraindication Add warning or precaution (e.g. monitoring) Add drug interaction Add ADR Inform users Drug Safety Update Dear Dr/Pharmacist letter
How can drug interaction be classified by Mechanism?
Pharmacodynamic
Drugs act on the same target site of clinical effect (receptor or body system)
Opiates and benzodiazepines causing respiratory depression
Pharmacodynamic Interactions
Pharmacokinetic
Altered drug concentration at target site of clinical effect
ADME
OCP failure with antibiotics
Synergism / summative - additive effects
rifampicin + isoniazid at Mycobacterium TB (antimicrobial)
alcohol + benzodiazepine at GABAa (sedative)
Antagonism - opposing effects
salbutamol + atenolol at ß-adrenoceptors (bronchodilation and bronchoconstriction)
naloxone + morphine at opioid receptor (reverses sedative effects of morphine and may precipitate opiate withdrawal
Pharmacokinetic interactions
Drugs interactions effect processes of Absorption Distribution Metabolism Excretion
How can drug distribution be affected?
Displacement from plasma protein binding increase in free drug concentration
Involves drugs with high protein-binding
warfarin, tolbutamide, phenytoin, sulphonamides
Usually minor and transient due to compensatory increase in metabolism and excretion
May become even more significant if 2nd mechanism
valproate displaces phenytoin + inhibits its metabolism
How can drug absorption be affected?
Rate
Faster or slower
Extent
Less or more complete
Mechanisms
pH
Antacids Less acidic stomach contents More drug ionisation Slower absorption
Alcohol More acidic stomach contents Less ionisation Faster absorption
Gastric emptying and intestinal motility
Slow
Opiate analgesics (e.g. morphine, pethidine) Much slower
Antimuscarinic drugs (e.g. atropine, propantheline) Slower
Tricyclic anti-depressants - antimuscarinic side-effects (e.g. imipramine) Slower
Faster
Metoclopramide
Muscarinic agents (e.g. bethanechol)
Physico-chemical interaction
Direct chemical interaction reduced absorption
Antacids form insoluble complexes with tetracyclines, quinolones, iron, bisphosphonates
Will reduce reduction in antibiotic absorption by as much as 60-70% leading to treatment failure
Cholestyramine binds non-selectively to acidic drugs e.g digoxin & warfarin
Activated charcoal binds certain drugs
Reduces absorption of toxins in the gut by up to 60%
Adsorbs toxins to surface of charcoal
Charcoal binds toxins in bowel
Not absorbed by digestive system so toxins excreted in faeces
What steps could be taken to reduce the risk of teratogenicity with anticonvulsants?
The MHRA has issued specific guidance that women of child-bearing age who are taking valproate should take part in a pregnancy prevention programme and should have an annual risk assessment.
Pre-pregnancy counselling and folic acid supplementation can reduce the risk of neural tube defects.
Anticonvulsant drugs such as lamotrigine and levetiracetam have lower teratogenic potential compared to phenytoin, carbamazepine and valproate.
Name some important teratogenic drugs?
Many drugs when taken by the mother during pregnancy can cause congenital malformations in the fetus. These include warfarin, lithium , valproate, thalidomide, phenytoin, isotretinoin etc..
It is therefore important to ensure that women of child-bearing age are not pregnant before prescribing potentially teratogenic drugs.
Is there a genetic predisposition to developing this drug adverse reaction?
True, it is associated with the HLA-B1502 allele which is more common in patients of Thai or Han Chinese origin
Gov.uk - Phenytoin: risk of Stevens-Johnson syndrome associated with HLA-B*1502 allele in patients of Thai or Han Chinese ethnic origin
Other examples of pharmacogenetic idiosyncratic reactions are:
Serious hypersensitivity with abacavir (HLA -B5701)
Steven Johnson Syndrome with carbamazepine (HLA -B1502)
Flucloxacillin and hepatitis
Chloramphenicol and aplastic anaemia
Simvastatin and rhabdomyolysis (SCLO1B1)
How does Toxic epidermal necrolysis (TEN) present?
This is an example of a Type B (bizarre) adverse drug reaction. It is unpredictable and not dose related.
erythema, pruritus, facial swelling, exfoliative dermatitis and an exanthematous rash on the face, arms, thighs, chest, and back with minimal mucosal involvement along with fever and shivering
Name examples of drugs with a narrow therapeutic index
Carbamazepine Cyclosporine Digoxin Levothyroxine Lithium carbonate Phenytoin Tacrolimus Theophylline Warfarin
What are the Inducer and Inhibitors of CYP450 enzyme
Mainly due to shared hepatic metabolism pathway through the cytochrome oxidase (CYP 450) system
CYP 450 Enzyme inducers accelerate metabolism reduced effect
CYP 450 Enzyme inhibitors slow metabolism enhanced effect
Induction
Additional P450 in the liver
General increase in hepatic function
Liver grows larger and blood flow increases
Drug metabolising enzymes (inc Cyt P450) increased
Increased clearance of a wide range of drugs, environmental chemicals and endogenous substances
Takes days or weeks
Inhibition
No reduction in quantity of P450
Existing P450 made less effective
Onset immediate
Inducers Phenytoin Carbamazepine Barbiturates Rifampicin Alcohol (chronic) St John’s Wort
Inhibitors Cimetidine Erythromycin / Clarithromycin Ciprofloxacin Sulphonamides Isoniazid Verapamil Metronidazole Omeprazole Grapefruit juice Alcohol (acute) Amiodarone Antifungals
What herbal medication can interact with drugs?
St John’s Wort Cytochrome P450 enzyme inducer Warfarin OCP SSRI (Serotonin syndrome) Ciclosporin (Transplant failure) Theophylline Digoxin Carbamazepine Phenytoin
Grapefruit / Cranberry juice Antioxidants (probably flavonoids) that inhibit CYP3A4 in the gut wall and liver Calcium channel blockers Benzodiazepines Simvastatin (Myopathy)
What to do when giving antibiotic with OCP?
Increase effect
- Combined pill with short course of antibiotics
- no additional contraceptive precautions are required when combined oral contraceptives are used with antibacterials that do not induce liver enzymes, unless diarrhoea or vomiting occur.
There have been concerns that some antibacterials that do not induce liver enzymes (e.g. ampicillin, doxycycline) reduce the efficacy of combined oral contraceptives by impairing the bacterial flora responsible for recycling ethinylestradiol from the large bowel (lack of evidence to support).
- Combined pill with long course of antibiotics
- (e.g. tetracylines for acne)
No. Gut is re-colonised by resistant bacteria.
- POP with antibiotics
No. Progestogen is not affected.
How does Serotonin syndrome present?
Mental, autonomic, neuromuscular changes due to increased sensitivity to serotonin
Essential drug interactions
Check notion
What are types of medication errors?
May be due to errors in
prescribing
dispensing
administration
Wrong patient Wrong drug Wrong dose Wrong route Inappropriate individual circumstances Drug interaction Contraindicated drug Inadequate monitoring warnings communication
calculation errors
What can cause medication errors?
Lack of knowledge About the drug About the patient Calculation errors (q,v,) Poor handwriting, inappropriate abbreviations, and poor use of zeros and decimal points Poor history taking (allergies, OTC drugs) Lack of time Carelessness Inadequate checking Poor communication
How can medication errors be avoided?
Appropriate policies in place and widely available
Checking patient identity and drug / solutions
Education, training & professional development
Undergraduate
Postgraduate, including induction and revalidation
Availability and use of information sources
Clear prescription writing
Electronic prescribing and warnings
Electronic patient record
Involvement of patient and carers
Medication review
Clinical pharmacy
Well designed clinical governance arrangements
Adverse event reporting with appropriate follow up mechanism
Audit
Original pack dispensing
Controlling the availability of high risk drugs
Adequate resources and staffing
Good drug and allergy history with appropriate documentation and warnings
How can consequences of medication errors be minimized?
Availability of extravasation kits with staff trained to use them
Automatic co-prescribing of antidotes with hazardous drugs, so that they can be given quickly if needed, e.g. naloxone with intravenous opiates
Availability of flumazenil in all locations where midazolam is used
Why aren’t medication errors and near misses reported?
lack of awareness that an error has occurred
lack of awareness of the need to report, what to report and why
perception that the patient is unharmed
fear of disciplinary action or litigation
lack of familiarity with reporting mechanisms
loss of self esteem
too busy
lack of feedback
How often do medication errors result in litigation?
During a 6 year period in which 660,000,000 GP prescriptions were written, the numbers of medicolegal claims involving medicines were
200 against GPs
400 against community pharmacists
How can risk be reduced with specific medication?
check notion
What is Surgical iatrogenesis?
Iatrogenesis is causation of harm or disease by medical intervention
Surgical iatrogenesis is harm resulting from surgical procedures
Recognised risk of surgery
Medical / surgical error
Expected sequelae of surgery
Psychological / social / cultural effects of surgical procedure
How can Surgical iatrogenesis be classified?
Timing:
Immediate
Early
Late
Immediate:
Bleeding
Nerve injury
Perforated viscus
Early (< 30 days): Sepsis Anaemia Shock Pain Neuropraxia
Late (>30 days): Stenosis Adhesions Fistulae Weakness / loss of function
Anatomical:
Local
Systemic
Local: Nerve palsy / paralysis Wound dehiscence Infection Haematoma
Systemic: Respiratory compromise Shock / cardiovascular instability Sepsis VTE Delerium
Severity:
Grade I - V
Grade I: any deviation from expected post op course, no treatment required
Grade II: Requires pharmacological treatment
Grade III: Requires surgical / endoscopic / radiological intervention
Grade IV: Life threatening complication
Grade V: Death
How can bleeding be controlled during surgery?
Pressure Communicate with anaesthetist Get help / prepare scrub team Light, retraction, equipment Identify source Suction / saline wash Consider anatomy: Small vessel – cautery Larger vessel – ligate vs repair Check haemostasis Check again later!
If unable to gain control:
Get help
Pack
Stabilise patient + leave 24-48 hrs before 2nd look
How can a peforation due to surgery be managed?
Suction / wash to clean leakage, assess damage Repair depends upon location: Pharynx / cervical oesophagus : most can be left to heal, rest with NGT Thoracic oesophagus small = endoscopic glue Large = endoscopic stent or surgical repair Bowel Small = endoscopic mucosal clipping Large = open surgery Ureter : stent or repair Bladder : surgical repair Consider feeding – enteral vs parenteral Antibiotic prophylaxis
How can nerve injury due to surgery be managed?
Identify nerve – assess expected deficit from injury
Assess damage
Complete vs partial transection
Opposed axons repair 1mm per day
Principle of nerve repair is to ensure optimal position for axonal repair
Suture peri-neurium
Microscopic surgery – plastic surgery
Repaired nerve will not regain full function
How can Surgical complications be managed?
Honesty is the best policy!
Explain events to patient & relatives
Apologise for outcome
Discuss likely impact of injury
Arrange physio / rehab / psychological support
Discuss with colleagues / reflect
Did this occur as a result of system error that requires process correction?
What can you do? Revise steps of procedure so far Double check anatomical landmarks Verbalise thought process to assistant / colleague Ask for help
How can expected sequele be managed in surgery?
Pain Analgesic ladder Patient controlled anaesthesia Local anaesthetic block / spinal Respiratory compromise Breathing exercises / physio Pre-hab Airway compromise Prolonged intubation Tracheostomy Uro / GI compromise Urinary catheter NGT – drainage Flatus tube Enteral vs parenteral feeding Anaemia Transfusion / pre-load Surgical sepsis Antibiotic prophylaxis (depends upon whether surgery is clean or contaminated) VTE prophylaxis
What are Surgical never events?and what are the causes?
Significant patient safety incidents that are considered preventable Wrong site surgery Wrong side Incorrect procedure 189 cases in 2016 / 17 Wrong implant / prosthesis 53 cases in 2016 / 17 Retained foreign objects 114 cases in 2016 / 17
Causes
Individual factors Situation awareness Failure to gather / review appropriate information Anomalies overlooked – ie anatomical variants Failure to recognise increased risks Decision making Failure to double check if uncertain Reliance upon assumptions Training issues Unfamiliarity with procedure / equipment
Institutional factors Team work / communication Failure of team members to speak up Inadequate exchange of information prior to case Organisation & management factors Pooled operating lists Poor documentation Patient factors Bilateral lesions Anatomical complexity Patient instability creating urgency
What does the WHO checklist contain?
Global patient safety challenge project led by WHO – Safe surgery saves lives
Predicted that half a million deaths related to surgery worldwide per year were preventable
Checklist published in 2008
Follows example from safety improvements in aviation
Opportunity for team brief at beginning of list
3 phase checks for each case
International audit demonstrating significant decrease in complication rate and death from surgery
3 phases
1) Before induction of anaesthesia
2) Before skin incision
3) Before patient leaves the operating room
