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
What are NatSSIPs and LocSSIPs
NatSSIP
National standards for safety in invasive procedures
LocSSIPs
Local standards for safety in invasive procedures
Procedures under local / regional anaesthesia that are performed outside theatre
Line insertion
Endoscopic procedures
Interventional radiology
Checklist for each procedure
Equipment count
How can a thyroid hematoma be managed?
Immediate management of thyroid haematomas is necessary to prevent airway obstruction. As the haematoma expands it compresses the airway and prevents venous drainage of the larynx – this leads to upper airway oedema.
SCOOP
How to get emergency front of neck acess
Immediate management of thyroid haematomas is necessary to prevent airway obstruction. As the haematoma expands it compresses the airway and prevents venous drainage of the larynx – this leads to upper airway oedema.
How can poisoning be classified?Who is at risk?
Poisoning can be Acute (e.g. drug overdose) Chronic Acute on chronic It can also be Deliberate Self-poisoning Homicidal Accidental
Exposure to poisons may be oral (e.g. drug overdose) Inhaled (e.g. smoke inhalation) Percutaneous (e.g. cyanide, organophosphates) Ocular (industrial chemicals) Most poisonings are Deliberate Self-poisoning Using drugs Taken by mouth
Most cases of poisoning affect 2 major age groups
Young children 1-5 y (Males > Females)
accidental ingestion
daytime presentation
Adolescents and young adults (Males = Females)
deliberate self-harm
evening/night presentation
chronic such as cumulative digoxin toxicity in the elderly or acute on chronic such as a collapse due to excessive diuretics attempting to treat ankle oedema.
accidental eg carbon monoxide poisoning in rented accommodation.
What common the common agents that can cause poisoning in the uk and world?
Paracetamol Tricyclic antidepressants Opiates (e.g. i/v heroin methadone Carbon monoxide (smoke from housefires)
In South-East Asia, poisoning from pesticides (e.g organophosphorus compounds), plants and venomous animals e.g snakes and scorpions are more common
What is the immediate management of a patient presenting with poisoning?
Airway Ensure adequate airway and gag reflex Coma position Breathing Respiratory rate Oxygen saturation Blood gases Circulation Assess pulse, BP, perfusion Obtain IV Access Consider IV fluids for hypotension
. The acute, for example, opiate, tricyclic antidepressant, beta blocker or ecstasy toxic patient can be extremely unwell and immediate appropriate action may be life saving. So as with all acute medical emergencies we follow the ATLS style of management. This is based on the thing that will kill you quickest and starts with airway. Many toxic substances will reduce conscious level and compromise an adequate airway for ventilation. Opiates, TCA’s, benzodiazepines, GHB, Severe cocaine or ecstasy poisoning, carbon monoxide, sleeping tablets and anti histamines to name a few.
Respiration may be stimulated eg by stimulants such as amphetamine, or due to metabolic acidosis eg TCA, or due to pulmonary injury eg cannabis induced pneumothorax. Respiration may be depressed classically by opiates
Circulatory collapse can follow poisoning by beta blockers, calcium channel blockers or other cardiac medication. However it may follow many of the recreational drug toxicities such as amphetamine, ecstasy, piperazines or cannabis. For example cocaine induced arrhythmias are not uncommon
What drugs can cause pupillary changes?
Pupil irregularites are helpful if present with opiates and organophosphates causing meiosis(constriction) and stimulants such as sympathomimetics or anticholinergics causing dilated mydriatic pupils.
What important to explore in the History and examination in poisoning?
Immediate information to guide acute management
(patient, relatives, ambulance crew)
When did the overdose take place?
What poisons were involved ? (enquire for bottles, tablets, prescribed drugs)
Mode and duration of exposure (e.g. smoke inhalation)
Symptoms (esp vomiting) ie features of toxicity
Later information to assess suicide risk
(multiple sources)
Why was the overdose taken ? Past history of self-harm ? Was the overdose concealed ? Consider Timing ? Precautions against discovery ? Medical help sought ? Final acts performed (will, insurance) ? Suicide note ? Overdose expected to be fatal ? Wanted to die ? Premeditation ? Symptoms of psychiatric illness ? Isolation ?
Examination
Skin colour Temperature Pulse rate and rhythm Blood pressure Coma scale Pupils Muscle tone Tendon reflexes Respiratory rate Needle marks Blisters Lacerations
What Investigations can be done in poisoning?
Some initial investigations are mandatory for all poisoned patients. Certainly renal function, electrolytes, full blood count. Arguably liver function tests, ECG and paracetamol concentration should also be done for everyone. In other poisonings specific tests may be indicated such as ethylene glycol concentration, troponin I in cocaine toxicity or ABG in salicylate or TCA poisoning.
Routine Full blood count Urea, electrolytes & creatinine Blood glucose Arterial blood gases ECG CXR
Tests for specific poisons’ concentrations Paracetamol Salicylate CarboxyHb [for CO] Lithium Paraquat Iron Methanol General urine toxicology screen (rarely indicated)
What management stratergies can be used in poisoning?
Support physiology Prevent absorption Specific antidote Chelation Enhance elimination
What are the common gastric decontamination methods?
Aim to reduce absorption of poisons taken by mouth when ingested poison carries significant risk
Little evidence for benefit unless used within 1 hr of poisoning(unless large overdoes,modified relase prep,and reduced gastric emptying due to meds)
Cannot be used in unconcious or drowsy patients unless the airway is protected because of aspiration risk
Methods available
Activated charcoal
Gastric aspiration / lavage
Induced emesis (Ipecacuanha) - no longer used
How is gastric lavage done and what are the advantages and disadvantages?
Suitable for
very large and life -threatening overdoses
poisons not absorbed by activated charcoal
More difficult and hazardous in children
In drowsy patients with inadequate gag reflexes, airway should be protected with a cuffed endotracheal tub
Complications Gut perforation Aspiration Laryngospasm Water intoxication (children) Dysrhythmias Pneumothorax Enhanced early drug absorption
Contraindications
Hydrocarbon ingestion
Caustic substance ingestion (risk of aspiration pneumonitis and perforation)
How can activated charcoal be used and what are the advantages and disadvantages?
Adsorbs poison in GI tract by direct contact and reduces absorption
Required charcoal to drug ratio is variable. In rat models 8:1 for >80% reduction in conc. (phenobarbitone, chloroquine, isoniazid)
Preferred method (simple) 10 x dose of poison taken, up to 50G Unpalatable (suspend in flat cola) Can be administered by NG tube to unconcious patients but the airway should be protected by a cuffed endotracheal tube if the gag reflex is inadequate Ineffective for some poisons
Complications
Aspiration pneumonitis
Reduced absorption of therapeutic agents (e.g. Methionine?)
Briquette formation / bowel obstruction
Contraindications
Absent bowel sounds (ileus)
Impaired gag reflex
Unsafe swallow
Ineffective Elemental metals/salts Lithium, iron, boron salts Insecticides Malathion DDT N-methyl carbamate Cyanide Strong acids/alkalis Alcohols Hydrocarbons
What methods can be used to increase drug elimination?
Methods: Multiple dose activated charcoal [MDAC] Chelation Urinary Alkalinisation Renal replacement therapies Haemodialysis [HD] Haemoperfusion [HP] Haemofiltration [CVVH] Combined methods haemodiafiltration MARS
How can multiple dose activated charcoal be used for elimination?
Method
50 g activated charcoal followed by further 25g every 2 hours
Laxative / stool softner to prevent constipation
Mechanism
Reduces elimination half life by
Interfering with enterohepatic circulation
(b) ‘Gastrointestinal dialysis’
Good evidence of efficacy Carbamazepine Dapsone Phenobarbitone Quinine Theophylline Sometimes also used for Salicylate Phenytoin
Complications
Intestinal obstruction
How can dialysis be used for elimination?What are the indications?
Useful when the poison Has a small volume of distribution Has a low inherent clearance rate Is sufficiently toxic Is small enough to cross the dialysis membrane (HD)
Can bind to activated charcoal (HP)
Indications
HD only Toxic alcohols Ethylene glycol Isopropanol Methanol
Salicylate
Sodium valproate
Lithium
Thallium
HD or hemoperfusion Theophylline Phenytoin Carbamazepine Barbiturates
NB Haemoperfusion now rarely used
high cost and poor availability of charcoal cartridges
systemic adverse effects
increased effectiveness of modern haemodialysis filters
What is mechanism of paracetamol poisoning?
Paracetamol- can undergo bioactivation via oxidation through CYP450-NAPQI-toxic(glutathione absent)
What are the clinical features of paracetamol poisoning?
Warning! – may be none
Non-specific
Nausea
Vomiting
Abdominal pain
delayed
Hepatic necrosis Takes 2-3 days Jaundice Liver pain Encephalopathy Coagulopathy Fulminant hepatic failure Death (3-6 days after overdose)
Renal failure Less common 2-7 days after poisoning Oliguria Loin pain
Others
Hypoglycaemia
Metabolic Acidosis
What are the investigations for paracetomol poisoning?
Paracetamol level Best early predictor of prognosis Determines need for antidotes Clotting esp. PT or INR Increased due to reduced clotting factor production (II,V,VII) Urea, electrolytes and creatinine elevated if renal damage NB urea may remain low due to reduced hepatic urea production
Blood gases
may show metabolic acidosis
indicates very severe poisoning
Liver function tests
INR or PT prolonged
Elevated transaminases common and poor prognosticator
Elevated bilirubin indicates significant hepatic necrosis
Poor prognostic factors
PT or INR rising after day 3 PT >100 s at any time Bilirubin > 70 micromol/l Metabolic acidosis Encephalopathy [III or IV] Raised Lactate Creatinine > 300 micromol/L
How can paracetamol overdose be treated?
Prevent absorption
Activated charcoal in large dose
Within 1 hour
Specific antidote
Provide glutathione for detoxification of NAPQI as IV acetyl cysteine
Warning! Value of antidotes decreases with time
Intravenous over 21 hours (UK)-3 different infusion
Oral over 72 hours(USA) appear equally effective
Highly effective up to 8 hours
Value decreases thereafter
Probably some effect up to 24 hours
Value after that unknown
Beneficial in patients with fulminant hepatic failure
Current opinion supports use at any time after severe poisoning
Vitamin K Fresh frozen plasma (for active bleeding only) Hepatic intensive care Fluid balance Inotropic support Intracranial pressure monitoring Dialysis for renal failure Orthotopic liver transplantation
What are complications of Acetylcysteine?
Complications Anaphylactoid reactions urticaria wheeze hypotension These are not true allergic reactions but rather caused by dose-related histamine release Reduce infusion rate and give antihistamines Steroids not indicated
why is drug misuse important in healthcare?
Drug misuse is important in healthcare because:
Drug misuse is common and leads to a relatively high burden on health and social care resources
Drug misuse is associated with wide- ranging societal effects
Drug misuse is associated with acute and chronic toxicity or harms including death
Drug misuse administration may lead to adverse health complications that may be severe and life threatening
What are the health impacts of drug misuse?
In addition to direct toxicity there are a number of other heath harms that result from drug misuse. There are consequences of intoxication such as physical accidents and trauma, Sexually Transmitted Diseases or unwanted pregnancies. Here we consider some of those harms according to the route of drug administration
Intravenous:
You will be well aware of the risk of transmission of blood borne viruses such as Hepatitis or HIV, through the shared use of intravenous needles. One harm reduction measure aim at this issue is the provision of needle exchange programmes. Intravenous use can also be associated with other infections such as bacteria and with chemical injury.
Smoking
Illicitly produced drugs of misuse are not subject to the same careful regulatory checks as medicines, of course! Production quality can be poor, for example control of pH, and impurities or directly toxic effects may occur. Smoking drugs often leads to direct injury to the respiratory system where increases in Chronic Obstructive Pulmonary Disease and lung cancer are reported. Cannabis, often smoked and without a filter, is an obvious example of this.
Inhalation
Pneumothorax may result form forceful inhalation of drugs. Many stimulants can be taken this was in order to achieve a rapid onset of drug action (“rush”
Damage to other parts of the respiratory tract also occur, for example destruction and collapse of the nasal septum has been reported following drug use by this route.
What are the societal harms associated with drug misuse?
Compromised employment & education
Financial hardship
Effects on personal relationships, families and children
Homelessness
Criminal behaviour such as theft, prostitution, drug dealing and violence
What is tolerance, physical and psychological dependance?
Tolerance - the diminishing effect of a drug following repeated administration at a given dose. Practically this means that a higher dose of the drug is needed to achieve the same level of response. This may lead to inadvertent overdose. Tolerance can be mediated by pharmacodynamic mechanisms such as changes in receptor density, for example with opioids, or via pharmacokinetic mechanisms such as induction of metabolic enzyme activity, such as with alcohol
Physical dependence - develops when neurones adapt to repeated drug exposure and only function normally in the presence of the drug. A key feature of physical dependence is that acute withdrawal precipitates unpleasant physiological effects. Drugs that act at the (inhibitory) GABA receptor such as benzodiazepines or Gamma HydroxyButyrate (GHB) are good examples of this, causing features such as tremor, sweating, anxiety, irritability, nausea and vomiting, abdominal pain, headache and seizures. A more gradual reduction in use over time may help to alleviate this syndrome.
Psychological dependence - emotional need for a drug or substance that has no underlying physical need. Behavioural addiction is defined as a biopsychosocial compulsion to engage in a natural reward and includes drug addiction. It is thought to be mediated by changes in the dopamine pathway in the nucleus accumbens, with overexpression of deltafosB a key common finding.
What non-toxic conditions may present in ways that mimic drug misuse?
acute psychosis, thyrotoxicosis, sepsis, encephalopathy, encephalitis, phaeochromocytoma, withdrawal syndromes.
What test can be done to identify drug use?
There are two types of test available that can help detect drugs of misuse or their metabolites, immunoassays and chromatography-mass spectrometry.
Immunoassays:
These are available in most Emergency Departments, i.e. at the point-of-care. They typically use a sample of patient urine. The image below shows one of the test sample pots used. You can see each strip tests for a different drug and these are limited to a few classical drugs such as Cocaine, Amphetamines, Cannabis, Opioids, Benzodiazepines and Phencyclidine.
New Psychoactive Substances (NPS)
Over the last 10-15 years a huge number and variety of new drugs have become available to users often sold via the internet. These so called NPS have typically but not exclusively been derived from classical drugs of misuse and may have evaded legal controls that are based on chemical structure. There are more than 500 such drugs that have been notified to regulatory authorities and often little is initially known about their pharmacology and toxicology. Immunoassays do not test for, and so will not detect, NPS.
As these urine drug screens test for so few substances and because there are more than 500 different drugs of misuse, it follows that false negative results are very common. In fact false positive results are also very common as the table below shows (Note - please do not try to remember any of these false positives specifically, just remember that they are common).
It is also true that in many cases users are intoxicated with more than one drug. Therefore in reality these immunoassay urine drug screens are of very little clinical use in the management of acute toxicity.
LC-MS-MS (Liquid Chromatography-tandem mass spectrometry)
The gold standard for drug analysis is provided by Mass Spectrometry. The requires specialist equipment and very careful set up and analysis. It requires in most cases reference standards of the various drugs of abuse and compares the findings in patient blood, urine or saliva with the reference standards. This complexity means that analysis is not available at the point of care and results may take days to weeks to become available. This link provides a simple explanation of the MS technology used although this is further or non-essential reading only.
As immunoassays are unreliable and because Mass Spectrometry results can take a number of days or weeks to be available, it follows that clinicians in acute settings will not typically be able to identify the drug causing toxicity at the point of care. Fortunately in most cases it is appropriate to manage the patient based on a recognition of the class or group of drugs. This can be best achieved by considering the spectrum of clinical features present (a Toxic syndrome or ‘toxidrome’) that are typical of one (or more) drug classes. The image below shows a page from Toxbase, the information database provided by the UK National Poisons information Service, that helps clinicians with this toxidrome recognition.
How are opioids taken and how do they work?
Opioids can be taken orally (for example MST, tramadol or codeine tablets), intravenously (for example heroin), smoked (heroin) or heated to form a pyrolysate that is then inhaled (some time called ‘chasing the dragon’).
Opioids cause their clinical effects through agonism at opioid receptors (G-Protein Coupled Receptors), most commonly µ (mu) and K (kappa) receptors. Classically Mu1 receptors cause analgesia while Mu2 cause respiratory depression and kappa receptors cause sedation - although this is a highly simplified statement and variation occurs in different brain regions and perhaps with different drugs.
What are signs of opioid overdose?how is it managed
CNS and respiratory depression ‘Pin-point’ pupils Hypotension, tachycardia Hallucinations Rhabdomyolysis Non-cardiac pulmonary oedema
Airway management if reduced GCS or respiratory rate Breathing Consider Opioid receptor antagonist Naloxone Ventilation Circulation Disability – reduced GCS Consider Opioid receptor antagonist Hepatitis B,C and HIV precautions (IV users)
Naloxone
Use in suspected opiate intoxication for
Diagnosis & Treatment
Indications
Reduced respiratory rate <10/min
Reduced conscious level <10/15
Use adequate doses
Adults: 400microgram up to 2.0 mg or more
Children: titrate up from 0.1 mg/kg
Repeat as necessary or use a continuous infusion
2/3 of initial dose required to rouse patient by IVI per hour
What are the side effects of Naloxone?
Shorter ½ life than most opioids-repeated doses ,infusion
Acute withdrawal syndrome
muscle aches, diarrhoea, palpitations, rhinorrhoea, yawning, irritability, nausea, fever, tremor, cramps
Self-discharge during alert phase with subsequent coma / death
Unmasking of pain
Hypertension
Behavioural disturbances (high doses)
Rarely fits, arrhythmias, pulmonary oedema
What are the pharmacological effects of benzodiazepines and how do they work?
Sedation Hypnotic Muscle relaxant CNS depressant Anaesthetic Amnesia Anxiolytic (Anti-anxiety)
Benzodiazepines (BZDs) work by enhancing the effects of the inhibitory neurotransmitter, GABA, particularly at GABAAreceptors(Increase cl –hyperpolarization of cells)
Toxicity is an extension of this effect
How does benzo overdose present and how is it managed
features
Drowsiness Ataxia Dysarthria Hypotension Bradycardia Respiratory depression Coma
Supportive
First priority which is standard is to maintain airway, breathing and circulation. If a toxic dose has been ingested then oral activated charcoal is indicated provided it is within the hour. Observation for a minimum of 4 hours is required. Monitoring of vital signs, 12 lead ECG and checking of capillary blood sugar should be done. In all patients who require assessment it is important to check FBC, U&Es and LFTS. Check Creatine Kinase if features of toxicity are present. The general management is good symptomatic and supportive care. There is an antidote that can be used and this is flumazenil
Flumazenil
First priority which is standard is to maintain airway, breathing and circulation. If a toxic dose has been ingested then oral activated charcoal is indicated provided it is within the hour. Observation for a minimum of 4 hours is required. Monitoring of vital signs, 12 lead ECG and checking of capillary blood sugar should be done. In all patients who require assessment it is important to check FBC, U&Es and LFTS. Check Creatine Kinase if features of toxicity are present. The general management is good symptomatic and supportive care. There is an antidote that can be used and this is flumazenil
What are stimulant drugs and how do they present in overdose?
Most stimulant drugs have a chemical structure that is related to natural catecholamines such as dopamine and serotonin (all derived from the amino acid phenylalanine). Amphetamines, cocaine, 3,4-methylenedioxymethamphetamine (ecstasy) and methamphetamine are typical classical examples. More recently a large number of new stimulants (NPS) have been detected globally, perhaps the most well known being mephedrone, at least in the UK where a number of deaths attracted high media attention.
They are generally taken by ingestion although nasal insufflation or injection may provide more rapid and intense effects. The tables below show examples of classical and new stimulants and their clinical effects. The typical toxidrome includes tachycardia, hypertension, mydriasis and agitation,arrthymias,sweating,seizures,metabolic acidosis, hyperthermia
timulants generally inhibit or even reverse catecholamine reuptake transporters on the pre-synaptic membrane of CNS neurones, more specifically at the dopamine reuptake transporter (DAT) the serotonin reuptake transporter (SERT) and the noradrenaline reuptake transporter (NET). The clinical differences in toxicity between various stimulants reflects the variation in effects at these three transporters. Drugs that have more activity at SERT have been found to be associated with greater toxicity and mortality perhaps through severe serotonin toxicity, although most of the stimulant drugs can cause death.
Note that cocaine is a local anaesthetic and additionally has inhibitory activity at sodium channels that may lead to a widening of the QRS complex on ECG, arrhythmias and seizures
How does Cannabis work and what are the effects?
Recall that cannabis is the most commonly used drug in the England and Wales, especially in young adults. Cannabis contains the active substance delta9-tetrahydrocannabinol (delta9-THC) which is a partial agonist at CB1 and CB2 cannabinoid receptors. The image below shows the distribution of cannabinoid receptors in the body. Desired effects are due to action primarily at the CB1 receptor although activation of the endocannabinoid system results in the inhibitory regulation of other neurotransmitter systems including GABAergic, glutamatergic, cholinergic, dopaminergic and serotoninergic systems.
CB1-motor activity, thinking,apetite,pain perception, short term memory, immune cells
Cannabis is typically smoked although can be ingested or vaped. Acute severe toxic effects are uncommon following cannabis use although longer term effects can include lung damage with bullae formation and a probable increased risk of lung cancer. Heavy cannabis use over a longer period has been associated with psychosis.
The most common New Psychoactive Substances (NPS) are synthetic cannabinoid receptor agonists (SCRA)
The SCRA toxidrome can be quite varied but typically can be described as;
A history of smoking or vaping
Cardiovascular dysfunction, typically tachycardia and hypertension but occasionally bradycardia
Neuropsychiatric dysfunction including reduced GSCS or agitation, panic or hallucinations
Gastrointestinal disturbance usually nausea and vomiting
Severe complications may include acute kidney injury, seizures, metabolic or respiratory acidosis, psychosis, acute coronary syndrome, arrhythmia or death.
- What are Hallucinogens and how do they present?
are substances capable of inducing distortion of perception, mood and thought in an otherwise normal sensorium. True hallucination is generally accepted to be due to agonism of the serotonin 2a receptor within specific parts of the central nervous system, although other neurotransmitter systems may be involved such as glutamate and dopamine.
Hallucinogens may be very potent agonists at the serotonin 2a receptor - LSD or the recent NPS ‘NBOMe’ drugs are very clear examples of this. They can therefore be ingested on very small blotters such as in the image below that are allowed to dissolve on the tongue or gum.
Clinical effects:
Usually hallucinogen toxicity presents with a neuropsychiatric toxidrome of hallucinations, agitation and psychosis. The duration of effect can vary greatly from 30 minutes, for example for Dimethyltryptamine (DMT or “the businessman’s lunch”) to days with some of the NBOMe drugs. Duration can also be influenced by dose.
Trauma, accidents and injury may therefore be associated with use. Occasionally mild to moderate increased temperature or blood pressure may be seen while massive ingestions may cause metabolic or haematological disorders and reduced consciousness. Overall there is a low direct mortality from most hallucinogen use. However an association with psychosis is controversial.
The most common examples of hallucinogens in the UK are LSD, NBOMe drugs and Psilocybin containing mushrooms (‘magic mushrooms’) shown below
How are volatile solvents abuse
Volatile agents or “inhalants”:
Nitrous Oxide -‘laughing gas’:
This is a colourless gas with a slightly sweet odour. It causes toxicity by displacing oxygen causing hypoxic asphyxia although also probably has a dissociative anaesthetic action via the NMDA receptor.
Clinical effects include euphoria and analgesia but hypoxia, reduction in GCS, arrhythmia and death are reported. The use of compressed nitrous oxide (cannisters are called whippets and shown below) can cause lung injury including pneumothorax and mucosal injury. Cold injuries to skin and mucosa may also occur. Chronic use may cause neurological dysfunction through Vitamin B12 depletion.
A range of solvents are used for recreational purposes usually those manufactured from hydrocarbons and found in household aerosol products as shown in the image below. As expected they are abused via inhalation.
The mechanism of action of solvents is varied according to the particularchemical in what is a broad chemical class. Certainly they penetrate theCNS and interact with multiplecellularprocesses and receptors.
Clinical features are classically consideredover time and listed below:
Early:
- Euphoria, Excitement, Ataxia, Tremor, Visual disturbances, Vomiting, Chest tightness, ventricular arrhythmias - sudden cardia death. the mechanism of arrhythmia is thought to be due to sensitisation of the myocardium to endogenous catecholamines)
Late:
- CNS Depression, Convulsions, Coma, Hepatic and renal Dysfunction
Volatile nitrites:
Commonly known as ‘poppers’ organic nitrites, such as amyl nitrite, are said to cause enhanced sexual pleasure, altered perceptions of reality and feelings of warmth. these effects are probably mediated through vasodilation and reflex tachycardia. In addition they may cause nitrite induced oxidation of ferrous (2+) to ferric (3+) haem which is then unable to participate in oxygen transport and leads to methaemoglobinaemia.
Clinical presentation is often with hypotension and dizziness although peripheral cyanosis due to methaemoglobinaemia. typically above 10%. In severe cases metabolic acidosis, seizures, cardiovascular collapse and death may occur. Treatment of methaemoglobinaemia is with methylene blue in severe cases where end organ ischaemia is present or a very high methaemoglobin concentration is found. The image below shows peripheral cyanosis.
What are the ecgs finding and causes of ecg finding in Cocaine overdose?
The ECG shows wide QRS complexes typical of sodium channel block. It is probably sinus tachycardia although ventricular tachycardia is possible. In this context cocaine use is most likely. Giving IV Sodium Bicarbonate is the immediately lifesaving treatment.
What are the pharmacodynamics action and clinical features of TCA poisoning?
Anticholinergic
Predominate early
Hot dry skin Dilated pupils Tachycardia Urinary retention Agitation Delirium Fits Coma Hypertonia Hyperreflexia
Sodium channel blocking effects
Cardiac Arrhythmias
Conduction block
Prolonged QRS and QT intervals
Alpha adrenoceptor antagonism
Hypotension
What Investigations are done for TCA overdose?
Urea & electrolytes
Blood glucose
Arterial blood gases
ECG
QRS duration
> 160 ms (4 small squares) = very high risk of arrhythmia
> 120 ms (3 small squares) = specific urgent action
Constant cardiovascular monitoring
CCU or ITU if large overdose or initial ECG abnormal
How can TCA toxicity be managed?
Gastric decontamination
Activated charcoal if within 1 h
Enhance elimination
MDAC: Further doses of activated charcoal every 2 hours may enhances elimination of some tricyclics (amitryptiline, nortryptiline)
More likely if pH < 7.4 Give Sodium Bicarbonate for Acidosis Wide QRS complex [120ms] Arrhythmias Correct K+ If bicarbonate fails consider DC cardioversion or overdrive pacing Danger DO NOT USE ANTI-ARRHYTHMICS (may worsen arrhythmias)
Use DIAZEPAM or LORAZEPAM
If fails, consider paralysis and mechanical ventilation
How does Serotonin syndrome present?
SSRIs (specific serotonin reuptake inhibitors)
citalopram, escitalopram , fluoxetine, paroxetine,sertraline
SNRI (serotonin noradrenergic reuptake inhibitors)
Venlafaxine
NaSSA (noradrenergic and specific serotonergic antidepressant)
Mirtazapine
NaRI (selective noradrenaline reuptake inhibitor)
Reboxetine
RIMA (reversible inhibitor of monoamine oxidase A)
moclobemide
Cognitive-behavioural changes
agitation, confusion, hallucinations, coma,
Neuromuscular dysfunction
tremor, teeth grinding, myoclonus, hyperreflexia
Autonomic dysfunction
tachycardia, fever, hyper or hypotension, flushing, diarrhoea
Others
Vomiting, seizures, hyperpyrexia, rhabdomyolysis, renal failure, coagulopathies
How does Organophosphorus compounds cause toxicity?
How do they present?
Commonly used pesticides in developing countries e.g South Asia
Major cause of morbidity and mortality from self-harm worldwide
Initially developed as chemical warfare agents.
Inhibition of cholinesterase enzymes, particularly acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE)
This leads to accumulation of acetylcholine at muscarinic receptors, nicotinic receptors and in the central nervous system.
Cholinergic
Muscarinic effects -dominate D iarrhoea U rination M iosis B radycardia, Bronchorrhoea, Bronchospasm E mesis L acrimation S alivation
Nicotinic effects Respiratory difficulty respiratory arrest diaphragmatic weakness Muscle Weakness fasciculations clonus tremor Stimulation of sympathetic nervous system Mydriasis, hypertension, tachycardia re-entrant dysrhythmias cardiorespiratory arrest
CNS off
How can Organophosphorus toxicity be investigated and managed?
Inx
ECG
Urea, electrolytes and glucose
Red cell cholinesterase activity-severity(takes time to get results)
There is a rough correlation between cholinesterase activity and clinical effects (~50% cholinesterase activity in subclinical poisoning, 20-50% activity in mild poisoning and less than 10% of normal cholinesterase activity in severe poisoning).
Clinical features are more helpful than red cell cholinesterase measurements (may not be available) in determining the severity of intoxication and prognosis.
There is wide inter-individual variation in cholinesterase activity.
Management
Resuscitation A - Airway and left lateral position Give oxygen B - Breathing C - Circulation IV access x 2
Antidote
Atropine reduces bronchorrhoea, bronchospasm, salivation and abdominal colic and should be repeated every ten minutes until signs of atropinisation develop (flushed red skin, tachycardia, dilated pupils, dry mouth).
Triggers for giving atropine:
Pinpoint pupils
Sweating
Difficulty breathing (“gasping”)
Large doses of atropine may be required in the first 24 hours and may have to be continued for a prolonged period.
Pralidoxime and obidoxime are cholinesterase reactivators, these drugs can reactivate the enzyme AChE inhibited by organophosphorus insecticides if given before the organophosphate-cholinesterase enzyme complex ‘ages’.
Supportive care
Clearing the airway Ensure adequate ventilation Give high flow oxygen Manage in intensive care unit Atropine for excessive secretions Diazepam for seizures
How does Aspirin poisoning present?
Less common o/d than paracetamol in UK Clinical Features Dizziness Sweating Tinnitus-classical in sa Vomiting Vasodilatation Hyperventilation Agitation Delirium Coma (esp’ children)
Metabolic abnormalities
Metabolic Acidosis
Salicylic acid
Uncouples oxidative phosphorylation(changes from aerobic to anerobic)
Respiratory alkalosis(early then metabolic acidosis overtakes as salicylic acids accumulates)
Direct CNS ‘respiratory centre’ stimulation
Hypoglycaemia
Hypokalaemia
What Investigations are done for aspirin poisoning and what is the management?
Inx
Plasma salicylate concentration
Urea,electrolytes,bicarbonate
Blood glucose
Arterial blood gases
Treatment Gastric decontamination 50g activated charcoal Within 1 hour ? gastric lavage + activated charcoal if very large o/d (rarely used) Prevention of CNS penetration Sodium bicarbonate Enhanced elimination Urinary alkalinisation (sodium bicarbonate) MDAC
Haemodialysis Highly effective at removing salicylate Also corrects metabolic abnormalities Consider if: pH < 7.3 salicylate level > 700 mg/l (600 mg/l in children) patients in renal failure
Airway I.V fluids Ventilation Glucose for hypoglycaemia KCl for hypokalaemia
What are the signs and symptoms of Iron Poisoning?
Warning - Corrosive!
Uncommon
May be serious [esp children]
Early (0-6 hours) Nausea and vomiting Abdo pain Diarrhoea [bloody] Massive GI fluid loss
Delayed (2-72 hours) Black offensive stools Drowsiness/coma Fits Circulatory collapse
Late (2-4 days) Acute liver necrosis Renal Failure Very late (2-5 weeks) Gastric strictures
How is Iron poisoning diagnosed and managed?
History - establish amount of elemental iron taken serious overdose >10mg/kg Iron concentration After at least 4 hours Repeat after 2-3 hours Blood count [usually see leucocytosis] U&E’s Bicarbonate - monitor daily Glucose [usually see hyperglycaemia] Clotting - monitor daily LFT’s
treatment
Gastric decontamination if large OD
Gastric lavage
Danger - Activated Charcoal ineffective
Induced emesis has been used in small children but vomiting may mask symptoms - not generally recommended
Desferrioxamine Chelates iron and reduces toxicity Chelate (ferrioxamine) is water soluble and excreted in urine (red discolouration) Can cause adverse effects, e.g. hypotension and pulmonary oedema Contraindicated in renal failure Used for patients with severe toxicity Fits, coma, circulatory collapse GI symptoms, leucocytosis, or hyperglycaemia and high iron concentration (>3 mg/l)
Supportive
Hypotension - I.V fluids
Vomiting - Antiemetics
Fits - Diazepam / Lorazepam
Acidosis - Correct with bicarbonate
Renal failure - Dialysis
King’s college criteria of paracetamol overdose
Arterial pH < 7.3, 24 hours after ingestion
or all of the following:
prothrombin time > 100 seconds
creatinine > 300 µmol/l
grade III or IV encephalopathy
How does lithium intoxication present?how is it managed?
Lithium is a mood stabilising drug used most commonly prophylactically in bipolar disorder but also as an adjunct in refractory depression. It has a very narrow therapeutic range (0.4-1.0 mmol/L) and a long plasma half-life being excreted primarily by the kidneys. Lithium toxicity generally occurs following concentrations > 1.5 mmol/L.
Toxicity may be precipitated by:
dehydration
renal failure
drugs: diuretics (especially thiazides), ACE inhibitors/angiotensin II receptor blockers, NSAIDs and metronidazole.
Features of toxicity coarse tremor (a fine tremor is seen in therapeutic levels) hyperreflexia acute confusion polyuria seizure coma
Management
mild-moderate toxicity may respond to volume resuscitation with normal saline
haemodialysis may be needed in severe toxicity
sodium bicarbonate is sometimes used but there is limited evidence to support this. By increasing the alkalinity of the urine it promotes lithium excretion
What analgesic is contraindicated in heart disease?
It is therefore advised that diclofenac is contraindicated in patients with the following:
ischaemic heart disease
peripheral arterial disease
cerebrovascular disease
congestive heart failure (New York Heart Association classification II-IV)
Patients should be switched from diclofenac to other NSAIDs such as naproxen or ibuprofen. This advice does not apply to topical diclofenac.
Studies have shown that naproxen and low-dose ibuprofen have the best cardiovascular risk profiles of the NSAIDs.
What are the side effects of CCB’s
Verapamil
SE-Angina, hypertension, arrhythmias
Highly negatively inotropic
Should not be given with beta-blockers as may cause heart block Heart failure, constipation, hypotension, bradycardia, flushing
Diltiazem
SE-Angina, hypertension
Less negatively inotropic than verapamil but caution should still be exercised when patients have heart failure or are taking beta-blockers Hypotension, bradycardia, heart failure, ankle swelling
Nifedipine, amlodipine, felodipine
(dihydropyridines) -
SE-Hypertension, angina, Raynaud’s
Affects the peripheral vascular smooth muscle more than the myocardium and therefore do not result in worsening of heart failure but may therefore cause ankle swelling Flushing, headache, ankle swelling
What are the side effects of anti TB ?
Rifampicin mechanism of action: inhibits bacterial DNA dependent RNA polymerase preventing transcription of DNA into mRNA potent liver enzyme inducer hepatitis, orange secretions flu-like symptoms
Isoniazid
mechanism of action: inhibits mycolic acid synthesis
peripheral neuropathy: prevent with pyridoxine (Vitamin B6)
hepatitis, agranulocytosis
liver enzyme inhibitor
Pyrazinamide mechanism of action: converted by pyrazinamidase into pyrazinoic acid which in turn inhibits fatty acid synthase (FAS) I hyperuricaemia causing gout arthralgia, myalgia hepatitis
Ethambutol
mechanism of action: inhibits the enzyme arabinosyl transferase which polymerizes arabinose into arabinan
optic neuritis: check visual acuity before and during treatment
dose needs adjusting in patients with renal impairment
Which antibiotics form a complex with antacids making them less orally bioavailable?
Quinolones and tetracyclines form a complex with antacids making them less orally bioavailable.
Absorption may be reduced by up to 70% causing treatment failure.
What drug can affect lithium levels?
Thiazides cause diuresis and initial sodium loss
Compensatory sodium retention in proximal tubules
Proximal tubules do not distinguish sodium from lithium
Lithium also retained and accumulates
This 15-year-old presented to the dentist with staining of the teeth. His mother was prescribed an antibiotic during pregnancy.What antibiotic is likely to cause this delayed adverse effect?
This is tetracycline staining of teeth. Tetracycline gets deposited in the enamel of the teeth and can also cause enamel hypoplasia.
What are the poor prognostic indicators for paracetamol overdose?
PT or INR rising after day 3 PT >180 at any time Bilirubin > 70 umol/l Metabolic acidosis Encephalopathy [III or IV] Raised Lactate Creatinine > 300 micromol/L
How can beta blocker overdose be managed
Management
if bradycardic then atropine
in resistant cases glucagon may be used
What are the side effects of cyclosporin
Ciclosporin side-effects: everything is increased - fluid, BP, K+, hair, gums, glucose nephrotoxicity hepatotoxicity fluid retention hypertension hyperkalaemia hypertrichosis gingival hyperplasia tremor impaired glucose tolerance hyperlipidaemia increased susceptibility to severe infection
Indication Indications following organ transplantation rheumatoid arthritis psoriasis (has a direct effect on keratinocytes as well as modulating T cell function) ulcerative colitis pure red cell aplasia
What causes hypermagnesmia and how can it be prevented?
Cause of low magnesium drugs: diuretics, proton pump inhibitors total parenteral nutrition diarrhoea alcohol hypokalaemia, hypocalcaemia conditions causing diarrhoea: Crohn's, ulcerative colitis metabolic disorders: Gitleman's and Bartter's
Features may be similar to hypocalcaemia: paraesthesia tetany seizures arrhythmias decreased PTH secretion → hypocalcaemia ECG features similar to those of hypokalaemia exacerbates digoxin toxicity
Treatment
<0.4 mmol/l
intravenous replacement is commonly given. An example regime would be 40 mmol of magnesium sulphate over 24 hours
> 0.4 mmol/l
oral magnesium salts (10-20 mmol orally per day)
diarrhoea can occur with oral magnesium salts
What are the side effects of heparin
Adverse effects of heparins include:
bleeding
thrombocytopenia - see below
osteoporosis and an increased risk of fractures
hyperkalaemia - this is thought to be caused by inhibition of aldosterone secretion
What are montinering requirements for common drugs?
Statins,ACEI,Amiodorone,methotrexate,Azathioprine and lithium
Statins LFT LFTs at baseline, 3 months and 12 months
ACE inhibitors U&E U&E prior to treatment
U&E after increasing dose
U&E at least annually
Amiodarone TFT, LFT TFT, LFT, U&E, CXR prior to treatment
TFT, LFT every 6 months
Rheumatology drugs
Methotrexate- FBC, LFT, U&E The Committee on Safety of Medicines recommend ‘FBC and renal and LFTs before starting treatment and repeated weekly until therapy stabilised, thereafter patients should be monitored every 2-3 months’
Azathioprine FBC, LFT FBC, LFT before treatment
FBC weekly for the first 4 weeks
FBC, LFT every 3 months
Neuropsychiatric drugs
Lithium Lithium level, TFT, U&E TFT, U&E prior to treatment
Lithium levels weekly until stabilised then every 3 months
TFT, U&E every 6 months
