Drug abuse Flashcards
Describe Serotonin syndrome
- mental effects e.g. agitation
- autonomic effects e.g. labile BP
- neuromuscular change e.g. clonus, tremor, hyperreflexia
Medication error
Any preventable event that may cause or lead to inappropriate medication use or patient harm while the medication is in the control of health professional, patient or consumer. Can be due to prescribing, dispensing or administration.
Types of medication error
- Wrong patient
- Wrong drug
- Wrong dose
- Wrong route
- Inappropriate individual circumstances: drug interactions or contraindicated drug
- Inadequate monitoring
Causes of medication error
- 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
- checking patient identity and drug
- education and training
- clear prescription writing
- electronic prescribing
- adverse event reporting
- controlling availability of high risk drugs
- adequate resources and staffing
- good drug and allergy history taking
- failsafe devices
- good communication at handover
Effects of anticonvulsants in pregnancy
- Effect of valproate in-utero: risk of developing autism spectrum disorder, ADHD
- Pre-pregnancy counselling and folate supplements can help
- Worse with phenytoin, carbamazepine and valproate. Better with Lamotrigine and Levetiracetam
Toxic epidermal necrosis
- Causes by: Phenytoin, sulphonamides, allopurinol, penicillins, Carbamazepine, NSAID
- Potentially life threatening skin disorder
- Presented with erythema, pruritus, facial swelling, exfoliative dermatitis and exanthematous rash
- Genetic predisposition: more common in thai or Han Chinese origin
- Management: intravenous immunoglobulins, extensive skin exfoliation
Common narrow therapeutic index drugs
- Carbamazepine
- Cyclosporine
- Digoxin
- Levothyroxine
- Lithium carbonate
- Phenytoin
- Tacrolimus
- Theophylline
- Warfarin
Drug misuse statistics
- 10% of the adult population used drugs in the last year
- 28883 drug misuse deaths last year
- 25,000 hospital admissions due to drug misuse last year
Drug misuse epidemiology
Most popular used drugs: Cannabis, cocaine, ectasy, Hallucinogens, Amphetamines
Age group with the most drug misuse: 25-45
Regions with the most drug misuse: North east, correlation with social deprivation
Most common cause of death due to drug misuse: 2/3rds are opioids particularly heroin and morphine
Other physical harms of drug use
- STI’s, pregnancy, physical accidents and trauma
- IV: blood borne viruses (Hepatitis or HIV), Necrotic ulcer. Get infections with chemical and bacteria injury
- Smoking: increased risk of COPD and cancer
- Inhalation (snorting): pneumothorax, destruction of the nasal septum
Tolerance
The diminishing effect of a drug following repeated administration at a given dose. 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. Gradual withdrawal of drugs is needed.
Psychological dependence
Emotional need for a drug or substance that has no underlying physical need. Caused by a changes in the dopamine pathway in the nucleus accumbens, with overexpression of deltafosB
Testing for drug use
- Immunoassays: used in patients urine test for classic drugs (Cocaine, Amphetamines, Cannabis, Opioids, Benzodiazepines and Phencyclidine). Don’t test for new Psychoactive substances. Common to get false positives and negatives
- Chromatography mass spectrometry: gold standard. Compares the patients blood, urine or saliva with the reference standard. Can take days-weeks to come back
-Often difficult to identify drug causing toxicity, Need to look at clinical features (Toxic syndrome or ‘Toxidrome)
Opioids clinical features and ingestion methods
- Reduced GCS, reduced ventilation, meiosis (pinpoint pupils), rhinorrhoea, watering eye, yawning. Can cause type 2 respiratory failure, respiratory arrest and aspiration pneumonia
- 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
- Issues with heroine being contaminated with synthetic opioids like fentanyl
Opioids MoA
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
How to give naloxone
- The starting dose in adults is 400microgram IV and if the clinical response is inadequate then escalating doses are given at 1 minute intervals aiming for a GCS above 10 and a respiratory rate above 10.
- Ensure period of observation after naloxone administration
Other sedative drugs
benzodiazepines and GHB type drugs don’t cause meiosis however. GHB type drugs have a shorter half life and causes bradycardia
Management of opioid dependence
- Methadone and Buprenorphine are offered first line in detoxification
- Methadone is a full agonist of the mu opioid receptor whilst Buprenorphine is only partial. Relieves withdrawal symptoms and cravings
- Compliance is monitored using urinalysis
- Normally lasts 4 weeks as a inpatient and 12 weeks in the community
Stimulant drugs
- Examples: amphetamines, cocaine, ectasy
- Clinical features: tachycardia, hypertension, mydriasis, agitation, hyperreflexia
- Causes Euphoria, sweating, hyperthermia
- MoA: inhibits catecholamine reuptake transporters on the pre-synaptic membrane of the CNS neurone. Specifically on the DAT, SERT and NET transporter.
Cocaine ECG and MoA
Cocaine ECG: wide QRS complexes typical of a sodium channel block with sinus tachycardia. Treatment is IV Sodium Bicarbonate.
Cocaine MoA: blocks the reuptake of dopamine, noradrenaline and serotonin
Cocaine adverse effects
- Cardiovascular: coronary artery spasm (myocardial ischaemia), both tachycardia and bradycardia can occur, hypertension, QRS widening and QT prolongation, aortic dissection
- Neurological: seizures, mydriasis, hypertonia, hyperreflexia
- Psychiatric: agitation, psychosis, hallucinations
- Other: ischaemic colitis, hyperthermia, metabolic acidosis, rhabdomyolysis
Management of cocaine toxicity
- Chest pain: Benzodiazepines + glycercyl trinitrate
- Hypertension: Benzodiazepine + sodium nitroprusside
Cannabis and synthetic cannabis
- Contains the active substance delta9-THC which is a partial agonist at CB1 and CB2 cannabinoid receptors
- Adverse effects: bullae formation, lung cancer, psychosis
- Synthetic Cannabis has a greater effect
Hallucinogens
- Examples: LSD, NBOMe, magic mushrooms
- Clinical effects: hallucinations, agitation, psychosis
- MoA: agonism at the serotonin 2a receptor within the CNS
- Can last from 30 mins (DMT) to days (NBOMe)
Volatile agents and solvents
Volatile agents or ‘inhalants’ example: Nitrous Oxide, Solvents and volatile nitrites or ‘poppers’
Solvents: abused by inhalation. Effects are euphoria, ataxia, tremor. Later on can cause CNS depression and renal dysfunction
Volatile nitrates (poppers): i.e. amyl nitrate. Enhances sexual pleasure, altered perceptions of reality and warmth Due to vasodilation and reflex tachycardia. Can organ ischaemia which is treated with methylene blue
Nitrous oxide
- Displaces oxygen causing hypoxic asphyxia also effect on NMDA receptor
- Clinical effects: euphoria, analgesia, hypoxia, reduction in GCS, arrhythmia and death
- Side effects: pneumothorax, cold injuries and chronically vitamin B12 depletion
How can poisonings be classified in terms of timing
- acute e.g. suicide attempt by paracetamol OD
- chronic e.g. cumulative digoxin toxicity
- acute on chronic e.g. collapse due to excess diuretics in heart failure
How can be poisonings be classified in terms of aetiology
- deliberate e.g. self-harm
- accidental e.g. carbon monoxide poisoning
Most poisonings are: Deliberate, self-poisoning, using drugs, taken by mouth
2 main groups for poisonings
- Young children 1-5 (males>females): accidental ingestion, daytime
- Adolescents and young adults (Males=females): deliberate self harm or recreational overdose, evening/night time presentation. Associated with alcohol intake and stress
Most common prescription overdoses and overdoses causing death
Most common prescription overdoses: Paracetamol, Ibuprofen, Citalopram, Zopiclone, Fluoxetine
Most common poisons causing death: Paracetamol, Tricyclic antidepressants, Opiates (IV heroin, methadone), carbon monoxide (smoke from housefires).
What to look for on examination of poisoning
- Pupil constriction (opiates, organophosphates)
- pupil dilation (sympathomimetics, anticholinergics)
- needle marks (IVDU)
- hypertension (cocaine)
- Coma, reduced respiratory rate (benzodiazepines, opiates)
- bradycardia (CCBs or digoxin)
- high temperature (cocaine, amphetamine, ecstasy)
Initial investigations of poisonings
- routine FBC, U+E, glucose, ABG, ECG, CXR (aspiration risk)
- levels of specific poisons e.g. paracetamol concentration, salicylate concentration
- troponin for cocaine toxicity
- General urine toxicology screen rarely indicated
- ABCDE
ABCDE in poisoning
- A: substances which can reduce consciousness and compromise the airway- opiates, TCA’s, Benzos, GHB, severe cocaine, Ectasy, CO, sleeping tablets, antihistamine
- B: stimulated respiratory rate (amphetamines, metabolic acidosis due to TCA), can get a cannabis induced pneumothorax, depress respiratory rate (opiates)
- C: circulatory collapse can follow poisoning by BB, CCB, amphetamines, ecstasy, cocaine (can cause arrhythmias), cannabis
History: in the acute incident need to deal with it medically then afterwards look at mental health risk
General management strategies for poisoning
- Support physiology: inotropes, incubation
- Prevent absorption
- Specific antidote
- Chelation: binds to drug helping removal
- Enhance elimination: dialysis
Gastric decontamination
- Aim to reduce absorption of poisons taken by mouth when they carry significant risk
- Should be used within 1hr
- Don’t use in unconscious or drowsy patients without airway protection due to aspiration risk (NG tube with airway protected by cuffed endotracheal tube)
- Methods: activated charcoal, gastric aspiration/lavage, induced emesis (no longer used)
Gastric lavage/Aspiration
- Suitable for: very large and life threatening overdoses and 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
- Rarely used
Gastric lavage/aspiration complications and contraindications
- Complications: gut perforation, aspiration, laryngospasm, water intoxication (children) causing hyponatraemia, Dysrhythmias, pneumothorax
- Contraindications: Hydrocarbon ingestion, caustic substance ingestion (risk of aspiration pneumonia and perforation of oesophagus)
Activated charcoal
- Charcoal activated by heating in steam, air or carbon dioxide at 600-900oC
- Adsorbs poison in GI tract by direct contact
- Reduces absorption of poison in the GI tract- earlier its given the better
- How much activated charcoal should be given: 10x dose of poison (up to 50g) and given suspended in flat cola (unpalatable)
Complications and contraindications of activated charcoal
- Complications: activated pneumonitis, reduced absorption of therapeutic agents (i.e. Methionine), Briquette formation/bowel obstruction
- Contraindications: absent bowel sounds (ileus), impaired gag reflex, unsafe swallow
What is activated charcoal ineffective in
- Insecticides: Malathion, DDT, N-methyl carbamate
- Cyanide
- Strong acids/alkalis
- Alcohols
- Hydrocarbons
- Elemental metals/salts: Lithium, Iron, baron salts
How can drug elimination be increased
- multiple dose activated charcoal (50g followed by 25g every 2hrs)
- chelation
- urinary alkalinisation
- renal replacement therapies (haemodialysis, haemoperfusion or haemofiltration)
Multiple dose activated charcoal: method and mechanism
- 50 g activated charcoal followed by further 25g every 2 hours: can also give laxatives
- Mechanism: reduces elimination half life by interfering with enterohepatic circulation. Means that the drug does not stay within the circulation and is broken down increasing elimination. Gastrointestinal dialysis- drug moved down to concentration gradient from intravascular space to the intraluminal activated charcoal.
When to use multiple dose activated charcoal
- Good evidence of efficacy: Carbamazepine, Dapsone, Phenobarbitone, Quinine, Theophylline
- Sometimes used in: Salicylate, phenytoin
- Complications: intestinal obstruction, vomiting, aspiration
Difference between haemodialysis, haemoperfusion and hemofiltration
- haemodialysis involves diffusion gradient. Poison needs to be small enough to cross dialysis membrane and cant be protein bound
- haemoperfusion uses charcoal filter. Poison must be able to bind to activated charcoal
- haemofiltration uses convection gradient
- Haemodialyfiltration: Combination of Haemodialysis and Haemofiltration
When do you use Haemodialysis and Haemoperfusion- poison is
- 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)
When do you use Haemodialysis only
- Toxic alcohols: Ethylene glycol, Isopropanol, Methanol
- Salicylate
- Sodium valproate
- Lithium
- Thallium
When do you use HD or Haemoperfusion
Theophylline, Phenytoin, Carbamezepine, Barbituates. Haemoperfusion is now rarely used
Specific antidotes (chelating or fixing agents)
- Iron: Desferrioxamine
- Heavy metals: Dimercaprol
- Cyanide: Edetate (dicobalt or sodium calcium), Hydroxocobalamin
- Fixes the metal in a structure so it can be excreted safely
