Intentional and Unintentional presentations Flashcards

Question

What are types of medication errors?

Answer 1

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

Answer 2

``` 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 ```

Answer 3

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

Answer 4

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

Answer 5

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

Answer 6

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

Answer 7

check notion

Answer 8

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

Answer 9

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

Answer 10

``` 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

Answer 11

``` 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 ```

Answer 12

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

Answer 13

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 ```

Answer 14

``` 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 ```

Answer 15

``` 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 ```

Answer 16

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

Answer 17

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

Answer 18

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

Answer 19

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.

Answer 20

``` 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.

Answer 21

``` 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

Answer 22

``` 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

Answer 23

Pupil irregularites are helpful if present with opiates and organophosphates causing meiosis(constriction) and stimulants such as sympathomimetics or anticholinergics causing dilated mydriatic pupils.

Answer 24

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 ```

Answer 25

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) ```

Answer 26

``` Support physiology Prevent absorption Specific antidote Chelation Enhance elimination ```

Answer 27

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

Answer 28

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)

Answer 29

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 ```

Answer 30

``` Methods: Multiple dose activated charcoal [MDAC] Chelation Urinary Alkalinisation Renal replacement therapies Haemodialysis [HD] Haemoperfusion [HP] Haemofiltration [CVVH] Combined methods haemodiafiltration MARS ```

Answer 31

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

Answer 32

``` 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

Answer 33

Paracetamol- can undergo bioactivation via oxidation through CYP450-NAPQI-toxic(glutathione absent)

Answer 34

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

Answer 35

``` 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 ```

Answer 36

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 ```

Answer 37

``` 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 ```

Answer 38

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

Answer 39

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.

Answer 40

Compromised employment & education Financial hardship Effects on personal relationships, families and children Homelessness Criminal behaviour such as theft, prostitution, drug dealing and violence

Answer 41

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.

Answer 42

acute psychosis, thyrotoxicosis, sepsis, encephalopathy, encephalitis, phaeochromocytoma, withdrawal syndromes.

Answer 43

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.

Answer 44

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.

Answer 45

``` 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

Answer 46

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

Answer 47

``` 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 GABAA receptors(Increase cl –hyperpolarization of cells) Toxicity is an extension of this effect

Answer 48

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

Answer 49

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

Answer 50

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.

Answer 51

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

Answer 52

**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 particular chemical in what is a broad chemical class. Certainly they penetrate the CNS and interact with multiple cellular processes and receptors. Clinical features are classically considered over 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.

Answer 53

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.

Answer 54

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

Answer 55

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

Answer 56

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

Answer 57

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

Answer 58

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

Answer 59

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 ```

Answer 60

``` 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

Answer 61

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 ```

Answer 62

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 ```

Answer 63

``` 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

Answer 64

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

Answer 65

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

Answer 66

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.

Answer 67

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

Answer 68

``` 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

Answer 69

Quinolones and tetracyclines form a complex with antacids making them less orally bioavailable. Absorption may be reduced by up to 70% causing treatment failure.

Answer 70

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

Answer 71

This is tetracycline staining of teeth. Tetracycline gets deposited in the enamel of the teeth and can also cause enamel hypoplasia.

Answer 72

``` 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 ```

Answer 73

Management if bradycardic then atropine in resistant cases glucagon may be used

Answer 74

``` 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 ```

Answer 75

``` 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

Answer 76

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

Answer 77

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

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