Block 6 - Psychiatry Flashcards

Question

What are the Mechanism, Effects (4) and Side Effects (11) of: ## Footnote **CNS Depressants - Benzodiazepines?** **Antidote?**

Answer 1

**_CNS Depressants - Benzodiazepines_** *→ YR Pharm lecture flashcards Benzodiazepines* * **Mechanism** * Binds allosterically to GABAA and potentiates GABA inhibitory neurotransmitters in CNS. * **Effects** 1. Sedation 2. Anxiolytic 3. Anticonvulsant 4. Muscle relaxant * **Sife effects** 1. Drowsiness and confusion 2. Dizziness and hallucinations 3. Respiratory depression 4. Hypotension 5. Slurred speech 6. Amnesia 7. Nystagmus 8. Ataxia 9. Coma paradoxical 10. Agitation 11. Aspiration pneumonia **NB:** Antidote is Flumazenil but it is not widely used (seizures)

Answer 2

**_CNS Depressants - Ethanol_** * **Mechanism** * Increases GABA receptor activity * Alcohol increases both the frequency and the duration of the opening of the GABA_A receptor chloride ion channel * **Effects** 1. Sedation 2. Anxiolytic 3. Anticonvulsant 4. Muscle relaxant * **Side Effects** 1. Disinhibition 2. Euphoria 3. Impulsivity 4. Aggression 5. *As benzos*

Answer 3

**_CNS Hallucinogens (Psychotomimetics) - Cannabis_** * **Mechanism** * Binds and activates pre- synaptic CB1 and CB2 receptors * Decreases neurotransmitter release * **Effects** 1. Analgesic 2. Antiemetic 3. Relaxation 4. Sharpened sensory awareness 5. Increased appetite * **Side Effects** 1. Sedation 2. Incoordination 3. Ataxia 4. Impairment of short-term memory 5. Impairment of motor coordination 6. Hypothermia

Answer 4

**_CNS Hallucinogens (Psychotomimetics) - LSD/Mushrooms_** * **Mechanism** * 5-HT receptor agonists (mostly 5-HT2A receptors) * **Effects** 1. Hallucinations 2. Energy 3. Creative thinking 4. Awareness of senses 5. Distortion of perceptions * **Side Effects** 1. Pupil dilation 2. Dizziness 3. Over-sensitisation to noises 4. Paranoia 5. Fear and panic

Answer 5

**Importance of History and Mental State Examination:** 1. **Risk Assessment:** To determine agent, dose, time of ingestion, clinical features and patient factors to help treat patient 2. **Suicidality:** To determine risk of suicide (SAD PERSONS) 3. **Medical Health:** To assess medical health and presence of drug complications 4. **Psychiatric Health:** To determine any mental disorders 5. **Dependence and Tolerance:** To assess level of drug use (recreational, dependence, tolerance or withdrawal) and assess readiness to change 6. **Psychosocial Situation:** To better understand situation of patient

Answer 6

**Potential Consequences of Drug Use:** 1. **Drug Dependence:** A chronic relapsing condition characterised by... 1. A compulsion to seek and take a drug 2. Tolerance and loss of control in limiting intake 3. Craving during periods of abstinence 4. Withdrawal emergence of a negative emotional state when access to the drug is prevented 5. Rapid reinstatement of dependence upon resumption of drug use 2. **Drug Tolerance:** The need for increased amounts of the drug to achieve a given response OR a markedly diminished effect with continued use of the same amount of the drug 3. **Withdrawal:** Onset of a set of syndromes when chronic drug use is ceased, circulating drug levels are significantly reduced OR an antagonist is administered 4. **Common Complications:** Arrhythmias, seizures, hypoxic brain damage, aspiration pneumonia, and hepatoxicity

Answer 7

**_Paracetamol_** * **Mechanism** * Not fully understood * Analgesic effect may include inhibition of central prostaglandin synthesis and modulation of inhibitory descending serotonergic pathways * The antipyretic effect is probably due to reduced production of prostaglandins in the hypothalamus * **Effects** 1. Analgesia 2. Antipyretic * **Side Effects** 1. Nausea and vomiting 2. Hepatotoxicity (can cause acute hepatic failure in OD) 3. Hypersensitivity reactions 4. Thrombocytopaenia 5. Neutropaenia **NB:** Check 4/24 paracetamol levels and plot on nomogram, if over the level treat with N- acetyl-cysteine

Answer 8

**Paracetamol Metabolism:** Paracetamol usually metabolised by phase II metabolism by conjugation with sulfate and glucuronide. Small portion is metabolised by CYP450 into toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) which is usually conjugated by glutathione into less toxic cysteine and mercapturic acid. In OD the phase II metabolism is overwhelmed and more is diverted into the CP450 pathway. When the glutathione is depleted the toxic NAPQI metabolite builds up. NAC replenishes glutathione hence deactivates and safely excretes NAPQI

Answer 9

**_SSRIs (E.g. Fluvoxamine)_** * **Mechanism** * Selectively inhibit the presynaptic reuptake of serotonin * Also weak affinity for noradrenaline and dopamine transporters * **Effects** 1. Antidepressant 2. Anxiolytic 3. Chronic pain relief * **Side Effects** 1. Serotonin syndrome 2. Nausea 3. Dry mouth 4. Diarrhoea/constipation 5. Decreased appetite 6. Decreased libido, ED and anorgasmia 7. Increased risk of bone fracture 8. Sedation/insomnia 9. Tremor 10. Dizziness 11. Sweating 12. Photosensitivity 13. Suicidal ideation (early)

Answer 10

**_Tricyclic Antidepressants (E.g. Amitriptyline)_** * **Mechanism** * Inhibit reuptake of noradrenaline and serotonin into presynaptic terminals * Also block cholinergic, histaminergic, alpha1- adrenergic and serotonergic receptors * Also blocks fast Na+ channels in myocardium * **Effects** 1. Antidepressant 2. OCD management 3. Chronic pain relief 4. Insomnia management 5. Migraine prophylaxis * **Side Effects** 1. Cardiotoxicity, palpitations, arrythmia and chest pain 2. Hypotension 3. Widened QRS, tall R in aVR, sinus tachycardia and long QT/ PR 4. Seizures and coma 5. Respiratory depression 6. Metabolic acidosis 7. Drowsiness 8. Confusion 9. Dry mouth 10. Fever 11. Urinary retention 12. Pupil dilation and blurred vision 13. Constipation 14. Rigidity

Answer 11

**_Serotonin Syndrome_** * May be caused by drugs which increase the concentration of serotonin (5-hydroxytryptamine, 5HT) in the brain * Possibly caused by an overstimulation of 5HT1A and 5HT2A receptors in the central grey nuclei and medulla * Involves a triad of mental, autonomic and neurological effects * Condition may deteriorate rapidly and may cause death **Medicines Which May Cause the Serotonin Syndrome →** Especially combinations of two or more serotonergic drugs e.g. SSRI, SNRI, TCA, tramadol, MAOI and amphetamines 1. Antidepressants e.g. SSRIs, MAOIs, tricyclics, SNRIs 2. Some opioid analgesics e.g. tramadol, pethidine, fentanyl 3. Some cough suppressants e.g. dextromethorphan 4. Sumatriptan, cocaine, ecstasy, St John’s wort **Clinical Features:** Hyperthermia, hypertension, tachycardia, agitation, hyperreflexia, rigidity/ hypertonia, clonus, diaphoresis, tremor and salivation **Treat:** Benzodiazepines, cooling, cyproheptadine (serotonin antagonist and call tox!

Answer 12

**_Antipsychotics (E.g. Quetiapine)_** * **Mechanism** * D2 antagonist * **Indications** * Schizophrenia, bipolar and psychosis management * **Side Effects** * Tachycardia, Hypotension, Sedation, Abnormal LFTs, Hypothyroidism, Anxiety, Dry Mouth, Hyperprolactinemia, Urinary retention, Sexual dysfunction, Parkinsonism, Extrapyramidal symptoms, Weight gain, Raised BSL, Hyperlipidaemia * **OD**: Arrythmia, hypotension, seizures, coma and delirium

Answer 13

**Substance Abuse Treatment Options:** 1. Counselling and Motivational Interviewing 2. Psychotherapy and Cognitive Behaviour Therapy 3. Pharmacotherapy 4. Self-Help AA/NA 5. Residential/Therapeutic Communities 6. Withdrawal Treatment 7. Substitution Treatment 8. Controlled Use 9. Reduce Risks of Drug Use

Answer 14

**General Principles of Treatment for Substance Abuse:** 1. Addiction is a complex but treatable disease 2. Match treatment to patient and their readiness to change (i.e. controlled use, withdrawal treatment or substitution treatment) 3. Treatment should be patient's choice following doctor's recommendations 4. No single treatment is right for everyone 5. Effective treatment addresses all of the patient’s needs, not just their drug use 6. Counselling and other behavioural therapies are the most commonly used forms of treatment 7. Medications are often an important part of treatment, especially when combined with behavioural therapies 8. Treatment plans must be reviewed often and modified to fit the patient’s changing needs 9. Treatment should address other possible mental disorders 10. Consider harm minimisation and reduction strategies if continual usage (i.e. needle exchange programs)

Answer 15

**_Pharmacological Treatment of Substance Abuse - Alcohol_** **1) Withdrawal:** 1. **Diazepam:** Normalises the down regulation of GABA 2. **Thiamine:** Replenish deficiency and prevent WKS **2) Relapse Prevention:** 1. **Naltrexone (ReVia):** Reversible antagonist at the μ opioid receptor. Blocks the effect of endogenous opioids and associated reward pathway. Reduces craving and pleasurable effects. 2. **Acamprosate (Campral):** Chemical structure is similar to GABA. Restores activity levels of GABA and reduces glutamate in the brain. Blocks glutamate function. 3. **Combinations Naltrexone/Acamprosate** 4. **Disulfiram (Antabuse):** Not commonly prescribed. Deters alcohol use. Prevents usual alcohol metabolism. Irreversibly inhibits aldehyde dehydrogenase, blocking acetaldehyde breakdown. This causes unpleasant, potentially serious effects if alcohol is consumed e.g. flushing, sweating, nausea, vomiting, palpitations, headache, dyspnoea, chest pain, hypotension, cardiovascular collapse, seizures, arrhythmias. **3) Substitution/Maintenance:** Nil

Answer 16

**_Pharmacological Treatment of Substance Abuse - Opiates_** **1) Withdrawal:** 1. **Naloxone:** Competitive opioid receptor antagonist. Reverses the effects of opioids/heroin. 2. **Clonidine:** α2 adrenergic agonist to reduce autonomic symptoms of diarrhoea, nausea and sweating 3. **Buprenorphine:** Partial opioid receptor agonist. Reduces withdrawal symptoms and craving in opioid dependence. Blocks effects of agonist (heroin) and displaces antagonists (naltrexone). **2) Relapse Prevention:** 1. **Naltrexone: As described above.** **3) Substitution/Maintenance:** 1. **Methadone:** Synthetic opioid agonist at the μ opioid receptor. Substitutes for heroin and is long-lasting. Gradual withdrawal. 2. **Buprenorphine:** As described above.

Answer 17

**_Pharmacological Treatment of Substance Abuse - Amphetamine_** **1) Withdrawal:** 1. **Benzodiazepines:** Potentiate the inhibitory effects of GABA throughout the CNS, resulting in anxiolytic, sedative, hypnotic, muscle relaxant and antiepileptic effects. 2. **Tetracyclic Antidepressant (Mirtazapine):** Postsynaptic blockade of serotonin 5HT2 and 5HT3 receptors and presynaptic blockade of central α2 adrenergic inhibitory autoreceptors (SNRI). Also a potent H1 antagonist which accounts for its sedative effects. **2) Relapse Prevention:** 1. **Antidepressants:** Inhibit the uptake of noradrenaline and serotonin 2. **Antipsychotics:** Block D2 receptors and dopamine transmission in brain **3) Substitution/Maintenance: Nil**

Answer 18

**_Pharmacological Treatment of Substance Abuse - Tobacco_** **1) Withdrawal:** Nil **2) Relapse Prevention:** 1. **Varenicline (Champix):** Partial agonist at nicotinic acetylcholine receptors. It blocks nicotine binding to these receptors, preventing the pleasurable effects of smoking, while its partial agonist activity reduces symptoms of nicotine withdrawal. 2. **Bupropion (Zyban):** Noradrenaline/dopamine reuptake inhibitor which reduces withdrawal symptoms and craving. **Substitution/Management:** 1. **Nicotine Gum/Patches:** Nicotine replacement reduces the severity of tobacco withdrawal symptoms and increases the likelihood of smoking cessation

Answer 19

**Delivering Bad News (SPIKES):** **Setting:** Mental and physical preparation for the discussion. Arrange for some privacy, involve significant others, sit down (don't rush), make connection with patient and manage time constraints and interruptions. Also review the plan for telling the patient and how one will respond to patients' emotional reactions or difficult questions. **Patient Perception:** Elicit the patient's perspective. Use open-ended questions to create a reasonably accurate picture of how the patient perceives the medical situation (what it is and whether it is serious or not). **Invitation:** Ask patient what they would like to know. Invite patient to disclose level of information they would like to receive about diagnosis, prognosis, and details of illness. If patients do not want to know details, offer to answer any questions they may have in the future or to talk to a relative or friend. **Knowledge:** Warn the patient that bad news is coming. Give information in small chunks and check patient's understanding periodically. Start at patient's level of comprehension, use simple language and avoiding excessive bluntness. **Explore Emotions and Empathise:** Offer support and solidarity to the patient by making an empathic response. Observe patient for emotions, identify emotion, identify reason for emotion and let the patient know that you have connected the emotion after you have given the patient a brief period of time to express his or her feelings. **Summary and Strategy:** Summarise what was discussed and set out a medical plan of action. Discuss prognosis and treatment options to patient if they are ready for the discussion.

Answer 20

**Substance Abuse Assessment:** 1. **Early Recognition and Screening:** 1. CAGE questionnaire 2. AUDIT 10 Items Alcohol Use Disorder’s Identification Test 2. **Withdrawal Scales:** 1. CIWA-Ar → Clinical Institute Withdrawal Assessment - Alcohol revised

Answer 21

**Substance Abuse History:** **Starting Questions** 1. “When did you start using?” 2. “Have you stopped before and if so, for how long?” 3. “What led you back to using” 4. “Have you had any treatment and what was the outcome?” 5. “What do you like about using drugs?” 6. “In what way does drug use help you to cope?” 7. “What concerns you about your drug use?”

Answer 22

**Drug Use History and Dependence Severity:** Drugs, dose, route, timing and type (accidental or recreational) 1. Drug(s) used recently and ever 2. Age of first use 3. Age when first became dependent 4. Pattern of use over time 5. Recent use (method, quantity and frequency) 6. Method(s) of use 7. What happens when use is stopped? Withdrawal? 8. Complications and problems from use * **Medical History**: Particularly, major co-morbidities, BBV, sepsis, trauma, overdose and pregnancy * **Psychiatric History:** Particularly, depression, anxiety, psychosis and personality disorder * **Psychosocial History:** * Relationships, family, social supports and activities * Education and employment * Legal issues * Living circumstances (stability and affordability) * Finances (legal sources of income and debts) * Involvement with other agencies (DCP) * Family history of substance use disorders * Social factors that may contribute to substance use or facilitate treatment * **Readiness to Change:** Ask about patient's perception of their use and readiness to change

Answer 23

**Substance Abuse Examination:** 1. **General Overview:** Vital signs including heart rate, blood pressure, temperature, respiratory rate and oxygen saturation. 2. **Observation:** Colour, injection sites, track marks, smell, bruising, skin changes, pressure sores, nutritional status, weight, teeth, stigmata of liver disease (i.e. jaundice, hepatomegaly), presence of intoxication or withdrawal. 3. **Neurological:** Glasgow Coma Scale, pupils, tone, limb movements, reflexes, clonus and fasciculations 4. **Mental State:** Appearance, behaviour, mood cognition and affect 5. **Other:** Signs of aspiration, secretions and signs of injury or trauma

Answer 24

**Substance Abuse Investigations:** ECG, BSL and Paracetamol Screen ALWAYS!! 1. Blood Glucose Levels 2. Electrocardiogram 3. Blood Gases 4. ß-HCG (in women of childbearing age) 5. Bloods: Paracetamol (in deliberate self-poisoning), drug screen, LFTs and hepatitis and HIV serology 6. Urine and Saliva: Drug testing 7. Breath Alcohol Screen

Answer 25

**_Assessment of the Unconscious Patient_** * **DANGER** → In any emergency situation, the safety of you and the other staff members comes first before the safety of the patient. * **RESPONSE** → Glasgow Coma Scale & AVPU Scale * **SEND FOR HELP** → Call for extra staff or a medical emergency team (MET) * **AIRWAYS** 1. Is C‐spine immobilisation required? Apply collar and log roll patient if necessary. 2. Is the airway patent? Inspect mouth, suction and apply airway manoeuvres if necessary. 3. **Basic Airway Management:**"GCS 8 Intubate" 1. Cervical spine control 2. **Clearance:** Mouth examination and clearance of airways (only if not breathing due to risk of bite injury). Consider Yankauer suction catheter. 3. **Airway Manoeuvres:** Chin lift +/- head tilt (not in spinal injury!) and jaw thrust 4. **Adjunctive Airway Devices:** Nasopharyngeal airway (used in spontaneous breathing patients to help with upper airway obstruction) or Guedel airway (only for unconscious patients). Advanced options include laryngeal mask airway (LMA), endotracheal intubation or surgical airway (cricothyroidotomy). 5. **Oxygen Therapy Devices:** Nasal prongs, simple Hudson mask, venturi mask, non- rebreather face mask or bag-valve mask (the lifesaver!)

Answer 26

**_Assessment of the Unconscious Patient_** * **CIRCULATION** 1. Check heart rate and rhythm, blood pressure and capillary refill (\< 2 seconds) 2. Auscultate precordium 3. Perform an ECG as soon as possible 4. Place IV access in order to take blood and give fluids/medications 5. Take bloods including a venous/arterial blood gas 1. VBG: pH, O2, CO2, Na+, K+, Hb and glucose 2. Paracetamol screen 3. U&Es including Ca2+, FBC, LFT, B-HCG, blood alcohol and toxicity/drug screen 6. Give fluids and medications if required 7. Look for a medicalert bracelet whilst assessing radial pulse * **DEFIBRILLATION** → Has the patient got a shockable rhythm? Defibrillate if needed. * **DON'T EVER FORGET GLUCOSE/ DISABILITY** 1. Check glucose and treat if low 2. Assess pupils for symmetry and size and gaze abnormalities 3. Neurological Exam: Look for obvious asymmetrical neurological weakness, tone, abnormal posturing and reflexes (lateralising signs). It is important to assess these prior to intubation or sedation which will alter neurological findings. 4. Assess for neck stiffness (only in patients where there is no concern of C ‐spine trauma) 5. **Battle** **Signs**: Assess tympanic membranes for blood, perforation and otorrhoea (discharge), nose and ears for discharge (CSF fluid), behind the ears for bleeding, eyes for racoon eyes (hemorrhage), scalp for lacerations and skull for fractures.

Answer 27

**_Assessment of the Unconscious Patient_** * **EXPOSURE** 1. Re‐examine the patient from top to toe. This includes rectal examination for anal tone and perianal sensation (spinal trauma). 2. ALWAYS remember to look at the back of the patient, this may mean log rolling the patient (if the cervical spine needs to remain immobilised). 3. In trauma patients it is important to palpate each bone in the vertebral column to elicit localised tenderness that may suggest spinal injury. * **EXTRAS** 1. Temperature 2. Tetanus status (particularly if open dirty wounds) 3. Confirm allergies if possible before administering medications 4. Check pregnancy status before any irradiating imaging is performed 5. Consider catheterisation (urine can be used for B-HCG and toxicity screen) if unconscious or low GCS 6. Consider CXR to assess lungs and CT head and CT c-spine to assess head/neck trauma * **SECONDARY** **SURVEY** → Cardiovascular, respiratory, abdominal and renal exams

Answer 28

**Reasons for Aggressive/Disruptive Behaviour:** 1. Person perceives that he or she is being treated unfairly or without respect 2. Aggression may give people a feeling of power in order to compensate for feelings of inadequacy and anxiety 3. Some neurological disorders (psychosis, mental disorders and substance-abuse disorders) have been associated with changes in personality that may also result in violence 4. May be a result of the effect of some therapeutic medications for example corticosteroids 5. Aggression or violence can occur when people have inappropriate skills for dealing with feelings of frustration, fear and anxiety, or as an expression of these feelings by people who are unwell (may be present in persons experiencing acute or chronic pain, drug or alcohol withdrawal, stroke, head injury or Alzheimer’s disease) **NB:** Always remember confidentiality of the patient. May not be appropriate to disclose information to family members.

Answer 29

**_BENZODIAZEPINES_** * **MOA**: potentiate GABA (inhibitory neurotransmitter in CNS). GABA binds to GABA A receptor which then opens its chloride channel, allowing chloride influx into neuron → cell hyperpolarises → inhibits cellular excitation. * Benzos are **positive allosteric modulators**: increase effect of GABA by increasing frequency of Cl channel opening → potentiates GABA effects. Binds to benzodiazepine site on GABA A receptor complex * **Effects**: 1. Sedation/ anxiolytic 2. Anticonvulsant 3. Muscle relaxant * **SE**: drowsiness, confusion, dizziness, hallucinations, respiratory depression, hypotension, slurred speech, amnesia, nystagmus, ataxia, coma, paradoxical agitation, aspiration pneumonia, more dangerous in combination * **Rx OD**:- largely supportive, ABC, possible airway support Antidote:-there is an antidote Flumazenil but it is not widely used, has risk of precipitating seizures especially in chronic user

Answer 30

**OPIATES:** Common overdose either intentional or unintentional/ iatrogenic * Recognisable opioid toxidrome: pinpoint pupils, respiratory depression and sedation * **MOA**: bind to opioid receptors on neuronal cell walls that also bind endogenous enkephalins and endorphins. * Opioid receptors: * μ1 → supraspinal analgesia, bradycardia, sedation * μ2 → respiratory depression, euphoria, physical dependence * δ → spinal analgesia, respiratory depression, * κ → spinal analgesia, respiratory depression, sedation * **Heroin** = converted to morphine, acts on μ receptors in CNS also dopamine receptors → nausea/ vomiting, histamine release → pruritis * **Naloxone** = pure opioid μ, κ, δ receptor antagonist Effects/use: analgesic, adjunct to anaesthesia, cough suppressant * **SE**: pinpoint pupils, respiratory depression, CNS depression, constipation, hypotension, confusion/ delirium * **Rx OD**: supportive care ABC/ respiratory support/ ventilation, reverse with antidote * **Antidote**: naloxone → note naloxone has shorter half-life than the opioid so may return to respiratory depression when wears off (dangerous in heroin OD if pt discharges self). May need small aliquots titrated to response or infusion.

Answer 31

**SSRIs:** Common overdose, less toxic than many (relatively safe in OD, not usually cardiotoxic) * **MOA**: limit presynaptic reuptake serotonin, which increases its availability to bind to postsynaptic cleft. Also weak affinity for noradrenaline and dopamine transporters * **Effects/ use**: 1. Antidepressant 2. Anxiety 3. Chronic pain * **SEs**: nausea, dry mouth, diarrhoea/ constipation, decreased appetite, decreased libido, retrograde ejaculation, anorgasmia, ED, increased risk bone #, akasthisia, tremor, sedation/ insomnia, dizziness, sweating, photosensitivity, suicidal ideation in early stages Rx, serotonin syndrome esp in combination with other drugs, discontinuation syndrome * **Rx OD**: largely supportive

Answer 32

**PARACETAMOL:** Common overdose (often in parasuicide context) potentially fatal * **MOA**: not fully understood, analgesic effect may include inhibition of central prostaglandin synthesis and modulation of inhibitory descending serotonergic pathways. The antipyretic effect is probably due to reduced production of prostaglandins in the hypothalamus. * **Effects/ use**: 1. Analgesia 2. Antipyretic * **SE**: hepatotoxic (can cause acute hepatic failure in OD), hypersensitivity reactions, thrombocytopaenia, neutropaenia * **Rx OD**: check 4/24 paracetamol levels and plot on nomogram, if over the level treat with N-acetyl-cysteine. * If given \<8/24 after ingestion-\>almost zero mortality from OD. * If present \>8/24 start NAC immediately while awaiting levels. * Paracetamol usually metabolised by phase II metabolism by conjugation with sulfate and glucuronide. Small portion is metabolised by CP450 into toxic metabolite *N*-acetyl-*p*-benzoquinone imine (NAPQI) which is usually conjugated by glutathione into less toxic cysteine and mercapturic acid. * In OD the phase II metabolism is overwhelmed and more is diverted into the CP450 pathway, when the glutathione is depleted the toxic NAPQI metabolite builds up. NAC replenishes glutathione hence deactivates and safely excretes NAPQI.

Answer 33

**ANTIPSYCHOTICS - e.g. Quetiapine** * **MOA**: D2 antagonist * **Effects/ use**: 1. Schizophrenia 2. Bipolar 3. Psychosis * **SE**: tachycardia, hypotension, sedation, abn LFTs, hypothyroidism, anxiety, dry mouth, hyperprolactinaemia, urinary retention, sexual dysfunction, NMS Extrapyramidal SEs: acute dystonic reaction, tardive dyskinesia, akasthesia, Parkinsonism * **Metabolic** **effects**: hyperlipidaemia, wt gain, raised BGL * **In OD**: arrhythmias, hypotension, seizures, coma, delirium * **Rx OD**: supportive Rx, especially respiratory support: if large dose \>3g or 10mg/kg likely to need intubation. Call tox Note Rx of acute dystonic reaction is anticholinergic (benztropine).

Answer 34

**AMPHETAMINES:** Common recreational overdose/ intoxication * Recognisable amphetamine toxidrome: aggression/agitation, hypertension, tachycardia, dilated pupils * **1) Methamphetamine** (meth, base, crystal meth, ice) → stimulates release & stops reuptake of monoamines (dopamines & NA), serotonin. * First synthesised 1919-used in WWII * crystal meth/ ice=more potent distilled form, rock/crystal-like (smoke/ inject) -speed-white powder form often snorted * base-oily thick brown-yellow substance * **2) Amphetamine sulphate**/ HCL-(speed) also prescription (e.g. dexamphetamine): initially used to Rx asthma, now used to Rx narcolepsy or ADHD * **3) MDMA** (ecstasy)-competitively binds to monoamine uptake receptors- → stimulates release, increases dopamine, 5HT, NA. Greater effect on serotonin than meth (primary effect=indirect serotonin agonist. Has hallucinogenic as well as stimulant effects

Answer 35

MOA: Sympathetic effects on: * **α1** → vascular smooth muscle, iris * **β1** → myocardium * **β2** → skeletal muscles, vascular smooth muscle

Answer 36

**AMPHETAMINES - Side Effects**: 1. Hyperthermia 2. Thirst, often volume deplete but may have water intoxication, 3. SIADH (esp MDMA) 4. Rhabdomyolysis 5. Metabolic acidosis, AKI, DIC, microinfarcts, serotonin syndrome, skin infections 6. CVS → hypertension, tachycardia, CCF, AMI, 7. Neuro → cerebral haemorrhage/ SAH, cerebral oedema, seizures, intellectual impairment 8. Psych → rapid speech pacing, trismus, hallucinations/ delusions, psychosis, paranoia, aggression, pupil dilation, jaw clenching, teeth grinding, sleep disturbance, memory impairment, depression/ anxiety long term 9. Resp → ARDS (fm hyperthermia) 10. GIT → hepatocellular necrosis (2 to hyperthermia)-\>hepatic failure, mesenteric ischaemia, wt loss, dental decay 11. GU → fetal anomalies, miscarriages **OD Rx**: benzodiazepine/ sedation (more extreme possibly propofol infusion/ intubation), dopamine antagonists e.g. droperidol, ketamine

Answer 37

**CANNABINOIDS - THC (tetrahydrocannabinol) & CBD (cannabidiol)** * **MOA**: stimulating cannabinoid receptor type 1 (CB1) & type 2 (CB2) within the endocannabinoid system * **Uses**: 1. Chronic pain 2. Cancer 3. MS 4. Epilepsy * **SE**: dry mouth, conjunctivitis, tachycardia, hypotension, bradypnoea, impairment of short-term memory, judgment and sensation, altered reaction time & movement, increased appetite, panic, paranoia, cannabinoid hyperemesis syndrome, psychosis, addiction, altered brain development, cognitive impairment in adolescents, loss of volition, myoclonus * **CVS**: Increased risk MI, stroke, thromboembolic events, postural hypotension Resp: chronic bronchitis, ARDS, lung cancer, bronchospasm

Answer 38

**SEROTONIN SYNDROME** (another toxidrome) * **Features**: 1. Hyperthermia 2. Hypertension 3. Tachycardia 4. Agitation 5. Hyperreflexia 6. Rigidity/ hypertonia 7. Clonus 8. Diaphoresis 9. Tremor 10. Salivation * **Drugs**: especially combinations of two or more serotonergic drugs e.g. SSRI, SNRI, TCA, tramadol, MAOi, amphetamines. * **Rx**: benzodiazepines, cooling, cyproheptadine (serotonin antagonist)-call tox!

Answer 39

**COCAINE** * **MOA**: blocks catecholamine/ serotonin reuptake, Na channel blockade, sympathomimetic, local anaesthetic, vasospasm, cardiotoxicity

Answer 40

* **SYNTHETIC CATHINONES (bath salts)** * “New psychoactive substances”, stimulants, similar to amphetamines, found in plants called khat e.g. mephedrone, methylene * **LSD** * Lysergic acid diethylamide (LSD, acid) * Possibly stimulates glutamate release in the cortex-\>excitation, mainly serotonergic effects (stimulates 5HT1A & 2A receptors), dopaminergic (D2) * Hallucinogenic effects * **N-BOMe** * “N-Bomb” or “Smiles” * Synthetic hallucinogen similar to LSD * **GBH (Gamma-hydroxybutyrate)** * “Grievous Bodily Harm” * Sedative and anaesthetic properties * Can → agitation, hallucinations, seizures, coma * **FLAKKA (alpha-pyrrolidinopentiophenone or alpha-PVP)** * Newer generation bath salts * Euphoria, bizarre behaviour, paranoia, agitation, delusions

Answer 41

**MEDICAL MANAGEMENT of HEROIN ADDICTION** 1. **Methadone** → oral opiate, harm minimisation, long term maintenance or can gradually reduce dose, issues: ‘authorised prescriber’, daily collect from chemist, present to ED’s ‘medication stolen’ out of hours, can still use heroin 2. **Buprenorphine** (subutuex) or Buprenorphine with naloxone (suboxone) → partial mu-opioid agonist (high affinity, low activity) & weak kappa antagonist 3. **Naltrexone** – abstinence maintenance, opioid antagonist

Answer 42

**MEDICAL MANAGEMENT of ALCOHOL ADDICTION** 1. **Detox**: management of withdrawal - e.g.benzos 2. **Naltrexone** → opioid antagonist 3. **Acamprosate** → structure alanalogue of GABA 4. **Disulfiram** → less commonly used now, not first line. Inhibits aldehyde dehydrogenase, prevents the metabolism of alcohol’s primary metabolite, acetaldehyde → deterrent effect (feel sick when drink ETOH) 5. Don’t forget thiamine

Answer 43

**Primary brain structure responsible for maintaining consciousness: Reticular activating system** **Functions**: 1. Maintain cerebral cortical alertness: 2. Filters out repetitive stimuli (awareness) – Thalamus w RAS projections are responsible for awareness to the environment 3. Regulates skeletal & visceral muscle activity

Answer 44

**Physiology of alertness**: Maintains arousal of the whole brain by having ascending sensory pathways synapse with the RAS neurons, keeping them active and enhancing their arousing effect on the cerebrum * **Increases alertness** 1. Serotonin 2. Histamine 3. Noradrenaline * **Reduces alertness** 1. Acetylcholine

Answer 45

**RAS is inhibited by**: sleep centres in the hypothalamus **RAS is depressed by**: alcohol, tranquilisers, etc. * Depressed RAS system (semi-comatose) → inability to respond to sensory information as well (visual, auditory, proprioception, painful stimuli) * Depressed RAS system → unable to regulate skeletal & visceral muscle activity * Severely depressed RAS (comatose) → unable to respond to stimuli such as pain & irritation which could normally stimulate reflexes → inability to protect their airway consciousness?

Answer 46

**Consciousness**: Ability to maintain awareness of self, access to memories, ability to manipulate abstract ideas and focus your attention **Difference between sleep and altered level of consciousness:** * **Sleep**: reduced state of interaction with the environment. Still able to respond to auditory, light, painful stimuli Altered * **LOC**: Alteration between a normal alertness and comatose state (GCS 8-14) * **Coma** * Unrousable, unresponsive (no response to pain) * Brainstem reflexes intact (some CN intact, vasomotor centre intact) * **Brain death** * Irreversible loss of brain function * No response to pain * No brainstem reflexes intact (Very specific diagnostic criteria to pronounce someone braindead) o Must exclude: hypothermia, long acting drugs, endocrine dysfunction, etc.

Answer 47

* **_Individual level:_** * **Physical health**: Nausea, aches and pains, sleep disturbance, weight gain/loss, infection, accidents, illness or chronic disease * **Mental** **health**: Depression, anxiety, paranoia, psychosis * **Personal relationships:** Family problems, arguments, relationship breakdowns, loss of friends, social isolation, loneliness * **Work or financial impact:** Job loss, trouble at work or study, truancy and/or absenteeism, debt, unemployment * Financial strain to support habit and potentially stealing from family and friends * **Social impact:** Loss of interest or time to do other things for pleasure, reduced participation in social activities, anti-social behaviour (e.g. domestic violence), criminal conduct * **_Family level:_** * Stress for family and friends * Violence (physical and psychological) towards medical staff and the public (social costs) * **_Community level:_** * Lost productivity * Cost to healthcare system (if hospitalisation/ambulance service required) * Cost of policing, child/spouse protection

Answer 48

**Normal Behaviour:** Behaviour that is aligned to what is normal and expected within a given culture (depends on social group, generation and culture). **Abnormal Human Behaviour:** Behaviour that deviates from what is normal (occurs frequently) and expected within a given culture (abnormality is a continuum rather than a category). It is culturally bound and developmentally influenced. 1. **Psychological Dysfunction:** A set of symptoms that leads to an interruption in occupational and social roles 2. **Personal Distress:** A set of symptoms that causes the person (or those close to them) to feel distressed 3. **Atypical Response:** Behaviours and psychological characteristics that are not common in a given cultural context

Answer 49

**Abnormal Beliefs and Thoughts:** 1. Are difficult for others to understand 2. Become distressing for the individual 3. Give rise to avoidance, attack or other responses that are not expected or appropriate 4. May be fixed and obsessional 5. Impede on ability to meet cultural expectations (work in a job, manage hygiene, pay rent on time etc.) 6. Often lead to alienation

Answer 50

**_Cultural Context & Abnormal Human Behaviour_** * **Name of Disorder** - Amok * **Culture** - Malaysia * **Description** - Sudden and violent outbursts often leading to homicidal behaviour. Triggered in usually withdrawn men.

Answer 51

**_Cultural Context & Abnormal Human Behaviour_** * **Name of Disorder** - Zar * **Culture** - North Africa * **Description** - A person believes he/she is possessed and may engage in random emotional expressions. May withdraw socially and so apathy to others.

Answer 52

**_Cultural Context & Abnormal Human Behaviour_** * **Name of Disorder** - Kitsunetsuki * **Culture** - Japan * **Description** - A disorder in which the victim believes he/she is a fox and changes their facial expressions accordingly.

Answer 53

**Psychosis Syndrome:** * A syndrome, not an illness, that warrants a diagnosis * A problem with brain function characterised by... * A loss of reality testing and impairment of mental functioning * Where patients incorrectly evaluate the accuracy of their perceptions and thoughts, and make incorrect inferences about external reality

Answer 54

**Clinical Features of Psychosis:** Delusions, Hallucination, Disorganised behaviour, speech and thought and altered mood and affect (not core features) * **Positive Symptoms:** 1. Delusions 2. Hallucinations 3. Passivity * **Negative Symptoms:** 1. *Affective* flattening 2. *Alogia* 3. *Avolition* 4. *Anhedonia* 5. **DEFICIT SYNDROME**

Answer 55

**Delusions (Disorder of Thought Content):** Fixed, false belief based on incorrect inference about external reality, firmly held despite evidence to the contrary, out of keeping with patient’s cultural background **Examples:** 1. Bizarre vs systematised delusions 2. Mood congruent vs mood incongruent delusions 3. Nihilistic, delusion of poverty 4. Somatic 5. Persecution, grandeur, reference 6. Control (thought broadcasting, insertion, withdrawal) 7. Jealousy, infidelity and erotomania (another person is in love with them)

Answer 56

* *Hallucinations (Perceptual Disturbances):** Sensory perception not associated with real external stimuli, there may or may not be delusional interpretation of the experience * *Examples:** 1. Auditory, visual, olfactory, somatic, tactile or gustatory perceptions 2. Lilliputian (very small person/being) 3. Synesthesia (i.e. hearing colours), trailing 4. Hypnagogic and hypnopompic (sleep/waking up hallucinations) → not a pathology

Answer 57

* *Thought Disorders (Disorder of Thought Form):** When the flow of ideas, symbols and associations initiated by a problem/task are not goal-directed * *Examples:** 1. Neologisms, word salad 2. Circumstantiality, tangentially 3. Derailment, loosening of associations 4. Perseveration, verbigeration, clang association 5. Flight of ideas 6. Blocking

Answer 58

**Mood and Affect:** Inappropriate affect **Examples:** Blunting, flat, isolation/dissociation and incongruent affect

Answer 59

* *Inappropriate appearance and behaviour** * *Examples:** Bizarre dress, catatonia, poor impulse control, anger, agitation and stereotypes

Answer 60

**_Differential Diagnoses of Psychosis - Medical_** * **Common:** Dementia or Delirium * **Brain Insult:** Neoplasms, CVD (esp. late- onset psychosis), Trauma (esp. frontal or limbic), MS (esp. many periventricular lesions), Huntington's Disease or Epilepsy (esp. TLE) * **Other:** Cushing's Disease, Thyroid Disease, B12, porphyria, CO, CJD, HSE, Neurosyphilis, HIV, NPH, SLE or Wilsons Disease * **Favours Medical Cause:** 1. Sudden 2. Old age 3. First episode 4. Current illness or injury or neurological symptoms * **NB1:** Always consider non-psychiatric medical conditions especially in patients with previous diagnosis of schizophrenia (may overlook something more sinister such as a SAH) * **NB2:** Comorbidity is the rule rather than the exception

Answer 61

**_Differential Diagnoses of Psychosis - Medications and Substances_** * **Drugs:** 1. Amphetamines 2. Cocaine 3. Hallucinogens 4. PSP 5. Alcohol * **Withdrawal States:** 1. BZD 2. Barbiturates 3. Alcohol * **Favours Drug-Induced Psychosis:** 1. Visual hallucinations 2. Hyperactivity 3. Hypersexuality 4. Confusion and incoherence * **Favours SCZ:** Presence of formal thought disorder and blunted or flattened affect

Answer 62

**_Differential Diagnoses of Psychosis - Mood Disorders_** ## Footnote **Bipolar:** Bipolar affective disorder (mania with psychosis) **Depression:** Major depressive disorder episode with psychosis **Favours Mood Disorder:** Mood-congruent delusions **Favours SCZ:** The affective and mood symptoms should be brief relative to the duration of active and residual periods

Answer 63

**_Differential Diagnoses of Psychosis - Anxiety_** ## Footnote **Anxiety:** PTSD with traumatic hallucinosis or dissociative disorders **Favours Anxiety Disorder:** Traumatic stressors and other anxiety symptoms to suggest anxiety disorder, derealisation and depersonalisation

Answer 64

**_Differential Diagnoses of Psychosis - Personality_** **_Personality Disorder (PDs):_** 1. Schizoid 2. Schizotypal 3. Paranoid 4. Borderline personality disorder 5. Obsessive compulsive personality disorder **Favours Personality Disorder:** Longstanding pervasive and maladaptive personality traits **NB:** PDs may often mask an underlying SCZ process and may often be comorbid with SCZ!

Answer 65

**_Differential Diagnoses of Psychosis - Malingering and Factitious Culture-Bound Syndromes_** 1. Koro in South East Asia 2. Religious experiences 3. Meditative states or belief in UFO’s etc.

Answer 66

**_Work up of a Psychotic Patient_** * Good clinical history: include a complete Fam Hx, an in-depth Hx of medical, neurological and psychiatric disoders * Physical exam (Neuro etc) * Tests & Investigations 1. FBC, UEC, LFT, TFT, B12, folate, ESR, CRP 2. Consider: CMP, Vit D, Iron studies, syphiils, hepatitis, HIV (if indicated) 3. Urinalysis, UDS 4. If indicated: CT or MRI, EEG, LP

Answer 67

**_Primary Psychotic Disorders_** 1. Brief Psychotic Episode 2. Schizophreniform 3. Schizophrenia 4. Schizoaffective 5. Delusional Disorder 6. Folie A Deux

Answer 68

**Primary Psychotic Disorders -** **Brief Psychotic Episode** 1. Presence of psychotic symptoms (delusions, hallucinations, disorganised speech and disorganised or catatonic behaviour), not better explained by other disorder 2. Duration of disturbance 1 day to 1 month 3. Not better explained by other illness 4. Eventual full return to premorbid functioning

Answer 69

**Primary Psychotic Disorders - Schizophreniform** 1. Presence of psychotic symptoms for at least 1 month 2. Episode (including prodrome, active and residual) lasts at least 1 month but less than 6 months 3. Not better explained by other illness Good prognosis features include absence of blunted/flat affect, good premorbid features, confusion on perplexity at the height of episode and onset of psychotic symptoms within 4 weeks

Answer 70

**_Primary Psychotic Disorders:**_ _**Schizophrenia_** 1. Presence of psychotic symptoms for at least 1 month 2. Functional impairment 3. Continuous disturbance for 6 months (may include prodrome and residual symptoms) 4. Not better explained by other illness Pure types are uncommon, mixtures of symptoms are more common. Other subtypes include catatonic (rare), disorganised, paranoid or undifferentiated and residual type.

Answer 71

**_Primary Psychotic Disorders:**_ _**Schizoaffective_** 1. An uninterrupted period of illness with a major depression episode, manic episode or mixed episode concurrent with symptoms of schizophrenia 2. Presence of delusions or hallucinations for two weeks in the absence of prominent mood symptoms, during the same period 3. Symptoms for a mood episode are present for a substantial proportion of the total duration, during the active and residual phase of the illness 4. Not better explained by other illness **Subtypes** **include**: bipolar type or depressive type.

Answer 72

**_Primary Psychotic Disorders: Delusional Disorder_** 1. Presence of non-bizarre delusions (involving situations that occur in real life i.e. being followed, loved and poisoned) for at least one month duration 2. Hallucinations may be present if they are related to the delusional theme 3. Functioning or behavior not markedly impaired 4. If mood episodes have occurred, they are brief 5. Not better explained by other illness **Subtypes** **include**: erotomanic, grandiose, jealous, persecutory, somatic and mixed types

Answer 73

**_Primary Psychotic Disorders:**_ _**Folie A Deux_** 1. Delusion develops in an individual in the context of a close relationship with another person who already has an established delusion 2. Delusion is similar in context 3. Not better explained by other illness

Answer 74

Comorbidties are common among schizophrenia patients * PSYCHIATRIC include (Buckley, 2009): 1. Substance abuse (47%) 2. Anxiety (panic 15%, 29% PTSD, 23% OCD) disorders 3. Depressive disorders (50%) 4. •MEDICAL include (Lambert, 2003): 5. Diabetes, Hyperlipidaemia, HT, arrhythmias, obesity 6. Neoplasms 7. HIV, hep C 8. OP, hyperprolactinaemia

Answer 75

**Prevalence and Risk Factors of Schizophrenia:** No population is free of schizophrenia! * **Point Prevalence:** 5 per 1000 Australian have schizophrenia * **Lifetime Prevalence:** 0.5% to 1.5% world-wide (WHO) have schizophrenia * **Incidence:** 15.2 per 100 000 * **Onset:** Males is mid 20s and females mid-late 20s (peak also in 40s). Males are more predisposed than females (3:2 ratio). * **Cost:** An estimated $1.45 billion per annum (Australian Government), while societal costs are at least $1.44 billion for schizophrenia alone * **Risk Factors:** Family history, CNS damage, bereavement and co-morbidities

Answer 76

**Clinical Features of Schizophrenia:** **Positive Symptoms:** Delusions, hallucinations and thought disorders **Negative Symptoms:** Affective flattening, alogia (poverty of speech), avolition (decreased motivation to complete purposeful tasks), anhedonia (loss of pleasure). Deficit Syndrome! **Cognitive Behavioural Disorganisation:** Thought and speech disorder, disorganised behaviour, catatonic behaviour and cognitive impairment (attention, verbal memory, working memory and executive dysfunction)

Answer 77

**Course of Schizophrenia:** 1. **Premorbid (Fetal-Childhood):** Mild motor cognitive and social impairments 2. **Prodromal (Puberty-Adolescence):** Unusual psychotic-like behaviours and negative symptoms 3. **Onset/Deterioration (Early Adulthood):** Positive, negative, cognitive and mood symptoms 1. **Adult Onset:** Most likely to exhibit positive and affective symptoms. Genetic predisposition drives manifestation of symptoms anywhere from BPAD, SCZA and SCZ. 2. **Late Onset (\>45):** Females more predisposed than males. Good premorbid functioning. Predominance of paranoid symptoms. 4. **Chronic/Residual (Adulthood-Senescence):** Positive, negative and cognitive symptoms

Answer 78

**Prognosis of Schizophrenia:** * 30% of individuals have complete or partial remission between episodes * 25% of individuals have negative symptoms between episodes * 45% of individuals experience functional decline with frequent or continuous psychotic symptoms * Positive psychotic symptoms tend to go away after first episode of psychosis (87%) with median time to remission 9 weeks (does not equate to functional recovery) * **Perpetuating Factors:** Suboptimal treatment, poor adherence, side effects of medications, substance abuse and family members with high expressed emotion (hostility, criticism and emotional over-involvement)

Answer 79

**Principles of Psychosis Pharmacotherapy:** **Do They Work?** * 80% remission of positive symptoms during first episode psychosis (SCZ) within 9 weeks * 10-20% of first episode psychosis fail to fully remit after a trial of two antipsychotics. With time this increases to 30-50% in enriched populations (treatment resistance). * First line is atypical antipsychotics given better tolerability and less chance of tardive dyskinesia * Antipsychotics have variable or low efficacy in psychosis secondary to medical, substance use or delusional disorder

Answer 80

**Why Take the Medication:** 1. To prevent distress, disability and suicide 2. First episode psychosis more responsive to treatment than subsequent episodes 3. Prolonged duration of untreated psychosis has poor response and outcome

Answer 81

**Principles of Psychosis Pharmacotherapy: How Long For?** * After first episode psychosis continue for at least 12 months and then attempt to withdraw over several weeks with further specialist follow up for 12 months * For relapse, monotherapy with atypical antipsychotics is first choice (unless intolerable side effects or remission on typical antipsychotics) * People who respond early tend to stay on their medication

Answer 82

**Principles of Psychosis Pharmacotherapy: What Happens When They Stop?** * Patient may not notice a difference initially * Possible relapse after 4-6 weeks * Stopping medication is the most powerful predictor of relapse

Answer 83

**Principles of Psychosis Pharmacotherapy:** **Which is The Right Medication?** * **Illness Profile:** History of illness onset an course, present signs and symptoms and past treatment response * **Patient Profile:** Vulnerability to side effects, tolerance to side effects, insight to illness and comorbidities * **Medication Profile:** Tolerability (short term and long term), delivery formulations, availability, cost and pharmacokinetics

Answer 84

**Principles of Psychosis Pharmacotherapy: What Happens If It Doesn't Work?** * Antipsychotics may take 4-6 weeks for effect. If no response at 4-6 weeks, then change. If partial response then wait 6-10 weeks * **No Response:** DR POSCAN * **Treatment Resistance:** Ensure at least 2 adequate trials of antipsychotics (\>6 weeks and at least 1 atypical). Clozapine is treatment of choice, consider depot antipsychotic if there is poor adherence and if fails, resort to antipsychotic that gave best response.

Answer 85

**_Typical APs (Older)_** * **Examples** 1. **Haloperidol (PO/IMI):** Aroused or agitated patient (IMI for highly aroused/agitated) 2. **Chlorpromazine (PO):** Aroused or agitated patient 3. **NB:** Often combined with BZD but can worsen delirium * **Mechanism of Action** * Blocks D2 receptors which decreases hyperactivity of mesolimbic dopamine pathway (decreases positive symptoms) * Blocks the hypoactive mesocortical pathway (increases negative symptoms?) * Blocks nigrostriatal and tuberoinfundibular pathways (extrapyramidal symptoms and hyperprolactinemia) * **Advantages** 1. Cheap (off patent) 2. Have depot (IMI) preparations 3. Many decades of experience 4. Established side effect profiles 5. Haloperidol lacks anticholinergic activity (hence is safer in the elderly) * **Disadvantages** 1. Lowers the seizure threshold 2. Low propensity to cause weight gain 3. Higher likelihood of tardive dyskinesia

Answer 86

**_Atypical APs (Newer Except Clozapine)_** * **Examples** 1. **Olanzapine (PO):** Aroused or agitated patient 2. **Quetiapine (PO):** Aroused or agitated patient 3. **Risperidone (PO):** Often used in short term Mx of A/A of delirium 4. **Clozapine** * **Mechanism of Action** * DA and 5HT blockade (risperidone) * D2/D3 activity (amisulpride) * DA partial agonist (aripiprazole) * Complex (CLOZ) * Decreases positive symptoms and improves negative and neurocognitive symptoms * **Advantages** 1. Generally have fewer side effects as decreases extrapyramidal symptoms and hyperprolactinemia (except risperidone) 2. Virtually NO TARDIVE DYSKINESIA * **Disadvantages** 1. More expensive (patents) but cost effective 2. Less well established side effects profiles 3. Limited depot options

Answer 87

**EXAMPLES OF CLINICALLY RELEVANT DRUG INTERACTIONS** 1. 1A2 inhibited by fluvoxamine (SSRI): clozapine level ↑ 2. 1A2 Induced by smoking: clozapine ↓ 3. 2D6 inhibited by fluoxetine and paroxetine (SSRIs): ↑AP levels 4. 3A4 inhibited by fluvoxamine and fluoxetine (SSRIs): ↑ AP levels

Answer 88

**_Side effects of APs_** 1. **Acute Dystonia** 2. **Parkinsonism** 3. **Akathisia (Psychomotor Restlessness):** 4. **Tardive Dyskinesia:** 5. **Hyperprolactinemia:** 6. **6. Prolongation of QTc Interval** 7. **Anticholinergic** 8. **Anti-Adrenergic (A1)** 9. **Antihistaminergic** 10. **Metabolic Syndrome** 11. **Neuroleptic Malignant Syndrome**

Answer 89

**Acute Dystonia:** Affects face, neck and trunk especially likely after IMI administration. Occurs within hours to days (24-72 hours after they leave ED), especially in young males. **Complications**: Laryngeal spasm (potentially fatal), oculogyric crisis (involuntary contractions of eye muscles resulting in conjugate gaze usually in upward direction) and opisthotonus (tetanic spasm in muscle of back) **Screen**: Abnormal involuntary movements scale (AIMS) **Treatment**: Benztropine 1-2mg IMI, every 10-15 min if necessary (max 6mg/24hr)

Answer 90

**Parkinsonism:** Bradykinesia, resting tremor (high frequency, pill rolling) and muscular rigidity (increased tone, lead pipe rigidity, cogwheeling). • **Treatment:** Benztropine 0.5mg

Answer 91

**Akathisia (Psychomotor Restlessness):** Severe sense of agitation and restlessness of the limbs, may present as a feeling of inner restlessness and develops within hours to days. Common with aripiprazole. **Complications:** May lead to suicide **Screen:** Barnes akathisia rating scale **Treatment:** Propranolol 20-40mg orally TDS-QID or diazepam 2-5mg orally, TDS. Recent trial mirtazapine 15mg.

Answer 92

**Tardive Dyskinesia**: Permanent oro-facial dyskinesia. Complex syndrome of involuntary hyperkinetic oral, lingual, buccal, facial, limb, trunk and finger movements. * **For diagnosis**, must be \> 3 months of treatment and \> 4 weeks of symptoms. * **Risk** **factors**: old age, potent typical antipsychotics (haloperidol 5% PA, 50-60% lifetime), long term use, head injury, drug and alcohol use, female and extra pyramidal side effects. * **Screen**: Abnormal involuntary movements scale (AIMS) * **Treatment**: No effect treatment! Slowly withdraw causative agent and consider alternative antipsychotic. Acting early can avoid onset. Prevent by using atypical antipsychotics (decrease incidence ten-fold).

Answer 93

**Hyperprolactinemia:** inhibition of dopamine at tuberoinfundibular pathway leads to increased prolactin causing weight gain, galactorrhoea (lactation), gynecomastia, sexual dysfunction, amenorrhoea/menstrual irregularity and infertility. Often with typical antipsychotics, amisulpride and risperidone * **Screen:** Measure prolactin levels and consider other differentials of increased levels (consider MRI of pituitary fossa)

Answer 94

**Prolongation of QTc Interval:** Due to effects on K channels and delayed repolarisation. Resting QTc typically \<420ms for male or \<430ms for females. Risk of sudden death with Torsades de pointes and VF at QTc \>500ms. High risk with thioridazine, droperidol, pimozide and ziprasidone. Low risk with atypicals. • **Screen:** Dizziness, syncope, presyncope and palpitations

Answer 95

**Anticholinergic:** Strong anticholinergic activity correlates with decreased extra pyramidal side effects (limits the procholinergic effect of dopamine blockade). Muscarinic blockade causes: 1. Dry mouth 2. Blurred vision (loss of accommodation) 3. Constipation 4. Urinary hesitancy/ retention 5. Cognitive blunting such as with Olanzapine.

Answer 96

**Anti-Adrenergic (A1):** 1. Postural hypotension 2. Hypothermia 3. Impotence and failure to ejaculate such as with Risperidone.

Answer 97

**Antihistaminergic:** Drowsiness such as with Quetiapine

Answer 98

**Metabolic Syndrome:** Weight gain, obesity, impaired glucose tolerance, hyperlipidemia and hypertension. * Mechanisms are complex and multifactorial. * Most offensive is clozapine (+4kg at 10 weeks) and olanzapine (+4.1kg), risperidone (+2.1kg) and other atypicals.

Answer 99

**Neuroleptic Malignant Syndrome:** Occur in 2% of patients on antipsychotics, at any time but usually in the first 30 days (mortality is 5-20%). * Symptoms evolve over 1-2 days and recover over 2-3 weeks. * Symptoms include change in mental state, autonomic dysfunction, neuromuscular hyperactivity (CAN). * **Differentials:** Serotonin syndrome, drug or alcohol intoxication/withdrawal or lithium toxicity * **Complications:** Metabolic acidosis, myoglobulinaemia, renal failure, pulmonary embolism, chronic cerebellar syndrome, disseminated intravascular coagulation (DIC) and death * **Investigations:** Observations, check med chart, IV access and measure CK, UEC, coagulation profile, lithium level, other drug levels and UDS * **Management:** Cease antipsychotics, resuscitate (cooling, BP, rehydrate), fluids, BZD, medical review and transfer to monitored ward (ICU for dopamine agonist, muscle relaxant, heparin and ECT).

Answer 100

**Dopaminergic Nuclei and Pathways (Context):** 1. **Mesolimbic Pathway:** VTA to limbic structures (motivation, reward and executive functions) 2. **Mesocortical Pathway:** VTA to prefrontal lobe (motivation, reward and executive functions) 3. **Nigrostriatal Pathway:** Substantia nigra to the striatum (part of extrapyramidal system and motor control) 4. **Tuberoinfundibular Pathway:** Arcuate nucleus of the hypothalamus to the anterior pituitary (inhibits prolactin release)

Answer 101

**Dopamine Hypothesis in Schizophrenia:** * **Theory:** Dysregulated dopamine results in aberrant salience (tendency for irrelevant stimuli to be attributed motivational salience and thus to attract attention and influence behaviour inappropriately). Psychotic symptoms are driven by inappropriate processing of stimuli that would normally be considered irrelevant. * **Mesolimbic Pathway:** Hyperactivity (positive symptoms) * **Mesocortical Pathway:** Hypoactivity (negative symptoms/cognitive impairment)

Answer 102

**_Neurotransmitter Hypothesis of**_ _**Schizophrenia_** * **Glutamate:** Low activity of the NMDA receptors of GABAergic inhibitory neurons in in prefrontal cortex. Antagonists of NMDA glutamate receptor such as phencyclidine (PCP) and ketamine transiently induce psychosis and symptoms of acute schizophrenia. * **GABA:** Loss of GABAergic neurons in hippocampus linked to psychosis. * **Serotonin:** 5HT receptor agonists such as LSD cause psychosis. * **Dopamine:** As described above.

Answer 103

**Diathesis-Stress Hypothesis:** Underlying vulnerability (genetic and/or acquired) is acted upon by a stress, resulting in onset of disease. Vulnerability likely to be inherited (60-90% heritability).

Answer 104

**Neurodevelopmental Hypothesis:** Structural brain abnormality from early neurodevelopmental insult. * Decrease in elaboration of inhibitory pathways and excessive pruning of excitatory pathways leads to altered excitatory-inhibitory balance in the prefrontal cortex. * Could explain neurotransmitter imbalance and reduced function of prefrontal cortex. * Imaging (MRI and CT) shows regional volume reductions in medial temporal and limbic (hippocampus, amygdala, parahippocampal gyrus) structures and increased volume of ventricles. * Post-mortem investigations confirm imaging and show histological evidence of disrupted migration (no gliosis) in medial and frontal lobes. * **Histological** **changes**: ↓ neuropil (dendritic arborisation), smaller cell bodies, ectopic neurons, impaired cortical inter-neurons

Answer 105

**Neurodegenerative Hypothesis:** Brain changes progress over the course of the illness. Series of brain insults results in structural changes during early development which alters disease course, in patients with chronic, relapsing illness (but no gliosis in recent post-mortum studies).

Answer 106

**Mechanism of Development of Psychotic Symptoms and Disorders:** 1. **Neurotransmitter Systems and Pathways:** *See neurotransmitter hypothesis above.* 2. **Genetic Factors:** *See diathesis-stress hypothesis above.* 3. **Exogenous Substances:** *Substance use can be linked to neurotransmitter changes, stress (diathesis model) and brain insult (neurodegeneration), see above.* 4. **Structural Brain Abnormality:** *See neurodevelopmental and neurodegenerative hypothesis above.* 5. **Information Processing:** *See changes to prefrontal cortex as described above.* 6. **Stressful Events or Situations:** *See diathesis-stress hypothesis above.*

Answer 107

**Clinical Formulation (Clinical Intuition and Judgement):** * A core clinical skill that links assessment information and treatment planning * It is a hypothesis about the mechanisms that cause and maintain the problem * **Answers the Question:** Why is this PARTICULAR patient here, with this PARTICULAR problem, at this PARTICULAR time in their life? * Performed after history and mental state examination but before diagnosis and treatment **Generate and Present a Clinical Formulation:** 1. **Cross Sectional:** Demographics, referral status, presenting complaint, history of presenting complain, mental state examination (observations and examinations) and current suicidality 2. **Longitudinal:** Past medical history, medication history, family history and psychiatry history 3. **Integrative and Dynamic:** Predisposing, precipitating, perpetuating and protective factors as well as prognosis and defense mechanisms, risk, strengths and gaps

Answer 108

**An Approach to Patient with Psychiatric Presentation:** 1. Psychiatric History 2. Mental State Examination 3. Physical Examination 4. Gather Collateral (Family and Friends) 5. Investigations (As Indicated) 6. Formulate, Diagnose and Communicate

Answer 109

**Emotion:** Short-lived feelings that come from a known cause e.g. happy, ecstatic, sad and prideful. **Mood:** Feelings that are longer lasting than emotions and have no clear starting point of formation e.g. positive or negative

Answer 110

**Neural Basis of Emotions (Context):** **Emotional Expression (Emotions):** Set of physiological responses when the brain detects a positively or negatively charged stimulus. In the brain it involves changes in arousal levels and cognitive functions (attention, memory and decision strategy). In the body it involves endocrine, autonomic and musculoskeletal responses. **Emotional Experience (Feelings):** The conscious experience of somatic and cognitive changes.

Answer 111

**Neural Basis of Emotions** * **Limbic System:** Cingulate gyrus and parahippocampal gyrus (cortical areas) and hippocampus, amygdala and septal areas (subcortical areas) * **Connections to Limbic System:** Ventral basal ganglia (nucleus accumbens), anterior and dorsomedial nuclei of the thalamus, prefrontal cortex, reticular formation and hypothalamus

Answer 112

**Neural Basis of Emotions -** **Hypothalamus-Pituitary Adrenal Axis (HPA):** * Stress response which includes the release of cortisol from the adrenal glands and activation of the sympathetic nervous system (stress → Corticotrophin-releasing hormone → Adrenocorticotrophin hormone → cortisol). * Works with amygdala to stimulate avoidance behaviour and increased vigilance and arousal. * Hippocampal activation suppresses CRH release. * Glucocorticoid receptors on hippocampal cells bind cortisol and feedback to the HPA axis to inhibit CRH release.

Answer 113

**Neural Basis of Emotions - Amygdala****:** **Amygdala:** Critical centre for coordinating behavioural, autonomic and endocrine responses to environmental stimuli, especially those with emotional content. Projections provide a key link between the experience of emotions and their expression (ink between sensory centres and hypothalamus outputs) and involved in emotional learning and memory through connections with hypothalamus (visceral and motor responses) and cortex dorsomedial nucleus of thalamus and orbitofrontal cortex. * **Medial Group:** Olfactory bulb and olfactory cortex * **Basal Lateral:** Orbital and medial prefrontal cortex and association cortex of anterior temporal lobe (especially large in humans) * **Central and Anterior Group:** Hypothalamus and brainstem

Answer 114

**Monoamine Theory (Basic Theory):** - Deficiency of one or more monoamines (DA, NA, A or 5HT) results in depression - Deficiency states linked to depression - Medication that decrease monoamines cause depression (B-Blockers) - Medication that increase monoamines treat depression (SSRIs, NRIs or MAOI). Cause downregulation of receptors (balance neurotransmitters and receptors). - Antidepressants increase monoamine neurotransmitters, and change gene expression in those neurons affected ( ↑ BDNF), which involves desensitisation of receptors. - Ability to measure monoamine metabolites (i.e. 5HIAA) in blood or CSF and link to abnormality

Answer 115

**Schema**: A set of pre-programmed interpretations about the world that are activated by specific situations i.e. the world is unsafe and harsh (negative cognitive style) or the world is full of exciting opportunities (positive cognitive style). Maladaptive schema can distort reality and lead to negative thinking and altered mood.

Answer 116

**Diathesis-Stress Model: **A psychological theory that attempts to explain a disorder as the result of an interaction between a pre-dispositional vulnerability and a stress caused by life experiences. Serves to explore how biological or genetic traits (diatheses) interact with environmental influences (stressors) to produce disorders such as depression, anxiety, or schizophrenia.

Answer 117

1. Stressful life events 2. Changes in life situation 3. Childhood trauma 4. Abuse and/or neglect 5. Personality factors (hopelessness and worthlessness, low self-esteem, self-criticism and pessimism) 6. Learned helplessness 7. Poor social support and isolation 8. Relationship breakdown, strain or problems 9. Gender and cultural roles and expectations

Answer 118

ECT > MAOIs > SNRIs > SSRIs > TCADs

Answer 119

**Induction Example** Smoking induces CYP1A2 and metabolism of clozapine (antipsychotic), reducing plasma levels of the drug (if the patient ceases smoking, may need dose reduction of clozapine). **Inhibition Example** SSRIs (especially fluvoxamine) inhibit CYP1A2 and metabolism of caffeine, potentially leading to toxic plasma levels of the drug (fluvoxamine and theophylline potentially lethal together).

Answer 120

Suicide Assessment Tool: SAD PERSONS Risk Assessment Scale

Answer 121

Suicide Assessment Tool: SAD PERSONS Risk Assessment Scale

Answer 122

1. **Major Depressive Disorder** - An episodic mood disorder primarily characterised by depressed mood and anhedonia that lasts for at least 2 weeks 2. **Adjustment Disorder** - Minor depressive symptoms following a stressor or bereavement 3. **Recurrent Major Depression** - Repeated episodes of major depression 4. **Dysthymia** - A chronic disorder of low mood for at least 2 years 5. **Personality Disorder** - A persistent, pervasive and maladaptive pattern of coping since late adolescence or early adulthood that can be characterised by affect dysregulation (including periods of low mood) 6. **Bipolar Disorder** - A history of episodic elevated mood (mania or hypomania) and at least one major depressive episode.

Answer 123

DASS-21: A clinical assessment that measures the three related states of depression, anxiety and stress. It has 21 questions and takes about 3 minutes to complete.

Block 6 - Psychiatry Flashcards

(192 cards)