Q11

What is the mechanism of action of the SSRI drugs?

  • Amine hypothesis – modulation of NET + SERT pathways by reuptake inhibition -> serotonin response
  • Prolonged synaptic exposure to Serotonin leads to
  • Probable time frame 3-6 weeks due to presynaptic/ post synaptic receptor / storage regulation
  • SSRIs v HT specific v TCA 300-7000:1

Pass Criteria: Knowledge of amine hypothesis AND

  • delayed response
  • probable alteration in pre/post synaptic

What receptor/channel effects lead to the SSRI side effect profile?

  • Very specific for HT (particularly 1) receptors –therefore serotonin syndrome/ restlessness.
  • Minimal autonomic NE activation + mild muscarinic / Na channel, H1 block effects (safety/ tolerance).
  • Possibly some alpha block (sexual dysfunction)

Pass Criteria: Specific HT PLUS one other


Q12

What is the mechanism of action of Carbimazepine?

  • Tricyclic Compound
  • Blocks sodium channels
  • Inhibits high frequency repetitive firing neurons
  • Decreases presynaptic transmission
  • Inhibits uptake and release of noradrenaline in brain

What are the clinical indications for its use?

  • Seizures
    • Partial
    • Tonic clonic
    • In combination with other seizure medications
    • Trigeminal neuralgia
    • Mood disorders

What are the potential adverse effects?

  • Diplopia
  • Ataxia
  • GIT upset
  • Blood dyscrasias
    • Aplastic anaemia
    • Agranulocytosis
    • Skin Rash
    • In toxicity
      • Cardiac sodium channel blocking effect
      • CNS depression
      • Alters clearance of other drugs

Q13

What is the mechanism of action of the tricyclic antidepressants?

  • Block amine (NAdr or Serotonin) reuptake pumps at presynaptic nerve endings
  • prolongs duration of action of neurotransmitters at postsynaptic receptors.
  • Most non selective

Pass Criteria: Amine block, Reuptake inhibitor

Describe the toxic effects in overdose and how are they mediated?

  • Antimuscarinic.  tachycardia, dry mouth, blurred vision, delirium, coma, Agitation;  Urinary retention, reduced gastric motility,
  • Sympathomimetic: tremor. Insomnia
  • Sedation: additive effects
  • Alpha1-antiadrenergic – postural hypotension, Hypotension, dizziness
  • Fast sodium-channel blockade – reduced myocardial contractility, QT prolongation, cardiac arrhythmias;
  • Respiratory depression;
  • Neuromuscular irritability and seizures

Pass Criteria:

  • Some antimuscarinic
  • Cardiac (mix)
  • Na channel block effects
 


Q14

What are the clinical uses of chlorpromazine?

  • Antipsychotic
  • Sedative for agitation
  • Antiemetic
  • D2 blockade in the mesolimbic and mesofrontal systems

 

What are the pharmocodynamic properties responsible for these effects?

  • Antipsychotic
    • D2 blockade in the mesolimbic and mesofrontal systems
    • Antiemetic
      • Dopamine receptor blockade in the medullary chemoreceptor trigger zone & peripherally on the receptors on the stomach
      • Sedation
        • 5HT blockade

What are its adverse effects?

  • Autonomic
    • Dry mouth
    • Loss of accommodation
    • Urinary retention
    • Constipation
    • Orthostatic hypotension
    • Sexual dysfunction
    • CNS
      • Parkinsonism
      • Akathisia
      • Dystonia
      • Neuroleptic Malignant syndrome
      • Tardive dyskinesia
      • Confusion
      • Seizures
      • Sedation
      • Endocrine
        • Hyperprolactinaemia
        • Infertility
        • impotence

Q15

What is the mechanism of action of amphetamines?

  • Indirectly cause increased release of catecholamines at synapses
  • Competitively inhibits dopamine transport in pre-synaptic neurone (DAT), inhibits VMAT causing non-vesicular release of dopamine into synapse (& similarly for other catecholamines)

Describe the effects of amphetamines?

  • Catecholamines; (increased arousal & decreased sleep) elevated HR (dysrhythmias) and BP (CVA)
  • Dopamine release; euphoria, potentially abnormal movements & psychosis
  • Serotonin; Appetite suppression, hallucinogenic & hyperthermia


Pass Criteria: CNS stimulation and cardiovascular effects to pass


Q16

How does ketamine affect the cardiovascular system?

  • HR, BP and cardiac output increase
  • Stimulate central SNS, and inhibits re-uptake of noradrenaline at sympathetic nerve terminals

Pass Criteria: Demonstrated understanding of CV effects of ketamine

What are the side effects of ketamine?

  • Sialorrhoea
  • Decreased RR
  • Postoperative disorientation
  • Sensory and perceptual illusions
  • Emergence phenomenon
  • Vomiting
  • Raised ICP– increases cerebral blood flow, oxygen consumption and ICP
  • Rash

Pass Criteria: 2 bold + 1 other


Q17

Describe the pharmacokinetics of propofol?

  • Intravenous administration
  • Distribution t1/2 2-8 min, redistribution t1/2 30-60 min
  • Metabolism- rapidly in liver; total body clearance is greater than hepatic blood flow, suggesting extrahepatic mechanisms
  • Excretion- urine as glucuronides and sulphates- <1% unchanged

Pass Criteria: Must get bolded point to pass

What are the side effects of propofol?

  • Respiratory- dose-related depression of central ventilatory drive, apnoea,
  • Cardiac- Marked decrease in blood pressure through decreased peripheral arterial resistance and venodilatation, and direct negative inotropic effect.
  • Soy/egg allergy,
  • Pain on injection

Pass Criteria: Knowledge of respiratory and cardiac effects of propofol


Q18

Describe how phenytoin is administered in status epilepticus?

  • IV load 13-20mg/kg
  • Given diluted in saline (precipitates in glucose)
  • Max rate in adults of 50mg/min
  • Continued 100mg Q6-8hrly

Pass Criteria: Dose mg/kg for iv route

Describe the adverse effects of phenytoin?

  • Dose related: nystagmus, ataxia, diplopia
  • Long term: gingival hypertrophy, hirsuitism, mild facial coarsening & peripheral neuropathy, abnormal Vit D levels (osteomalacia), low folate levels; megaloblastic anaemia;  Foetal hydantoin syndrome.
  • Idiosyncratic: skin rash; SJ syndrome; Lymphadenopathy; agranulocytosis.
  • Rapid IV may cause hypotension/arrhythmia
  • Drug interactions; reduced CL & binding in neonates

Pass Criteria: CNS + skin + CVS in iv admin


Q19

Describe the general pharmacokinetic characteristics of antipsychotic drugs?

  • Most are readily but incompletely absorbed.
  • Many undergo significant first pass metabolism
  • Most are lipid soluble (lipophilic)
  • Most have high PPB (92-99%)
  • Most are completely metabolised by hepatic enzymes (oxidation; demethylation)
  • These are catalysed by liver enzymes.

Pass Criteria: Lipid soluble. Hepatic metabolism. PLUS 1 other

Define the term “atypical” antipsychotic and provide an example?

  • Newer antipsychotic agents with less propensity to cause extra-pyramidal side-effects. Better at treating negative features of schizophrenia.
  • They share a greater ability to alter 5HT2A receptor activity than to interfere with D2-receptor action.
  • Examples: olanzapine; clozapine; quetiapine; risperidone; loxapine

Pass Criteria: Less EPS. One example

Describe the adverse drug reactions to olanzapine?

  • Weight gain
  • Sedation (but less than typical antipsychotics)
  • Minor orthostatic hypotension
  • Minor anticholinergic effects (dry mouth, urine retention etc)
  • (Extrapyramidal effects less prominent)

Pass Criteria: 2 Effects


Q20

What is the mechanism of action of flumazenil?

  • Antagonist at the BZD binding site on the GABAA receptor (ligand-gated chloride channel).
  • Decreases the binding of GABA.
  • Blocks GABA-induced increase in Cl permeability and influx of Clinto the cell causing hyperpolarisation and decreased excitability of the neuron.

Pass Criteria: Specific BZD receptor antagonist at GABA receptor

What are the indications for flumazenil use?

  • Avoid intubation or ICU admission in BZD overdose.
  • Reverse BZD sedation after procedures
  • Diagnostic role

Pass Criteria: Reverse the sedative effects of BZD

What potential problems should be anticipated when using flumazenil?

  • Precipitate seizures in mixed overdoses with BZD and proconvulsants
  • Precipitate seizures in pts taking BZD to control epilepsy
  • Precipitate withdrawal symptoms and seizures in BDZ-dependent
  • Duration of action is only 1-3hrs thus repeated administration may be necessary
  • Reversal of BZD-induced respiratory depression has not been demonstrated, so respiratory and cardiovascular support may be required
  • Adverse Effects:  headache, visual disturbance, increased anxiety, nausea, light-headedness

 

Pass Criteria:Precipitate fits. Need for repeated doses


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