Q1

What is the mechanism of action of Midazolam?

Binds to the GABA receptor complex. This increases Cl- channel opening, decreasing neuron membrane potential having an inhibitory effect on the CNS.

What is the antagonist of Midazolam?

Flumazenil

What adverse events may be associated with the use of flumazenil of midazolam toxicity?

Benzodiazepine with drawl / seizures. Resedation.


Q2

What are the advantages of olanzapine over older antipsychotics?

  • Increased
    • Sedation
    • Anticholinergic symptoms
    • More weight gain
  • Less
    • Extrapyramidal side effects
    • QT interval prolonging effect
  • Dose = 5-20mg

What clinical conditions is olanzapine prescribed for?

  • Behavioural emergencies
  • Schizophrenia
  • Mania / mood disorders
  • Delirium with behavioural disturbances
  • Autism spectrum
  


Q3

What properties does Propofol have that make it a good IV anaesthetic?

  • Rate of recovery is more rapid than other drugs i.e. thiopentone
  • Antiemetic effect
  • Short distribution 1/2 life (2-8 min)
  • Does not cause cumulative effect (because of its short 1/2 life)

Outline the pharmacokinetic profile of Propofol?

  • Distribution 1/2 life: 2-8 min
  • Elimination  1/2 life: 30-60 min
  • Rapidly metabolised in liver by conjugation to glucoronide sulphate and excreted in urine
  • <1% of drug is excreted unchanged
  • Clearance of propofol > hepatic blood flow. Hence there is an extrahepatic route of elimination in addition to the liver enzyme metabolism

Q4

What is benztropine?

  • Centrally acting anti-muscarinic
  • Used in treating acute dystonia and Parkinsons

What are the adverse effects of benztropine?

  • CNS – drowsy, confusion, hallucinations
  • PNS –dry mouth, blurred vision, mydriasis, retention, N/V, constipation
  • Cardiac – tachycardia, palpitations

Q5

What is the mechanism of action of midazolam?

  • Binds to GABA-A Chloride channels
  • Potentiates GABAergic inhibition through hyperpolarisation
  • Acts throughout brain

What are the pharmacokinetics of Midazolam?

  • Water soluble hence oral/IM/intranasal
  • Crosses BB barrier easily at body pH.
  • Short elimination half-life 2-4 hours.
  • 56% renal excretion

What are the pharmacodynamics of Midazolam?

  • Strong amnestic effect
  • Anticonvulsant
  • Anxiolytic
  • Sedative-hypnotic

Q6

What classes of drug can be used as antiemetics?

  • Serotonin 5-HT3 antagonists: the “trons”
  • Phenothiazines: prochlorperazine, promethazine, chlopromazine
    • Butyrophenones: haloperidol, droperidol
    • Substituted benzamides: metoclopramide
    • H1 antihistamines: diphenhydramine
    • Anticholinergics: hyoscine

List and explain the adverse effects of prochlorperazine?

  • Acute dystonia (dopamine blockade)
  • Sedation (antihistamine effects)
  • Anticholinergic effects (antimuscarine effects)
  • Allergy

Q7

Describe the pharmacokinetics of thiopentone.

  • After IV bolus, rapidly crosses the blood-brain barrier.
  • Plasma:brain equilibrium occurs < 1 min because of high lipid solubility.
  • Rapidly diffuses out of the brain and highly vascular tissues, and redistributed to muscle and fat.
  • Metabolized at rate of 12–16% per hour. <1% of the administered dose excreted unchanged by kidney

What adverse effects does it cause when used as an anaesthetic induction agent?

  • Hypotension: Drops BP, SV, CO due to myocardial depressant effect and increased venous capacitance.
  • Apnoea.
  • Rarely precipitates porphyric crisis by inducing ALA synthase in liver

Q8

How do anti-depressants exert their action?

  • Thought to enhance amine-dependent synaptic transmission (serotonin and noradrenalin) by:
    • Inhibition of metabolism within nerve terminal (MAOIs)
    • Inhibition of reuptake from synapse (TCAs, SSRIs)
    • Increased release due to antagonism of specific serotonin and alpha2 noradrenalin receptors (Mirtazapine)

What are the relative advantages of different classes of antidepressants?

Adverse effect profile

Cost

Efficacy

Risk of overdose

Dosing schedule

Drug interactions


Q9

Describe the pharmacokinetics of phenytoin?

  • Weak acid pKa 8.3; oral abs almost complete 90%, with peak serum conc 3-12hrs later.  Slow release formulation also.
  • IMI: incomplete abs with drug precipitation in the muscle, fosP OK
  • Highly plasma protein bound, metabolised to inactive metabolities with urinary excretion, < 2% exc unchanged in urine.
  • Dose dependant kinetics; Vd 45L/70kg.  t1/2 av 24 hours (conc dependant).  Therapeutic level 10-20mg/L.  Drug interactions via plasma protein binding or via enz induction (CYP2C19 & CYP2C9).  Alters TFT results; reduced CL neonates; foetal hydantoin syndrome


Pass Criteria: Highly protein bound AND dose dependant kinetics

Describe the pharmacodynamics of phenytoin?

  • Block sodium channels & inhibits the generation of repetitive APs blocks sustained high frequency repetitive firing of APs).
    • Preferential binding to & prolongation of the inactivated state of the Na channel (use dependant effect on Na conductance).
    • Other electrolyte effects
      • alters K conductance;
      • alters Ca conductance ad decreases Ca permeability, inhibits Ca influx therefore affecting neurotransmitter & hormone release;
      • interacts with membrane lipids stabilising membranes;
      • paradoxical excitation in some neurones;
      • alters membrane potentials and the conc of amino acids;
      • affects neurotransmitters NA, Ach & GABA.
      • High conc inhibits serotonin and NA release, promotes uptake of DA & inhibits MAO activity

Pass Criteria: Na channel AND 1 other effect


Q10

Describe the mechanism of action of metoclopramide?

  • Dopamine antagonist ( D2 receptors)
  • Central
    • Anti-nauseant and anti-emetic effect on the Chemoreceptor Trigger Zone (area postrema)
    • Peripheral
      • Blockade of GI dopamine receptors allowing cholinergic smooth muscle stimulation
        • increases oesophageal peristaltic amplitude
        • increases lower oesophageal sphincter pressure
        • enhances gastric emptying

 Pass Criteria: Dopamine antagonist, peripheral & central action

List the adverse effects of metoclopramide?

  • Relate to central dopamine antagonist action
    • restlessness, drowsiness, insomnia, anxiety, agitation
    • extrapyrimadal effects – dystonias, akathisia, parkinsonian features.
    • risk of tardive dyskinesia with chronic use
    • hyperprolactinemia (galactorrhoea, gynecomastia, impotence, menstrual disorders)

Pass Criteria: Extrapyramidal AND 1 other effect


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