CNS Drugs 21 to 30
What are the indications for benzodiazepine use?
- Anxiety Disorders
- Preoperative Medication
- Sleep Disturbances
- Seizure Disorders
- Panic Disorder
- Alcohol Withdrawal
- Muscle Spasm
- Induce amnesia during procedural sedation
Pass Criteria: Seizures PLUS 2 others
Explain the rationale for use of benzodiazepines in alcohol withdrawal.
- Down-regulation of neuro-inhibitory GABA receptors in alcohol dependent individual leads to symptoms of GABA deficiency in withdrawal.
- BZD act at a modulatory site on the the GABAA receptor to facilitate GABA binding to the GABAA receptors, enhance chloride channel opening, and overcome neuroexcitatory symptoms of GABA deficiency
Facilitate GABA binding to the GABAA receptors
Control neuroexcitatory symptoms of alcohol withdrawal
Describe the pharmacokinetics of lithium.
- Rapidly absorbed (except SR preparations) with peak plasma concs in 1-3hrs. High bioavailability.
- Not metabolised
- Renally excreted unchanged with partial reabsorption from PT.
- Long T ½ of 24hrs in adults
- Steady state plasma concs not reached for 5-7 days
Long T ½ so steady state plasma concs not reached for days.
Renally excreted unchanged
What are the adverse effects of Lithium at therapeutic levels?
- Short termTremor, nausea, polydypsia /polyuria, diarrhoea, weight gain.
- Acne / psoriasis,
- nephrogenic diabetes insipidus
Pass Criteria: Polyuria & Polydipsia OR NDI
What are the signs/symptoms of lithium toxicity?
- GIT: Vomiting.
- Neuro: Tremors, confusion, slurred speech, ataxia, drowsiness, blurred vision, seizures
Pass Criteria: CNS effects with at least 3 symptoms
Describe the distribution of thiopentone following an IV bolus.
- To highly vascular tissue and rapidly crosses BBB.
- High lipid solubility.
- Then rapidly redistributed to body fat.
What are the potential adverse effects of thiopentone?
- Reduction of ICP,
- Venous irritant,
- Myocardial depression,
- minimal muscle relaxation and analgesia,
- hepatic metabolism (vs inhalational agents)
Pass criteria: Bold
How do benzodiazepines work at the receptor level?
- Bind to the GABA receptor at a site separate to GABA binding
- GABA opens Chloride channels increasing the membrane potential
- Does not directly activate the receptor but facilitates the effect of GABA on the receptor.
What are the clinical effects of benzodiazepines?
- Muscle relaxation
- Respiratory depression
- CVS depression
What is flumazenil?
- Antagonist of benzodiazepines at the GABA receptor.
- Can cause benzodiazepine withdrawal.
List the major categories of the antiemetic agents.
- Antimuscarinic, sedative and H1 blocking
- Effective in motion sickness
- Prochlorperazine, Chlorpromazine
- Dopamine anatagonists
- Can cause extrapyramidal symptoms
- Dopamine antagonist
- 5-HT inhibitors
- Ondanestron, Gransitiron
- Unknown mechanism
Describe the mechanism of action of valproate.
- Sodium Channel blocker
- Enhances K+ efflux
- Increase in GABA
- Inhibition of GABA T
- Decrease in GABA breakdown.
What potential drug interactions can occur with valproate?
- Decrease metabolism of
- Displaces phenytoin from plasma proteins
- Inhibits its own metabolism at low doses.
What adverse reactions can be associated with the use of antipsychotic agents?
- Extrapyramidal Side effects
- Tardive dyskinesia
- Neuroleptic Malignant Syndrome
- Alpha adrenergic antagonism
How does ondansetron work as an anti-emetic?
- 5-HT3 antagonism (gut and brain / central)
What are the routes of administration and dose of ondansetron?
- Similar doses 4-8 mg oral – tablet/wafer, IV
What type of anaesthesia does ketamine produce?
- Dissociative anaesthetic: analgesia, amnesia, catatonia +/- LOC
- Blockade of glutamic acid (excitatory neurotransmitter) at NMDA receptor
What are the cardiorespiratory effects of ketamine?
- CVS: HR, BP, CO increase central SNS excitation
- Resp: decreased rate, airway reflexes remain intact, bronchodilator
What drugs can be used in the treatment of an acute attack of migraine?
- simple analgesia (eg paracetamol, aspirin, codeine);
- triptans eg sumatriptan (opoids can be used but not choice)
- ergot alkaloids eg ergotamine ( +/- caffeine added);
How do triptans work?
- structural analogue of 5-HT;
- selective agonists at 5-HT1 receptors;
- cause vasoconstriction,
- particularly on cerebral arteries
Chlorpromazine can be used to treat acute migraine. What are the major side effects of chlorpromazine?
- anticholinergic (dry mouth, dry eyes, urinary retention, constipation);
- extrapyramidal (eg acute dystonia);
- pain with IM injections, risk of muscle necrosis
Pass criteria: Bold