Drugs used in Premedication

• Drugs used in premedication

  • Anxiolytics
  • Analgesics
  • Anti-autonomic
  • Anti-emetic
  • Anti-acid
• Anxiolytics


  • Decrease anxiety of patients
  • Make patients sedative and calm
  • Produce amnesia
  • Act predominantly on GABA receptor
  • Minimum cardiac and respiratory depression
  • Do not produce nausea and vomiting
  • Lack analgesic effect
  • Cross the placenta and may cause neonatal depression
• Benzodiazepines


  • Main anxiolytic drugs used (Diazepam, Midazolam, Lorazepam, Alprazolam)
  • Exhibit anxiolytic, sedative, amnesic and anticonvulsant properties
  • Differ in pharmacokinetic properties, some short acting others slowly eliminated
• Diazepam


  • Dominant sedative and anxiolytic for oral premedication
  • Rapidly absorbed when given orally
  • Causes anterograde amnesia
  • Devoid of emetic side effects
  • Variable and unpredictable anxiolytic and sedative action
  • Long elimination half-life
  • Duration prolonged by active metabolites
  • Intramuscular injection is painful and not recommended
• Midazolam


  • Water-soluble benzodiazepine
  • Water-soluble at pH<4, highly lipid-soluble at physiological pH
  • Water solubility minimizes pain at injection site
  • Lipid solubility ensures rapid distribution in tissues
  • More potent, faster onset and shorter duration of action than diazepam
  • Elimination half-life 1.5-3.5 hours vs 20 hours for diazepam
  • Metabolites have negligible soporific effects
  • Suitable for conscious sedation, pre-operative sedation, induction of general anesthesia
  • Provides superior pre-operative sedative effect compared to diazepam
  • Good local tolerability and hemodynamic stability

  
• Analgesic drugs used in premedication

  • Opioids
  • Paracetamol
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
• Analgesic drugs in premedication

  • Reduce required dose of anesthetic agent
  • Improve patient comfort in immediate postoperative period
• NSAIDs


  Commonly used, particularly in day surgery, unless contraindicated
• Opioids


  • Usually the agents of choice in presence of acute severe pain
  • May cause intense dysphoria in absence of pain
  • Cause variable sedation and cardiorespiratory depression
  • Can cause nausea and vomiting
  • May precipitate bronchospasm or anaphylaxis
• Clonidine

  Given as premedication, shown to reduce postoperative pain in children
• Classification of opioids


  • Natural Opium Alkaloids: Morphine, Codeine
  • Semi-synthetic: Diacetylmorphine (Heroin), Pholcodeine
  • Synthetic Opioids: Pethidine, Fentanyl, Remifentanil
• Pethidine


  • 1/10th as potent as Morphine
  • Efficacy similar to Morphine
  • Produces as much sedation, euphoria and respiratory depression as Morphine
  • Less spasmodic action in smooth muscles
  • Less miosis, constipation and urinary retention
  • Rapid but short duration of action (2-3 hours)
  • Vagolytic effect: tachycardia, devoid of antitussive action, less histamine release, safer in asthmatics

  
• Pethidine pharmacokinetics


  • Well absorbed orally
  • Bioavailability 50%
  • Effects appear in 10-15 minutes after oral absorption
  • Parenteral administration lasts for 2-3 hours
  • Metabolized in liver, excreted in urine
• Fentanyl


  • Potent analgesic 100 times more than morphine
  • Metabolized in liver, excreted in urine
  • Produces respiratory depression, use with caution in COPD
  • Causes less nausea and vomiting
  • Can be reversed by naloxone
  • Dose 1-5 micrograms/kg IV
  • Preferred due to rapid onset and short duration of action
• Remifentanil


  • Potent ultra-short-acting synthetic opioid
  • Specific mu-type-opioid receptor agonist
  • Reduces sympathetic nervous system tone, causes respiratory depression and analgesia
  • Rapid onset and peak effect, ultrashort duration of action
  • Opioid activity antagonized by naloxone
  • Analgesic effects rapid in onset and offset
  • Effects and side effects dose dependent, similar to other opioids (hypotension most common)
• Anti-autonomic drugs used in premedication

  • Anti-cholinergics: Atropine, Hyoscine, Glycopyrrolate
  • Beta blockers
• Atropine


  • Dose 0.3-0.4 mg IV
  • Causes vagal inhibition (tachycardia)
  • Causes CNS stimulation
  • Acts as antisialagogue (decreases salivation)
  • May cause central anticholinergic syndrome (reversible by physostigmine)
• Hyoscine


  • Less vagal inhibition effect, more effect on salivation
  • Produces sedation and amnesia, should be avoided in elderly
• Glycopyrrolate


  • No central action as it does not cross blood brain barrier
  • Longer duration and less tachycardia than other anticholinergics

  
• Anti-cholinergics produce dry mouth and mydriasis (pupil dilation) except Glycopyrrolate
• Anti-emetic drugs used in premedication

  • Ondansetron
  • Metoclopramide
• Metoclopramide


  • Most commonly used antiemetic drug
  • Dose 0.15-0.3 mg/kg, lasts 12 hours
  • Acts centrally as dopaminergic antagonist on vomiting center
  • Acts peripherally by increasing gastric emptying and gut peristalsis
  • May produce oculogyric (extrapyramidal) side effects
• Ondansetron


  • Selective 5-HT3 serotonin-receptor antagonist
  • Acts both centrally and peripherally to prevent and treat nausea and vomiting
  • Central effects mediated by 5HT-3 receptor antagonism
  • Peripheral effects by acting on vagus nerve terminals
• Anti-acid drugs used in premedication

  • Histamine H2 receptor antagonists (cimetidine, ranitidine)
  • Proton pump inhibitors (omeprazole, lansoprazole)
  • Sodium citrate
• Anti-acid drugs


  • Increase gastric pH and decrease volume to reduce risk of pulmonary aspiration
  • Not recommended for patients without aspiration risk
• Oral route is better than IV for anti-acid drugs