MS pharm word slides

1

• Anesthetics and Anesthetic Adjuncts
• Analgesics Opiates, fentanyl (Sublimaze)
• General depressants
• a. Benzodiazepines benzodiazepines midazolam
  (Versed)
• b. Barbiturates secobarbital
• Neuroleptics droperidol (Inapsine)
• Muscarinic blockers (atropine, scopolomine,
  glycopyrate)
• Neuromuscular blockers (paralytics)
• Miscellaneous Agents (antagonists naloxone,
  flumazanil, neostigmine)

2
Analgesics

• Used with anesthesia to provide analgesia.
• Important ADRs respiratory depression,
  cardiovascular depression.
• Potent Analgesics (opiates) morphine, fentanyl,
  nalbuphine, alfentanil, sufentanil.

3
Pre-Anesthetic Depressants

• Benzodiazepinesdiazepam, lorazepam, midazolam
• Barbiturates secobarbital, pentobarbital
• Mechanism - enhancement of GABA action.

4
Neuroleptics

• Antipsychotic agents droperidol
• Produces a trance-like state, for neuroleptic
  anesthesia.
• Effective antiemetics

5

• Antagonists of Adjuncts to Anesthesia
• ChEI - competitive NMBs
• Naloxone - opiates
• Flumazenil - BZD

6
Miscellaneous Drugs

• anticholinergic agents atropine, scopolamine,
  glycopyrrolate.
• Use to reduce secretions.

7
GABAA Receptors

• The GABAA receptor is a heteromeric-pentamer.
• Binding of GABA to its site on the GABAA receptor
  opens the chloride channel generally resulting in
  an IPSC (hyperpolarizing the postsynaptic neuron
  reducing excitation).
• At least 21 different subunits have been
  identified.
• Specific GABAA subunit combinations define the
  nature of the BDZ response.
• Different subtype combinations appear to mediate
  the different actions of BDZs, including amnesia,
  anxiolysis, sedation, antispasticity.
• Midazolam has twice the affinity for BDZ
  receptors than does diazepam.
• The antianxiety action of BDZs may be a result of
  their ability to selectively block subunit
  constructs found in cortical and limbic arousal
  following stimulation of the reticular pathways.

8
Midazolam

• Midazolam is a short-acting benzodiazepine.
• Midazolam is used for conscious sedation,
  anxiolysis, and amnesia during minor surgical or
  diagnostic procedures.
• Midazolam is used as an inducing agent, and as an
  adjunct to regional anesthesia.
• Midazolam, as other benzodiazepines (BDZs) act at
  limbic, thalamic, and hypothalamic structures
  producing a dose dependant CNS depression
  including sedation, hypnosis, skeletal muscle
  relaxation, and anticonvulsant activity.
• BDZs act by potentiating the action of GABA at
  GABAA receptors. Benzodiazepines cause allosteric
  modulation of GABAA receptor complex, but do not
  activate the channel.
• Unlike barbiturates which augment GABA responses
  by increasing the length of time that chloride
  channels remain open, BDZs enhance GABA efficacy
  by increasing the affinity of GABA to its binding
  site on the GABAA receptor.

9
Propofol

• Propofol (2,6-diisopropylphenol) is an
  intravenous anesthetic.
• Propofol induces anesthesia that can be
  maintained by continuous infusion.
• Propofol induces anesthesia as quickly as
  thiopental, but emergence from anesthesia is 10
  times more rapid than with thiopental and is
  associated with minimal postoperative confusion.
• Only desflurane has a more rapid recovery time
  than propofol, but desflurane is associated with
  more nausea/vomiting. Unlike many other general
  anesthetics, propofol possesses an antiemetic
  action.
• Propofol acts by binding to unique a3/a5
  containing GABAA receptor subunit constructs.
• Propofol anesthesia is immediate and short-lived.
  
• Cardiorespiratory depression, apnea and
  significant hypotension are possible and are
  dose-related.

10
Fentanyl

• Fentanyl is a potent synthetic opiate agonist.
• Fentanyl is a phenylpiperidine derivative,
  structurally similar to meperidine,
• Fentanyl is highly lipid soluble.
• Fentanyl is used to aid induction and maintenance
  of general anesthesia and to supplement regional
  and spinal analgesia.
• Fentanyl is preferred to morphine in anesthesia
  due to its ability to attenuate hemodynamic
  responses and maintain cardiac stability.
• Fentnayl may be administered alone or in
  combination with inhaled anesthetics, local
  anesthetics such as bupivacaine, or
  benzodiazepines.

11
Fentanyl Mechanism of Action

• Fentanyl is a strong agonist at µ- and kappa-
  opiate receptors.
• Opioids close N-type voltage-operated calcium
  channels (kappa-receptor agonist) and open
  calcium-dependent inwardly rectifying potassium
  channels (µ and delta receptor agonist) resulting
  in hyperpolarization and reduced neuronal
  excitability.
• Analgesia is mediated through changes in the
  perception of pain at spinal cord (µ2-, delta-,
  kappa-receptors) and brain (µ1- and kappa3
  receptors).
• Opiate receptors are G-protein coupled receptors.
  Opioid-G-protein systems include cAMP and
  PLC-intositol triphosphate.
• The emotional response to pain is altered.
  Opiates do not alter the pain threshold of
  afferent nerve endings to noxious stimuli.
• Opioids can modulate the endocrine and immune
  systems inhibiting release of vasopressin,
  somatostatin, insulin and glucagons.
• Stimulatory effects of opioids are the result of
  "disinhibition" as the release of inhibitory
  neurotransmitters such as GABA is blocked.

12
Opiate Actions

• Clinically, stimulation of µ-receptors produces
  analgesia, euphoria, respiratory depression,
  miosis, decreased gastrointestinal motility, and
  physical dependence.
• Kappa-receptor stimulation produces analgesia,
  miosis, respiratory depression, as well as,
  dysphoria and some psychomimetic effects (i.e.,
  disorientation and/or depersonalization).
• Miosis is produced by excitatory action on the
  autonomic segment of the nucleus of the
  oculomotor nerve.
• Opiate-induced respiratory depression is caused
  by direct action on brain stem. respiratory
  centers while bradycardia is due to depression of
  the medullary vasomotor center and vagal nucleus
  stimulation.
• Opiate agonists action on the GI tract results in
  constipation and delayed digestion, while urinary
  smooth muscle tone is increased by opiate
  agonists, sometimes causes urinary retention.