General and Intravenous Anesthetics

• The information below provides essential notes on general and intravenous anesthetics, focusing on their pharmacological properties, uses, and key considerations for clinical application.

Intravenous Anesthetics

• Intravenous anesthetics are characterized by a rapid onset and capability for quick induction of stage III surgical anesthesia.
• Administration is easy.
• Ventilation cannot reverse the effects
• Caution is needed to avoid severe medullary depression.

Short-Acting Barbiturates

• Sodium thiopental (Pentothal) and Methohexital (Brevital sodium) are examples of short-acting barbiturates.
• These drugs enhance the effects of GABA on GABAA channels. Higher doses open GABAA channels, even without GABA.
• They depress respiratory and cardiac function, decreasing MAP (mean arterial pressure) and CO (cardiac output).
• They do not increase cerebral blood flow, making them advantageous for head trauma and brain tumors.
• Liver metabolizes these drugs
• Induction of hepatic ALA synthase, a rate-limiting step in heme synthesis, may precipitate acute intermittent porphyria.
• They are highly lipid-soluble, allowing rapid induction
• Rapid redistribution from the CNS allows for rapid recovery.

IV Benzodiazepines

• Examples include Diazepam (Valium) and Midazolam (Versed), which has a water-soluble formulation.
• They enhance the effects of GABA on GABAA channels, but, unlike barbiturates, inhalation anesthetics, and ethanol, they do not open channels in the absence of GABA.
• They depress the CNS to a level below a true anesthetic state.
• They produce preoperative sedation and amnesia
• They depress respiratory function.
• Flumazenil is a benzodiazepine receptor antagonist used to accelerate recovery from benzodiazepine sedation.
• Respiratory depression is less reversible with flumazenil.

Ketamine (Ketalar)

• Ketamine induces dissociative anesthesia, characterized by amnesia, catatonia, and analgesia; patients may not lose consciousness, and their eyes may remain open.
• It has a rapid, short duration and shares a chemical similarity to PCP.
• Ketamine blocks NMDA receptors, which are excitatory receptors activated by glutamate.
• It is the only IV anesthetic that produces cardiovascular stimulation via central stimulation of the sympathetic system, increasing heart rate, blood pressure, and cardiac output.
• Useful for poor-risk geriatric patients and those with cardiogenic or septic shock.
• It increases cerebral blood flow and intracranial pressure.
• Diazepam or midazolam reduces the incidence of emergence reactions like vivid dreams and hallucinations.

Propofol (Diprivan)

• Propofol is an extremely important IV anesthetic that enhances GABAA-mediated inhibition, leading to very rapid onset and recovery.
• It is suitable for outpatient surgery due to rapid liver metabolization
• It also has antiemetic properties, which results in less postoperative nausea and vomiting
• Used for both induction and maintenance of anesthesia
• It depresses respiratory function and causes marked hypotension through vasodilation.
• Propofol has a negative inotropic effect.
• Prolonged infusion does not increase its half-life.

Etomidate (Amidate)

• Etomidate has minimal cardiovascular and respiratory depression
• Etomidate is useful in patients with limited cardiovascular reserve.
• Enhances GABA-mediated inhibition
• Etomidate has no analgesic effects and may require coadministered opioids.
• It has rapid onset and recovery due to redistribution and is extensively metabolized by the liver.
• Adverse effects include pain on injection, involuntary muscle movements in 50% of patients, postoperative nausea and vomiting, and adrenal suppression.
• Adrenal suppression occurs via inhibition of steroidogenesis, blocking 11-β-hydroxylation and decreasing cortisol after a single dose.

Dexmedetomidine (Precedex)

• Dexmedetomidine is a highly selective α2-adrenergic agonist.
• Dexmedetomidine causes hypnosis, presumably from stimulation of α2 receptors in the locus coeruleus, resembling a physiologic sleep state by activating endogenous sleep pathways.
• It provides analgesia in the spinal cord.
• Dexmedetomidine decreases heart rate and systemic vascular resistance, leading to decreased blood pressure.
• Has mild respiratory effects
• Has a water-soluble parenteral formulation
• It offers sedative and analgesic effects without respiratory depression
• Used for short-term sedation of intubated and ventilated patients in an ICU setting.
• It serves as an adjunct to general anesthesia or to provide sedation during awake fiberoptic tracheal intubation or regional anesthesia.
• Dexmedetomidine decreases the dose requirements for inhaled and injected anesthetics.

Opioid Analgesics

• Fentanyl (Sublimaze) is a potent analgesic and a Mu opioid receptor agonist with a shorter duration of action than other opioids.
• High IV doses can cause chest wall rigidity and prolong post-operative respiratory depression.
• Remifentanil (Ultiva) is an extremely short-acting opioid that is rapidly metabolized by esterases in blood and muscle.
• Opioid analgesics have minimal cardiovascular effects, beneficial for patients with minimal circulatory reserve.
• Naloxone reverses the effects

Neuroleptanesthesia

• Neuroleptanesthesia is achieved through a combination of Fentanyl, droperidol (a neuroleptic related to haloperidol that acts as a Dopamine receptor blocker), and nitrous oxide.
• Droperidol is used to control nausea and vomiting but has no analgesic effect.
• N₂O often causes nausea and vomiting.