INTRAVENOUSANESTHESIA

Intravenous Anesthetics

widely used to facilitate rapid induction of anesthesia or to provide sedation during monitored anesthesia care (MAC)

NON-OPIOID IV ANESTHETICS

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Induction of anesthesiaMaintenance of anesthesia Sedation Antiemetic

PROPOFOL

PROPOFOL

Acts through potentiation of the chloride current through the -aminobutryric acid Type A (GABA-A) receptor complex

2,6 diisopropylphenol Alkyl phenol with HYPNOTIC properties Usually contains:

10% soybean oil 2.25% glycerol 1.2% lecithin

Milky-white Slightly viscous pH ~ 7 Rapidly metabolized in the liver Excreted through the kidneys

PROPOFOL

Cardiovascular EffectsVasodilation systemic blood pressure (SBP) is more

pronouncedExacerbates hypotensive effectProfound bradycardia and asystole

PROPOFOL

Respiratory EffectsPotent respiratory depressant >>

produces apnea post-inductionReduction in tidal volume and respiratory

rateReduces upper airway reflexes >>

Hence, the use of laryngeal mask airwayDecreases incidence of wheezing and

tracheal intubation among healthy and asthmatic patients

PROPOFOL

BARBITURATES

ThiopentalMethohexital

Barbituric acid

BARBITURATES Induction of Anesthesia

NMBDs are often administered shortly after the barbiturate to produce skeletal muscle relaxation

Thiopental + Succinylcholine: Classic drug regimen for rapid sequence induction of anesthesia

Neuroprotection

BARBITURATES

Lacks hypnotic effect

Formulated as sodium salts mixed with anhydrous sodium carbonate

After reconstitution with water and NSS, the solution is alkaline with pH >10 prevents bacterial growth and helps increase the shelf-life

BARBITURATES Central Nervous System Effects

Sedation to general anesthesia in induction doses

No analgesic effect (reduces the pain threshold)

Potent cerebral vasoconstrictor

Decrease CBF, CBV, ICP

Useful in management of patient with space-occupying intracranial lesions

BARBITURATESCardiovascular System EffectsDecreases BP VasodilationBarbiturate-induced depression of the medullary vasomotor center and decreased sympathetic nervous system outflow from the CNS

BARBITURATESRespiratory System Effects Depresses the respiration >> leads

to decreased minute ventilationthrough reduced tidal volume and RR.

Induction doses induces transient apnea

Decreases ventilatory response to hypercapnia and hypoxia

BENZODIAZEPINES

Midazolam

Lorazepam

Diazepam

Flumazenil

Preoperative medication Intravenous sedation Intravenous induction of anesthesia

Suppression of seizure activity

BENZODIAZEPINES

BENZODIAZEPINES

Activation of GABAA receptor complex and enhancement of GABA-mediated chloride currents leads to hyperpolarization of neurons and reduced excitability

Spectrum of EFFECTS: Sedative-hypnotic Amnestic Used to treat seizure Anxiolysis Mediated through the

-subunit of the GABA receptors

Mediated through the

1-subunit of the GABA receptors

BENZODIAZEPINES

BENZODIAZEPINES

Highly lipid soluble Rapid onset of action Metabolism in the liver through microsomal oxidation, N-dealkylation and aliphatic hydroxylation or glucuronide conjugation

Midazolam has the shortest context-sensitive half-time, which makes it the only one that is suitable for continuous infusion

KETAMINE

KETAMINE

Induction and Maintenance of Anesthesia

Analgesia (CS and neuraxial anesthesia)

KETAMINE

- Phencyclidine derivative

- Produces significant analgesia

- Known as dissociative anesthesia -patients eyes remain open with a slow nystagmus gaze (cataleptic gaze)

- Partially water-soluble, but highly lipophilic

KETAMINE Lacrimation and salivation are increased and

premedication with an anticholinergic is indicated to limit the effect

EMERGENCE reactions:

Vivid colorful dreams

Hallucinations

Out-of body experience

Increased and distorted visual, tactile, and auditory sensation

Associated with fear and confusion

ETOMIDATE

Carboxylated imidazole derivative

IV anesthetic with hypnotic but notanalgesic properties and with minimal hemodynamic effects

Alternative to Propofol and Barbiturates

ETOMIDATE

EFFECT on ENDOCRINE SYSTEM

Causes adrenocortical suppression by producing a dose-dependent 11 -hydroxylase, an enzyme necessary for the conversion of cholesterol to cortisol

Suppression last 4 to 8 hours

DEXMEDETOMIDATE

Short-term sedation

Adjunct to general anesthesia to provide sedation

DEXMEDETOMIDATE

Active S-enantiomer of medetomidine

Used in veterinary medicine

Highly selective 2-adrenergic agonist

DEXMEDETOMIDATE

Hypnosis results from structure of 2receptor in the locus ceruleus and the analgesic effect at the level of spinal cord

OPIOID IV ANESTHETICS

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OPIOIDS

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Receptor Clinical Effect Agonists

Mu

Supraspinal analgesia (-1)Respiratory depression (-2)Physical dependenceMuscle rigidity

MorphineMet-enkephalinBeta-endorphinFentanyl

KappaSedationSpinal analgesia

MorphineNalbuphineButorphanolDynorphinOxycodone

DeltaAnalgesiaBehavioralEpiletogenic

Leu-enkephalinBeta-endorphin

SigmaDysphoriaHallucinationsRespiratory stimulation

PentazocineNalorphineKetamine

Inhibits the presynaptic release and postsynaptic response to excitatory neurotransmitters (acetylchloine, substance P) from neurons.

Transmission of pain impulses can be interrupted at the dorsal horn of the spinal cord

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OPIOIDS

OPIOIDS

AbsorptionFentanyl - low molecular weight

and high lipid solubility (rapid onset = 10 min, but short duration of action)

Morphine - low lipid solubility (slows passage across the blood brain barrier)

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OPIOIDS

Excretion

Eliminated via kidneys (10% via biliary excretion)

Morphine 3-glucuronide & morphine 6-glucuronide (morphine metabolites) that could lead to narcosis and ventilatory depression in renal failure

Normeperidine (meperidine end product) has an excitatory effect on the CNS (myoclonic activity and seizures)

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OPIOIDS

Cardiovascular effects

Meperidine - increases heart rate

Morphine, fentanyl, sufentanil, remifentanil, alfentanil - bradycardia (vagus-mediated)

Meperidine & morphine - decrease BP and systemic vascular resistance (histamine release)

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OPIOIDS

Respiratory effects

depress ventilation and respiratory rate

Morphine and meperidine -histamine induced bronchospasm

Fentanyl, sufentanil and alfentanil -chest wall rigidity 36

OPIOIDS Cerebral effects

reduce cerebral oxygen consumption, cerebral blood flow and intracranial pressure

nausea and vomiting are due to stimulation of the medullary chemoreceptor trigger zone

Meperidine - decreases shivering 37

OPIOIDS Gastrointestinal

reduces peristalsis by slowing the gastric emptying time

Biliary colic is due to opioid-induced contraction of the sphincter of Oddi

Constipation due to decrease GI motility

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OPIOIDS

Endocrine

blocks the release of hormones (catecholamines, antidiuretic hormone and cortisol) during surgical stimulation

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"Anesthetics have been used for 160 years, and how they work is one of the greatest mysteries of neuroscience,"

-James Sonner,

M.D. (UCSF)

Thank You &Good Morning!