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Hypnosis (unconsciousness)
Amnesia
Analgesia
Immobility/decreased muscle tone
(relaxation of skeletal muscle)
Inhibition of nociceptive reflexes
Reduction of certain autonomic reflexes
(gag reflex, tachycardia, vasoconstriction)
Intravenous Anesthetics
Ideal Intravenous anesthetic
Water-soluble, no pain on injection
no release of histamine…….
Pharmacological Principles
IV anesthetics completely bypasses the process of
absorption, because the drug is placed directly into the
bloodstream.
Highly perfused organs (vessel rich) including the brain
take up disproportionately large amount of drug
compared to less perfused areas (the muscle, fat, and
vessel-poor groups).
Drugs bound to plasma proteins are unavailable for
uptake by an organ.
Pharmacological Principles
After the highly perfused organs are saturated
during initial distribution, the greater mass of the
less perfused organs continue to take up drug
from the bloodstream.
As plasma concentration falls, some drug leaves
the highly perfused organs to maintain
equilibrium.
This redistribution from the vessel-rich group is
responsible for termination of effect of many
anesthetic drugs.
Pharmacological Principles
Compartment Model
Offers a simple way to characterize the distribution of
drugs in the body
Can be conceptualized as a group of tissues that posses
similar pharmacokinetics (Central and peripheral
compartments)
Distribution phase vs. Elimination phase
Intravenous Anesthetics
Barbiturates (Thiopental, methohexital)
Depress the reticular activating system located in the
brain stem that controls several vital functions,
consciousness
Affect the function of nerve synapses not axons
Suppress transmission of excitatory neurotransmitter
and enhance transmission of inhibitory
neurotransmitter
They are barbituric acid derivatives, substitution at the
number 5 carbon determines hypnotic potency and
anticonvulsant activity
Barbituric Acid
Intravenous Anesthetics
Methohexital
Methylated Oxybarbiturate.
Methylation of an active barbiturate at position 1 (Methohexital)
will give a drug with increased incidence of excitatory side
effects.
Methohexital is excreted in the feces
Methohexital) may induce involuntary skeletal muscle
contractions.
Dosage : IV 1-2 mg/kg
Intravenous Anesthetics
Absorption (Barbiturates)
Administered mostly IV for induction in adults and children
Rectal thiopental or methohexital in children
IM pentobarbital or secobarbital for premedication
Distribution
Duration of action of highly lipid soluble is determined by
redistribution (Thiopental)
Thiopental is highly protein bound (80%)
Maximum brain uptake within 30s
Induction dose depends on body weight and age
The elimination half-life from 3-12 h
Intravenous Anesthetics
Biotransformation
Mainly hepatic oxidation to inactive water-soluble metabolites
Anaesthetic properties
It is a sedative hypnotic used in the induction and maintenance
of anesthesia.
Induction is achieved in one brain arm circulation time i.e. 15
seconds. Consciousness is regained after 2-8 minutes due to
redistribution.
Elimination half life is 2-4 hrs, recovery is rapid & associated
with less hangover than thiopentone.
It has no analgesic property.
It is not a muscle relaxant.
Metabolism
It is chiefly eliminated by hepatic
conjugation to inactive metabolites which
are excreted by the kidney.
Elimination half life is 2-4 hrs ,recovery is
rapid.
All metabolic products of propofol are
inactive.
Systemic Effects
Cardiovascular
Hypotension produced is significant & it also impairs baroreceptor
response to hypotension.
Respiratory
The first respiratory disturbance after a bolus dose of propofol is a
profound fall in tidal volume leading to apnea in many patients.
There has been no accompanying cough or hiccup and otherwise
anesthesia is smooth.
Induces bronchodilatation.
Cerebral
It also has cerebral protection effect by decreasing cerebral oxygen
consumption, cerebral metabolic rate and intracranial pressure.
It is also a reliable amnestic agent.
It can sometimes produce muscle twitching & myoclonic activity.
Eye
Reduces intraocular pressure.
GIT
It is anti-emetic
Immunologic
It is antipruritic.
DOSAGE AND ADMINISTRATION
Healthy Adults Less Than 55 Years of Age: 40 mg
every 10 seconds until induction onset (2 to 2.5 mg/kg).
Elderly, Debilitated, or ASA III/IV Patients: 20 mg
every 10 seconds until induction onset (1 to 1.5 mg/kg).
Cardiac Anesthesia: 20 mg every 10 seconds until
induction onset (0.5 to 1.5 mg/kg).
Neurosurgical Patients: 20 mg every 10 seconds until
induction onset (1 to 2 mg/kg).
Pediatric - healthy, 3 years of age or older: 2.5 to 3.5
mg/kg administered over 20-30 seconds.
Indications
Because of its early induction, early & smooth
recovery, inactive metabolites & anti emetic
effects it is,the IV agent of choice for day care
surgery.
Along with opioids (alfentanil or remifentanil ) it
is the agent of choice for total intravenous
anaesthesia (TIVA).
Propofol injection can be used to produce
sedation in ICU patients.
Agent of choice for induction in susceptible
individuals for malignant hyperthermia.
Advantages of propofol over
thiopentone
Rapid and smooth recovery.
Completely eliminated from body in 4
hours so patient is ambulatory early.
Anti-emetic.
Anti-pruritic.
Bronchodilator.
Disadvantages
Apnea is more profound and longer.
Hypotension is more severe.
Injection is painful.
Solution is less stable (6 hrs).
Chances of sepsis with contaminated solution is high.
Myoclonic activity.
Sexual fantasies and hallucination.
Expensive than thiopentone.
Allergic reactions in individuals who are allergic to egg lecitin.
Propofol addiction has also been reported.
Propofol infusion syndrome: It is very rare but is a lethal
complication. Usually seen if infusion is continued for more than
48 hrs & is much more common in children.
Etomidate
Etomidate is a carboxylated imidazole
derivative. Etomidate has anesthetic and
amnetic properties, but has no analgesic
properties
Uses
Etomidate is commonly used in the
emergency setting as part of a rapid sequence
induction to induce anesthesia or for
conscious sedation. It is often used in this
setting since it has a rapid onset of action and
a low cardiovascular risk profile, and
therefore is less likely to cause a significant
drop in blood pressure than other induction
agents
It is the agent IV anesthetic agent of choice
for aneurysm surgery & patients with cardiac
disease.
Dosage
The anaesthetic induction dose for adult
humans is 0.3 mg/kg intravenously, with a
typical dose being 20 mg. In common with all
induction agents, etomidate causes loss of
consciousness after one arm-brain
circulation time.
At the typical dose, anesthesia is induced for
about 5–10 minutes even though the half-life
of drug metabolism is approximately 75
minutes. This is because etomidate is
redistributed from the plasma to other
tissues.
Metabolism
Respiratory
Minimal effect on the ventilatory drive
Potent bronchodilator
Intravenous Anesthetics
Cerebral
Increase cerebral oxygen consumption, cerebral blood flow and
intracranial pressure
Myoclonic activity is associated increased subcortical electrical
activity
Undesirable psychotomimetic effects (illusions, disturbing,
dreams and delirium)
Have analgesic effects
Intravenous Anesthetics
Benzodiazepines
Interact with specific receptors in the CNS mainly in the cortex
Binding to receptors enhances the inhibitory effects of various
neurotransmitters (GABA)
Flumazenil is a specific benzodiazepine-receptor antagonist that
effectively reverses most of the CNS effect
Chemical structure includes a benzene ring and a 7-member
diazepine ring, substitution ay various positions on these rings
affect potency and biotransformation
Agent Use Route Dose
Premedication Oral 0.2-0.5 mg/kg upto 15
mg
Sedation IV 0.04-0.2 mg/kg
Diazepam
Induction of hypnosis IV 0.3-0.6 mg/kg
Excretion
Metabolites are excreted mainly in the urine
Respiratory
Depresses ventilatory response to CO2
Name derived from Poppy juice (opium), first obtained from the
capsules of the unripe oriental Poppy seed (papaver somniferum),
of which Morphine is the principal active ingredient.
Opioid receptor activation inhibits the presynaptic release and post-synaptic response
to excitatory neurotransmitters (e.g. Acetyl-choline, substance P).
Intravenous Anesthetics
Opioids classification
1- Agonists:
- Strong: Morphine, pethidine, Methadone, Fentanyl,…
- Moderate: Codeine, Oxycodone, Hydrocodone
- Weak: Propoxyphene
Endocrine:
More effective than inhalational anesthetics in blocking the
stress response to surgical stimulation.
Ophthalmic: Miosis.
Intravenous Anesthetics
Concurrent use of:
MAOI drugs Respiratory arrest, hypertension or
Hypotension, coma and Hyperpyrexia. (esp. with
Meperidine).
Other Hypnotic and sedative drugs synergism in sedative,
cardiovascular, and respiratory effects.
Erythromycin: impairment of alfentanyl biotransformation.
Intravenous Anesthetics
Dexmedetomidine
Is a sedative medication used by intensive care units and
anesthesiologists, and is marketed under the brand name
Precedex
It is relatively unique in its ability to provide sedation without
causing respiratory depression
Its mechanism of action is agonism of alpha-2 receptors in
certain parts of the brain
It is the S-enantiomer of medetomidine
Has sedative, analgesic, sympatholytic, and anxiolytic
effects
Intravenous Anesthetics
Reduces the volatile anesthetic, sedative and analgesic
requirements of the patient without causing significant
respiratory depression
Effective treatment for the dangerous cardiovascular symptoms
of cocaine intoxication and overdose
Has an opiod sparing effect
The recommended dosage is 1 µg/kg IV over 10 min
Maintenance infusion rate of 0.2-0.7 µg/kg/hr
Metabolized in the liver and its metabolite is eliminated in the
urine
Side effects include bradycardia, heart block and hypotension
Summary of Intravenous Anesthetic Agents
Drug Speed of Induction Main Unwanted Notes
and Recovery Effects
Thiopental Fast (accumulation occurs, Cardiovascular and Used as induction agent declining.
giving slow recovery) respiratory depression Decreases cerebral blood flow and
Hangover O2 consumption.
Etomidate Fast onset, fairly fast Excitatory effects during Less cardiovascular and
recovery induction and recovery, respiratory depression than with
Adrenocortical suppression thiopental, Causes pain at injection
site
Propofol Fast onset, very fast Cardiovascular and Most common induction agent.
recovery respiratory depression. Pain Rapidly metabolized; possible to
at injection site. use as continuous infusion.
Ketamine Slow onset, after-effects Psychotomimetic effects Produces good analgesia and
common during recovery following recovery, amnesia
Postoperative nausea,
vomiting and salivation
Midazolam Slower than other agents Little respiratory or cardiovascular
depression
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