INTRAVENOUS

ANESTHETICS
JRRMMC PGI Regalado, Trina Elisse T..
 IDEAL IV ANESTHETIC
PHARMACODYNAMIC / PHYSIOCHEMICAL PROPERTIES
PHARMACOKINETIC PROPERTY
 Hypnosis and amnesia  Water soluble
 Rapid onset  Stable formulation,
 Rapid metabolism to inactive nonpyrogenic
metabolites  Nonirritating : painless on IV
 Minimal cardiovascular and injection
respiratory depression  Small volume needed for
 No histamine release or induction
hypersensitivity reactions  Inexpensive to prepare
 Nontoxic, nonmutagenic, formulate
noncarcinogenic  Antimicrobial preparation
 No untoward neurologic effects
(seizure, myoclonus,
antanalgesia, nurotoxicity)
 Other beneficial effects :
analgesia, antiemetic,
neuroprotection,
cardioprotection
 MODE OF ACTION

• Most IV anesthetic agents produce

CNS depression by action on the γ-
aminobutyric acid A (GABA-A)
chloride ion channel receptor.

• GABA is the principal inhibitory

neurotransmitter in the CNS.

• When endogenous GABA binds to

these receptor it causes a
conformational change which opens
chloride channels allowing them to
flow into the neuron making it more
negative or hyperpolarized and thus
less likely generate an action
potential.
 MODE OF ACTION

• GABA A has allosteric binding sites for

other substances known as GABA
modulators which can increase GABA
effect or decrease GABA effect.

• Propofol
• Etomidate
• Benzodiazepines
• Ketamine – effect mediated by NMDA receptor
• NMDA are loc in the spinal cord and are crucial in pain
modulation and processing
• When neurotransimitter glutamate bind to NMDA receptor,
it causes inflow of extracellular calcium in the postsynaptic
neuron which then activates a series of signalling molecules
causing the pain signal to increase and fire more frequently
• They selective inhibit NMDA receptors which ultimately
prevents or decreases neurotransmission of pain
• Also affect 2 pore domain K channels. They promote
opening of these channels leading to increase potassium
efflux producing in a reduction in neuronal excitability
which contributes to its sedative effect.
 PHARMACOKINETICS
• The onset and duration of effect are the most
important pharmacokinetic properties of IV
anesthetic agents when used for induction of
anesthesia.

• In general, the commonly used IV induction agents

have a rapid onset of action and short clinical
duration, with the short clinical duration resulting
from redistribution of the drug from the brain to
other tissue sites (e.g.,muscle, fat).
PHARMACOKINETICS
 CONTEXT SENSITIVE HALF-TIME
- The time to achieve a 50% reduction in concentration after stopping a
continuous infusion
- important factor in the suitability of a drug for use as maintenance
anesthetic.
 DRUGS
USED IN
INTRAVENOUS
ANESTHETIA
 PROPOFOL
MOA Potentiates inhibitory effect of GABA through binding
to GABA-A receptor
Predictable context-sensitive half-time across various
comorbidities
CNS depressant, neuroprotective, anticonvulsant,
decreases CMR02, CBF, ICP
Used for EEG burst suppression
Cardiovascular : significant decreases in systemic vascular
resistance, stroke volume and cardiac output
Pulmonary : respiratory depressant and potent
bronchodilator
Clinical General anesthesia induction and maintenance
Use Commonly used for TIVA
Conscious deep sedation, including out of operative room
settings
ICU sedation
PONV prophylaxis
Safe for patients with malignant hyperthermia
 PROPOFOL
Side Bradycardia
Effects Vasodilation
Hypotension
Negative inotropism
Pain at injection site
Anterograde amnesia
Administra Induction of general anesthesia by bolus injection of 1–2.5
tion mg/kg IV (loss of consciousness is commonly achieved at
corresponding blood concentration close to 3 μg/kg)

Maintenance of general anesthesia with propofol can

commonly be achieved with infusions between 100 and
200 μg/kg/min.

Prevention of postoperative nausea and vomiting (PONV)

- Maintenance infusions as low as 10 μg/kg/min and blood
concentration levels as low as 350 ng/mL

For sedation in ICU and also in OPD surgeries (Typical

 ETOMIDATE
MOA Potentiates inhibitory effect of GABA through binding
to GABA-A receptor
Clinical General anesthesia
Use
Side Pain on injection site, myoclonus, postoperative nausea
Effects and vomiting,
Adrenocortical suppression (on prolonged administration)
– inhibits the activity of enzyme 11B-hydroxylase and
prevents conversion of cholesterol to cortisol
Notes Hemodynamically stable induction medication
Frequently use as anesthsia in cardiac operating rooms
because e it has minimal effect on MAP, PA, PAWP, CVP,
SV, SVR, PVR
Used in trauma patients that are hemodynamically
unstable and are often hypovolemic
Has minimal effect on MAP, therefore CPP is either
maintained or increased
At high doses it s oftem associated with escitatory spikes
 KETAMINE
MOA Blocks excitation by glutamate at NMDA receptors / NMDA receptor
antagonist
Ketamine binds preferentially to the NMDA receptors on inhibitory
interneurons in the cortex, limbic system, and hippocampus that
promote uncoordinated increase in neuronal activity and an active
EEG pattern, and produce unconsciousness
Clinical Use Anesthesia – IV and IM
Analgesia
Chronic Pain
Depression
Bronchodilator
Procedural sedation, especially in pediatric and burn patients
low dose ketamine has an opiate sparing effect in mamagement of
acute pain
Side Effects Cardiovascular stimulation, hypertension, increased ICP, emergence
delirium (post-op effects : disorientationm, hallucination, excitation,
nystagmus, increased salivation)
Trance-like cataleptic unconscious state “dissociative anesthesia”

Notes Phencylidine (PCP; angel dust) derivative – remarkable analgesic and

anesthetic effects but fewer psychomimmetic effects
Cardiovascular stability – increases heart rate and blood pressure
Mild respiratory depression
 DEXMEDETOMIDINE
MOA Alpha 2 adrenergic agonist

Clinical Sedation with minimal respiratory depression

Use Mimics normal sleep pattern on electroencephalogram
Provides analgesia at the spinal cord level
Intensive care unit sedation in mechanically ventilated
patients
Procedural sedation
Pediatrics : preoperative anxiolysis and emergence
delirium

Side Bradycardia, hypotension

Effects
Administra Bolus 0.5-1 ug/kg over 15 mins followed by 0.3-0.7
tion ug/kg/hr infusion
 BENZODIZEPINES (MIDAZOLAM)
MOA Potentiates inhibitory effect of GABA through binding
to GABA-A receptor
Minimal respiratory depression
Minimal cardiovascular depression
Large therapeutic window
Reversible with Flumazenil

Clinical Anesthetic induction, preoperative sedation

Use Acute anxiety, panic attacks
Anxiolysis
Anterograde amnesia
Sedation
Induction anesthesia, hemodynamically stable
Anticonvuslant

Side Anterograde amnesia, decreased psychomotor skills,

Effects unwanted daytime sedation, dependence liability,
postoperative respiratory depression
Notes
 BARBITURATES (THIOPENTAL)
MOA Potentiates inhibitory effect of GABA through binding
to GABA-A receptor
Prolonged context-sensitive half-time
CNS depressant, neuroprotective, anticonvulsant,
decreases CMRO2, CBF, ICP
EEG burs suppression (thiopental)
Cardio : decreases MAP, venous vascular tone, and CO
Pulmo : Dose-dependent respiratory depression, does not
cause bronchodilation
Clinical Anesthesia induction
Use Methohexital use for sedation, premedication and
electroconvulsive therapy
Barbiturate coma (thiopental)
Side Extension of CNS depressant actions, tolerance, acute
Effects intermittent porphyria
Notes
 REFERENCES
• Clinical Anesthesia 8th edition by Paul G. Barash
• Applied Therapeutics : The Clinical Use of Drugs 10th edition
by Koda – Kimble and Young et.al.
• Basic and Clinical Pharmcacology 12th edition by Katzung et.al