Intravenous anesthetics are fast-acting agents used for sedation and induction, with propofol being the most common due to its properties and pharmacokinetics. Ketamine offers dissociative anesthesia and is effective in cardiovascular patients, while midazolam is favored for its stability and utility in critical care settings. The document discusses the mechanisms, benefits, and side effects of these anesthetics, alongside dosage recommendations for various applications.

1. IV INDUCTION AGENTS
DR.DEVASHISH YADAV

2. DEFINITION
Intravenous anesthetics are a group of fast acting
compounds that are used to induce a state of impaired
awareness or complete sedation.

3. CLASSIFICATION
The commonest drugs currently in use can be classified according
to their chemical structure and include:
Barbiturates– THIOPENTOL, METHOHEXITOL
Phenols – PROPOFOL
Imidazoles –ETOMIDATE
Phencyclidines– KETAMINE
Benzodiazepines– MIDAZOLAM, DIAZEPAM, LORAZEPAM

4. WHAT IS THE USES OF IV
ANESTHETIC AGENT?
• Induction : most commonly used iv anaesthetic for induction is
propofol. Ketamine is used only in specific situation.
• For analgesia (largely opioids) As a sole anaesthetic agent for
minor procedures, eg: ketamine or propofol+ fentanyl
• For amnesia (mainly benzodiazepines)
• For sedation (mainly benzodiazepines

5. PROPOFOL
 Since its introduction in the 1970 propofol has become the
most used IV hypnotic today.
 Chemical name:-2,6-diisopropylphenol

6. MECHANISM OF ACTION
 Propofol relatively selective modulator of GABA receptors
 Propofol decreases the rate of dissociation of inhibitory neurotransmitter
 thereby increasing the duration of GABA activated opening of chloride
channel
 resulting hyperpolarisation of cell membranes.

7. PHYSIOCHEMICAL CHARACTERSTICS
 Propofol is one of a group of alkylphenols. It
is viscous , milky white substance , a result of
small lipid droplets in solution.
 The formulation most used is that of 1%
propofol, 10% soyabean oil and 1.2% purified
egg phospholipid added as a emulsifier with
2.25% of glycerol as a tonicity adjusting agent
and sodium hydroxide to change the pH.
 For preventing microbial growth EDTA was
added for its bacteriostatic activities.

8. PHARMACOKINETICS
• Propofol( 2,6-diisopropylphenol) is oxidized to
1,4 Di isopropyl quinoline in the liver.
• Propofol is known as CYP3A4 inhibitor.
• Most important extrahepatic site for propofol
metabolism is the kidney.
• Renal metabolism of propofol up to 30%
• propofol clearance the pharmacokinetics of
propofol may be altered by various factors like
gender, weight, pre-existing disease, age and
concomitant medication
Propofol & 1,4 Di isopropyl quinol
Glucuronic acid
1. Propfol-1- Glucuronide
2. Quinol-1- Glucuronide
3. Quinol-4- Glucuronide
Excreted by Kidney

9. PHARMACODYNAMICS
• EFFECT ON THE CENTRAL NERVOUS SYSTEM
• The hypnotic action of propofol is mostly mediated by enhancing gamma-
aminobutyric acid(GABA) induced chloride current through its binding to beta
subunit of GABA A receptor.
• Propofol hypnosis related with reduced activity in the thalamic and precuneus
region.
• A sense of well being in patient related to increase in dopamine concentration in
nucleus accumbance

10. • Propofol’s antiemetic action is due to decrease in serotonin levels it produces in the
area postrema.
• Propofol decreases ICP in patient with normal or increased ICP and acutely reduces
intraocular pressure by 30-40 %
• Propofol may suppress seizures via GABA agonism, inhibition of NMDA receptors ,
and modulation of slow calcium ion channel.
• Neuronal protective due to attenuation of changes in adenosine , calcium, sodium
and potassium caused by hypoxic injury and its antioxidant action by inhibiting lipid
peroxidation.

11. EFFECT ON CARDIOVASCULAR SYSTEM
• The most prominent effect of propofol is a decrease in arterial blood pressure during
induction of anesthesia.
• Induction dose of 2 to 2.5 mg/kg produce a 25% to 40% reduction of SBP and similar
changes are seen in MAP and DBP.
•
• Also associated with a decrease in cardiac output/ cardiac index (+-15%),stroke volume
index(+-20%) and systemic vascular resistance (15-25%). Left ventricular stroke work index
also decreased (30%)
• Heart rate dose not change significantly.
• Propofol has a minimal direct effect in SA node function or on atrioventricular and
accessory pathway conduction.

12. EFFECT ON THE RESPIRATORY SYSTEM
• Apnea occurs after administration of an induction dose of propofol; the
incidence and duration of apnea depend on dose, speed of injection
and concomitant premedication.
• Duration of prolonged apnea (30sec) is increased further by addition of
an opiate , either as premedication or just before induction of
anesthesia.
• Propofol induce bronchodilation in COPD patient.
• Due to depression of upper airway reflexes it is preferred for surgeries
done under LMA without muscle relaxant.

13. OTHER EFFECTS
Propofol in the emulsion formulation does not alter hepatic,
hematologic or fibrinolytic function
At infusion rate of 1mg/kg/h provide excellent antiemetic action even in
anticancer chemotherapy.
Relives cholestatic pruritis
Propofol decreases polymorphonuclear leucocytes chemotaxis but not
phagocytosis and killing except staph aureus and e.coli
May be related to pancreatitis and hypertriglyceridemia.

14. USES AND DOSES
Induction of general
anaesthesia
1 -2.5 mg/kg iv , dose
reduced with increasing age
Maintenance of general
anaesthesia
50-150 micro gm/kg/min IV
combined with N2O or an
opiate
Sedation 25- 75 microgram/kg/min iv
Antiemetic action 10- 20 mg IV , can repeat
every 5 -10 min or start
infusion of 10 micro
gram/kg/min
• It is IV agent of choice for day care
surgery.
• Along with opioids it is the agent of
choice for total intravenous
anesthesia (TIVA).
• Propofol infusion can be used to
produce sedation in ICU.
• It is agent of choice in a patient with
malignant hyperthermia

15. Advantages Disadvantages
1. Rapid and smooth
recovery
1. Apnea is more profound
and longer
2. Completely eliminated
from body in 4 hours.
2. Hypotension
3. Antiemetic 3. Injection is painful
4. Antipruritic 4. Chance of sepsis with
contaminated solution are
high
5. Bronchodilator 5. Myoclonic activity may
occur
6. Allergic reactions
7. Thrombophlebitis

16. PROPOFOL INFUSION SYNDROME
• Propofol infusion syndrome is a rare but lethal syndrome associated with propofol
infusion at 4 mg/kg/hr or more for 48 hours or longer.
• it is most commonly seen in children.
• Clinical features include acute refractory bradycardia leading to asystole associated
with metabolic acidosis(base deficit >10 mmol/L-1), rhabdomyolysis, hyperlipidaemia
and enlarged or fatty liver.
• Other feature include cardiomyopathy, hyperkalaemia and lipemia
• Risk factors poor oxygen delivery, sepsis, cerebral injury and large dosage

17. Popstar died due to
overdose of Propofol that
recently brought the
danger of propofol
misuse.

18. KETAMINE
• Ketamine(ketalar) produces dissociative anesthesia
rather than generalized depression of the CNS through
antagonistic action at the phencyclidine site of the N-
methyl-D aspartate receptor(NMDA-R) .
• The S(+) isomers is 3 to 4 times more potent as an
analgesic with a faster clearance and recovery and with
fewer psychomimetic side effects.

19. PHYSIOCHEMICAL CHARACTERSTICS
 It has a lipid solubility 5 to 10 times that of
thiopental .
 Its bioavailability is 93% after parental
administration but only 20% after oral use,
due to its high first pass metabolism.

20. PHARMACOKINETICS
 Ketamine is metabolized by hepatic
microsomal enzyme.
 The pharmacokinetics of the two
isomers is different . S(+) ketamine has a
larger elimination clearance and larger
volume of distribution than R(-)
ketamine.
Ketamine
N-
Demethylation
water soluble glucuronide derivatives
Hydroxy Nor ketamine
Excreted in urine
Nor ketamine
Hydroxylation
Conjugation

21. PHARMACODYNAMICS
• EFFECT ON THE CENTRAL NERVOUS SYSTEM
• Ketamine produces dose related unconsciousness and analgesia.
• Inhibition of NMDR mediated glutaminergic input to GABAergic system
leading to a changing excitatory activity in the cortex and limbic system
that is the end result in unconsciousness.
• Ketamine acts at multiple receptors including the NMDA-Receptor,
opioid receptors and mono-aminergic receptor

22. • The anesthetized state has been termed Dissociative anesthesia because
patient who receive ketamine alone appear to be in a cataleptic state , in
contrast with other states of anesthesia that resemble normal sleep.
• Patients anaesthetized with ketamine have profound analgesia but keep their
eyes open and maintain many reflexes like corneal reflex ,cough reflex and
swallow reflexes all may be presents but should not be assumed to be
protective.
• After ketamine administration pupils dilate moderately and nystagmus
occurs

23. • Lacrimation and salivation are common and increased muscle tone often with
coordinated but seemingly purposeless movements of the arms, legs, trunk and
head.
• There is no recall of surgery or anesthesia but amnesia is not as prominent with
ketamine as with the benzodiazepines.
• It crosses the blood- brain barrier rapidly and has an onset of action within 30 to 60
seconds of administration. So maximal effect occurs in about 1 minutes
• The duration of ketamine anesthesia after single iv dose of 2mg/kg is 10-15
minutes and full orientation to person ,place and time occurs within 15-30 minutes
• Ketamine provide important postoperative analgesia.

24. • Because of its excitatory CNS effects- Ketamine increases cerebral
metabolism, cerebral blood flow and ICP.
• Ketamine similar to other phencyclidines produces undesirable
psychological reaction which occur during awakening from ketamine
anesthesia and are termed Emergence reaction – common
manifestation are vivid dreaming , extracorporeal experiences( sense
of floating out of body), illusion ( misinterpretation of a real, external
sensory experience).
• These incident of dreaming and illusion are often associated with
excitement, confusion, euphoria and fear. They occur in the first hour
of emergence and usually abate within one to several hour.
• antidepressant effect – dose 0.5mg/kg given as 40 minutes infusion.
This results in dramatic mood changes within a day often lasting for 3
to 12 days.

25. EFFECT ON RESPIRSTORY SYSTEM
• Ketamine has minimal effects on the central respiratory drive.
• There can be transient (1-3 minutes) decrease in minute ventilation
after the bolus administration of an induction dose of ketamine (2
mg/kg iv).
• Ketamine is a bronchial smooth muscle relaxant so it is given in
patient with reactive airway disease

26. EFFECT ON CARDIOVASCULAR SYSTEM
• Ketamine increases arterial blood pressure, heart rate and cardiac
output.
• Cardio depression occurs after large dose of ketamine or after repeated
administration when presynaptic catecholamine stores become depleted
• Cardiovascular stimulation after small dose ketamine infusion is
characteristics by tachycardia, systemic and pulmonary hypertension,
increases in cardiac output and myocardial oxygen consumption

27. USES & DOSES:-
• It is used for premedication.
• Small dose of ketamine use in
preventive analgesia for the
treatment of prevention of
opiate tolerance and
hyperalgesia also used in
treatment of acute and chronic
pain
Induction of general
anaesthesia
0.5-2 mg/kg iv or 4-6 mg/kg
IM
Maintenance of general
anaesthesia
0.5-1 mg/kg iv with N2O
50% in O2.
Sedation & Analgesia 0.2-0.8 mg/kg iv over2-3
min or 2-4 mg/kg im
Preventive analgesia 0.15-0.25 mg/kg iv

28. INDUCTION AND MAINTAINANCE OF
ANAESTHESIA
• Due to cardiovascular stimulatory effects ketamine is used in cardiovascular
patient suffering from hypovolemia, hemorrhagic shock or cardiovascular
depression in sepsis, cardiac tamponade and restrictive pericarditis .
• Ketamine also is used in congenital heart disease especially patient with right to
left shunting exists. Ketamine is used as one of the constituent of multimodal
analgesia.
• In mechanical ventilated patients ketamine retains the response of CBF to carbon
dioxide which makes it useful in head injured patient because of its potential
neuroprotective effect

29. SIDE EFFECTS AND CONTRAINDICATION
• Ketamine increases IOP so it is contraindicated in patients with an open eye injury.
• Contraindicated in patients with vascular aneurysms because of the possible sudden
change in arterial blood pressure.
• Psychiatric disease such as schizophrenia
• Contraindicated as the sole anesthetic in patient with ischemic heart disease
• Increases ICP and breathing spontaneously ,ketamine should be used with caution
because it can increases ICP and has been reported to cause apnea

30. MIDAZOLAM
• Water soluble Benzodiazepine with an IMIDAZOLE ring in its structure, that accounts
for stability in aqueous solutions & rapid metabolism
• The solubility of midazolam is pH dependent.
• At pH 3.5, imidazole ring is open--- WATER SOLUBLE
• At body pH imidazole ring closes LIPID SOLUBLE-- RAPID ONSET
• Availability : 5 ml vials containing 1 mg/ml & 1 ml ampoules containing 5 mg/ml
• It doesn’t cause pain on injection

31. • Mechanism of action : Activation of Chloride channels of GABA
receptors enhancing inhibitory synaptic transmission
• Onset of action : 30-60 seconds
• Duration of action : 1 hour when given i.v.
• Elimination : metabolized by CYP3A4 and CYP3A5 to 1 hydroxymethyl
midazolam and 4 hydroxy midazolam Metabolites rapidly conjugated
and excreted in the urine
• Pharmacokinetics affected by obesity , clearance not affected but
elimination half life prolonged( because of adipose tissue)
• metabolites are little concern with normal hepatic and renal function.
In patient with renal impairment …they can cause profound sedation.

32. • After oral ingestion midazolam is absorbed completely and peak plasma
concentration achieved in 30-80 min . The bioavailability is less then 50% due
to significant first pass metabolism.
• After IV administration midazolam rapidly distributed, with distribution half
life of 6-15 min.
• REMIMAZOLAM , ultrashort acting GABAa receptor agonist , may be vey
useful in future anaesthetic practice due to its properties like greater depth of
sedation , rapid recovery and no relation between body weight and clearance
• As it is not metabolised by CYP enzymes which decreases the chances of
significant drug interaction.

33. USES AND DOSES
• Popular drug for sedating
critically ill patients in the ICU
as it is cardio stable.
• Also used as an
ANTICONVULSANT
• Anti tumorigenic properties in
certain type of cancer in
supraclinical doses.
• Post operative nausea vomiting
Induction of anesthesia 0.05-0.15 mg/Kg
intravenously
Commonly used to
supplement to regional
anesthesia for
SEDATION (0.5-1 mg
repeated)
PREMEDICATION Midazolam is given in a
dose of 7.5 to 15 mg
ORALLY
Maintenance 0.05 mg/kg or 1
mcg/kg/min
Sedation 0.5- 1 mg repeated

34. EFFECTS ON BODY
• CNS : Dose dependent depression of the CNS. Hypnotic , sedative,
anxiolytic , amnesic ,anticonvulsant , and muscle relaxant.
• CVS : Relatively CARDIOSTABLE Doesn’t affect Heart rate and Blood
pressure much.
• Respiratory System : dose related respiratory system depression by 2
ways
• The have effect on the muscular tone leading to an increased risk of
upper airway obstruction
Or they may flatten the response of respiratory curve to carbon dioxide
• In addition sedative dose of midazolam depress the hypoxic ventilatory
response

35. SIDE EFFECTS
• The most significant side effects with midazolam is respiratory
depression
• May produce undesirable degree or prolonged interval of
postoperative amnesia ,sedation and rarely, respiratory
depression.
• These residual effects can be reversed with flumazenil

36. THIOPENTONE SODIUM
 Ultra-short acting barbiturate
 Available as Hygroscopic, pale YELLOW powder Ampoules
commonly contain- 500mg of sodium thiopental + 6% sodium
carbonate in an inert atmosphere of nitrogen. ( to prevent
precipitation of insoluble acid form of barbiturate by
atmospheric CO2)
 Reconstituted with 20ml of water - 2.5% solution (25mg/ml)
with a pH of 10.8.
 The alkaline solution bacteriostatis and safe to keep for 48hrs

37. • Mechanism of action :
• Mainly through interaction with inhibitory
neurotransmitter – GABA in CNS
• Binds to GABAa receptor and mimics the action
of GABA by increasing chloride conductance
through ion channel this causes
hyperpolarisation of cell membrane and
increases the threshold of excitability of the post
synaptic neuron.

38. PHARMACODYNAMICS
• Cause loss of consciousness, amnesia and respiratory and cardiovascular
depression known as general anaesthesia .
• Peak respiratory depression and maximum depression of minute ventilation
after delivery of thiopental occurs 1-1.5 minutes after administration.
• Usually reversed within 15 minutes
• The ventilation pattern with thiopental induction described as double apnea
that is initial apnoea of few seconds after drug administration which is
followed by a more prolonged period of apnoea that is of 25 seconds seen
in 20% cases.

39. • Cardiac output decreases by following mechanism
• Direct negative inotropic action
• Decreased ventricular filling
• Transient decreased sympathetic outflow
• Increases in heart rate probably results from the baroreceptor
mediated sympathetic reflex stimulation of heart in response to
decreases in output and pressure
• Cardiac index and MAP unchanged or reduced

40. USES AND DOSES
• Always given intravenously (i.v)
• Can be given through rectal route for
sedation, but the absorption is erratic.
• For induction of anesthesia : 3-4
mg/Kg in adults. Children require
slightly higher doses (5-6 mg/Kg) due
to larger volume of distribution (Vd)

41. • Status Epilepticus – Single bolus of 3-5
mg/Kg to treat an episode of
convulsion f/b INFUSION ( 3-5
mg/Kg/hr) in status epilepticus
refractory to conventional treatment.
• Cerebral protection – Bolus of 3
mg/Kg followed by an infusion of 5-6
mg/Kg/hr to protect ischemic brain in
neurosurgical patients

42. Onset of action : One arm-brain circulation time (15-20 sec)
Elimination : Metabolized by LIVER & excreted by KIDNEY
Clearance : 3.4 ml/Kg/min
Volume of distribution : 2.5 liters/Kg

43. ADVERSE EFFECTS
Inadvertent intra-arterial injection of thiopentone – causes intense spasm of the
artery & therefore must be avoided. If occurs ( a. Stop further injection but keep
cannula in place). ( b. Inject saline into the cannula & flush it). ( c. Inject through same
cannula, preservative free LIGNOCAINE to reduce pain).
PAPAVERINE 40-80 mg to provide local vasodilatation, HEPARIN to prevent thrombus
formation.
Stellate ganglion block or brachial plexus block to achieve sympatholytic if intense pain
& if tissue perfusion in jeopardy
Others are garlic odor, allergic reaction, local tissue irritation and tissue necrosis
Urticarial rash in head trunk region and facial edema, hives, bronchospasm and
anaphylaxis

44. CONTRAINDICATION
Respiratory obstruction
Severe cardiovascular instability or shock
Status asthmatics
Porphyria
Without proper induction equipment and airway equipment

45.  Thiopentone should be avoided in patients with
sulpha drug allergy
 Extravasation of thiopentone at i.v. site can cause
local tissue destruction
 Thiopentone can be used safely in caesarean
deliveries
 But doses greater than 8 mg/Kg can cause
neonatal depression due to placental transfer of
the drug.