Anesthetic agents and adjuvants

General anesthetic agents

• Modern anesthetic practice is a classic example of
polypharmacy. The use of anesthetic drugs and their
dosage depends on various factors like body weight,
age, associate disease, site operation, intercurrent
therapy and drug history.
• It was a hitherto thought that general anesthetic agents
act at the cerebral neuronal cell membrane by
reversible binding of protein. But now experiments
have shown that there are specific receptor sites in the
cell membrane for gamma-hydroxy-butyric acid
(GABA) neurotransmitter, where the binding occurs.
Inhalational agents – general principles and
individual agents

• Inhalational agents are mainly used in anesthesia for maintenance

of anesthesia, for induction (especially in children) and also as a
sole agent for small procedures (especially ether).
• The best estimate for determining the potency of inhalational agents is
minimum alveolar concentration (MAC) which is defined as
minimum concentration of agent required to produce immobility in
50% of the subjects given noxious stimuli which is surgical (skin)
incision in human beings and tail clamping in rats. MAC95 (effect in
95% individuals) is usually 1.5 times of MAC50. So the agent with
minimum MAC will be most potent. MAC for different anesthetic
agents is different.
• Factors effecting MAC are age, temperature, barometric pressure,
anaemia, hypoxia, hypercarbia, alcohol, pregnancy, i.v. anesthetics,
local anesthetics, electrolytes.
Mechanism of action of inhaled agents

• Exact mechanism is not clear. There are number of theories

but the most acceptable theory is volume expansion or
fluidization theory. This states that inhalational agent
incorporates in lipid molecules of membrane (hydrophobic
action) causing fluidization of membrane blocking the ion
channels, especially sodium channel thus preventing
depolarization. Potassium and chloride conductance is
increased causing hyperpolarization.
• Other possible mechanisms are: inhalational anesthetics
interact directly with cellular proteins altering the enzymes;
anesthetics enhance the GABA mediated inhibition of CNS.
Site of action of inhalational agents

• These agents mainly act on CNS and dorsal horn cells of spinal cord.
• Mainly acts on synapses (in high doses can block axonal transmission).
• Acts as both pre- and postsynaptic level.
• Meyer Overton Rule: anesthetic potency is directly proportional to
lipid solubility.
• Inhalational agents delivered by vaporizer and mixed with carrier gas
(oxygen + nitrous oxide or oxygen alone) reach the patient’s alveoli,
from where it is taken up by blood and reach different tissues. The
concentration in brain determines the effect inhalational
agent. There are a number of factors effecting the uptake and
distribution: inspired concentration (Fi), alveolar concentration (Fa),
blood gas partition coefficient (B/G coff.), cardiac output, alveolar to
venous partial pressure, ventilation.
Uptake and distribution of inhalational
agents
• Inhalational agents delivered by vaporizer and mixed with carrier gas
(oxygen + nitrous oxide or oxygen alone) reach the patient’s alveoli, from
where it is taken up by blood and reach different tissues. The
concentration in brain determines the effect inhalational agent.
There are a number of factors effecting the uptake and distribution: inspired
concentration (Fi), alveolar concentration (Fa), blood gas partition
coefficient (B/G coff.), cardiac output, alveolar to venous partial pressure,
ventilation.
• Inspired concentration (FI): It depends upon the concentration
delivered by vaporizer, fresh gas flow, absorption by breathing circuit and
most importantly ventilation.
• Alveolar concentration (FA): It depends on inspired concentration and
uptake by blood. After equilibrium is achieved between brain and blood,
alveolar concentration reflects the concentration in brain. In tissues with
high perfusion like brain, the equilibrium is achieved in 4 to 8 minutes.
• Blood gas partition coefficient (B/G coff.): This is the most important factor
determining the uptake of agent and s the speed of induction and recovery. Agents with
low blood gas partition coefficient will have high alveolar concentration e.g., nitrous
oxide with blood gas partition coefficient of 0.47 means concentration (or partial
pressure) in blood is 47% of alveolar concentration. Since alveolar concentration
determines the induction and recovery, induction and recovery will be fast with agent
with less B/G partition coefficient and induction and recovery will be slower with
agents with high B/G partition coefficients.
• Cardiac output: Increasing cardiac output increases the uptake, decreasing the
alveolar concentration and induction is delayed. In low cardiac output states like shock,
the agents with high B/G partition coefficient can achieve dangerously high alveolar
concentration if inspired concentrations are not decreased but the alveolar
concentration of agents with low B/G coefficient will not be so high. That is why in
shock, agents with low B/G coefficient like nitrous oxide are safe.
• Alveolar to venous partial pressure: Once the tissues have taken up the agent the
gradient reverses and the agent enters the venous system and carried back to lungs. If
venous partial pressure is high uptake will be less.
• Ventilation: Increasing ventilation will increase the alveolar concentration of agents
with B/G coefficient (increased uptake will decrease alveolar concentration so more
room for inspired agent). Agent with low B/G coefficient are least affected with
increasing ventilation.
 
Concentration effect, second gas effect and diffusion hypoxia

• Concentration effect: If an anesthetic agent is given in high

concentration the alveolar concentration rises much more than
expected and also the rate of rise is high. This is seen with nitrous
oxide which is given in high concentration (66%).
• Second gas effect: If another agent like halothane is given along with
nitrous oxide, by the same mechanism of concentration effect by which
nitrous oxide increases its own concentration of halothane (or any
other agent) is also increased (one agent effecting the concentration of
other).
• Diffusion hypoxia (Fink effect): Towards the end of surgery when
nitrous oxide is closed the gradient reverses and the nitrous oxide from
blood gushes in alveoli replacing the oxygen from there causing
hypoxia. To avoid this diffusion hypoxia 100% oxygen should be given
for 5 minutes after discontinuing nitrous oxide.
Recovery from inhalational agents
• It depends on lowering the concentration of agen
in brain tissue. So recovery depends on
pulmonaryexhalation of agent, metabolismand
excretion, transcutaneous loss (seen only with
nitrous oxide).Recovery is rapid with agents with
low B/G coefficient.
• Anesthetic teether: It is ratio of delivered
concentration to alveolar concentration (FD/FA).
Metabolism
• All inhalational agents undergo oxidation
(dealkylation or dehagonation) in liver (halothane
also undergoes reduction) by cytochrome P450
enzymes in Phase I reactions and by conjugation
in Phase II reactions.
• All enzyme inducers like isoniazid, phenytoin,
phenobarbital, ethanol, diazepam increases the
metabolism of inhalational agents.
• Nitrous oxide does not undergo any metabolism in
human body
Systemic effects, side effects and toxicity
of inhalational agents

• Respiratory system:
Ventilation – Initially all agents decrease the tidal volume and increase the
frequency but with increasing dose, frequency also decreases, so finally decreasing
minute volume (except ether). Maximum depression of respiration is seen with
halothane. Ventilatory responses (to increased CO2 and hypoxia) are blunted with
inhalational agents (except nitrous oxide and minimum with ether). Maximum
inhibition to ventilator response is with halothane.
Bronchial muscles – All inhalational agents are bronchodilators with maximum
bronchodilatation with halothane, that is why halothane is the agent of choice for
asthmatic patients. Bronchodilatation is not because of direct effect of agents on
bronchial muscles but by inhibition of central pathways for bronchoconstriction.
Effects on hypoxic pulmonary vasoconstriction (HPV): All agents blunt HPV
response; maximally inhibited by halothane.
Effect on ciliary activity: All agents (except ether) inhibit the ciliary activity
thereby reducing capability of patient to cough out secretions in postoperative
period.
• Cardiovascular system: Nitrous oxide has negligible effect
on cardiovascular system.
Cardiac output: All agents decrease the cardiac output
(except ether and cyclopropane which maintain the output by
sympathetic stimulation). Cardiac output is also well
maintained with isoflurane (by reflex tachycardia). Maximum
decrease is seen with halothane.
Systemic vascular resistance (SVR): SVR is decreased by all
agents (except cyclopropane and ether). Maximum
hypotension is caused by isoflurane therefore is the
inhalational agent of choice for controlled hypotension.
Myocardial contractility: There is significant inhibition of
myocardial contractility with halothane.
Baroreceptor reflex: All protective cardiovascular responses
are blunted by inhalational agents (except ether), maximum
with halothane.
• Liver: All agents produce some degree of hepatotoxicity by
decreasing the blood supply to liver (indirect effect). Direct
hepatocellular damage is seen with halothane, chloroform,
methoxyflurane.
• Renal system: All inhalational agents depress renal function
by decreasing the renal blood flow. Direct renal toxicity has been
attributed to inorganic fluoride produced by fluorinated
compounds. Inhalational agents are fluroniated to decrease
their flammability). The nephrotoxicity produced by fluroniated
agents is vasopressin resistant polyuric renal failure.
• Haematopoetic system: Nitrous oxide interacts with vitamin
B12 and inhibits many pathways involved in one carbon moiety.
Nitrous oxide inhibits the enzyme methionine synthetase and
hence the production of thymidate and DNA formation. Due to
these effects nitrous oxide can produce megaloblastic and
aplastic anemia. These changes are seen only on prolonged
exposure.
• Spinal cord: Nitrous oxide by inhibiting the production of thymidate
can impair myelin formation which can lead to subacute degeneration of
spinal cord.
• Neuromuscular system: All inhalational agents produce some degree
of muscle relaxation (except nitrous oxide). Maximum relaxation is
produced by ether.
• Teratogenecity: Only some studies have shown increased incidence of
spontaneous abortions and congenital abnormalities in females who
underwent anesthesia during pregnancy and females chronically exposed
to inhalational agents (nitrous oxide), but exact data and conclusive
evidence to prove teratogenecity of inhalational agents is not yet
available.
• Analgesia: Inhalational agents have analgesic properties which is
maximum with trielene, moderate with ether, methoxyflurane. While
agents now a days in common use like isoflurane are not good analgesics.
• Metabolic: Hyperglycemia is seen with ether, cyclopropane,
choloroform. Hyperglycemia is because of the stimulation of sympathetic
system caused by these agents.
Individual agents

• Nitrous oxide (laughing gas, name given by Humpry

Davy). It was first prepared by Joseph Pristley in 1774.
• Halothane
• Isoflurane
• Enflurane
• Desflurane
• Sevoflurane
• Ether, fluroxene, ethyl chloride, methoxyflurane,
cyclopropane, trichloroethylene, chloroform – these
agents are no more in common use.
Intravenous agents

• Intravenous anesthetics are used in anesthesia

for: induction, for analgesia (opioids), as a
sole anesthetic agent for minor procedures,
for amnesia, (benzodiazepines), to blunt
cardiovascular response to intubation
(opioids), for sedation (benzodiazepines).
• Classification:
1.Barbiturates – Tiopental, Methohexital
2.Non barbiturates – Ketamine, Propofol,
Etomidate, Opioids, Benzodiazepines,
Phenotiazines
Thiopental
• It was discovered by Water and Lundy in 1934. It is ultrashort acting barbiturate. Chemically it is
sodium ethyl thiobarbiturate.
• pH -10.4 – highly alkaline
• Systemic effects:
1.CNS – unconscious is produced in 15 seconds but max depth is achieved in 60 seconds. Cerebral
oxygen consumption, cerebral metabolitic rate and intracranial tension are decreased. So it is
the agent of choice for cerebral protection. Anticonvulsant action, antanalgesic action (at
subanesthetic doses).
2.Cardiovascular system – it causes hypotension which is more because of venodilatation but
also because of different depression of vasomotor centre. It is also direct myocardial depressant.
3.Respiratory system – if a painful stimulus is given at inadequate depth, severe laryngospasm
and bronchospasm may occur. Transient apnea
4.Eye – thiopental decreases the intraocular pressure.
5.Pregnancy – it crosses the placental barrier and achieves high concentration in brain of fetus.
6.Kidney – it stimulates ADH action.
7.Thyroid – antithyroid activity
8.Muscular system – it is a poor muscle relaxant.
Thiopental - complications
• General:
1.Respiratory depression
2.Cardiovascular depression
3.Laryngospasm and bronchospasm
4.Hiccups
5.Allergic manifestations – from cutaneous rash, pruritus, severe
anaphylactic reaction.
6.Postoperative disorientation, vertigo.
• Local:
1.Perivenous (subcutaneous) and intramuscular injection – the high
alkanity leads to tissue necrosis and ulceration – so always use 2.5%
solution!
2.Inta-arterial injection – it leads to gangrene and loss of limb if not
diagnosed and managed timely.
Thiopental - contraindications
• Absolute:
1.Porphyria
2.History of previous anaphylaxis to thiopental.
• Relative:
1.Shock and hypotension
2.Patient with fixed cardiac output lesions – aortic stenosis.
3.Heart blocks
4.Patient with beta blockers
5.Uncontrolled hypertensives
6.Asthmatics
7.Inflammatory conditions in oral cavity
8.Dystrophia myotonica
9.Familial hypokalemic periodic paralysis
10.Hepatic disease
11.Renal disease – doses are reduced.
Propofol – 2 mg/kg
• Now a days very commonly used drug.
• It consists of a phenol ring with isopropyl group
attached. It is oil based preparation containing
soyabean oil, egg lecithin and glycerol. So
injection is painful!! The color of solution is milky
white and available in 1% and 2% concentration.
• Metabolism – metabolized in liver and excreted
via kidneys. Clearance rate is 10 times more rapid
than thiopental so recovery is rapid.
Propofol – systemic effects
• Cardiovascular system: hypotension is significant
and it also impairs baroreceptor response to
hypotension.
• Respiratory system: respiratory depression is more
severe and prolongated than thiopental.
• Cerebral: it is equally effective as thiopental for brain
protection. It is not anticonvulsant rather sometimes it
can produce muscle twitchings and myoclonic activity.
• Eye: reduces intraocular pressure.
• GIT: it is antiemetic.
• Immunologic: it is antipruritic.
Propofol - uses
• The agent of choice for day care surgery – early
induction, early and smooth recovery.
• The agent of choice for TIVA – along with
opioids (fentanyl or alfentanil).
• Propofol infusion is used to produce sedation in
ICU.
• Agent of choice for induction in susceptible
individuals for malignant hyperthermia.
Etomidate
• Not readily available.
• It is cardiovascular stable agent, no respiratory
depression.
• Side effects – adrenocortical suppression on long
term infusion; nausea and vomiting; high
incidence of myoclonus; injection is painful; high
incidence of thrombophlebitis; it can cause vitamin
C deficiency.
• Uses – i.v. anesthetic of choice for aneurysm
surgery and patients with cardiac disease.
Ketamine (Dissociative anesthesia)
• It was synthesized by Stevens in 1962 and first used in humans by
Domino and Corsen in 1965. It is very commonly used drug in
anesthesia.
• It is phencyclidine derivative.
• Onset of action in 30 to 60 seconds.
• Strong analgesic.
• Metabolized in liver to form norketamine and hydroxynorketamine.
Products are excreted in urine.
• Not a muscle relaxant.
• Site of action – primary site of action is thalamoneocortical projection.
Ketamine inhibits cortex (unconsciousness) and thalamus (analgesia)
and stimulates limbic system (emergence reaction and hallucinations).
It also acts on medullary reticular formation and spinal cord.
Ketamine – systemic effects
• It produces dissociative anesthesia – a state which dissociates the individual from
surroundings and himself, i.e., individual is in cataleptic state.
• CNS – increases brain oxygen consumption and metabolic rate, intracranial tension
is highly raised. Strong analgesic. Emergence reactions (vivid dreaming, illusions,
extracorporeal experiences like floating out of body, excitement, confusion, euphoria,
fear). Hallucinations – both auditory and visual. These hallucinations and emergence
reactions can be decreased by giving benzodiazepines along with ketamine.
• Cardiovascular system – ketamine stimulates sympathetic system causing
tachycardia and hypertension so it is intravenous anesthetic of choice for
shock.
• Respiratory system – it stimulates respiration (in children can cause respiratory
depression); it is potent bronchodilator; pharyngeal and laryngeal reflexes are
preserved; tracheobronchial and salivary secretions are increased.
• Eye – increases intraocular tension; pupils dilate moderately; nystagmus.
• GIT – increases intragastric pressure.
• Muscular system – increases muscle tone.
Ketamine – dose and contraindications
• It can be given i.v., i.m., oral, per rectal and intrathecally.
I.v. dose is 2mg/kg, i.m. dose is 5 to 10 mg/kg.
• Contraindications:
 Head injury.
 Patient with intracranial space occupying lesion.
 Eye injury or other ophthalmic pathology.
 Ischemic heart disease (it increases myocardial oxygen
demand).
 Vascular aneurysm (it causes hypertension).
 Patient with psychiatric diseases and drug addicts.
 Hypertensives.
Droperidol

• It is butyrophenne structurally related to haloperidol. It is dopamine

antagonist. It is a potent antiemtic and sedative. Rarely used in anesthesia as
a sole agent. Can be used as s premedicant.
• Side effects – hypotension and extrapyramidal reactions.
• It is used in combination with fentanyl to produce neuroleptanalgesia,
characterized by analgesia, sedation and variable amnesia.
• Uses of neuroleptanalgesia: as an induction agent (very rarely), as a
premedication, as sedation for certain minor procedures, surgeries associated
with high incidence of postoperative nausea and vomiting like middle ear
surgery, neurosurgical procedures.
• Neurleptanesthesia – if a inhalational agent especially nitrous oxide
added to the droperidol and fentanyl it constitutes neuroleptanesthesia
characterized by unconsciousness, analgesia and amnesia. The general
anesthesia produced by this method is somewhat similar to that produced by
ketamine.
Benzodiazpines
• BZ are used in anesthesia for:
Premedication - the aim is to reduce anxiety,
anterograde amnesia, to induce good sleep.
As adjunct to regional anesthesia.
As a sole agent to non painful procedures like
bronchoscopy, gastroscopy, etc.
As induction agent – rarely used.
To prevent hallucinations by ketamine.
To control convulsions.
Benzodiazepines – mechanism of action,
systematic effects and metabolism
• BZ’s bind to specific receptors in brain which facilitates GABA receptor
binding which in turn increases the membrane conductance to chloride ion
causing hyperpolarization of membrane.
• Systematic effects:
CNS – mainly acts on reticular activating system and amygdala (limbic
system) producing sedation, anxiolysis and amnesia. Also acts on medulla
producing muscle relaxation and on cerebellum producing ataxia. BZ’s are
anticonvulsants, they are not analgetics. Reduces cerebral metabolic rate,
brain oxygen consumption and intracranial pressure.
Respiratory system – in higher doses BZ’s cause respiratory depression.
Cardiovascular system – minimal reduction in blood pressure, heart
rate and cardiac input.
• Metabolism – they are metabolized in liver. Metabolites are excreted in gut
and urine. There is significant enterohepatic recirculation.
Benzodiazpines
• Diazepam
• Midazolam
• Lorazepam
• BZ antagonist – Flumazenil a competitive
antagonist at BZ receptors. It antagonizes
hypnosis, respiratory depression and sedation
but amnesia is minimally reversed. Onset of
action is within 1 to 3 minutes.
Opioids
Uses in aneshtesia
• Mainly used for analgesia – intraoperative and postoperative.
• For premedication.
• As an inducing agent (requires very high doses so rarely used for
induction).
• Blunting cardiovascular response to intubation. Fentanyl is most
commonly used.
• For day care surgery (Propofol + Alfentanil – combination of choice).
• Sedation in ICU.
• Painless labor (Fentanyl + Bupivacain by epidural catether).
• Pulmonary edema (Morphine is agent of choice).
• Intraoperative myocardial ischemia (Morphine is used).
• To abolish shivering (Pethidine and Tramadol).
Opioids - classification
Naturally occurring: Synthetic:
Semisynthetic:
 Morphine
 Butorphanol
 Codeine
 Heroin  Levorphanol
 Thebaine
 Dihydromorphone  Pentazocine
 Oxymorphone  Pethidine
 Pentamorphone  Fentanyl, Alfentanil,
Sufentanil, Remifentani
 Tramadol
 Buprenorphine
Opioid receptors
• Opioids act through specific receptors which are divided into 5
types: μ (mu), κ (kappa), δ (delta), σ (sigma), ε (epsilon).
• Μ (mu) receptors are most important receptors for action of
opioids. These are present mainly in periaqueductal grey matter,
lamina I and II of thalamus and midbrain.
• Based on receptor interaction opioids are classified as pure agonist,
mixed agonist and antagonists and pure antagonists.
• Pure agonists are agonist at all receptors with highest propensity for
μ receptors.
• Agonist-antagonist are agonist at κ and δ and antagonist at μ
receptors, except buprenorphine which is agonist at μ receptors at
lower dose and becomes antagonist at μ receptor at higher dosage.
• Pure antagonist are antagonist at all receptors.
Opioids – mechanism of action
• Supraspinal – opioids bind with receptors in
rostroventral region od medulla and causes
stimulation of off cells present there, thereby
blocking nociceptive stimuli transmission.
• At spinal level – they act in substantia
gelatinosa of dorsal horn cells and inhibit the
release of excitatory transmitters.
Systemic effects
(morphine as prototype)
• Cardiovascular system – hypotension, bradycardia, shifting of blood
from pulmonary to systemic circulation.
• Respiratory system – opioids inhibit the respiration, both volume and
rate are decreased. Respiratory depression is the usual cause of death in
morphine poisoning. Opioids inhibit the ventilator response to hypoxia and
hypercarbia. Bronchi: causes bronchoconstriction by releasing histamine.
Inhibits airway and tracheal reflex that is why opioids are used to attenuate
the cardiovascular response (tachycardia, hypertension) to intubation and
laryngoscopy and is used in cough syrups (Codeine).
• CNS – Analgesia – visceral pain relieved better than somatic pain. Sedation.
Intracranial tension – opioids are cerebral vasodilators so increases
intracranial tension although cerebral oxygen consumption is decreased.
Stimulation of chemoreceptor trigger zone causes nausea and vomiting.
Mood changes, mental clouding. Inhibits temperature regulating centers
causing hypothermia.
Systemic effects
• Muscular system - opioids can cause muscle rigidity which can sometimes be so
severe in thoracic muscles that hypoxia occurs (Wooden chest syndrome). This is
relieved by muscle relaxants. Muscle rigidity is most commonly seen with fentanyl.
• Endocrine system – decreased ACTH, FSH, LH and cortisol synthesis. Increased
ADH, GH, prolactin synthesis.
• GIT – Opioids inhibit the gut motility and decrease the gastric emptying causing
constipation and there is no tolerance to constipation.
• Biliary tract – causes constriction of sphincter of Oddi, increasing biliary duct
pressure.
• Eye – causes miosis and there is no tolerance to this action.
• Renal – relaxes urinary bladder causing urinary retention.
• Dependence – it is both physical and psychological
• Tolerance – tolerance is seen to all actions of opioids except constipation and miosis
and tolerance is manly pharmacodynamics.
• Morphine can be given by i.v., i.m., s.c., p.o., p.r., transcutaneous,
intratracheal and epidural routes. Dose – 0.1 to 0.2 mg/kg
Pethidine (Meperidine, Lydol)
• It is an atropine congener. One tenth potent than morphine.
• Has also got local analgesic properties.
• Action on smooth muscle is less marked than morphine so
miosis, urinary retention and constipation are less than
morphine and that is why it can be safely used in biliary
colic.
• Histamine release is less than morphin.
• Additional side effect (atropine like effects) like blurred
vision, dry mouth, tachycardia are seen with pethidine.
• A metabolic product norpethidine can cause convulsions
and delirium.
Fentanyl
• It is more potent than morphine. Now a days very commonly used opioid
in anesthesia. The advantages of fentanyl are:
Rapid onset (2 to 5 mins) and rapid recovery (1 to 2 hours).
It can be given by i.m., i.v., transmucosal, transdermal, intrathecal and
epidural route.
Opioids of choice for hepatic and renal diseases.
Forms an excellent combination with propofol for TIVA.
With bupivacaine used epidurally for painless labour.
Better than morphine in preventing stress response to laryngoscopy,
intubation and surgery.
Systemic effects are similar to morphine except that it has negligible effect
on GIT and urine output.
Fentanyl can produce significant muscle rigidity.
Dose 2 to 5 μg/kg
Other opioid agonists
• Codeine is used for suppressing cough.
• Heroin has got the highest addiction potential.
• Methadone – mainly used in prevention of
opioid withdraw symptoms.
• Tramadol – it is a mixed compound which other
than stimulating opioid receptors also inhibits
neuronal norepinephrine uptake and serotonin
release. Respiratory depression is less than other
opioid agonists.
Agonist-antagonist drugs
• They are less prone for abuse. The aim of agonist-antagonist
compound is to produce a ceiling effect to respiratory depression
which means that after a certain level higher doses will not cause
further respiratory depression rather ventilation is further increased
because of antagonist effect at higher dose.
• Pentazocine – it is agonist at κ and δ receptors and antagonist at μ
receptors. Mainly acts on κ receptors at spinal level. It is 1/3 as potent
as morphine. Pentazocine stimulates sympathetic system so causes
tachycardia and hypertension. It depresses respiration but has ceiling
effect on respiratory depression. Biliary spasm and constipation are
less severe. Less nausea and vomiting. Addiction potential is less than
morphine. Pentazocine is used for sequential analgesic anesthesia. In
this technique pentazocine is administrated after fentanyl is given in
moderate doses.
Opioid antagonists
Naloxone
• It is a pure opioid antagonist acting on all opioid receptors with maximum
propensity for μ receptors. It reverses the actions of all opioids.
• Onset of action is rapid (1 to 2 mins) and duration of acton is 30 to 60
mins but half life of long acting narcotics is longer so chances of
renarcotization are always there. Naloxone is metabolized in liver.
• Systemic effects: Cardiovascular effects – Naloxone causes
sympathetic stimulation and can produce sever hypertension and
tachycardia. CNS – Naloxone has no specific analeptic effect. Cerebral
metabolic rate, oxygen consumption and blood flow is increased and so
there is increased intracranial tension.
• Contraindications (relative) – myocardial ischemia, intracranial lesions,
pheochromocytoma.
• Dose – 40 to 80 μg i.v. to a max of 400 μg. Naloxone can be given
intratrachealy.
Endogenous opioids
• Enkephalins
• Endorphins
• Dynorphins
• Enkephalins and endorphins mediate
supraspinal control of pain while dynorphins
mediate pain control at spinal level.
• Enkephalins are responsible for producing
acupuncture mediated analgesia.