Pharmacology Viva Manual Prefinal PDF PR

PHARMACOLOGY VIVA FOR THE
ANAESTHESIA POSTGRADUATE
Editors
Dr Anitha Shenoy
Professor of Anaesthesiology
Kasturba Medical College, Manipal
and
Dr Umesh Goneppanavar
Associate Professor of Anaesthesiology
Kasturba Medical College, Manipal
1
CONTENTS
Serial Chapter Page No

No
1 Pharmacokinetics 3
2 Intravenous anaesthetics 6
3 Inhalation anaesthetics 16
4 Local anaesthetic agents 26
5 Neuromuscular blockers 33
6 Analgesics 43
7 Vasopressors and inotropes 57
8 Vasodilators 68
9 Antiarrhythmics 72
10 Anticholinergics 82
11 Anticoagulants and reversal 85
12 Diuretics 90
13 Bronchodilators 93
14 Antiemetics 100
15 Intravenous fluids 104
2
CERTAIN PHARMACOKINETIC CONCEPTS
3
VOLUME OF DISTRIBUTION (APPARENT):
This is the apparent volume into which a drug distributes itself after administration into the
body. It is called apparent because it is not a real volume but an apparent volume as deter-
mined by the plasma concentration achieved after a certain dose.
If the plasma concentration is measured shortly after administration, it is called initial volume
of distribution. If the plasma concentration is measured after a steady state is achieved, it is
called volume of distribution at steady state. If a drug is bound extensively to tissues, the
plasma concentration will be lower and the volume of distribution will be high.
VD = Dose / Plasma concentration
This concept is useful for calculating loading dose and steady state for infusion.
VD of around 5 L = Very high; low molecular weight drugs or drugs that bind to plasma proteins
extensively, e.g., heparin
5 – 14 L = Drugs that have low molecular weight but are hydrophilic, e.g., atracurium
> 14 L or more than total body water: Diffusion to intracellular fluid space = Alcohol
Drugs that bind strongly to tissues: Fentanyl = 280 L, Propofol = 560 L
PLASMA PROTEIN BINDING
Plasma proteins that bind drugs are mainly albumin and globulin
Alpha1acid glycoprotein: Binds basic drugs and specific carriers for cortisol and thyroxine.
DRUG AFFINITY FOR PLASMA PROTEINS

Predominantly bound to Predominantly bound to
albumin globulin
Basic Bilirubin Chlorpromazine
Fatty acids Lidocaine, Bupivacaine
Propranolol
Opioids
Acidic or neutral Salicylates
Warfarin
Clearance: The amount of plasma cleared of a drug/min. Low volume of distribution results in
higher elimination of the drug. This value is obtained as follows:
Dose / AUC (Area under curve). Infusion rate to achieve a steady state plasma concentration =
C x Cl
Half life: Time taken for plasma concentration to reduce to half its initial value after a bolus.
Context sensitive half life: The time taken for plasma concentration to reduce to half its initial
value after stopping an infusion.
4
ISOMERS
Structural isomerism: The molecular formula of two compounds are same but the arrange-
ment of atoms is different. They have different physical and chemical properties,
e.g., Enflurane and isoflurane
Dynamic isomerism (Tautomerism): These are two different forms of the same compound
due to rearrangement of an atom (H+ ion), e.g., Keto and enol forms of barbiturates
Stereoisomerism: Three dimensional spatial arrangement is different but sequence of atoms
is the same.
Enantiomers: These compounds have the same physical properties but rotate polarized
light in different directions. r and s ketamine, r and s etomidate, r and s epinephrine, dex-
medetomidine (nonsuperimposable or mirror images);
Geometric isomerism: This describes the orientation of functional groups around a double
bond or a ring structure. Cis and Trans atracurium
METABOLISM
First order kinetics: A constant fraction of the initial drug dose is eliminated from the body,
e.g., most anaesthetic drugs.
Zero order kinetics: A constant amount of the initial drug dose is eliminated from the body,
ethanol, phenytoin, barbiturates in high doses.
EXTRACTION RATIO: This is a measure of effectiveness of an organ to remove or process a

substance. Hepatic extraction is the proportion of the drug delivered to the liver and does not
appear in hepatic vein. ER – Ca – CV/Ca ; Hepatic clearance = HBF x ER
A high ER (> 0.7) results in hepatic clearance being highly dependent on liver blood flowbe-
cause most of the drug delivered is extracted. Enzyme activity, protein binding etc have less
influence on hepatic extraction, e.g., Propofol, etomidate, ketamine. Intermediate –
methohexital, midazolam (perfusion limited clearance)
A low ER (< 0.3) will have less dependency on blood flow but a high dependency on other fac-
tors, e.g., Thiopentone, diazepam, lorazepam (capacity dependent clearance).
In severe hepatic disease, metabolism and elimination of drugs with high extraction ratio are
affected. At the same time, drugs bound to protein (low extraction ratio) may be affected by
lower plasma protein concentration.
CREATININE CLEARANCE: Creatinine clearance ml/min = [140 – Age (y) x Weight (kg)]
72 x Serum creatinine (mg%)
OSMOLALITY AND OSMOLARITY: Osmolarity of a solution in terms of osmoles of solute per
litre of solution. Osmolality is concentration of a solution in terms of osmoles per kilogram of
solvent. Osmolality is independent of the temperature of the solution and the volume of the
solute. Hence, osmolality is the preferred term in clinical practice.
5
INTRAVENOUS ANAESTHETICS
6
PROPOFOL
Name: Propofol
Chemical composition: 2,6,di-iso-propylphenol. It has a pH of 7-8.5. It is available in emulsified
formulation containing 1% propofol, 10% soybean oil (provides lipid base), 2.25% glycerol
(maintains isotonicity), and 1.2% egg phosphatide (emulsifier).
Availability: It is available in 20 ml ampoules or vials containing 10 mg/ml. It is also available in
50 ml vials and also in a 2% concentration (Europe) for continuous infusions. Prefilled syringes
are available for total intravenous anaesthesia. These are marked with computer chips and are
meant for use with dedicated TIVA (total intravenous anaesthesia) pumps (e.g., Diginfusa®)
Propofol Lipuro, another preparation of propofol made available recently contains both long
and medium chain triglycerides in 1:1 ratio. This apparently reduces pain on injection.
Mechanism of action: It activates the chloride channels of GABAA (Gamma Amino Butyric Acid)
receptor thus enhancing inhibitory synaptic transmission. It also inhibits N-methyl D-aspartate
(NMDA) subtype of glutamate receptors.
Uses, dose and route: It is always given intravenously.
For induction of anaesthesia: 2 – 2.5 mg/kg IV in adults, 2.5 – 3 mg/kg in children.
Maintenance of anaesthesia: It may be used in a dose of 50 – 150 µg/kg/min to maintain
anaesthesia along with nitrous oxide or opiate.
Conscious sedation: Doses of 50 - 75 µg/kg/min (Ex: Awake craniotomy, dental extraction)
Sole anaesthetic for small procedures, e.g., cardioversion
Total intravenous anaesthesia: A plasma concentration of 2.5 to 8 µg/ml is required, de-
pending on concomitant use of nitrous oxide and opioids. TIVA can be given manually as
follows: 1 mg/kg bolus followed by 10 mg/kg/h for 10 min, 8 mg/kg/h for next 10 min and
6 mg/kg/h thereafter. A plasma concentration of propofol of 3 µg/ml may be expected.
It is very useful in day care anaesthesia and surgery.
It is useful in patients susceptible to malignant hyperthermia and porphyria.
Sedation of the critically ill patient in ICU: 1 – 3 mg/kg/h
As an anticonvulsant
It may also be used as an antipruritic and antiemetic (10 – 20 mg boluses every 5-10 min or
10 µg/kg/min perioperatively.
May be used for the treatment of bronchial asthma, bronchospasm, laryngospasm and hy-
pertensive responses to intubation / extubation (by deepening anaesthesia).
Onset: One arm-brain circulation time (15 – 20 s)
Duration: 3 – 5 minutes when given IV
Half life: t1/2 α = 2-5 min; t1/2 β = 20 – 50 min; t1/2 γ = 200 – 500 min;
α half life denotes time taken to redistribute the drug from central compartment to peripheral
tissues. β-half-life denotes redistribution of the drug from the muscle group to less vascular
tissues. -half life denotes elimination of the drug from the body. The patient wakens from an-
aesthesia when the plasma concentration reduces at the end of alpha half life even though it
is not eliminated from the body.
Context sensitive half time: Approximately 10 minutes when infused for less than 3 hours and
less than 40 minutes when infused for up to 8 hours.
Elimination: It is metabolized by conjugation to glucuronide and sulphate by liver. It also un-

dergoes extrahepatic metabolism in the kidney and lungs (30%).
7
Effects on the body:
Central nervous system (CNS): It produces dose-dependent depression of the CNS. Induction of
anaesthesia is usually heralded by loss of verbal contact rather than loss of eyelash reflex. It
may be used as an anticonvulsant. It reduces the cerebral metabolic rate, reduces cerebral
blood flow through autoregulation and thus reduces intracranial pressure and intraocular
pressure. However, it may reduce cerebral perfusion pressure by producing greater reduction
in mean arterial pressure than intracranial pressure. It may cause some involuntary move-
ments during induction.
Cardiovascular system: It causes hypotension due to peripheral vasodilatation. The change in
heart rate is unpredictable. Propofol completely obtunds the baroreceptor reflex responses.
Respiratory system: It may cause transient apnoea. It obtunds the airway reflexes well. It does
not increase airway secretions. Helps in achieving good intubating conditions even with
smaller doses of muscle relaxants.
Gastrointestinal system: It has antiemetic properties.
Adverse effects: Hypotension, allergic reactions to egg protein. Propofol causes pain on injec-
tion and to reduce it, lignocaine (20 mg to be added to 20 ml) is usually added to this solution
before injection. Other measures that can help reduce pain on injection of propofol are storing
the propofol at 4°C until it is ready for use, choosing a large vein and a small size intravenous
cannula, rapid injection, pretreatment with lidocaine, aspirating blood into propofol syringe
prior to injection, use of new propofol—‘propofol lipuro’. This is an emulsion of both long and
medium chain triglycerides in a ratio of 1:1 which helps reduce the proportion of free propofol
in the aqueous phase.
Caution: To be used with caution in patients who are hypovolaemic. Propofol being a lipid so-
lution is susceptible to growth of micro-organisms. Hence, care should be taken while handling
these solutions, especially when given as infusions. The tubing and any unused portions of pro-
pofol injectable emulsion should be discarded after 12 hours because it contains no preserva-
tives and is capable of supporting growth of microorganisms.
PROPOFOL INFUSION SYNDROME

Propofol is not recommended for prolonged infusion in small children and infants. It has been
known to cause metabolic acidosis (> 10 mmol/L), hyperkalaemia, rhabdomyolysis, renal fail-
ure, hepatomegaly, cardiac failure, hyperlipidaemia and asystole. This has been known to
occur when propofol is used in excess of 4 mg/kg/h for greater than 48 h. This is called
‘propofol infusion syndrome’. It is hypothesised that propofol may interfere with mitochondrial
mechanisms. An early sign of cardiac instability with this syndrome is the development of right
bundle branch block and convex-curved (coved type) ST elevation in the right precordial leads.
Haemodialysis with cardiorespiratory support has been found to be effective.
8
THIOPENTONE
Name: Sodium thiopentone
Availability: Available as yellow amorphous powder in vials containing 500 mg and 1000 mg. It
also contains 6% anhydrous sodium carbonate and is maintained in an atmosphere of nitrogen
to prevent reaction with carbon dioxide. It is diluted in saline or water (not Ringer lactate or
any acidic solution as it can precipitate). Thiopentone is bacteriostatic in nature. pH of thio-
pentone when reconstituted with saline is 10.8. It is an ultra short acting barbiturate.
Mechanism of action: It activates the chloride channels of GABA receptor thus enhancing in-
hibitory synaptic transmission.
Uses, dose and route: It is always given intravenously. It may be administered by rectal route
for sedation but the absorption is erratic. This route of administration is not used any more as
better drugs are available for sedation.
For induction of anaesthesia: 4 - 5 mg/kg IV in adults. Children require slightly higher doses
(5- 6 mg/kg) due to larger volume of distribution.
Status epilepticus: A single bolus of 3-5 mg/kg may be used to treat an episode of convul-
sion followed by an infusion (3-5 mg/kg/h) is necessary in status epilepticus refractory to
conventional treatment.
Cerebral protection: It may be used as a bolus of 3 mg/kg followed by an infusion (5-6 mg/
kg/h) to protect ischaemic brain in neurosurgery although varied dosage regimens to main-
tain burst suppression are present in the literature.
Duration: Half life: t1/2 α = 10 min; t1/2 β = 45 min; t1/2 γ = 6 – 20 hours; Even though the
patient may seem to wake up as the plasma level reduces due to redistribution, ‘street-fitness’
takes a much longer time than propofol due to its longer elimination half-life.
Elimination: It is metabolised by liver
Central nervous system (CNS): It produces dose-dependent depression of the CNS. Induction of
anaesthesia is usually heralded by loss of eyelash reflex. It reduces the cerebral metabolic rate,
reduces cerebral blood flow through autoregulation and thus reduces intracranial pressure. It
may be used as an anticonvulsant. It is an ‘antanalgesic’ at subanaesthetic doses as it de-
creases the threshold to pain.
Cardiovascular system: It causes hypotension due to peripheral vasodilatation (mainly venodi-
latation) and a reflex tachycardia. It also causes negative inotropic effect and should be used
with caution in patients with hypovolaemia and ischaemic heart disease. Baroreceptor reflex
response is not completely obtunded.
Respiratory system: It may cause transient apnoea. It does not obtund airway reflexes well and
if there is airway obstruction, laryngospasm and bronchospasm may occur in susceptible indi-
viduals (e.g., asthmatics).
Adverse effects:
Urticaria, anaphylactoid reactions, excessive salivation
Intra-arterial injection of thiopentone can cause thiopentone crystals to get deposited into ar-
terioles resulting in intense spasm of the artery, further it may cause destruction of the
vessel wall and ischaemia and this must be avoided.
9
If intra-arterial injection of thiopentone occurs, the following measures may be taken:
Stop the injection but keep the cannula in place.
Inject saline into the cannula and flush it.
Inject through the same cannula - preservative free lignocaine to reduce pain, papaver-
ine 40 to 80 mg to provide local vasodilatation, heparin to prevent thrombus formation.
May require continuous stellate ganglion block or a brachial plexus block to achieve
sympatholysis if there is intense pain and spasm, and tissue perfusion is in jeopardy.
Thiopentone should be avoided in patients with acute intermittent hepatic porphyria and
variegate porphyria as it can precipitate acute life threatening attacks. Acute intermittent
porphyria (AIP) is an autosomal dominant disease that results from defects in the enzyme
porphobilinogen-deaminase. In AIP, the porphyrin precursors, porphobilinogen and amino-
levulinic acid (ALA), accumulate. The predominant problem appears to be neurologic dam-
age that leads to peripheral and autonomic neuropathies and psychiatric manifestations.
The sequence of events in attacks usually is (1) abdominal pain, (2) psychiatric symptoms,
such as hysteria, and (3) peripheral neuropathies, mainly motor neuropathies. AIP patients
may have central nervous system signs consisting of seizures, mental status changes, corti-
cal blindness, and coma. Barbiturates cause increased activity of cytochrome P450 and
stimulate heme synthesis.
Safe anaesthetic plan for a patient with porphyria : A total intravenous anaesthesia (TIVA)
technique. Premedication—midazolam; Propofol—Induction agent; Fentanyl—analgesic;
Any of the current generation relaxants (vecuronium, rocuronium, atracurium, cis-
atracurium) and reversal drugs. (Should we avoid inhalation anaesthetics? - YES)
It should also be avoided in patients known to have sulpha drug allergy

Extravasation of thiopentone at IV site can cause local tissue destruction.
10
KETAMINE
Name: Ketamine hydrochloride
Availability: It is available in vials containing 10 mg/ml and 50 mg/ml. Preservative-free keta-
mine is available for use with central neuraxis block. The commercial preparation available is a
racemic mixture of S and R-enantiomers (mirror images – nonsuperimposable). S-ketamine (5
times more potent than the racemic mix) has much less adverse effects and is now made avail-
able in the pure form. pH 4.5. Caution about preservatives: benzalconium chloride (allergic
tendency) or chlorobutanol (neurotoxic).
Mechanism of action: It inhibits the NMDA receptors which have been activated by gluta-
mate, an excitatory neurotransmitter. It also inhibits serotonin and muscarinic receptors. It is
an agonist of mu type of opioid receptors.
Uses, dose and route: It may be given by various routes; intravenously, intramuscularly, orally,
intranasally, epidurally.
For induction of anaesthesia: 1 - 2 mg/kg IV. It is particularly useful in the induction of anaes-
thesia in patients with asthma due to its bronchodilatory effect. It is also useful in patients
with tetralogy of Fallot, where it maintains systemic vascular resistance and reduces the
right to left shunt. It is also useful for induction of anaesthesia in hypovolaemic patients.
For analgesia: 0.5 mg/kg IV. This is particularly useful as a supplement to regional anaesthe-
sia, including obstetric anaesthesia.
Low dose ketamine for intra and postoperative analgesia: An initial bolus of 0.5 mg/kg of
ketamine followed by a continuous infusion of 3 µg/kg/min during surgery and 1.5 µg/kg/
min for 48 hours after surgery has been used successfully in total knee arthroplasty .
As a bronchodilator: It may be used to treat status asthmaticus along with other bronchodi-
lators (30-40 µg/kg/min)
As a premedicant: 3 – 5 mg/kg IM (onset 5 min), nasal – 3-6 mg/kg (5 min); oral – 3-10 mg/kg
(onset 20-45 min) or rectal 10 mg/kg.
As a sole anaesthetic for short procedures, which do not require muscle relaxation and do
not cause intense activation of reflexes. It may be used as an infusion in the dose of 15-45
µg/kg/min with 50-70% nitrous oxide and 30-90 µg/kg/min without nitrous oxide.
Preservative free ketamine has been used for epidural analgesia. However, it has not yet re-
ceived regulatory approval.
Points to remember with the use of ketamine:
Ketamine can produce hallucinations and an increase in secretions. Hence, administration of

intravenous ketamine should always be preceded by a benzodiazepine (to reduce hallucina-
tions) such as midazolam and an antisialogogue such as glycopyrrolate.
When ketamine is given intramuscularly for premedication, it may be mixed with glycopyr-
rolate to produce drying of secretions.
When ketamine is used orally for premedication, it should be mixed with atropine and not
glycopyrrolate. Glycopyrrolate is a quarternary ammonium compound and does not get ab-
sorbed from the gut.
Onset: More than one arm-brain circulation time (30 – 60 s) when given IV, 5 minutes when
given IM and 25 – 45 minutes when given orally.
11
Duration: 10 - 15 minutes when given IV. Half life: t1/2 α = 10-15 min; t1/2 γ = 2 – 3 hours
Elimination: It is metabolized by liver to norketamine which has 30% activity of ketamine. This
is then conjugated and gets eliminated in the urine.
Central nervous system (CNS): It has a biphasic action on the CNS. Ketamine produces dissocia-
tive anaesthesia resembling a cataleptic state. It causes functional and electrophysiological
dissociation of thalamocortical system (depressed) from the limbic system (stimulated). There
is intense analgesia and amnesia as the sensory impulses from the body do not reach the cor-
tex. It has been postulated that the psychic emergence reactions occur secondary to ketamine
-induced depression of auditory and visual relay nuclei, leading to misperception or misinter-
pretation of auditory and visual stimuli. It increases skeletal muscle tone. It increases the cere-
bral metabolic rate, increases cerebral blood flow through autoregulation and thus increases
intracranial pressure. It also increases intraocular pressure. However, in higher doses, it pro-
duces generalized depression of the central nervous system.
Cardiovascular system: It has a dual effect on the cardiovascular system. It indirectly stimu-
lates the sympathetic nervous system, releasing catecholamines causing hypertension and
tachycardia. In larger doses or in patients with suppressed sympathetic nervous system, it may
cause hypotension due to direct myocardial depression.
Respiratory system: It does not obtund airway reflexes but is a very good bronchodilator. It
also causes dose dependent respiratory depression.
Gastrointestinal system: It causes increased secretions, especially salivary and bronchial.
Adverse effects:
It causes hallucinations, also called emergence reactions which may be unpleasant in na-
ture and can last up to a week. Hence, a benzodiazepine such as midazolam must be given
before administration of ketamine.
It causes hypertension and tachycardia
It causes muscle rigidity
Caution: To be used with caution in patients with pulmonary hypertension or ischaemic heart
disease.
12
ETOMIDATE
Name: Etomidate hydrochloride
Availability: It is available in 10 ml ampoules containing 2 mg/ml. It is an imidazole derivative.
The solvent used is propylene glycol. It has a pH of 7.0.
Uses, dose and route: It is always given intravenously.
For induction of anaesthesia: 0.3 mg/kg IV.
Duration: 3 – 5 minutes when given IV.
Elimination: It is metabolised by liver.
Central nervous system (CNS): It produces dose-dependent depression of the CNS. Induc-
tion of anaesthesia is usually heralded by loss of eyelash reflex. It may produce some invol-
untary movements during induction.
Cardiovascular system: It is a very cardiostable agent and does not change blood pressure
or heart rate.
Respiratory system: It has no significant effect on respiratory system.
Gastrointestinal system: The use of etomidate is associated with increased incidence of
postoperative nausea and vomiting.
Main indication: It is mainly used in patients requiring cardiovascular stability at induction of
anaesthesia.
Adverse effects:
Injection of etomidate causes pain on injection. The incidence of thrombophlebitis is high
due to venous irritation as etomidate solution is highly osmolar (4600 mOsm/L). It is now
formulated in a lipid base to reduce this pain.
Etomidate is associated with suppression of steroidogenesis, particularly when used as infu-
sion. Temporary adrenocortical suppression, as measured by a reduced response to ACTH
stimulation, was documented for 6 hours postoperatively and returned to normal by 20
hours postoperatively. However, a single induction dose does not cause this phenomenon.
There have been a few reports on induction of pharmacological adrenal suppression even
with single dose of etomidate, especially in septic patients. The extent and duration of this
adrenal suppression is not clear. Infusion of etomidate is certainly not recommended. How-
ever, whether a single dose of etomidate is safe for rapid sequence intubation in septic pa-
tients or not is still controversial. If used, corticosteroid supplementation may be necessary
for up to 72 h after its administration.
13
MIDAZOLAM
Name: Midazolam hydrochloride

Availability: It is available in 5 ml vials containing 1 mg/ml and 1 ml ampules containing 5 mg/
ml. Preservative free midazolam in ampoules are also available. The solubility of midazolam is
pH-dependent. At a pH of 3.5, the imidazole ring is open and it is water-soluble. At body pH,
the imidazole ring closes and makes the molecule lipid-soluble.
Uses, dose and route: It is usually given intravenously. It may be administered by oral/
intranasal route for premedication in children to allow easy separation from parents.
For induction of anaesthesia: It may be used in a dose of 0.1 to 0.2 mg/kg intravenously for
induction.
For sedation: It is most commonly used to produce sedation during conscious sedation,
supplement to regional anaesthesia or as a premedicant.
For premedication: Midazolam is given in a dose of 0.5 mg/kg orally (or 0.2 mg/kg intrana-
sally) up to a maximum dose of 10 mg, to easily separate children from parents. This
should be possible in 15 to 30 minutes of administering the drug.
Sedation in ICU: It is a popular drug for sedating critically ill patients in the ICU as it has a
short context sensitive half-life and is cardiostable.
Anticonvulsant: It may be given as bolus or infusion as an anticonvulsant.
Onset: More than one arm-brain circulation time (30 – 60 s)
Duration: 1 hour when given IV.
Elimination: It is metabolized by liver by hydroxylation and then conjugation. The metabolite,
hydroxymidazolam has no clinically significant sedative effects.
Central nervous system (CNS): It produces dose-dependent depression of the CNS.
Cardiovascular system: It is relatively cardiostable and does not affect blood pressure or
heart rate. However, in hypovolaemic patients, it can produce significant hypotension as it
reduces the systemic vascular resistance.
Respiratory system: At sedation doses, it does not produce any change in respiration. How-
ever, higher doses can cause dose dependent respiratory depression.
Cautions: To be used with caution in patients who are hypovolaemic as it may aggravate hy-
potension.
FLUMAZENIL:
It is a competitive benzodiazepine antagonist.
It is available as vials containing 0.3 mg. It is given in 100 µg boluses, to a total of 1 mg as

needed.
Onset: Two minutes
Duration of action: About an hour. Hence it is suitable to reverse a short acting benzodi-
azepine.
14
DIAZEPAM
Name: Diazepam hydrochloride

Availability: It is available in 2 ml ampoules containing 5 mg/ml. Solvents: propylene glycol
and sodium benzoate.
Uses, dose and route: It is usually given intravenously. It may be administered by oral route.
Intramuscular injection of diazepam is very painful and should be avoided.
For premedication: It may be used in a dose of 0.1 to 0.2 mg/kg orally.
Anticonvulsant: It may be given as a bolus as an anticonvulsant.
It is not used a sedative because of its long duration of action and the availability of
shorter acting drugs.
Onset: More than one arm-brain circulation time (30 – 60 s)
Duration of action: 6 – 8 hours when given IV.
Elimination: It is metabolized by liver by hydroxylation and conjugation. The metabolites, Des-
methyl diazepam, Oxazepam and Temazepam (can be remembered as DOT) are active and
contribute to its prolonged sedative effects. Diazepam has an elimination half-life of 20 – 70
hours.
Central nervous system (CNS): It produces dose-dependent depression of the CNS. It can
be used as an anticonvulsant. It is a centrally acting skeletal muscle relaxant and this effect
is quite useful in reducing the intensity and frequency of spasm associated with tetanus
and lumbar disc disease.
Cardiovascular system: It is relatively cardiostable and does not affect blood pressure or
heart rate.
Respiratory system: It does not produce any change in respiration.
Cautions: To be used with caution in patients i) who are hypovolaemic as it may aggravate hy-
potension ii) who are in borderline respiratory failure iii) those with hepatic and renal dysfunc-
tion.
15
INHALATION ANAESTHETICS
16
Tips to remember:
1. Molecular weight of volatile anaesthetic agents
HIS DEN
HIS (Halothane, Isoflurane and Sevoflurane) - all have mol. Weight of approximately 180-200
Desflurane— approximately 160
Ether—half of desflurane— approximately 80
Nitrous oxide—half of desflurane– approximately 40
2. Boiling point of volatile anaesthetic agents
Starts to HIS at 50°C— i.e., Halothane, Isoflurane and Sevoflurane all have a boiling point around 50°C
Daily theatre temperature for Desflurane 23°C
Environmental temperature for Ether 35°C

Negative for Nitrous oxide (-88°C)
3. Saturated vapour pressure for volatile anaesthetic agents
HI—SaturateD— Halothane and Isoflurane have SVP @ 240-250, while Sevoflurane SVP @ 160 and
desflurane gets saturated last @ 660. Exception to this is Ether which has SVP 60.
4. Metabolism of volatile anaesthetic agents in human body
HIS DEN—Halothane (Highest 20%), Isoflurane (I of isoflurane for <1%), Sevoflurane (S of sevoflurane
for 5%)
DEN (Desflurane, Ether, Nitrous oxide) - No metabolism in the human body.
Second gas effect: When a volatile anaesthetic (ex: isoflurane, sevoflurane) is administered with ni-
trous oxide (first gas), the rate of rise of alveolar isoflurane or sevoflurane is more rapid than when it is
given alone. This is "second gas effect". The second gas effect applies to the situation in anaesthetic
practice where N2O is given in a high enough concentration so that its subsequent uptake from
the alveolus causes an increase in the concentration of the other gases. For example if breathing
20% oxygen and 80% N2O (nitrous oxide) in the alveoli say half the N2O was taken up into
the bloodstream then of the original 100% of the mixture 20% oxygen will remain with 40% N2O. The
new concentration of oxygen will thus be increased with now 33.3% of the gas mixture being oxygen.
This can also be applied to increase the alveolar concentration of a volatile anaesthetic. Imagine in the
above example that there was 19% oxygen and 1% anaesthetic gas then after N2O uptake there would
be 1.7% anaesthetic gas and 31.7% oxygen.
Third gas effect (Fink effect): Also known as diffusion hypoxia or diffusion anoxia. When soluble gases
are inhaled, large quantity of these gases may get dissolved in body fluids. Higher the solubility, more
will be the fraction that gets dissolved. However, once the supply of gases caeses in inhaled gases, due
to concentration gradient, they try to rapidly come out of body fluids to alveoli, thus diluting the oxy-
gen.
When this is applied to anaesthesia with oxygen, nitrous oxide and volatile anaesthetic agent, during
recovery when the volatile anaesthetic and the nitrous oxide are turned off, large quantities of N2O
may come to the alveoli from blood (down its concentration gradient). This may result in significant
dilution of the alveolar oxygen levels causing a rapid fall in alveolar PO2 and thus may lead to tempo-
rary hypoxia. This can be avoided by increasing the FiO2 during recovery from N2O anaesthesia.
Over pressure technique: During inhalational induction, gases with larger blood gas solubility (Ex: halo-
thane compared to sevoflurane) are likely to take longer time for induction if used at their MAC value.
However, the induction can be hastened in such situations by using the “overpressure” technique
whereby the concentration of the volatile anaesthetic used is increased many folds (5% halothane, 8%
sevoflurane).
17
HALOTHANE, ISOFLURANE, SEVOFLURANE, ETHER, DESFLURANE
Can be classified as halogenated hydrocarbons (halothane) and ethers (all fluranes).
What physical properties of inhalation anaesthetics are important to the anaesthetists?
Illustrate with examples.
Table showing physical properties of inhalation anaesthetics.

Nitrous ox-
Halothane Isoflurane Sevoflurane Desflurane Diethyl ether
ide
Molecular weight
197 184.5 200 168 74 44
Boiling point (°C)

50.2 48.5 58.5 23.5 35 - 88
SVP (mmHg) 243 238 160 668 59
MAC (in oxygen)

0.75 1.15 2 6 1.9 105
Blood-gas solubil-
2.3 1.4 0.69 0.42 12 0.47
ity coefficient
Molecular weight: According to Avogadro’s law, 1 mole of any substance occupies 22.4 L at
STP. If the density of the liquid is also known the amount of vapour that can be obtained from
a given amount of liquid can be calculated.
Illustration:
Molecular weight of sevoflurane is 200 ; 200 g of sevoflurane occupies 22.4 L at STP
1 g of sevoflurane occupies 22400 ml/200 = 112 ml of sevoflurane vapour
Density of sevoflurane is 1.5. This means that 1 ml of liquid sevoflurane weighs 1.5 g.
Thus 1 ml of liquid sevoflurane will give 112 x 1.5 ml = 168 ml of sevoflurane vapour at STP.
Using Charles’ law, the amount of sevoflurane vapour obtained at room temperature may be
deduced. At 20°C (293 K), 168 ml of sevoflurane vapour (at 273 K) would have expanded to
168 x 293/273 = 180 ml.
Thus, 1 ml of sevoflurane liquid gives rise to 180 ml of sevoflurane vapour at 20°C.
LIQUID VOLATILE AGENT USED PER HOUR:

Ehrenwerth and Eisenkraft formula may be used to calculate the amount of liquid volatile
agent used per hour.
3 x FGF (L/min) x Vol % = ml liquid used/h
Typically 1 ml of liquid volatile agent yields about 200 ml vapour.
Boiling point: The ease with which a liquid can evaporate is indicated by its boiling point. This
is an important consideration in the manufacture of vaporizers. For e.g.. desfIurane has a very
low boiling point and exists as vapour at room temperature. This evaporation draws a large
amount of latent heat of vaporization and the liquid cools down. Hence a heated vaporizer is
required to ensure continued vaporization.
Saturated vapour pressure (SVP): This is the pressure exerted by the vapour above the liquid
at STP. Greater the volatility of the liquid, higher is its saturated vapour pressure. A knowledge
of SVP is necessary for the construction and calibration of vaporizers.
MAC: It is the minimum alveolar concentration of an inhaled anesthetic required to prevent

purposeful movement in response to a noxious stimulus at one atmospheric pressure in 50%
of individuals. It reflects the potency of the anaesthetic.
18
MAC50 – MAC that prevents movement in 50% of individuals to noxious stimulus
MACAwake – 0.3-0.5 of MAC for modern inhalation anaesthetic agents such as isoflurane,
sevoflurane and desflurane.
MACBAR (Blocks Adrenergic Response) – 1.7-2 MAC .
MACEI (Endotracheal Intubation) – 1.3 x MAC
End-tidal concentration reflects the alveolar concentration of the anaesthetic and is used
to assess MAC.
MAC, being additive, reduces with the addition of nitrous oxide to the inhaled gas mixture.
For e.g., if 60% nitrous oxide is being used, MAC of halothane reduces from 0.75 to 0.3.
Remember: MAC for all volatile anaesthetic agents varies proportionately with changes in
atmospheric pressure and temperature. Therefore, MAC of all agents is decreased with
decreases in atmospheric temperature and pressure and vice versa.
Blood-gas solubility coefficient: The solubility of an anaesthetic agent in blood is indicated by

its blood gas solubility. Lower the blood-gas solubility, lesser is the amount of anaesthetic car-
ried away by blood and faster is the induction. Similarly, emergence is faster with less soluble
anaesthetics.
Figure 2: Illustration of distribution of anaesthetic gases in the gaseous (alveolus) and liquid
(blood) phase according to their blood gas solubility coefficient.
The blood gas partition coefficient (l) describes the relative affinity of an anaesthetic for two
phases. It describes how the anaesthetic distributes itself between the two phases e.g., when
the blood-gas solubility is 2, at equilibrium, blood will contain twice the amount of anaesthetic
as in the gaseous phase.
At any given temperature and pressure, a gas dissolves in a given liquid only to a certain ex-
tent. When no further gas dissolves in the liquid, a state of equilibrium exists between the gas
over the liquid and the gas dissolved in it. At that point, the liquid is said to be fully saturated
with the gas at that temperature and pressure.
It is a convention to state that the gas in solution exerts the same “tension” as the partial pres-
sure of the gas over the liquid in equilibrium with it. In other words, at equilibrium the partial
pressure of the substance in the gaseous phase will be the same as the “tension” of the sub-
stance in the liquid phase.
The rapidity of induction with any volatile anaesthetic depends on how fast its partial pressure
builds up in brain. As brain belongs to vessel-rich group of tissues, this is indirectly reflected by
partial pressure achieved in the alveolus at equilibrium.
19
If an anaesthetic has a low blood-gas solubility co-efficient, lesser amount of it dissolves in the
blood and its alveolar concentration rises faster. This means that its partial pressure in the
brain also rises faster, thus hastening induction.
Higher the blood-gas partition coefficient, higher is the amount of anaesthetic that dissolves in
blood. This means two things: i) an increased uptake from the alveoli ii) delay in the build up
of partial pressure of the anaesthetic in the alveoli. This in turn delays the development of an
adequate partial pressure in the brain.
This effect can be reduced by using anaesthetic overpressure. Thus, on induction of anaesthe-
sia, one may use 4 -5 % halothane to achieve an alveolar concentration of 1%.
Oil-gas solubility coefficient: Higher the lipid solubility of an anaesthetic, greater is its concen-
tration in the brain and greater is its potency.
Mechanism of action: Various theories have been-proposed to explain the mechanism of ac-
tion of inhaled anaesthetics. The most acceptable ones are as follows:
Meyer-Overton Rule – Implies a hydrophobic site of action. It postulates that anaesthe-
sia occurs when sufficient numbers of anaesthetic molecules dissolve in the hydropho-
bic sites of the brain.
Critical volume hypothesis: Anaesthesia occurs when the absorption of anaesthetic
molecules expands the volume of a hydrophobic region beyond a critical amount. Such
an expansion might produce anaesthesia by obstructing ion channels or by altering the
electrical properties of neurons.
Binding of inhaled anaesthetics to membrane lipids may alter the physical characteris-
tics of the membrane such as its thickness, fluidity and its permeability.
Inhaled anaesthetics may exert a direct action by binding to specific proteins and re-
ceptors in the cell membrane.
20
HALOTHANE
Name: Halothane
Availability: As a liquid containing thymol as a preservative. Stored in amber coloured bottles
to prevent photodegradation. As halothane vaporises, thymol tends to accumulate in the va-
poriser. This is indicated by yellowish discoloration of the liquid.
Central nervous system (CNS): It produces dose-dependent depression of CNS and cerebral
metabolic rate. Halothane, like other inhaled anaesthetics produces dissociation between
cerebral metabolic rate (CMRO2) and cerebral blood flow (CBF). It produces vasodilatation
of the cerebral vessels, increases cerebral blood flow and can increase intracranial pres-
sure when used in excess of I MAC.
Cardiovascular system: It causes hypotension mainly due to myocardial depression. It re-
duces contractility, heart rate and cardiac output. Blunts baroreceptor reflex responses
completely. It delays AV nodal conduction and therefore, may precipitate bradyarrhyth-
mias, such as junctional bradycardia. It sensitises the myocardium to both endogenous as
well as exogenously administered catecholamines and predisposes to arrhythmias.
Respiratory system: It is a pleasant agent to inhale and is an agent commonly used for in-
halation induction. It progressively decreases tidal volume and depresses respiration. It
may cause an increase in respiratory rate but alveolar ventilation is reduced. Halothane
raises the apnoeic threshold and shifts the carbon dioxide response curve to the right. It
obtunds the airway reflexes well. It is a good bronchodilator (mediated through calcium
channel blockade).
Musculoskeletal system: Halothane prolongs non-depolarising neuromuscular blockade by
several mechanisms: depression of central nervous system, increased delivery of muscle
relaxants to the neuromuscular junction and direct relaxation of skeletal muscle.
Gastrointestinal system: It delays gastric emptying.
Metabolism: Halothane is mainly eliminated from the body through the lungs. Up to 20% of
halothane is metabolized in the liver.
Adverse effects: Hypotension, bradycardia, arrhythmias.
HALOTHANE HEPATITIS: Since halothane undergoes metabolism in the liver even though to a
small extent, it can rarely cause hepatitis. Halothane hepatitis may be one of two types:
Type 1 – Milder form, occurs mainly due to anaerobic metabolism due to hypoxia. It occurs
within hours of exposure to halothane and is associated with mild elevations in serum
transaminases. It is usually self-limiting.
Type II – Is more rare, is immune-mediated, can be fulminant and fatal. The incidence
quoted in the literature is I: 35,000 halothane anaesthetics. Patients with conditions reduc-
ing liver blood flow, repeated exposure to halothane, those with liver disease, especially
primary biliary cirrhosis are prone for it. It occurs 5 – 7 days after exposure to halothane. It
is characterized by fever, leukocytosis and eosinophilia. It may be associated with nausea,
vomiting and other GI symptoms.
Drug interactions: Caution should be exercised when halothane is used along with beta block-
ers, calcium channel blockers or opioids as it may predispose to bradycardia and asystole.
21
ISOFLURANE
Name: Isoflurane
Availability: It is available as a liquid but without any preservative.
Uses: Isoflurane is popular in providing anaesthesia for neurosurgery, cardiac surgery and pa-
tients with altered liver function. With decreased cost, it is now being used routinely for all
cases.
Central nervous system (CNS): It produces dose-dependent depression of CNS. It reduces
CMRO2 more than halothane. It produces vasodilatation of the cerebral vessels, increases
cerebral blood flow and can increase intracranial pressure when used in excess of I MAC.
Its cerebral vasodilatory properties are less than halothane.
Cardiovascular system: It causes hypotension mainly due to peripheral vasodilatation. In
higher doses, it causes myocardial depression. It may cause a reflex increase in heart rate
as it does not obtund the baroreceptor reflex action completely. It does not sensitise the
myocardium to endogenous catecholamines. It does not predispose to arrhythmias. It was
initially suspected that isoflurane enhances coronary steal syndrome but has been found
to be clinically insignificant. In fact, isoflurane has been found to be particularly useful in
myocardial protection due to ischaemic preconditioning.
Respiratory system: It is a pungent agent to inhale and cannot be used for inhalation induc-
tion. It progressively decreases tidal volume and depresses respiration. It may cause an
increase in respiratory rate but alveolar ventilation is reduced. Isoflurane raises the
apnoeic threshold and shifts the carbon dioxide response curve to the right. It obtunds the
airway reflexes well. It is a good bronchodilator.
Musculoskeletal system: Isoflurane prolongs non depolarising neuromuscular blockade by
several mechanisms: depression of central nervous system, increased delivery of muscle
relaxants to the neuromuscular junction and direct relaxation of skeletal muscle.
Liver: Isoflurane preserves autoregulatory mechanism of hepatic blood flow. Hence it is
useful in patients with liver disease.
Metabolism: Isoflurane is mainly eliminated from the body through the lungs. Up to 0.1% of
isoflurane is metabolized in the liver.
Adverse effects: Hypotension.
Hepatitis: Since isoflurane undergoes metabolism in the liver to a smaller extent, it can rarely
cause hepatitis.
22
SEVOFLURANE
Name: Sevoflurane
Availability: As a liquid that does not contain a preservative.
Uses: Sevoflurane is popular for inhalation induction in children, patients with difficult airway
and in day-care surgery.
Central nervous system (CNS): It produces dose-dependent depression of CNS. It produces
vasodilatation of the cerebral vessels, increases cerebral blood flow and can increase in-
tracranial pressure when used in excess of I MAC (similar to isoflurane).
Cardiovascular system: It is a very cardiostable agent. It does not produce significant hy-
potension due to either myocardial depression or peripheral vasodilatation.
Respiratory system: It is a pleasant agent to inhale and is the agent of choice for inhalation
induction. It progressively decreases tidal volume and depresses respiration. It may cause
an increase in respiratory rate but alveolar ventilation is reduced.
Musculoskeletal system: Sevoflurane prolongs neuromuscular blockade by mechanisms
similar to halothane and isoflurane.
Metabolism: Sevoflurane is mainly eliminated from the body through the lungs. Up to 1-5 % of
sevoflurane is metabolized in the liver.
Sevoflurane anaesthesia may result in fluoride concentration above the nephrotoxic

threshold of 50 mmol/L. However, clinical studies have revealed the renal damage caused
by sevoflurane is clinically insignificant.
Prolonged use of sevoflurane in high concentrations with soda lime may result in produc-
tion of Compound A, when the temperature exceeds 65°C. Compound A (trifluoroacetyl
radical) is found to be harmful to the liver, kidneys and brain in rats but its effects on hu-
mans is not established. The potential to produce Compound A is enhanced when circle
system with low flows is used.
When sevoflurane is used with soda lime, the following is recommended:

Do not exceed 1.25 MAC
Do not administer for more than four hours
Do not use fresh gas flow less than 2 L/min
Soda lime is preferred to baralyme.
23
DESFLURANE
Name: Desflurane
Availability: As a liquid
Use: Desflurane is useful in anaesthesia for day-care surgery.
tracranial pressure when used in excess of I MAC.
Cardiovascular system: It is a relatively cardiostable agent but causes tachycardia (more
than isoflurane at equipotent concentrations). It maintains cardiac output. It does not sen-
sitise the myocardium to catecholamines or predispose to arrhythmias.
Respiratory system: It is a pungent agent to inhale and cannot be used for inhalation induc-
tion. It progressively decreases tidal volume and depresses respiration. It may cause an
increase in respiratory rate but alveolar ventilation is reduced.
Musculoskeletal system: Desflurane prolongs neuromuscular blockade by mechanism simi-
lar to isoflurane.
Metabolism: Desflurane is mainly eliminated from the body through the lungs. Only about
0.02% is metabolised in the body.
24
ETHER
Name: Diethyl ether
Availability: As a liquid
tracranial pressure when used in excess of I MAC.
Cardiovascular system: It is a relatively cardiostable drug. It produces release of endoge-
nous catecholamines and maintains contractility, heart rate and cardiac output.
Respiratory system: It is a good bronchodilator.
The effects of ether on respiration together with changes in pupillary size were used by
Guedel to describe stages of anaesthesia. Since ether has a high blood gas solubility co-
efficient, onset of action is slow enabling observation of stages of anaesthesia very
clearly.
Stage 1 (Induction): Beginning of administration until loss of consciousness. Respiration
is regular, pupils normal, gaze is central.
Stage 2 (Delirium): From loss of consciousness to onset of surgical anaesthesia. It pro-
gressively increases tidal volume and stimulates respiration. Since ether is a pungent
gas, it causes breath-holding. Respiration is irregular. Pupils dilate and there is an up-
ward gaze.
Stage 3 (Surgical anesthesia): Characterized by deep, regular, automatic breathing. Cor-
neal reflex is lost. Pupils are mid-dilated and gaze is central. Stage 3 has been further
subdivided into four planes, during which there is progressive depression of respiration
and dilatation of pupils.
Stage 4 (Bulbar paralysis): No exact signs except shallow, irregular breathing and di-
lated pupils that no longer react to light.
Musculoskeletal system: Ether produces good muscle relaxation.
Gastrointestinal system: It delays gastric emptying. It produces nausea and vomiting. It
causes an increase in secretions.
Metabolism: Ether is mainly eliminated from the body through the lungs.
Adverse effects: The adage, ‘It is difficult to kill a patient with ether’ is very apt. The main rea-
sons why ether is not used presently are as follows:
Ether is inflammable and there is an ever present danger of fire and explosions when it is
used.
It is a slow acting agent, both the onset and emergence are slow.
It has a very pungent odour and is irritating to the OR personnel.
Pleasant and noninflammable inhalational anaesthetic agents that have a quick onset and
offset are now available.
MALIGNANT HYPERTHERMIA
Malignant hyperthermia is a condition that can be precipitated in susceptible patients on ex-
posure to drugs such as succinyl choline and inhalation anaesthetics. This is due to an abnor-
mality in the ryanodine receptor in the muscle membrane resulting in an inability to reuptake
calcium by the sarcoplasmic reticulum. Hence, these drugs must be avoided in these patients.
25
LOCAL ANAESTHETIC AGENTS
26
How are local anaesthetics classified?
Local anaesthetics can be classified as amino amides and amino esters. Local anaesthetics con-
sist of a hydrophilic aromatic section linked to a lipophilic tertiary amine group either by an
ester group or an amide group.
Tips to remember: All local anaesthetic drugs with double ‘i’ in their name are amino amides
(lignocaine, bupivacaine, ropivacaine except cocaine. Cocaine although has only one ‘i’ in its
name, it is an amino-amide local anaesthetic).
What are the important physical properties of a local anaesthetic agent that determine its
pharmacodynamics?
Aminoamide or aminoester: Allergic reactions are more common with the aminoester com-
pounds.
pKa: The pKa of a drug is the pH at which both the ionized and nonionised forms of the drug
are in equal proportions. The closer the pKa of a drug is to the tissue pH, faster is its action.
The closer the pKa of a drug is to the tissue pH, higher is the amount of nonionised form. The
nonionised form is more lipid soluble and is able to penetrate cell membranes faster. Once the
membrane is crossed, the drug blocks the receptor from inside.
If the tissue pH is acidic, the amount of nonionised form reduces and the effect of local anaes-
thetic reduces (infected tissue).
Protein-binding and Lipid solubility: The higher the lipid solubility of a local anaesthetic,
faster is its action. Higher the protein-binding, longer is its duration of action.
Ion trapping: Usually, foetal blood has slightly lesser pH compared to maternal blood which
results in increased uptake of drugs that are basic such as local anaesthetic agents (especially
lignocaine due to its low pKa). These agents can cross the foeto-placental membrane barrier in
non-ionized state and tend to accumulate in foetal circulation in ionized form. In ionized form,
the local anaesthetic will not be able to cross back to maternal circulation resulting in ‘ion
trapping’. In situations of foetal distress where the foetus would be much more acidotic than
usual, this ion trapping reach significant proportions endangering the life of the foetus. There-
fore, it is best to avoid lignocaine for epidural labour analgesia.
27
LIGNOCAINE
Name: Lignocaine hydrochloride
Availability: It is available in the following forms:
Preservative-free solutions:
2% solution for intravenous use, as an antiarrhythmic agent or to blunt responses to en-

dotracheal intubation;
5%, ‘heavy’ solution for intrathecal use. It is made hyperbaric by the addition of 7.5% dex-
trose.
With preservative (methyl paraben):

1%, 2% solutions for use as local anaesthetic – intradermal, subcutaneous injections, epi-
dural anaesthesia and nerve blocks.
2% viscous solution for gargling, 2% jelly for mucosal analgesia

2% lignocaine with adrenaline (5µg/ml) for local infiltration. This can also be used for pe-
ripheral nerve blocks.
4% solution for mucosal analgesia
4% (provides 4mg/spray) and 10% (provides 10mg/spray) lignocaine spray
Mechanism of action: It inhibits the sodium channels and prevents depolarization and propa-
gation of nerve impulse.
Pharmacology: It is an amino-amide type of local anaesthetic. It has a pKa of 7.6.
Uses, dose and route: It is a sodium channel blocker and stabilizes the membrane
As a local anaesthetic, it acts on the nodes of Ranvier to block conduction along various
nerves and plexuses. Consequently, its effect is faster on myelinated nerves than on non-
myelinated nerve fibres. It may be used in a dose of 3 mg/kg, if used plain and 7 mg/kg if
used with adrenaline.
It may be used to produce topical anesthesia.
To produce central neuraxis block, both epidural as well as spinal anaesthesia.
As an anti-arrhythmic agent (Class I b), it is useful to treat ventricular arrhythmias.
For intravenous regional anaesthesia (Bier’s block) – 30 – 40 ml of 0.5-1% lignocaine for
upper limb and 70 ml of 0.25-0.5% lignocaine for lower limb). The total dose should not
exceed the maximum recommended dose of 5 mg/kg.
Lignocaine (20 mg to be added to 20 ml) usually added to 1% propofol solution before in-
jection further reduces the pain on injection.
Onset and Duration: Varies with the site of injection, dose and concentration of the drug, ad-
ditives to the solution and certain tissue characteristics.
Elimination: It is metabolized by liver
Lignocaine acts on the nerves close to the site of injection, blocks sodium channels, pre-
vents depolarization and conduction of impulses.
Lignocaine deposited in the tissues is gradually absorbed into the blood. The systemic ef-
fects of lignocaine are related to the plasma concentration. Initially, as the concentration
28
increases, neurological symptoms such as tinnitus, dizziness, neuromuscular twitches,
change in taste and restlessness occur (up to 5 µg/ml). As the concentration increases,
other symptoms appear such as convulsions (15 µg/ml), respiratory depression (20 µg/ml)
and finally cardiovascular collapse (25 µg/ml). Thus, the margin of safety for lignocaine is
high. The dose required to produce cardiovascular toxicity is said to be approximately 7
times higher than that required to produce central nervous system toxicity.
Maximum recommended dose: Lignocaine, when used for nerve blocks or infiltration may
be used in a maximum dose of 3 mg/kg if used alone; when combined with adrenaline, it
may be used up to 7 mg/kg.
For topical anaesthesia of both upper and lower airway, lignocaine can be given as nebuli-
sation upto 10 mg/kg.
As an antiarrhythmic agent for the treatment of ventricular arrhythmias, it is given in a

dose of 1 – 1.5 mg/kg. It may be repeated up to a maximum of 3 mg/kg. Following the bo-
lus dose, lignocaine may be administered as an infusion at a rate of 1-4 mg/min.
The plasma concentration reached depends on dose of lignocaine, site of injection (rate of
absorption is very high in intercostal spaces—intercostals > epidural > plexus blocks > pe-
ripheral > subcutaneous), addition of vasoconstrictors (such as adrenaline which slows ab-
sorption), pregnancy (free drug concentration is higher), presence of cardiac and renal fail-
ure.
TUMESCENT ANAESTHESIA
Maximum dosage of lidocaine with epinephrine (2 µg/ml) for providing tumescent anaesthesia
is a concentration between 0.05% and 0.1%, up to 45 mg/kg.
29
BUPIVACAINE
Name: Bupivacaine hydrochloride

Availability: It is available in the following forms:
Preservative-free solutions: 0.5% solution, made hyperbaric by the addition of 8% dextrose – 4
ml ampoule for intrathecal use.
With preservative (methylparaben): 0.25%, 0.5% solutions for use as local anaesthetic – in-
tradermal, subcutaneous injections, epidural anaesthesia and nerve blocks.
Mechanism of action: It inhibits the sodium channels and prevents depolarization and propa-
gation of nerve impulse.
Pharmacology: It is an amino-amide type of local anaesthetic. It has a pKa of 8.2.
Uses, dose and route: It is a sodium channel blocker and stabilizes the membrane
As a local anaesthetic, to block various nerves and plexuses
To produce central neuraxis block
Labour analgesia
Onset and Duration: Depends on the site of injection, dose and concentration of the drug, ad-
ditives to the solution and certain tissue characteristics.
Bupivacaine acts on the nerves close to the site of injection, blocks sodium channels and
prevents depolarization and conduction of impulses.
The drug injected into the tissues is gradually absorbed into the plasma. The systemic ef-
fects of bupivacaine are related to the plasma concentration. Initially, as the concentration
increases, neurological symptoms such as tinnitus, dizziness, neuromuscular twitches,
change in taste and restlessness occur. As the concentration increases, other symptoms ap-
pear such as convulsions, respiratory depression and finally cardiovascular collapse. How-
ever, the margin of safety for bupivacaine is much lower than lignocaine. The dose required
to produce cardiovascular toxicity with bupivacaine is approximately 3.5 times higher than
that required to produce central nervous system toxicity. It avidly binds to the cardiac so-
dium channels but unlike lignocaine is slow to dissociate and so, produces cardiac toxicity.
Maximum recommended dose: Bupivacaine, when used for nerve blocks or infiltration may be
used in a maximum dose of 2.5 mg/kg (a 0.25% bupivacaine solution can be used as 1 ml/kg
dose safely as a rule of thumb). Unlike lignocaine, addition of adrenaline to bupivacaine does
not prolong its action but by reducing the rate of its absorption into plasma, reduces its toxic-
ity.
The plasma concentration reached depends on dose of bupivacaine, site of injection (rate of
absorption is very high in intercostal spaces), addition of vasoconstrictors (such as adrenaline
which slow absorption), pregnancy (free drug concentration is higher), presence of cardiac and
renal failure.
Mixture of local anaesthetics: Two local anaesthetics are often mixed so as to obtain advan-
30
tages of both,e.g., lignocaine and bupivacaine may be mixed so that the onset is faster and the
duration is longer. However, it should be remembered that the adverse effects can be syner-
gistic and the maximum doses of each must be reduced. Hence, it is recommended that local
anaesthetics should not be mixed.
In general, both lignocaine and bupivacaine produce both sensory and motor blockade. How-
ever, lignocaine tends to produce more profound motor blockade whereas bupivacaine pro-
duces more of sensory blockade.
TREATMENT OF LOCAL ANAESTHETIC TOXICITY
The treatment of local anaesthetic toxicity depends on the drug and the manifestations.
Lignocaine causes neurological symptoms initially. This needs only supportive treatment such
as oxygen, maintenance of airway and breathing. The convulsions although brief and self-
limiting are better treated with midazolam or thiopentone. If the plasma level is too high, car-
diovascular collapse may occur. This may require cardiovascular support.
Bupivacaine, unlike lignocaine, is very cardiotoxic. It is described as a ‘slow-in, slow-out’ agent.

Neurological symptoms occur early and can be treated symptomatically. However, cardiac tox-
icity occurs sooner than with lignocaine and is much more difficult to treat.
Bupivacaine toxicity may be treated as follows:
A) Give 100% oxygen. Support airway and breathing to avoid hypoxia and acidosis.
B) If seizures occur, treat with benzodiazepines. If not readily available, use small doses of
thiopentone or propofol. If seizures persist, may paralyse with succinyl choline and intu-
bate the trachea.
C) Cardiac arrest: Give adrenaline as per ACLS protocol. Use of vasopressin is not advocated.
Use amiodarone for ventricular arrhythmias. Avoid calcium channel blockers and beta
blockers. A pacemaker may be required.
D) Intralipid 20% infusion has been found to behave like a ‘lipid sink’ drawing lipid soluble
bupivacaine from the heart. It may be given as follows: Bolus of 1.5 ml/kg over 1 min (100
ml approx) followed by 0.25 ml/kg/min infusion to be continued for at least 10 min after
successful resuscitation. If unsuccessful or blood pressure remains low, another bolus fol-
lowed by 0.5 ml/kg/min may be given. Approximately 10 ml/kg for 30 min is considered
the upper limit of lipid emulsion dosing.
E) If still unsuccessful, consider cardiopulmonary bypass.
31
OTHER LOCAL ANAESTHETICS
ROPIVACAINE HYDROCHLORIDE
It is available as s-ropivacaine enantiomer, as 0.2% and 0.75% solutions for nerve blocks
and epidural use. It is available as 0.75% hyperbaric solution for intrathecal use. It is an am-
ide local anaesthetic similar to bupivacaine but the butyl group is replaced by propyl group.
It has a differential blocking effect on nerve fibres and, at the lowest concentration used,
there is good differentiation between sensory and motor block. It causes predominantly
sensory anaesthesia.
Cardiotoxicity is less than bupivacaine and resuscitation from ropivacaine toxicity is more
effective than from bupivacaine toxicity.
Maximum recommended dose is 3.5 mg/kg (> 150 mg for Caesarean section under epidural
anaesthesia). However it must be remembered that the plasma levels reached depend on
several factors including site of injection, vascularity, dose, age, metabolic rate etc.
Has been used for providing labour analgesia by epidural route
LEVOBUPIVACAINE
Bupivacaine is usually available as a racemic mixture of its two isomers, laevo and dextro
forms. The levo form has much reduced cardiotoxicity but has all the nerve blocking proper-
ties of bupivacaine. This is marketed as levobupivacaine.
PRILOCAINE
It is an aminoester local anaesthetic agent that can be used for intravenous regional anaesthe-
sia. Its adverse effects include methaemoglobinaemia in addition to the above. Felypressin is a
vasoconstrictor added to prilocaine to prolong its effects. It is recently made available as 2%,
hyperbaric solution for spinal anaesthesia. (Priloketal—trade name). Advantages claimed are
rapid onset and offset of sensory and motor block. A number of precautions are mentioned
with its use including cardiac, liver and renal decompensation, drug interaction with amiodar-
one, and porphyria.
EMLA
It is an acronym for eutectic mixture of local anaesthetics. This eutectic mixture has a melting
point below the room temperature. Therefore both local anaesthetics exist in liquid oil form
rather than as crystals. EMLA is a mixture of 2.5% lignocaine and 2.5% prilocaine, used for lo-
cal application (dermal analgesia). Thus it is used for securing intravenous access, harvest split
skin grafts and superficial biopsies. It needs to be applied under occlusive dressing for atleast
an hour. It should not be applied on mucosa and abraded skin as it may get absorbed signifi-
cantly to cause methaemoglobinaemia. The dose to be used depends on the age and body
weight and is described by the manufacturer in terms of thickness of the layer and the area
over which it is spread.
AMETOP
It is a 4% gel containing tetracaine used for topical application.
32
NEUROMUSCULAR BLOCKERS
33
CLASSIFICATION OF NEUROMUSCULAR BLOCKERS
Depolarising – Succinylcholine (suxamethonium), decamethonium
Nondepolarising : They may be subclassified as follows:
Depending on duration of action
Short-acting: Mivacurium
Intermediate-acting: Atracurium, Cisatracurium, Vecuronium, Rocuronium
Long-acting: Pancuronium, Pipecuronium
Depending on structure:
Aminosteroids - Vecuronium, Pancuronium, Pipecuronium, Rocuronium
Benzylisoquinolinium compounds - Mivacurium, Atracurium, Cisatracurium
[remember as MAC]
ED95: The ED95 of a muscle relaxant is the dose that produces 95% suppression of single twitch
response to a supramaximal stimulus.
Special attributes of neuromuscular blockers: All are quaternary ammonium compounds and
hence are water soluble and do not cross placental barrier (except gallamine). They need to be
refrigerated at 4-8° C and to be removed only when needed to be used.
34
SUCCINYLCHOLINE
Name: Succinylcholine chloride, suxamethonium
Availability: It is available in 2 ml ampoules and 10 ml vials containing 50 mg/ml of Succinyl-
choline.
Mechanism of action: Succinylcholine molecule is two molecules of acetyl choline combined
back to back. It combines with the nicotinic receptor and unlike acetyl choline, produces per-
sistent depolarization resulting in muscle paralysis. Since this depolarisation is not a co-
ordinated contraction, it produces fasciculations.
Uses, dose and route:
Endotracheal intubation: Succinylcholine was used routinely to facilitate endotracheal in-
tubation. The trend has changed due to increasing recognition of the complications associ-
ated with succinylcholine and availability of fast-acting nondepolarising muscle relaxants.
The ED95 of succinylcholine is 0.3 mg/kg. It is used in a dose of 1 – 1.5 mg/kg IV to facilitate
endotracheal intubation. This is done only in 2 situations: rapid-sequence induction of an-
aesthesia for full-stomach and in difficult airway management when ventilation is possible.
Treatment of laryngospasm: It may be given during the management of laryngospasm in-
travenously or intramuscularly (3-4 mg/kg) when an IV is not in place. It may be injected
sublingually/intralingually in a dose of 2-3 mg/kg. The onset of action of intramuscularly
injected Succinylcholine is three to five minutes and may last for ten minutes. If an IV is in
place, the dose required to break laryngospasm is just 0.1 – 0.3 mg/kg.
Adverse effects on the body:
Muscle pains: Within 60 s of injection of Succinylcholine, unco-ordinated muscle contractions
occur and manifests as muscle fasciculations. These can be vigorous in some young and mus-
cular individuals causing muscle pain postoperatively. The extent of fasciculations and muscle
pains may be blunted using any of the following: a) Precurarisation – One-tenth of the intubat-
ing dose of a nondepolariser may be injected three minutes prior to full dose of Succinylcho-
line. However, this increases the dose of succinylcholine required for providing adequate intu-
bating conditions b) Self-taming – One tenth of the intubating dose of Succinylcholine is given
three minutes prior to full dose of Succinylcholine c) A larger dose of thiopentone may be used
for induction prior to paralysis with Succinylcholine d) Lignocaine in a dose of 1.5 – 2 mg/kg IV
before Succinylcholine may also help.
Masseter spasm: Succinylcholine sometimes causes spasm of masseter strong enough to pre-
vent mouth opening and intubation. It is not always associated with malignant hyperthermia.
Hyperkalaemia: Succinylcholine causes an increase in serum potassium concentrations of up
to 0.5 mmol/L. In certain group of patients, this response is exaggerated: patients with burns
(2 days to 2 years), denervation such as hemiplegia/paraplegia/quadriplegia (6 days to 6
months), muscle dystrophy, massive abdominal infection, rhabdomyolysis and crush injuries
administration of succinylcholine results in the release of large amounts of potassium into the
intravascular space. This hyperkalaemia can result in cardiac arrest. In renal failure, where the
baseline serum potassium is already elevated (> 5.5 mmol/L), any further increase can be life-
threatening. So, succinylcholine is best avoided in these patients.
Raised intracranial pressure: Succinylcholine causes an increase in intracranial pressure. Al-
though fasciculations may be the cause of rise in ICP, abolition of fasciculations does not pre-
vent rise in intracranial pressure. Therefore, it is better to avoid it in such patients.
35
Raised intraocular pressure: Unco-ordinated contraction of the intraorbital muscles causes
raised intraocular pressure after succinylcholine. Therefore, it is better to avoid it in patients
with raised intraocular pressure and open-eye injuries.
Raised intragastric pressure: Contraction of the abdominal muscles causes raised intragastric
pressure. However, this is not a major problem as barrier pressure across the lower oesophag-
eal sphincter is also increased.
Malignant hyperthermia: This is a unique condition seen in susceptible individuals. These pa-
tients have abnormal ryanodine receptors at their muscle membranes, giving rise to defective
reuptake of calcium into the sarcoplasmic reticulum. Malignant hyperthermia may be precipi-
tated by succinylcholine and inhalation anaesthetics such as halothane.
Bradycardia: Succinylcholine, especially the second dose can stimulate the vagus nerve and
cause bradycardia. It can occasionally be severe enough to cause cardiac arrest. Succinylcho-
line gets metabolized by plasma pseudocholinesterase to succinyl monocholine which then
sensitizes the SA node to a second dose causing severe bradycardia. Therefore, when a second
dose of succinylcholine is to be administered, it should always be preceded by atropine. Suc-
cinylcholine is photosensitive and hence comes in amber coloured vials. On long duration ex-
posure to light, it can breakdown to acetylcholine molecules and this might produce severe
bradyarrhythmias when injected.
Succinylcholine apnoea: In patients who are deficient in pseudocholinesterase or in those
with atypical pseudocholinesterase (e.g., Vysya community), duration of action of succinylcho-
line is much longer (1/2 hour to several hours). This phenomenon is called succinylcholine ap-
noea. The deficiency of pseudocholinesterase may be congenital or acquired. Acquired pseu-
docholinesterase deficiency may be seen in patients with liver disease. Although it is men-
tioned that this condition may be treated with blood transfusions, it is more appropriate to
ventilate these patients mechanically till complete recovery occurs. Congenital pseudocholi-
nesterase deficiency may be homozygous or heterozygous. It is often described using Dibu-
caine number.
Dibucaine is a local anaesthetic molecule that inhibits pseudocholinesterase. Dibucaine inhib-
its normal pseudocholinesterase to a greater extent than atypical pseudocholinesterases. The
dibucaine number is the percent inhibition of hydrolysis of benzyl choline by dibucaine added
to the plasma sample. Depending on the extent of inhibition of pseudocholinesterase, a dibu-
caine number is given. Normal pseudocholinetserase has a dibucaine number of > 70. This
means that normal pseudocholinesterase is > 70% inhibited by dibucaine. If it is 50 – 60, the
individual is heterozygous for atypical pseudocholinesterase. If it is 20 – 30, the individual is
homozygous for atypical pseudocholinesterase.
Fluoride number: This is a number derived from percentage inhibition of hydrolysis of benzyl-
choline by fluoride. A number of > 60 is normal. Those who are homozygous for atypical en-
zyme will have a number of < 36.
The incidence of severe pseudocholinesterase deficiency (with no detectable enzyme activity,

homozygous for the silent genotype) is very rare (1:100000). They may exhibit prolonged pa-
ralysis (up to 8 hours) after a single dose of succinylcholine.
Phase II block: Occasionally, repeated doses of succinyl choline or its infusion may be used.
When the total dose exceeds 6 mg/kg, phase II block may result at the neuromuscular junc-
tion. The pattern of depolarizing block changes to nondepolarising type of block with features
such as fade, posttetanic potentiation and even partial reversal with neostigmine. Mechanism
of production of Phase II block is not known.
36
Non depolarizing muscle relaxants:
Mechanism of action:
These molecules compete with acetylcholine to bind to the post junctional nicotinic receptors
at the neuromuscular junction. Structure of the post junctional nicotinic receptors involves 5
subunits, 2 α (alpha), 1 β (beta), 1 δ (delta) and 1 ε (epsilon) subunit. One molecule of acetyl-
choline must bind with each of the alpha subunits to open the channel inside the nicotinic re-
ceptor. Even if one alpha subunit is occupied by a NDMR, the receptor channel remains closed
and neuromuscular transmission does not take place. This results in muscle paralysis. Since
this blockade is competitive in nature, this type of blockade is termed competitive type of neu-
romuscular blockade.
Hysteresis: Soon after intravenous administration of the NDMR, the plasma concentration of
the drug will be much higher than its concentration at the neuromuscular junction. However,
subsequently with passage of time, the concentration at the neuromuscular junction falls be-
low the plasma concentration. This phenomenon is called hysteresis.
Once a receptor is blocked by NDMR, it shall remain closed until NDMR dissociates from the
receptor. This happens when the plasma concentration of the NDMR falls below its concentra-
tion at the neuromuscular junction. Fall in the plasma concentration of the NDMR depends on
its hepatic metabolism and renal excretion. This is the reason why it is not possible to reverse
the effects of neuromuscular blockade immediately after administering the NDMR even if
large doses of neostigmine and glycopyrrolate are administered. This again is the reason why
in patients with hepatic / renal disease, the duration of action of aminosteroid NDMR gets
prolonged.
Extrajunctional receptors:
The immature / extrajunctional/foetal form of receptors will also have 5 subunits like the ma-
ture receptors. The only difference is that they have a ‘γ’ subunit in their structure instead of
‘ε’ subunit. This results in longer opening time for the channels and creates low amplitude cur-
rents unlike the mature receptors where the opening time for the channels is much shorter
and they create high amplitude currents. Immature receptors are normally present in foetus
when there is minimal muscle activity before innervation. Similarly, they can replace mature
receptors whenever there is denervation injury such as after upper or lower motor neuron in-
jury, burns and severe sepsis.
Depolarising drugs or agonist drugs such as succinylcholine and acetylcholine depolarise im-
mature receptors easily. Therefore, even a small dose of succinylcholine (much less than its
ED95) can activate a large number of extrajunctional receptors resulting in life-threatening hy-
perkalaemia. Non-depolarising drugs do not act on these immature receptors and hence resis-
tance to non-depolarisers is observed if peripheral nerve activity is monitored in the affected
limbs.
Memory aid: Remember about junctional and extrajunctional receptors: English alphabets
ABCDEFG. In the sequence, A (alpha), B (beta) and E (epsilon) come first and this is normal.
Hence, this combination represents normal unit. However, in disease states, the extrajunc-
tional receptors that are abnormal shall have abnormal sequence in the form of A, B and G
(gamma) instead of E (epsilon).
37
VECURONIUM
Name: Vecuronium bromide
Availability: As a powder to be reconstituted with water. It is available in 4 mg ampoules and
10 mg vials.
Mechanism of action: Similar to NDMR action.
Uses, dose and route: Nondepolarising muscle relaxants are used to provide muscle relaxation
for endotracheal intubation, during surgery and rarely, in the ICU to facilitate mechanical ven-
tilation. ED95 for vecuronium along with oxygen and nitrous oxide is 0.05 mg/kg. For all neuro-
muscular blockers, the intubating dose would be two to three times their ED 95. Therefore, the
intubating dose of vecuronium is 0.1 mg/kg IV. Adequate intubating conditions may be
achieved after three minutes.
To hasten the onset of adequate intubating conditions and to minimize the period of apnea
after induction of anaesthesia, the following techniques may be used:
High dose: Three to four times the ED95 would enable intubation in 90 s.
Priming technique: One tenth of this total dose is given three minutes prior to induction
followed by induction of anaesthesia and administration of the rest of the dose. The pa-
tient should be carefully observed when priming technique is employed as an occasional
patient may complain of difficulty in breathing or double vision warranting immediate se-
dation or induction of anaesthesia.
Timing technique: The full dose of relaxant is given initially and induction of anaesthesia
commenced 90—120 s after that. An occasional patient may start feeling weak or may not
be able to maintain airway before anaesthesia is induced.
If a patient is already intubated (either with suxamethonium or without any relaxant),
slightly less than ED95 of the NDMR would be sufficient to produce adequate skeletal mus-
cle relaxation for surgery.
Infusion: The dose of vecuronium for maintenance of neuromuscular blockade with an infu-
sion is 1-2 μg/kg/min. Infusions can be used for intraoperative muscle relaxation or in the in-
tensive care management of patients.
Duration of action: It is a muscle relaxant with an intermediate duration of action. After the
intubating dose, the effect would last for around 45-90 minutes and the effects of the inter-
mittent boluses for maintenance of paralysis (1/4-1/6 of the intubating dose) would last for
about 15 – 30 minutes.
Metabolism: It is metabolized in the liver and excreted by the kidney. Its metabolites have re-
duced potency but longer duration of action.
Effects on the body: Vecuronium is a cardiostable agent and does not alter heart rate or blood
pressure. It does not cause histamine release. It does not cross placental barrier.
38
PANCURONIUM
Name: Pancuronium bromide
Availability: As a liquid, in ampoules containing 2 mg/ml, 2 ml (4 mg total).
Mechanism of action: Pancuronium is a nondepolarising muscle relaxant, competing with ace-
tyl choline to bind to the nicotinic receptor at the neuromuscular junction. The mechanism of
action is same as that of vecuronium.
tilation. The intubating dose of pancuronium is 0.08 to 0.12 mg/kg IV. Adequate intubating
conditions may be achieved by three minutes. Priming technique can be used with pan-
curonium.
Duration of action: It is a muscle relaxant with a longer duration of action of 1-2 h following
intubating dose and about 30 - 60 minutes following the maintenance dose.
Metabolism: A small quantity of pancuronium is metabolised in the liver (15%) but the rest is
excreted unchanged, mostly through kidney.
Effects on the body: Pancuronium has an atropine-like moiety in its molecule and hence
causes tachycardia and hypertension. It should be used with caution in patients with ischaemic
heart disease. It does not cause histamine release. It does not cross placental barrier.
39
ROCURONIUM
Name: Rocuronium bromide

Availability: As a liquid, containing 10 mg/ml, 10 ml vial.
Mechanism of action: Rocuronium is a nondepolarising muscle relaxant, competing with ace-
tyl choline to bind to the nicotinic receptor at the neuromuscular junction. The mechanism of
action is same as that of vecuronium.
tilation. The intubating dose of rocuronium is 0.3 to 0.6 mg/kg IV. Intubation may be achieved
by 3 minutes. When given in a dose of 1-1.2 mg/kg IV intubating conditions will be achieved
within 90 s. This is the only nondepolarising muscle relaxant that can produce neuromuscular
blockade suitable for endotracheal intubation in a time equivalent to succinylcholine. Hence, it
may be used instead of succinylcholine for rapid sequence induction of anaesthesia.
Duration of action: It is a muscle relaxant with an intermediate duration of action with effects
lasting for 30-60 min following intubating dose and 15 - 20 minutes following maintenance
dose.
Metabolism: It is metabolised and eliminated by the liver. The action of rocuronium may also
be terminated using a new drug called sugammadex, which instantly mops up any circulating
rocuronium. Sugammadex and aminosteroid NDMR especially rocuronium have structural an-
tagonism. It is akin to a lock and key model where sugammadex is like a lock and rocuronium
is the correct key. The moment rocuronium sits in the slot, it gets locked with sugammadex
and becomes unavailable for neuromuscular blockade. However, the rapidity of reversal of
effects of rocuronium with sugammadex depends on the depth of block and dose of sugam-
madex administered. While for a lighter depth of block, 1-1.3 mg/kg of sugammadex may be
sufficient to reverse the effects within 3 minutes; for a deep block or immediately after intu-
bating dose of rocuronium, upto 8 mg/kg of sugammadex may be needed for instant reversal.
Effects on the body: Rocuronium is cardiostable drug and does not alter haemodynamics.
However, when given in doses above 1 mg/kg it can cause tachycardia due to its mild vagolytic
effects. It does not cause histamine release. It does not cross placental barrier.
40
ATRACURIUM
Name: Atracurium besylate
Availability: As a liquid, containing 10 mg/ml, 2.5 ml vial.
Mechanism of action: Atracurium is a nondepolarising muscle relaxant, competing with acetyl
choline to bind to the nicotinic receptor at the neuromuscular junction. The mechanism of ac-
tion is same as that of vecuronium.
tilation. The intubating dose of atracurium is 0.5 to 0.6 mg/kg IV. Intubation may be achieved
by 3 minutes. It can be given as infusion for maintenance of neuromuscular blockade in dose
of 4-12 μg/kg/min.
Duration of action: It is a muscle relaxant with an intermediate duration of action with effects
lasting for 30-45 min following intubating dose and 15 - 20 minutes following maintenance
dose.
Metabolism: Atracurium undergoes two different ways of metabolism. One is by ester hy-
drolysis which is brought about by liver. The other mechanism is Hofmann elimination which is
a pure chemical degradation of atracurium. Hofmann elimination is accelerated by alkaline pH
and increases in temperature. Laudanosine is a major metabolite of atracurium. Laudanosine
is a tertiary ammonium compound and hence can cross the blood brain barrier or the placen-
tal barrier. When laudanosine levels are high (5-15 µg/kg), it may contribute to neuroexcita-
tion.
Effects on the body: Atracurium causes release of histamine when given rapidly in the intubat-
ing doses and can result in hypotension and may precipitate bronchospasm. Therefore, atracu-
rium bolus should be injected slowly.
CISATRACURIUM
Cisatracurium is a geometric stereoisomer of atracurium which is 4 times more potent and has
less side effects than atracurium. Cisatracurium is one of the 10 isomers that are present in
atracurium. Therefore, the intubating dose for cisatracurium is only 0.15-0.2 mg/kg. Cisatracu-
rium also undergoes Hofmann elimination.
DRUGS METABOLISED BY ESTERASES
Succinyl choline, and mivacurium are metabolized by pseudocholinesterase.
Procaine and other amino ester local anaesthetics are metabolized by liver and plasma
esterases
Esmolol is metabolized by red cell esterases.
Remifentanyl is metaboised by non-specific plasma esteraces.
41
NEOSTIGMINE
Name: Neostigmine sulphate
Availability: As a liquid, containing 0.5 mg/ml, 1 ml ampoules, or as a premixed solution with
glycopyrrolate (5 ml ampoule containing 2.5 mg of neostigmine and 0.5 mg glycopyrrolate).
Mechanism of action: Neostigmine is an anticholineterase. It inhibits cholinesterase enzyme,
reducing the breakdown of acetyl choline. As acetyl choline accumulates, it competes with the
nondepolarising muscle relaxant to bind to the nicotinic receptor at the neuromuscular junc-
tion. Acetyl choline opens the nicotininc receptor channel, permitting sodium ions to move in
to the cell which will promote transmission of the action potential and muscle contraction.
Uses, dose and route: Neostigmine is the only anticholinesterase available to be used to re-
verse nondepolarising muscle relaxants. It is used in a dose of 50 – 80 µg/kg. The extent of re-
versal depends on the extent of neuromuscular blockade present when the reversal agent is
given. This may be monitored using train-of-four stimulus. If all four responses are present,
reversal should be complete within 7-10 minutes. Deeper the blockade, longer is the time
taken to reverse neuromuscular blockade and higher will be the dose of neostigmine needed.
Duration of action: It has a duration of action of 4 hours.
Metabolism: It is metabolized in the liver.
Effects on the body: Neostigmine can cause bradycardia, increased secretions and increased
gastrointestinal peristalsis through its muscarinic effects. An anticholinergic agent must always
be given along with it. It does not cause histamine release. It does not cross placental barrier.
OTHER ANTICHOLINESTERASES
Physostigmine: It is the only anticholinesterase that can cross the blood brain barrier and is
used to reverse central anticholinergic syndrome, one of the causes of postoperative cogni-
tive dysfunction.
Pyridostigmine: It is the only anticholinesterase that is available as an oral preparation. It is

used to improve muscle power in patients with myaesthenia gravis.
Edrophonium: This is a short-acting anticholinesterase used to differentiate between
myaesthenic crisis and cholinergic crisis (Tensilon test).
42
ANALGESICS
43
Opioids
Classification of opioids:
Based on origin, opioids can be subclassified into
A. Naturally occurring opioids—Morphine, codeine, papaverine
B. Semisynthetic opioids—heroin, buprenorphine
C. Synthetic opioids—Pethidine, pentazocine, fentanyl, sufentanil, alfentanyl, remifentanil
Based on their action on opioid receptors, they can be classified into

A. Agonists (stimulate opioid receptors)—morphine, pethidine, fentanyl, sufentanil, alfen-
tanyl, remifentanil
B. Partial agonists (agonist antagonists) - that act as agonists in the absence of other agonists
and act as antagonists in the presence of other agonists. Ex: Pentazocine, buprenorphine
C. Antagonists (inhibit opioid receptors)—Naloxone, naltriaxone
Opioid receptors are classified as

A. Orphanin (Op) 1—δ (Delta receptors)
B. Orphanin (Op)2—κ (Kappa receptors)
C. Orphanin (Op)3—µ (Mu receptors)
44
MORPHINE
Name: Morphine sulfate
Availability: It is available as 1 ml ampoules containing 10 mg/ml or 16 mg / ml
It is also available as oral tablets containing 15 mg, 30 mg or 60 mg of morphine.
Mechanism of action: It stimulates µ type of opioid receptors to produce analgesia. It also acts
on delta and kappa opioid receptors.
Uses, dose and route: It can be given practically by any route: intravenously, intramuscularly,
subcutaneously, epidurally, intrathecally or orally.
Premedication for anaesthesia: 0.1 to 0.2 mg/kg IM, 0.05 to 0.1 mg/kg IV
Induction of anaesthesia: Morphine was used to induce anaesthesia in cardiac patients as
it is a cardiostable agent. It was given in a dose of 1.5 - 2 mg/kg, given slowly not exceeding
5 mg/min to prevent/minimize bradycardia and hypotension. The hypotension is due to
histamine release and this may be prevented by premedicating with H1 and H2 blockers. In
such high doses, morphine can also cause chest rigidity.
Currently, it is a popular drug for providing analgesia for acute postoperative pain relief
and cancer pain relief. Oral preparations are mainly used for relief of chronic cancer pain.
Intermittent dosing: It is given intermittently in a dose of 0.1 – 0.2 mg, in divided doses, IM
or IV.
Continuous infusion: After the initial bolus is given, the analgesia may be continued with an
infusion at a rate of 1 – 2 mg/h IV. Alternately, it may be given using IV patient-controlled
analgesia (PCA) as follows: 1 mg bolus, 5 – 10 minutes lock-out period, maximum 0.1 – 0.2
mg/kg/h.
Epidural dose: 30-50 µg/kg body weight and can be given as twice daily dose for postop-
erative pain relief.
Intrathecal dose—preservative free morphine 0.1-0.2 mg for adults
It is used commonly in pulmonary oedema and myocardial infarction to reduce the preload
to heart by causing peripheral pooling of blood. Also, its euphoric effects help in these con-
ditions.
Onset: More than one arm-brain circulation time (1 – 2 minutes) when given IV, 15 minutes
when given IM.
Duration: One hour when given IV, four to six hours when given IM, 12-24 h when
given epidural / intrathecal.
Elimination: It is metabolized by liver to morphine-3-glucuronide and morphine-6-glucuronide
and excreted by the kidney. Morphine-3-glucuronide has nearly one third the effect of the par-
ent drug, however it is longer acting than the parent compound and can accumulate with long
duration infusion especially in patients with renal impairment.
Central nervous system (CNS): Initially it causes euphoria and then sedation. It is a very
good analgesic. Later, it produces dose-dependent depression of the CNS. Induction of an-
aesthesia is usually heralded by loss of verbal contact but this is usually maintained even
after large doses. Characteristically, morphine produces respiratory depression, but as long
as the patient remains conscious, verbal contact can be made and he is reminded to
breathe. This pattern of respiratory depression is called Ondine’s curse. It has a cerebral
protective effect by reducing cerebral metabolic rate and blood flow.
45
Cardiovascular system: It causes hypotension due to peripheral vasodilatation. It also has a
vagotonic effect and causes bradycardia.
Respiratory system: It produces dose-dependent reduction in respiratory rate and in large
doses, apnoea. The tidal volume is well-maintained till late. Minute ventilation reduces
causing hypercarbia. It obtunds the airway reflexes well. It can cause bronchospasm
through histamine release.
Gastrointestinal system: It has emetic properties, delays gastric emptying and produces
constipation. It can precipitate biliary colic in susceptible individuals.
Adverse effects: Respiratory depression, pruritus, urinary retention, allergic reactions due to
histamine release.
Cautions: To be used with caution in patients in respiratory failure, hepatic / renal impair-
ment. Since morphine is poorly lipid-soluble, patients with head injury with a breach in the
blood-brain barrier may show a very prolonged effect.
46
FENTANYL
Name: Fentanyl hydrochloride
Availability: It is available as 2 ml and 10 ml ampoules containing 50 µg/ml
Mechanism of action: It stimulates the µ type of opioid receptors and produces analgesia. It
also acts on delta and kappa opioid receptors.
subcutaneously, transdermally, epidurally, intrathecally or orally.
Analgesia: Fentanyl is given in a dose of 1 – 2 µg/kg, given intravenously for providing
postoperative pain relief. It may be repeated in a dose of 1 – 2 µg/kg intravenously. After
the initial bolus is given, the analgesia may also be continued with an infusion at a rate of
1 – 2 µg/kg/h IV.
Onset: More than one arm-brain circulation time (1 – 2 minutes) when given IV,
Duration: One hour when given IV.
Elimination: It is metabolised by liver and excreted by the kidney.
Central nervous system (CNS): Initially it causes euphoria and then sedation. It is a good
analgesic. Later, it produces dose-dependent depression of the CNS. The pattern of respi-
ratory depression is similar to morphine. It has a cerebral protective effect by reducing
cerebral metabolic rate and blood flow.
Cardiovascular system: It does not cause histamine release and is much more cardiostable.
through histamine release. Fentanyl induced cough occurs immediately after IV admini-
stration and its mechanism is not known.
constipation.
Musculoskeletal system: Fentanyl causes muscle rigidity. This depends on the dose and
speed of administration of fentanyl. If intense, it can be treated with induction or deepen-
ing of anaesthesia followed by muscle relaxants.
Adverse effects: Respiratory depression, pruritus, urinary retention, biliary colic, allergic reac-
tions due to histamine release.
Cautions: To be used with caution in patients with respiratory failure. Delayed respiratory de-
pression (about 30-45 min after IV administration) is known to occur with fentanyl.
47
TRAMADOL
Name: Tramadol hydrochloride
Availability: It is available as 1 ml ampoule containing 50 mg/ml
Mechanism of action: It stimulates the µ, δ and k type of opioid receptors and produces anal-
gesia. It is a weak opioid.
Uses, dose and route: It can be given intravenously, intramuscularly, epidurally or orally.
Analgesia: Tramadol is given in a dose of 1 – 2 mg/kg, given intravenously for providing post-
operative pain relief. It may be repeated 8th hourly.
Onset: More than one arm-brain circulation time (1 – 2 minutes) when given IV,
Duration: Four to six hours
Elimination: It is metabolized by liver and excreted by the kidney.
ratory depression is similar to morphine.
Cardiovascular system: It causes less histamine release and produces less hypotension.
through histamine release.
Gastrointestinal system: It has emetic properties (high incidence), delays gastric emptying
and produces constipation.
Adverse effects: Respiratory depression, pruritus, urinary retention,
Cautions: To be used with caution in patients with respiratory failure.
48
BUPRENORPHINE
Name: Buprenorphine hydrochloride
Availability: It is available as 1 ml ampoule containing 300 µg
Mechanism of action: It stimulates the µ type of opioid receptors and produces analgesia. It is
a mixed agonist-antagonist (partial agonist).
subcutaneously, epidurally, intrathecally, orally and even sublingually.
Analgesia: It is not so popular for intravenous use. Buprenorphine is given in a dose of 1 – 1.5
µg/kg intrathecally or 1.5 - 2 µg/kg epidurally for providing postoperative pain relief.
Onset: Five minutes
Duration: Its duration of action can vary from 12-24 hours depending on the route of admini-
stration.
Cardiovascular system: It does not cause histamine release and is much more cardiostable.
causing hypercarbia.
constipation.
Adverse effects: Respiratory depression, pruritus, urinary retention
Cautions: To be used with caution in patients with respiratory failure. In larger doses (> five
times the therapeutic dose), there is a ceiling effect on the analgesic effect and its antagonistic
properties become more prominent.
49
PETHIDINE
Name: Pethidine hydrochloride. Also known as meperidine hydrochloride.
Availability: It is available as 2 ml ampoules containing 50 mg/ml
Mechanism of action: It stimulates the µ opioid receptors and produces analgesia. It is about
one tenth potent as morphine. Therefore, its dose is usually about 10 times the recommended
dose for morphine. It also acts on delta and kappa opioid receptors.
subcutaneously, epidurally, intrathecally or orally.
Premedication of anaesthesia: 1 to 2 mg/kg IM or IV
Analgesia: Pethidine is given in a dose of 1 – 1.5 mg/kg, given intramuscularly for providing
postoperative pain relief. It may also be given in a dose of 0.5 – 1 mg/kg intravenously. Af-
ter the initial bolus is given, the analgesia may be continued with an infusion at a rate of
10 – 20 mg/h IV. Alternately, it may be given using IV patient-controlled analgesia (PCA) as
follows: 10 mg bolus, 5 – 10 minutes lock-out period, maximum 0.5 mg/kg/h.
Shivering: Used routinely to treat of postoperative shivering in adults. (15-25 mg IV).
Onset: 1 – 2 minutes when given IV, 15 minutes when given IM.
Duration: Three to four hours when given IV, four to six hours when given IM.
Elimination: It is metabolised by liver to norpethidine and excreted by kidney. Accumulation of
norpethidine can precipitate seizures. So, prolonged infusion of pethidine is not recom-
mended.
Central nervous system (CNS): Euphoria, sedation, analgesia and dose dependent depres-
sion of the CNS and respiratory system. Norpethidine can precipitate seizures.
Cardiovascular system: It causes hypotension due to negative inotropic effects and periph-
eral vasodilatation and tachycardia due to atropine-like moiety in it. The vasodilation is
due to histamine release and may be prevented by premedicating with H1 and H2 blockers.
Respiratory system: Dose-dependent depression of respiration and in large doses, apnoea.
The tidal volume is well-maintained till late. Minute ventilation reduces causing hypercar-
bia. It obtunds the airway reflexes well. Histamine release may cause bronchospasm.
constipation.
Adverse effects: Respiratory depression, pruritus, urinary retention, allergic reactions due to
histamine release.
Cautions (similar to morphine): To be used with caution in patients with respiratory failure,
hepatic / renal impairment. Since pethidine is poorly lipid-soluble, patients with head injury
with a breach in the blood-brain barrier may show a very prolonged effect.
Pethidine is known to have 5 like effects: atropine like (causes tachycardia), papaverine like (causes
bronchodilation, vasodilation and uterine dilatation), morphine like (analgesia through opioid receptor
stimulation), histamine like (pruritus) and lignocaine like (analgesia mediated by inhibition of sodium
channels at nerve endings.
Lytic cocktail: A mixture of pethidine with chlorpromazine and promethazine was used for treatment of
eclampsia.
Interaction with MAO inhibitors: Pethidine is known to have dangerous interactions in patients re-
ceiving MAO inhibitors and is best avoided in these patients. 50
PENTAZOCINE
Name: Pentazocine hydrochloride
Availability: It is available as 1 ml ampoule containing 30 mg
Mechanism of action: It stimulates the µ type of opioid receptors and produces analgesia. It is
a mixed agonist-antagonist.
Uses, dose and route: It can be given intravenously, intramuscularly or subcutaneously.
Analgesia: Its intravenous dose is 15 – 30 mg for providing pain relief.
Onset: Five minutes
Duration: Six to eight hours
Cardiovascular system: It can cause hypertension, and myocardial ischaemia in susceptible
patients.
causing hypercarbia.
Gastrointestinal system: It has emetic properties (high incidence), delays gastric emptying
and produces constipation.
Adverse effects: Respiratory depression, pruritus, urinary retention
Cautions: To be used with caution in patients with respiratory failure and in those with cardiac
pathology.
51
DICLOFENAC
Name: Diclofenac sodium
Availability: It is available as 3 ml ampoule containing 75 mg; As 50 mg tablets; As supposito-
ries containing 12.5, 25 and 100 mg diclofenac and as a gel (1%) for topical application.
Mechanism of action: It is a nonsteroidal anti-inflammatory drug. It produces analgesia by in-
hibiting prostaglandin synthesis secondary to inflammation. It inhibits both COX – 1 and COX –
2 (cyclo-oxygenase enzymes). COX-2 inhibition produces analgesia and anti-inflammatory ef-
fect whereas COX-1 inhibition produces adverse effects such as bronchospasm, platelet inhibi-
tion and gastric mucosal erosions. This is the rationale for the use of COX-2 inhibitors such as
parecoxib and celecoxib as analgesics in susceptible patients.
Uses, dose and route: It can be given intravenously, intramuscularly, orally and even rectally.
Benzyl chloride is used as a preservative in some preparations. Care should be taken to use
only preservative free preparations for intravenous administration.
Analgesia: It is given in a dose of 1 – 1.5 mg/kg intramuscularly or intravenously slowly as an
infusion. It is used as suppositories in a dose of 1.5 - 2 mg/kg, for providing postoperative pain
relief.
Onset: Five minutes, when given IV, 15 – 30 minutes when given orally or rectally
Central nervous system (CNS): It is a good analgesic. It has no effect on the CNS.
Cardiovascular system: It is cardiostable.
Respiratory system: It can cause bronchospasm in susceptible individuals. NSAIDS should
be avoided in asthmatics.
Gastrointestinal system: It can cause gastric irritation, ulcers, bleeding or perforation.
Hence it should be avoided in patients with known acid-peptic disease or appropriate anti-
ulcer measures taken.
Adverse effects: Asthma, peptic ulcer, bleeding
Cautions: To be used with caution in patients with renal impairment. It can precipitate renal
failure by reducing renal flow due to prostaglandin inhibition (analgesic nephropathy).
52
PARACETAMOL
Name: Paracetamol (acetaminophen)
Availability: It is available as 2 ml ampoules, containing 300 mg. It is also available in tablet
form (500 mg), syrup (125 mg/5 ml), suppositories (80 mg, 160 mg, 325 mg, 1 g) and an intra-
venous injection formulation containing 1 g in 100 ml of saline.
Mechanism of action: It inhibits cyclo-oxygenase II and prevents prostaglandin release in re-
sponse to inflammation.
Uses, dose and route: It can be given intravenously, intramuscularly, orally and rectally.
Analgesia: It can be given intravenously slowly. The dose is 1-4 g IV in divided doses. Daily total
dose should not exceed 60 mg/kg when used for providing postoperative pain relief. Rectal
suppository dose: 30-40 mg/kg as initial dose and subsequently 15 mg/kg to a total of 60 mg/
kg can be given.
Onset: Five minutes
Elimination: It is metabolized by liver.
It is mainly used as an antipyretic. In larger doses, it also provided analgesia.
Gastrointestinal system: It is well absorbed when given orally. In susceptible individuals, it
can causes gastric ulcers.
Cautions: To be used with caution in patients with liver dysfunction.
Antidote: N-acetyl cysteine
53
NALOXONE
Name: Naloxone hydrochloride
Availability: It is available in three concentrations: 20 µg/ml, 400 µg/ml and 1000 µg/ml.
Mechanism of action: Naloxone is an antagonist at the µ receptor and is a competitive inhibi-
tor of pure agonists such as morphine.
Uses: It is used to diagnose and treat opioid overdose.
Onset: 1-2 minutes
Dose: It can be given as a bolus of 20-40 µg every 2-3 minutes until satisfactory response is
obtained. Infusion dose is 400 µg/h. Persistence of respiratory depression even after 10 mg
naloxone administration (20-40 µg every 2-3 minutes) indicates opioid induced respiratory de-
pression to be an unlikely cause.
Duration of action: varies between 45 minutes to 3 hours. Remember that often the duration
of action of naloxone may be shorter than that of the opioids and hence either it needs to be
administered in repeated doses or should be given as an infusion.
Cardiovascular system: Naloxone should be carefully administered to patients with respi-
ratory depression. In the presence of hypercarbia, naloxone can cause tachycardia, hyper-
tension and arrhythmias. The patient must be manually ventilated to treat hypercarbia and
naloxone administered slowly.
Respiratory system: Naloxone effectively reverses respiratory depression due to opioids.
However, it should be remembered that the duration of action of naloxone is one hour
whereas the opioid may be of longer duration of action. Hence, resedation and recurrence
of respiratory depression is possible when the effect of naloxone wears off.
Central nervous system: The administration of naloxone is accompanied by reversal of an-
algesia. Hence, the patient can become restless and agitated due to perception of pain.
54
CLONIDINE
Name: Clonidine hydrochloride
Availability: It is available as 1 ml ampoules containing 150 µg. It is available as a oral prepa-
ration of 100, 200 and 300 µg strength. After oral administration, its antihypertensive effects
are brought about within 30-60 min while the peak effects come around 2-4 h.
Mechanism of action: It acts as an alpha2 agonist although it has actions on alpha 1 receptors
also. The ratio of a2 to a1 receptor selectivity is 200:1.
Clonidine is known to have a long elimination half-life (8.5 h). This is four times more than that
for dexmedetomidine.
It is used as an antihypertensive, usually given orally in a dose of 75 to 150 µg upto 4-6
doses.
It is used to prevent tachycardia response to vasodilators when used to induce hypoten-
sion. It is given as oral premedication (75 to 150 µg). It is also a sedative and anxiolytic. IV
dose: 4-5 µg/kg for sedation, analgesia
It can be used as an analgesic supplement when used epidurally or intrathecally
It can be used to prolong the action of local anaesthetics during spinal anaesthesia (30 to
45 µg)
It can be used to prolong the action of local anaesthetics during nerve blocks (75 µg).
Clonidine has also been used to treat alcohol withdrawal, for treatment of migraine head-
ache etc.
Central nervous system: It causes drowsiness and dryness of mouth. It reduces MAC of inhala-
tion anaesthetics. It produces analgesia. It reduces the MAC of volatile anaesthetic agents
Cardiovascular system: It causes bradycardia, hypotension and decrease in cardiac output.

Lower doses of clonidine when given as a bolus might cause initial transient hypertension due
to its alpha-1 stimulant activity. This will soon be followed by hypotension, sedation and anal-
gesia. After chronic use, if discontinued, can cause rebound hypertension.
55
DEXMEDETOMIDINE
Name: Dexmedetomidine hydrochlride
Availability: It is available as 2 ml vials containing 200 µg (100 µg/ml).
Mechanism of action: It is an enantiomer of medetomidine. It acts as an alpha2 agonist al-
though it has mild actions on alpha 1 receptors also. The ratio of 2 to receptor selectivity
is
It is always given intravenously as an infusion. 200 µg of dexmedetomidine is diluted to 50 ml
with saline to give a concentration of 4 µg/ml.
It is given in a bolus dose of 1 µg/kg over 10 min (which is also given as an infusion) followed
by 0.3 to 0.7 µg/kg/h.
It is mainly used as a sedative agent in the ICU.
It can be used for procedural sedation (such as fibreoptic bronchoscopy, colonoscopy)
(procedures done under monitored anaesthesia care)
It can be used to blunt haemodynamic responses to intubation and extubation
It can be used as a supplement to general anaesthesia
It has been used intrathecally (3—5 µg) to prolong the action of local anaesthetics.
Onset: 6 min when given intravenously
Duration of action: Two hours.
Metabolism: It is metabolized in the liver and excreted mainly by the kidney.
Central nervous system: It causes drowsiness and dryness of mouth. It reduces MAC of inha-
lation anaesthetics. It produces analgesia.
Cardiovascular system: It causes bradycardia, hypotension and decrease in cardiac output.
Respiratory system: It has no effect on the respiratory system.
Caution:
It is best avoided in patients with pre-existing heart blocks and hypotension.
It is not licensed for use in the pregnant patient.
The dose must be reduced in liver disease.
Although its pharmacokinetics are not altered in renal disease, reduction of its dose is rea-
sonable as dexmedetomidine is mainly excreted through kidney.
It is licensed for use as an infusion for only 24 hours. Its safety beyond that period is not
known.
Its safety in children is not established.
56
VASOPRESSORS AND INOTROPES
57
ADRENALINE
Name: Adrenaline tartrate (also known as epinephrine)
Availability: It is available in ampoules containing 1 mg/ml.
Receptors and effects: It is an agonist at α1, α2, β1 and β2 receptors
For cardiopulmonary resuscitation: 1 mg IV every 3 – 5 minutes. It exerts an α-effect in
these doses, producing peripheral vasoconstriction and raises coronary perfusion pressure.
By its lusitropic property, adrenaline improves ventricular relaxation thereby improving dia-
stolic coronary blood flow.
To treat anaphylaxis: 50 – 100 µg boluses IV or 0.5 to 1 mg IM, if intravenous access is not
available. It is a histamine antagonist. To treat bone cement reaction, adrenaline is used in
intravenous boluses of 25 µg -50 µg .
As an additive to local anaesthetics: Used in a concentration of 1:200,000 (5 µg/ml).
1. As a vasoconstrictor to delay absorption and thereby increasing the duration of ac
tion, reducing the toxicity and raising the maximum dose of local anaesthetic that can
be used.
2. As a component of epidural test dose (to identify accidental intravascular injection
of local anaesthetic).
3. To reduce bleeding at the site of surgical incision.
As an inotrope: 0.05 to 0.2 µg/kg/min infusion. In lower doses, its β-effects are prominent
(inotropy, chronotropy) but in larger doses, α-effect (vasoconstriction) is more prominent.
As a bronchodilator in extreme situations: 1 mg s/c
As a vasoconstrictor to reduce vascularity of surgical site: 1:200,000 solution.
Racemic adrenaline (2.25%) is a mixture of laevo and dextro-isomers of adrenaline. This
causes less tachycardia and is used to treat laryngeal oedema. The doses are as follows:
Adults: 0.75 ml, child: 0.5 ml and in a child < 6 months, 0.25 ml. This is diluted with 3 ml of
saline and nebulised. It may be repeated in 30 minutes. If racemic epinephrine is not avail-
able, there is evidence in the literature that 0.5 ml/kg of 1:1000 adrenaline (laevo-isomer)
up to a maximum of 5 ml nebulisation undiluted may be helpful in children with severe
croup. Heart rate must be monitored closely after nebulisation. This is contra-indicated in
children with ventricular outlet obstruction. One should watch out for rebound increase in
stridor about 30 minutes after the nebulisation is over, as the effects of adrenaline wear off.
Onset: Immediate if given IV.
Metabolism and elimination: It is metabolized by COMT (catechol-O-methyl transferase) and
MAO (monoamine oxidase) enzymes.
Adverse effects: Tachycardia, hypertension, myocardial ischaemia, arrhythmias etc
Cautions: To be used with caution in patients with cardiovascular and cerebrovascular disease.
All catecholamine infusions can contribute to hyperglycaemia.
Special precautions: Maximum recommended dose of adrenaline that can be used for local
infiltration: 3.3 µg/kg with Halothane (except in children up to 10 µg/kg can be used), 6 µg/kg
with Isoflurane, 10 µg/kg with Sevoflurane. [Easy to remember: HIS— 3 x1, 3x2, 3x3]
Important drug interactions: Exogenously administered adrenaline aggravates the myocardial
irritant potential of halothane and can precipitate arrhythmias. Ventricular arrhythmias are
more likely with halothane, especially when associated with hypercarbia, hypoxia and acidosis.
58
Q) What does 1:1000 mean?
A) It means that there is 1 g of adrenaline in 1000 ml of that solution. This works out to be
1000 mg in 1000 ml. In other words, each ml of this solution contains 1 mg of adrenaline.
Q) What does 1:200,000 mean?
A) This means that there is 1 g of adrenaline in 200,000 ml of the solution. This works out to
be 1000 mg in 200,000 ml or 1 mg in 200 ml of the solution. This means it contains 1000 µg in
200 ml of the solution. In other words, each ml of this solution contains 5 µg of adrenaline.
NORADRENALINE
Name: Noradrenaline bitartarate (also known as norepinephrine)
Availability: It is available in 2 ml ampoules containing 2 mg/ml of noradrenaline bitartarate.
This is equivalent to 1 mg/ml of noradrenaline.
Receptors and effects: It is an agonist at α1, α2 and β1 receptors
As a vasopressor: Noradrenaline is a naturally occurring, directly-acting catecholamine. It is
a powerful vasopressor, acting on the alpha1 receptors. It is also an inotrope as it has beta1
receptor stimulant properties but the vasoconstrictive properties predominate.
It is given as an intravenous infusion only. The dose is 0.05 to 0.2 µg/kg/min (2 – 10 µg/
min). It is the vasopressor of choice in septic shock. It may also be used to counter pro-
found peripheral vasodilatation (e.g., drug-induced as with milrinone in the treatment of
left ventricular failure).
Onset: Immediate.
Duration: 3 – 5 minutes
Adverse effects: Hypertension, myocardial ischaemia, arrhythmias
Cautions: To be used with caution in patients with cardiovascular and cerebrovascular disease.
Infusions of catecholamines should preferably be given through central venous catheters.
Special precautions: Since it is a powerful vasoconstrictor, it can increase the afterload to the
left ventricle, can affect splanchnic circulation and other peripheral tissues if used indiscrimi-
nately. Hence, whenever noradrenaline infusion is required, invasive blood pressure monitor-
ing is warranted. It is desirable that the systemic vascular resistance is measured, particularly
when renal dysfunction is also present and higher dose of noradrenaline is being used to main-
tain blood pressure.
Treatment of anaphylaxis
Primary treatment
100% oxygen. Take care of airway and breathing.
Adrenaline, 50—100 µg boluses intravenously as required. If an intravenous access is not

available, 0.5 to 1 mg adrenaline may be given intramuscularly. There is no role for subcuta-
neous adrenaline in anaphylaxis.
Rapid infusion of intravenous fluids, preferably Ringer lactate to counter the relative hypo-
volaemia
59
Leg end elevation with the patient’s back flat.
Secondary treatment
Chlorpheniramine maleate, 10 mg, intravenously
Hydrocortisone 100 mg, IV
Salbutamol nebulisation for bronchospasm
Adrenaline infusion to maintain circulation.
DOPAMINE
Name: Dopamine hydrochloride
Availability: It is available in 5 ml ampoules containing 40 mg/ml of dopamine
Receptors and effects: It is an agonist at α1, β1, β2 and DA1 receptors
As an inotrope and vasopressor: Dopamine is a directly-acting inotrope and vasopressor. It
is always used as an infusion in a dose ranging from 2 – 20 µg/kg/min. By its indirect action,
dopamine aids in release of norepinephrine.
Its actions are dose-dependent.
At 1-2 µg/kg/min, it acts on dopaminergic (DA1) receptors and has a renal vasodilatory ef-
fect.
At 5-10 µg/kg/min, it acts on beta receptors and improves contractility of the heart, in-
creases heart rate and cardiac output.
When given at a rate of more than 10 µg/kg/min, it begins to act on the alpha receptors
also and increases blood pressure.
Adverse effects: Dose related tachycardia. When administered in higher doses (> 10 µg/kg/
min), it behaves like noradrenaline.
60
DOBUTAMINE
Name: Dobutamine hydrochloride. It is a synthetic catecholamine.
Availability: It is available in 5 ml ampoules containing 50 mg/ml of dobutamine
Receptors and effects: It is an agonist at α1, β1 and β2 receptors. However, its major effects
are on the β1 receptors.
As an inotrope: Dobutamine is a directly-acting inotrope and is always used as an infusion in
doses of 2-20 µg/kg/min. It is a beta1 and beta2 stimulant. It acts on beta1 receptors and im-
proves contractility of the heart but has a more predominant action on beta 2 receptors
causing peripheral vasodilatation and reduction in afterload. Consequently the heart rate
and cardiac output increase. Thus it acts similar to an inodilator (inotrope + vasodilator).
Hence, it is very useful to improve cardiac output in patients with low ejection fraction.
Metabolism and elimination: It is metabolized by conjugation in the liver and eliminated by
kidney.
Adverse effects: Dose related tachycardia, may cause hypotension and should not be used as
an inotrope if the systolic blood pressure is less than 80 mmHg.
DOPEXAMINE
Dopexamine hydrochloride is a synthetic catecholamine, structurally related to dopamine,

with marked intrinsic agonist activity at beta 2-adrenoceptors, lesser agonist activity at dopa-
mine receptors and beta 1-adrenoceptors. It is administered by intravenous infusion as it has a
rapid onset and short duration of action similar to dopamine. It reduces afterload through pro-
nounced arterial vasodilatation, increases renal perfusion by selective renal vasodilation and
evokes mild cardiac stimulation through direct and indirect positive inotropism. Dopexamine
hydrochloride may be useful in the treatment of acute heart failure and the postoperative
management of low cardiac output states.
61
PHENYLEPHRINE HYDROCHLORIDE
Name: Phenylephrine hydrochloride
Availability: It is a synthetic noncatecholamine. It is available in 1 ml ampoule containing 10
mg/ml of phenylephrine
As a vasopressor: Phenylephrine is a directly-acting vasopressor, acting on the alpha recep-
tors. It has no inotropic action. It may be given as a bolus (1 to 2 µg/kg). It may also be
given as an infusion at a rate of 1-2 µg/kg/min and titrated to blood pressure.
It is most often used to treat hypotension due to vasodilatation in patients with ischaemic
heart disease where any tachycardia may be undesirable.
It is a useful drug for management of patients with hypertrophic obstructive cardiomyopa-
thy or stenotic heart disease (mitral stenosis and aortic stenosis) as this drug can improve
systemic vascular resistance and blood pressure without increasing heart rate.
It may also be used to treat hypotension consequent to spinal/epidural anaesthesia in
pregnant patients for Caesarean section.
As a mydriatic: It is used as a 10% eye drops to produce mydriasis. When used for this pur-
pose, it is important to monitor the patient for its haemodynamic effects.
Duration: < 5 minutes when given IV
Elimination: It is readily metabolized by liver and gastro-intestinal tract.
Adverse effects: Dose related hypertension and reflex bradycardia
Special precautions: Since it is a powerful vasoconstrictor, it can increase afterload to the left
ventricle.
62
MEPHENTERMINE
Name: Mephentermine sulphate
Availability: It is available in 10 ml vials containing 30 mg/ml of mephentermine. It is also
available as 1 ml ampoule containing 15 mg/ml of mephentermine.
As a vasopressor: Mephentermine is an indirectly-acting vasopressor, acting on both alpha
and beta receptors. It is usually diluted to a concentration of 3 mg/ml. It is given as 3 mg
bolus and repeated as required. It is one of the commonest vasopressors used to treat hy-
potension under anaesthesia.
Adverse effects: Mephentermine may cause uterine artery constriction and is not the pre-
ferred drug to treat hypotension consequent to spinal anaesthesia in pregnant patients for
Caesarean section.
Onset: Almost immediately if given IV, within 5-15 min if given IM
Duration: 15-30 minutes when given IV, 1-4 hours if given IM
Elimination: It is metabolized by liver by demethylation and excreted in the urine.
63
EPHEDRINE
Name: Ephedrine hydrochloride
Availability and action: It is available in 1 ml ampoules containing 30 mg/ml of ephedrine. It
acts by releasing noradrenaline at sympathetic nerve endings.
As a vasopressor: Ephedrine is an indirectly-acting vasopressor, acting on both alpha and
beta receptors. It is usually diluted to a concentration of 6 mg/ml. It is given as 6 mg bolus
and repeated as required. Ephedrine does not cause uterine artery vasoconstriction and is
the preferred drug to treat hypotension consequent to spinal anaesthesia in pregnant pa-
tients for Caesarean section.
Onset: Immediately if given IV, 15 min if given IM
Duration: One hour when given IV. Half life is 3-6 hours.
Elimination: Majority of ephedrine is excreted unchanged in urine. A small amount is metabo-
lized by liver.
64
VASOPRESSIN
Name: Vasopressin
Availability: It is available in 2 ml ampoules containing 20 IU/ml of synthetic vasopressin
(arginine vasopressin).
As a vasopressor: Vasopressin acts on vasopressin receptors to cause vasoconstriction. It is
used in septic shock where there is a possible vasopressin deficiency and resistance to cate-
cholamines. It has been recently recommended to be used in the treatment of resistant
septic and anaphylactic shock. The dose is 0.01 – 0.04 IU/min (0.6 – 2.4 IU/h).
In CPR: Vasopressin is used as a single dose of 40 IU to produce vasoconstriction and in-
creases in diastolic blood pressure during cardiopulmonary resuscitation (CPR) to replace
either the first or the second dose of epinephrine.
Duration: 20 minutes when given IV
Adverse effects: In larger doses, it can produce hypertension, bradycardia, myocardial ischae-
mia, and splanchnic vasoconstriction.
65
DIGOXIN
Name: Digoxin hydrochloride
Availability: It is available in 2 ml ampoules containing 0.25 mg/ml of digoxin
Mechanism of action: It inhibits the Na+/K+ ATPase pump, thus encouraging the slow Na+-Ca++
channels resulting in intracellular accumulation of calcium.
Digoxin may be used as an inotrope and as an antiarrhythmic agent. It may be given orally
or intravenously. When a loading dose of digoxin followed by a maintenance dose is given,
therapeutic levels of digoxin are achieved faster. This is called rapid digitalization. Rapid
intravenous digitalization can be achieved in an average adult as follows: 0.5 mg digoxin
diluted and given over 20 to 30 minutes followed by 0.25 mg eighth hourly x 2 doses, fol-
lowed by 0.25 mg/day maintenance dose.
Digoxin is a useful inotrope in cardiac failure. It improves contractility but does not cause
tachycardia. It acts on the atrioventricular node and slows conduction. Thus, it is useful to
treat supraventricular tachyarrhythmias.
Therapeutic plasma level is 0.8 – 2 ng/ml and its therapeutic index is very narrow. It is impor-
tant to monitor plasma levels in patients receiving chronic digoxin therapy.
Onset: 5 – 30 minutes if given IV.
Peak effect: One to four hours
Duration: 36 – 48 hours
Elimination: It is metabolized by liver and eliminated by the kidney.
Caution: Digoxin should be used with caution in patients receiving drugs that reduce atrioven-
tricular conduction such as beta blockers and calcium channel blockers.
Cardioversion in patients receiving digitalis or digitalised patients, for the treatment of severe
supraventricular dysrhythmias may be hazardous as it may precipitate ventricular tachycardia
and fibrillation. If there is a wide-complex tachycardia with severe haemodynamic instability,
cardioversion with lower doses is recommended (e.g., 100 J for ventricular tachycardia rather
than 200 J).
Adverse effects: Digoxin toxicity
DIGOXIN TOXICITY:
Clinical features: Symptoms: Nausea, vomiting, yellow vision, palpitations, drowsiness, syn-
cope.
Signs: Bradycardia, ventricular ectopics, prolongation of PR interval, Reverse ‘tick’ sign on the
ECG, ventricular bigeminy.
Factors predisposing to digoxin toxicity: Hypokalaemia, higher doses, renal failure, hepatic
failure and hypoalbuminaemia.
Treatment: Fab antibodies, supportive measures, treatment of electrolyte imbalances such as
hypokalaemia, hypomagnesemia, phenytoin and lidocaine, temporary pacing.
Do not treat hyperkalaemia in a patient on digoxin therapy with calcium.
66
MILRINONE
Name: Milrinone lactate
Availability: It is available in 10 ml ampoules containing 1 mg/ml of milrinone lactate
Mechanism of action: It is a phosphodiesterase III inhibitor, increases intracellular concentra-
tion of cyclic AMP and calcium, causing inotropy.
It is used as an inodilator, mainly for failing hearts. The increase in inotropy together with
vasodilatation (inodilator) is beneficial to a failing left ventricle. It is used as an infusion. A
loading dose may or may not be given.
The dose is 0.05 mg/kg bolus over 10 minutes followed by 0.375 – 0.75 µg/kg/min.
Duration: 3 – 6 hours when given IV
Adverse effects: Profound hypotension due to vasodilatation, requiring infusion of noradrena-
line to improve blood pressures. It is important to monitor arterial blood pressures invasively
in such situations. It should not be used in patients with significant valvular stenotic lesions.
Elimination: Liver
67
VASODILATORS
68
SODIUM NITROPRUSSIDE
Name: Sodium nitroprusside
Availability: It is available in powder form, 50 mg vial which is amber coloured.
Mechanism of action: It acts by releasing endothelial nitric oxide and is an arterial and venodi-
lator. It acts mainly on the resistance vessels.
To treat hypertension
To induce hypotension
To obtund hypertensive response to intubation
In ergot alkaloid poisoning, to reverse the effects of ergot on vessels
It is given intravenously as an infusion, in a dose range of 0.5 to 5 µg/kg/min.
Onset: Immediate.
Elimination: It is metabolized in the liver. The nitroprusside radical breaks down into five cya-
nide molecules.
These cyanide molecules combine with thiosulphate molecules to form thiocyanate in the
presence of hepatic enzyme rhodanase. Thiocyanate is then eliminated from the kidney.
Some of the cyanide molecules may combine with methaemoglogin to form cyan-
methaemoglobin and get eliminated from the kidney.
Some cyanide molecules will combine with hydroxocobalamine and get eliminated as
cyanocobalamine.
Adverse effects: Tachycardia, hypotension, headache, cyanide toxicity, methaemoglobinaemia
Cautions: To be used with caution in patients with low intravascular volume.
Special precautions: Sodium nitroprusside gets degraded on exposure to light. The syringe as
well as the infusion set is covered to prevent degradation by light. Alternately, black opaque
syringes are available to administer sodium nitroprusside. When freshly diluted and properly
protected from light, it can remain stable for 24 hours.
It should be avoided in patients with raised intracranial pressure.
CYANIDE TOXICITY
How can cyanide toxicity be identified?
When the cyanide concentration in the blood exceeds safe levels, it combines with cyto-
chrome oxidases preventing formation of ATP in the cells. Thus, it produces histotoxic hypoxia.
Manifestations: Cyanide toxicity is likely when increasingly larger doses are used and for pro-
longed periods. Tachyphylaxis to the effect of sodium nitroprusside may be noticed. The pa-
tient would present with clinical features of hypoxia. This may be difficult to detect if the pa-
tient is under general anaesthesia and a high degree of suspicion and vigilance is required to
detect cyanide toxicity.
The patient presents with unexplained tachycardia and hypotension. Electrocardiographic
changes of myocardial ischaemia may be seen. The pulse oximeter will not be helpful in the
detection of histotoxic hypoxia as the oxygen saturation will be normal. Blood gas analysis
would reveal the presence of metabolic acidosis. The colour of venous blood resembles arte-
rial blood. Venous oxygen tension rises and arteriovenous oxygen tension difference reduces.
69
Management:
Discontinue nitroprusside administration
IV Sodium nitrite (3%): 4-6 mg/kg over 2-4 minutes. Nitrites produce methaemoglobin
which can combine with cyanide molecules to produce cyanmethaemoglobin and get
eliminated from the kidney. Amyl nitrite ampoules, if available, can be broken and the
drug dropped into the reservoir bag or breathing system. Amyl nitrite on inhalation can be
as useful as sodium nitrite.
IV Sodium thiosulphate: Available as a 25% or a 50% solution. 150-200 mg/kg. Thiosul-

phate acts as a substrate to which cyanide radicals can bind to produce thiocyanate and
get eliminated by the kidney.
Hydroxocobalamine is another compound that can combine with cyanide radicals to pro-
duce cyanocobalamine and get excreted.
Supportive management
Methylene blue: 1-2 mg/kg IV over several minutes to treat methaemoglobinaemia, if it

becomes severe.
Haemodialysis is not effective in removing cyanide.
70
DILUTION TECHNIQUES FOR VASOACTIVE DRUGS:
Each institution adopts its own dilution policies but the following is an easy to use dilution
method.
DOPAMINE/DOBUTAMINE
Add *3 x Body weight (kg) = ‘x’ mg+ of dopamine or dobutamine in 50 ml of saline or 5%
dextrose.
1 ml/h of infusion gives 1 µg/kg/min
ADRENALINE/NORADRENALINE/ISOPRENALINE
Add *0.15 x Body weight (kg) = ‘x’ mg+ of adrenaline / noradrenaline / isoprenaline to 50 ml
of saline or 5% dextrose. 1 ml/h of infusion gives 50 ng/kg/min
SODIUM NITROPRUSSIDE AND NITROGLYCERINE

Add *.3 x Body weight (kg) = ‘x’ mg+ of sodium nitroprusside in 50 ml of 5% dextrose.
Add *0.3 x Body weight (kg) = ‘x’ mg+ of nitroglycerine in 50 ml of saline or 5% dextrose.
1 ml/h of infusion gives 1 µg/kg/min
71
ANTIARRHYTHMICS
72
Vaughan Williams classification of antiarrhythmics
Class I (Sodium channel blockers) A) Quinidine, Procainamide
B) Lignocaine, Phenytoin
C) Flecainide, Propafenone
Class II (Beta-receptor blockers) Propranolol, esmolol, metoprolol
Class III (Potassium channel blockers) Amiodarone, Bretylium, Sotalol
Class IV (Calcium channel blockers) Verapamil, Diltiazem
Class V Adenosine
Cardiac glycosides Digitalis
Memory aid
Stupid Ball Pen—Colourful ADDGEL
Stupid for Sodium channel blockers (Class I)
Ball for Beta blockers (Class II)
Pen for Potassium channel blockers (Class III)
Colourful for Calcium channel blockers (Class IV)
ADDGEL for Adenosine and Digitalis
73
NITROGLYCERINE
Name: Nitroglycerine
Availability: It is available in 5 ml ampoules containing 5 mg/ml
Mechanism of action: It acts by releasing endothelial nitric oxide and in clinically used doses,
is a venodilator. It acts mainly on the capacitance vessels.
To treat hypertensive crisis
To treat myocardial ischaemia
To induce hypotension
To obtund hypertensive response to intubation
It is usually given intravenously as an infusion, in a dose range of 0.5 to 5 µg/kg/min. It is avail-

able as a spray, each spray delivering 400 µg. It is also available as an ointment which can be
used transdermally.
Onset: One to two minutes if given IV.
Elimination: It is metabolized in the liver.
Adverse effects: Tachycardia, hypotension, headache. If used as an infusion for prolonged pe-
riods, tachyphylaxis can occur.
Cautions: To be used with caution in patients with low intravascular volume.
Special precautions: It should be avoided in patients with raised intracranial pressure. It can
produce ventilation-perfusion mismatch in patients with lung disease. Can precipitate glau-
coma in susceptible patients.
74
ESMOLOL
Name: Esmolol hydrochloride
Availability: It is available in 10 ml vials containing 10 mg/ml.
Mechanism of action: It inhibits the β1 receptors selectively. It is a Class II antiarrhythmic
agent.
Indications:
To treat tachycardia
To control heart rate in supraventricular arrhythmias,
To blunt responses to endotracheal intubation and extubation.
Dose and route: It is always given intravenously. The dose is 0.5 mg/kg intravenously followed
by 50 µg/kg/min. The infusion rate may be gradually increased to 300 µg/kg/min. It may also
be given as a bolus of 1-2 mg/kg to blunt haemodynamic responses to laryngoscopy, intuba-
tion and extubation.
Onset: Two minutes
Duration: 10 minutes.
Elimination: It is metabolized by nonspecific esterases.
Cardiovascular system: It slows down the heart rate and reduces blood pressure. It slows
down conduction and acts as an antiarrhythmic agent (useful for supraventricular arrhyth-
mias).
Respiratory system: It may cause bronchospasm in a susceptible patient.
Absolute / relative contraindications for the use of any β blockers:

Remember as ABCD&E—AV block, Bronchial asthma, Congestive cardiac failure, Diabetes mel-
litus and pEripheral vascular disease
Related questions:
In what clinical conditions would you ensure esmolol / metoprolol is readily available for
use?
It is important to keep esmolol readily available in any clinical condition where a tachycardia
can be harmful, e.g., ischaemic heart disease, stenotic valve disease, raised intracranial pres-
sure.
75
METOPROLOL
Name: Metoprolol hydrochloride
Availability: It is available in 5 ml ampoules containing 1 mg/ml. It is also available as 25 mg
tablets.
Mechanism of action: It is a selective beta-1 receptor blocker.
Indications: Tachycardia, supraventricular arrhythmias, to blunt responses to endotracheal
intubation
Dose and route: It may be given orally or intravenously.
The intravenous dose is 0.5 – 1 mg increments every two minutes up to a total of 5 mg or till
desired effect is seen.
The oral dose is 12.5 mg to 25 mg BD.
Onset: Two - five minutes
Duration: 3 - 4 hours
down conduction and acts as an antiarrhythmic agent (useful for supraventricular arrhyth-
mias).
Respiratory system: It may cause bronchospasm in a susceptible patient.
Absolute / relative contraindications for the use of any β blockers:

Remember as ABCD&E—AV block, Bronchial asthma, Congestive cardiac failure, Diabetes mel-
litus and pEripheral vascular disease
Caution:
It should be used with caution when administered concurrently with calcium channel block-
ing drugs, digitalis and halothane.
It may mask hypoglycaemia in diabetic patients.
76
How do you treat betablocker overdose?
Atropine – Atropine may be given up to a maximum dose of 40 µg/kg (3 mg in an adult) to
counter bradycardia due to its vagolytic effect.
Calcium – 10 ml of 10% calcium chloride may be given. Calcium acts directly on the cardiac
muscle and acts as a stimulant.
Isoprenaline – Isoprenaline is a selective beta agonist, stimulating both beta-1 and beta – 2
receptors. It may be given as an infusion of 0.05 to 0.2 µg/kg/min.
Aminophylline – it is a phosphodiesterase inhibitor, and increases cyclicAMP by preventing
its breakdown.
Pacemaker – A temporary transvenous (if not available, transcutaneous) pacemaker may be
inserted in severe bradycardia.
Glucagon – Glucagon in a dose of 1 – 5 mg is said to counter the effects of beta blockade
but is not readily available. It stimulates cAMP synthesis independent of the beta-
adrenergic receptor.
Can you name any other indication for beta blockers?

Propranolol is a very useful drug in the management of thyrotoxic crisis.
Labetolol is useful in the control of blood pressures in patients with severe pre-eclampsia.
LABETOLOL:
Available as ampoules containing 10 mg/ml. It has both α and βreceptor blocking properties.
The dose is 20 mg IV over two min. Additional doses of 40 mg and then 80 mg every ten min
to a maximum of 300 mg may be given as required. It may be administered as an infusion at a
rate of 2 mg/min with a maximum dose of 300 mg.
What is the current status of beta blocker therapy for patients with ischaemic heart disease
before non cardiac surgery?
If the patient is on chronic beta blocker therapy, continue it.
If the patient is scheduled for high or intermediate risk surgery, start them on beta block-
ers.
If there are no risk factors (Lee’s predictors), do not start beta blocker therapy.
Do not use beta blockers to treat tachycardia during surgery.
77
AMIODARONE
Name: Amiodarone hydrochloride
Availability: It is available in 3 ml ampoules containing 50 mg/ml. It is also available as 100 and
200 mg tablets.
Mechanism of action: It is a Class III antiarrhythmic agent and inhibits mainly potassium re-
ceptors but also blocks beta receptors, sodium and calcium channels to a lesser extent.
Uses, dose and route: It may be given intravenously or orally. It should be diluted in 5% dex-
trose.
It can be used to treat haemodynamically stable tachyarrhythmias, both supraventricular
and ventricular in origin. The dose is 150 mg intravenously over 20 minutes, followed by an
infusion of amiodarone at 1 mg/min for 6 hours followed by 0.5 mg/min for the next 18
hours.
Cardiac arrest victims with ventricular fibrillation or ventricular tachycardia without pulse:
The dose is 300 mg bolus followed by another 150 mg if necessary. This is followed by infu-
sion as mentioned above.
Duration: Long and variable; Half life may be up to 8 - 12 weeks. Peak plasma concentration
will be achieved by 30 minutes if given IV and 2-3 days if given orally.
Cardiovascular system: It slows conduction across AV node, prolongs the action potential
duration and reduces heart rate. It can cause hypotension although it is safe to use it in pa-
tients with reduced left ventricular function.
Adverse effects/ contra-indications:

Short term effects:
Severe bradycardia
Heart blocks
Hypotension
Long term effects:
Peripheral neuropathy, corneal microdeposits.
Thyroid disorders: It blocks conversion of T3 to T4 and may cause hypo or hyperthyroidism.
It can cause interstitial fibrosis when given over a long period of time. The most serious ad-
verse effect of chronic amiodarone therapy is pulmonary toxicity, characterized by cough
and progressive dyspnoea. Chest X-ray would show patchy infiltrates and pulmonary func-
tion tests would show reduced diffusing capacity for carbon monoxide.
78
MAGNESIUM
Name: Magnesium sulphate
Availability: It is available as 25% and 50% solutions in 2 ml ampoules.
Mechanism of action: It is described as a physiological antagonist of calcium. It is the second
most abundant intracellular ion and is a cofactor to many enzymatic reactions. It depresses
myocardium and vascular smooth muscle directly.
Uses, dose and route: It is given intravenously or intramuscularly.
As an antihypertensive agent: Magnesium is a popular antihypertensive/anticonvulsive
agent for pre-eclamptic patients, eclamptic seizures. It is given in a dose of 1-2 g IV bolus
followed by an intravenous infusion of 1 g/h, monitoring for depression of deep tendon re-
flexes, reduction in urine output, any widening of QRS complex or prolongation of PR inter-
val. It may also be used as an adjunct to reduce hypertension during excision of phaeochro-
mocytoma, where it is used in a bolus of 40 mg/kg followed by 2 g/h.
As an antiarrhythmic agent: The dose is 2 g (8 mmol) intravenously over 20 minutes fol-
lowed by 16 g (64 mmol) over 24 hours. It is indicated in the treatment of Torsade de
Pointes. It is very commonly used to treat arrhythmias after cardiopulmonary bypass.
To prevent/treat cerebral vasospasm, as a cerebroprotective agent in neurosurgery
To blunt hypertensive response to intubation: 40 mg/kg IV.
As a bronchodilator: Magnesium is used in a dose of 500 mg daily as an adjunct to other
bronchodilator therapy in resistant cases.
As replacement in hypomagnesemia: Magnesium is the second most abundant intracellular
ion. Hypomagnesemia may manifest as resistant hypokalaemia.
Onset: Two minutes
down conduction and acts as an antiarrhythmic agent (useful for ventricular tachycardia,
particularly torsade de pointes).
Respiratory system: It is a bronchodilator.
Central nervous system: It reduces nerve excitability and conduction
Neuromuscular junction: It prolongs the effect of depolarizing and nondepolarising muscle
relaxants.
Adverse effects:
Bradycardia
Hypotension
Hypermagnesemia causing reflex btundation, respiratory depression and cardiac arrest.
Caution: Monitor ankle jerk to detect hypermagnesemia early during therapy of pre-eclampsia
and eclampsia.
Relationship between plasma concentration of magnesium and clinical effects:
1 – 2 (mEq/L) - Normal range; 4 – 7 (mEq/L) - Therapeutic; 7 – 10 (mEq/L) – Depression of
deep tendon reflexes; 10 – 14 (mEq/L) - Respiratory depression and > 14 (mEq/L) – Cardiovas-
cular collapse
79
ADENOSINE
Name: Adenosine hydrochloride
Mechanism of action: It stimulates adenosine receptors.
It is the drug of choice to terminate supraventricular tachycardia (including patients with
WPW syndrome). It is used to differentiate ventricular tachycardia from wide complex su-
praventricular tachycardia (SVT with aberrant conduction).
It is always given rapidly intravenously and followed by a saline flush.
The dose is 6 mg stat intravenously, if required this can be followed by 6 mg and 12 mg, at
5 minute intervals. These doses may be halved if a central venous line is being used for its
administration.
Patients on theophylline need to be given a higher dose and those on dypyridamole need to
be given a smaller dose.
Onset: Immediate
Elimination: It is rapidly taken up by cells and metabolized by adenosine deaminase.
down conduction and acts as an antiarrhythmic agent (useful for supraventricular tacycar-
dia).
It can cause flushing (due to vasodilation) and transient chest pain. The conscious patient
must be warned and reassured about these symptoms before administration of adenosine.
Respiratory system: It may cause bronchospasm in a susceptible patient. Even though
adenosine has a very short duration of action, bronchospasm induced by it may last as long
as half an hour. Hence, it is best avoided in asthmatics.
Adverse effects:
Severe bradycardia, occasionally asystole but transient
Heart blocks
Hypotension
Bronchospasm.
80
DILTIAZEM
Name: Diltiazem hydrochloride
Availability: It is available as 5 mg/ml in 10 ml vials.
Mechanism of action: It is a calcium channel blocker.
Uses, dose and route
It is used as an antiarrhythmic for treating supraventricular tachycardias for rate control.
(0.25 mg/kg IV over 2 min followed as necessary fifteen min later with another bolus of 0.35
mg/kg IV over 2 min. This can be followed by an infusion of 5-15 mg/kg as needed which
can be maintained for up to 24 h.
It is also used as an antihypertensive (given orally).
Cardiovascular system: It reduces the heart rate, contractility and produces peripheral vaso-
dilatation.
It has no effects on other organ systems of the body.
NIFEDIPINE
It is a calcium channel blocker with only vasodilatory properties. It produces no myocardial
depression. It is used as an antihypertensive agent. It is available as 5 and 10 mg dragees use-
ful for perioperative use. These dragees can be punctured with a needle and the contents
squeezed and administered sublingually or intranasally.
VERAPAMIL
It is available as verapamil hydrochloride, 5 mg in 2 ml ampoules. It is a calcium channel
blocker with more effects on the cardiac muscle than peripheral smooth muscle. Thus, reduc-
tion in contractility, heart rate and rhythm control are its main uses.
Uses: To treat supraventricular tachycardia
Dose: Minimum dose is 2.5 mg. The usual dose is 5—10 mg IV over 2 min. If the response is
inadequate, may repeat a bolus dose of 10 mg IV after 30 min.
Onset: 2 min
Duration of action: 4 –6 h.
Adverse effects:
Bradycardia and hypotension.
It should be used with caution in patients on beta blockers as their effects are additive.
It should be avoided in patients with Wolff Parkinson White syndrome as life threatening
arhhythmias may be precipitated.
81
ANTICHOLINERGICS
82
ATROPINE
Name: Atropine sulphate
Availability 1 ml ampoules, containing 0.6 mg/ml. It is also available as 1 mg/ml, 50 ml bottles.
Mechanism of action: It counters the effect of acetyl choline on the muscarinic receptors of
the body.
Onset of action: 30-45 s when given IV (45 seconds)
Duration of action: 45-60 minutes (45 minutes)
Uses, dose and route: Atropine is used as a vagolytic drug.
To treat bradycardia: It is given in the dose of 10 µg/kg to treat simple bradycardia, symp-
tomatic bradycardia, oculocardiac reflex. If adequate response is not achieved, can admin-
ister increments of atropine to a total vagolytic dose of 40 µg/kg. It can be given IV, IM, or
endotracheally.
As an antisialogogue: When given orally, it needs to be given in a dose of 20 µg/kg and acts
mainly as an antisialogogue. IV dose for antisialogogue effects is 4 µg/kg.
As an antispasmodic
To counter vagotonic effects of drugs such as neostigmine or a cholinergic poison such as
organophosphorus compounds.
When atropine is administered through tracheal route, the dose of the drug needs to be
increased by 2-3 times and it should be delivered at the tip of the tracheal tube with a suc-
tion catheter for best results. This was advocated for treatment of cardiac arrest victims
(without an intravenous or intraosseous access) with slow pulseless electrical activity or
asystole. However, present cardiopulmonary resuscitation guidelines (2010) do not recom-
mend atropine for cardiac arrest victims.
Cardiovascular system: The main effect of atropine is on the heart. It increases heart rate
by a vagolytic effect on the SA node and the AV node. It may increase cardiac output
through an increase in heart rate. It has no effect on myocardial contractility.
Respiratory system: It produces bronchodilatation through its inhibitory action on the mus-
carinic receptors situated in the bronchi.
Gastrointestinal system: It delays gastric emptying by reducing GI motility through its para-
sympatholytic action.
Central nervous system: It crosses blood-brain barrier and can cause confusion, irritability
and restlessness particularly when given in high doses, as for treatment of organophos-
phorus poisoning. It can also inhibit sweating and cause a rise in body temperature. It
causes mydriasis and its analogues such as homatropine are used by ophthalmologists for
this purpose.
Overdose: The effects are easily remembered as follows:
Blind as a bat, mad as a hatter, hot as a hen, red as a beet and dry as a bone.
83
GLYCOPYRROLATE
Name: Glycopyrrolate
Availability: It is available as 1 ml ampoules, containing 0.2 mg/ml
Mechanism of action: It counters the effect of acetyl choline on the muscarinic receptors of
the body.
Its effects are very similar to atropine but the onset is slower (2-3 min).
Glycopyrrolate is used as a vagolytic drug; to treat bradycardia, as an antisialogogue, or to
counter vagotonic effects of drugs such as neostigmine or a cholinergic poison such as or-
ganophosphorus compounds.
It is commonly used as an antisialogogue at 2-4 µg/kg e.g., to facilitate fiberoptic intuba-
tion, to reduce secretions in the oral cavity following ketamine.
It is the drug of choice for countering the muscarinic side effects of neostigmine as both
have an onset time of 2-3 minutes, both reach their peak action around 7-10 minutes and
both have a duration of action of around 4 h.
It is given in the dose of 5-10 µg/kg to treat simple bradycardia which is not progressing to
asystole. If adequate response is not achieved, another dose of glycopyrrolate may be
given. However, if the bradycardia is severe or rapidly progressing to asystole, atropine
must be used rather than glycopyrrolate.
Glycopyrrolate can be given IV or IM. It is a quaternary compound and is not effective
orally.
Cardiovascular system: Glycopyrrolate causes less increase in heart rate compared to atro-
pine. It increases heart rate by a vagolytic effect on the SA node and the AV node. It may
increase cardiac output through an increase in heart rate. It has no effect on myocardial
contractility.
Respiratory system: It produces bronchodilatation through its inhibitory action on the mus-
carinic receptors situated in the bronchi but to lesser extent than atropine.
Gastrointestinal system: It delays gastric emptying by reducing GI motility through its para-
sympatholytic action.
Central nervous system: Glycopyrrolate is a quaternary ammonium compound and hence it
does not cross blood-brain barrier. Therefore, it does not cause confusion, irritability and
restlessness like atropine. Hence, it is often given alone or in combination with atropine for
treatment of organophosphorus poisoning. It can also inhibit sweating and cause a rise in
body temperature.
84
ANTICOAGULANTS AND REVERSAL
85
HEPARIN
Name: Heparin sodium
Availability: It is available in 5 ml vials containing 1000 IU/ml. It is also available in 5 ml vials
containing 5000 IU/ml.
Mechanism of action: It binds to antithrombin III, blocks the effects of Factor II and Factor X
and produces anticoagulation by affecting the intrinsic pathway of coagulation.
It is used as an anticoagulant, in the following situations:
Cardiac surgery: The full anticoagulating dose (cardiopulmonary bypass) is 3 mg/kg. (1 mg =
100 IU), aiming to achieve an Activated Clotting Time (ACT) > 400 s.
Vascular surgery: The dose of heparin is reduced for vascular surgery or cardiac surgeries
without CPB to 1– 1.5 mg/kg.
Prophylaxis of thromboembolism: When given prophylactically (against DVT), it is given in a
dose of 5000 IU subcutaneously twice daily.
Treatment of deep vein thrombosis or thromboembolism: It is given as a bolus of 5000 IU
intravenously followed by 1000 IU/h. Its effect is monitored using APTT keeping it between
2 – 2.5 times normal.
For perioperative maintenance of anticoagulation in patients who have been on oral antico-
agulants, e.g., patients with prosthetic heart valves, atrial fibrillation etc.
Other uses: Heparin is also used to prevent clotting of blood in vitro when blood samples
are taken for blood gas analysis, electrolyte estimation etc. It is also used in blood storage
bags for preventing clotting of blood within the blood bag. Slow diluted infusion of heparin
(1U/ml) is useful to prevent clotting of blood in the indwelling catheters such as arterial
lines, central venous catheters, pulmonary arterial catheters etc. Heparin is also used to
maintain anticoagulation during interventional cardiology / radiological procedures that re-
quire temporary insertion of foreign body into vascular access such as cardiac catheteriza-
tion, percutaneous angioplasty, etc.
It may be given subcutaneously or intravenously.
Onset: Five minutes when given intravenously.
Duration: Ninety minutes when given intravenously. Eight to twelve hours when given subcu-
taneously.
Elimination: It is metabolized by lungs and liver.
Adverse effects: Bleeding, heparin-induced thrombocytopaenia, tachyphylaxis.
ALTERNATIVES TO HEPARIN
Hirudin, Argatroban
86
PROTAMINE
Name: Protamine sulphate
Availability: It is available in 5 ml ampoules and vials containing 10 mg/ml.
Mechanism of action: It is a strong base and heparin is a strong acid. Protamine binds to circu-
lating heparin to form chemical complexes and produces coagulation.
Uses, dose and route: To reverse effects of heparin. It is given in a dose of 1 to 1.3 mg for
every 100 IU (1 mg) of circulating heparin.
Onset: Five minutes.
Duration: Few minutes to an hour
Adverse effects: The adverse reactions to protamine can be of three types:
Type 1: This is common and is due to histamine release causing peripheral vasodilatation
Type 2: Anaphylactic or anaphylactoid reactions (IgG and IgE-mediated)
Type 3: Rarely, protamine can cause catastrophic pulmonary hypertension, right ventricular
dysfunction and elevation of right atrial pressure. This is said to be complement-mediated.
It can also cause bronchoconstriction and can act as an anticoagulant in larger doses.
Caution: It should be administered slowly in a peripheral line to prevent hypotension. Since it
is prepared from sperm of salmon fish, it must be either avoided or used with caution in pa-
tients with known fish allergy.
87
ASRA Guidelines for neuraxial anaesthesia in patients receiving anticoagulants (ASRA –
American Society of Regional Anesthesiology and Pain Medicine):
Guidelines for neuraxial anaesthesia in patients receiving NSAIDs or aspirin:
These drugs when used in the absence of other anticoagulants do not represent any
additional risk for development of spinal haematoma. Therefore, epidural catheter in-
sertion or removal can be done any time in patients receiving only these medications.
ASRA Guidelines for neuraxial anaesthesia in patients receiving theinopyridines (Clopidogrel
and Ticlopidine):
Stop ticlopidine 14 days prior to neuraxial block
Stop clopidogrel 7 days prior to neuraxial block
ASRA Guidelines for neuraxial anaesthesia in patients receiving glycoprotein IIb/IIIa inhibi-
tors (Abciximab, Eptifibatide and Tirofiban):
Discontinue abciximab 48 h prior to neuraxial block
Discontinue eptifibatide and tirofiban 8 h prior to neuraxial block
ASRA Guidelines for neuraxial anaesthesia in patients receiving unfractionated heparin:
Subcutaneous mini-dose heparin – No contraindication. If difficult spinal / epidural is
anticipated, consider delaying the heparin till the block is performed.
Intravenous heparin – Administer heparin 1 h after the block. Neuraxial catheter can
be removed 2-4 h after the last dose of heparin. No need to alter these guidelines in
case of traumatic block.
ASRA Guidelines for neuraxial anaesthesia in patients receiving fractionated heparin (LMWH
– low molecular weight heparin):
In case of twice daily dosing: LMWH can only be administered 24 h after the neuraxial
technique. Neuraxial catheter can be removed 2 h prior to next LMWH dose.
Single daily dosing: Neuraxial needle / catheter can be placed at least 12 h after the
last dose of LMWH, while the first postoperative dose of LMWH can be given 4-12 h
after the neuraxial block. Neuraxial catheters can be removed at least 12 h after last
dose of LMWH and at least 4 h prior to the next dose.
ASRA Guidelines for neuraxial anaesthesia in patients receiving warfarin:
Normal INR (international normalized ratio) to be achieved prior to performing neurax-
ial technique
Neuraxial catheter can be removed only when there is ≤ 1.5 INR.
ASRA Guidelines for neuraxial anaesthesia in patients receiving thrombolytics:
No data is available on this issue. ASRA recommends follow up of fibrinogen levels.
ASRA Guidelines for neuraxial anaesthesia in patients receiving herbal medications that
might interfere with coagulation:
No clear evidence. To be aware of potential interactions.
Guidelines for performing peripheral nerve blocks in patients receiving anticoagulants:
There are no clear guidelines available. More important concern in these cases is that
the risk of blood loss from surgical site would be much more than the risk of haema-
toma formation at the site of nerve block. Although there is no consensus on antico-
agulation and peripheral nerve blocks, the same guidelines may be extended as for
other neuraxial techniques.
88
Mechanism of action of anticoagulants:
Warfarin: Acts on the extrinsic pathway of coagulation profile (factor IIa, VIIa, IXa and Xa).
Its anticoagulant activity is best assessed using prothrombin time (PT).
Heparin: Heparin has a unique pentasaccharide that binds to antithrombin which acceler-
ates heparin’s ability to inactivate thrombin (factor IIa), Xa and IXa. Affects the intrinsic
pathway of coagulation. aPTT is the test that is used to assess status of anticoagulation
with heparin.
LMWH: It acts against factor Xa. However, there is no clear test that helps to assess the
anti-Xa activity.
Theinopyridines: Clopidogrel irreversibly inhibits platelet aggregation by selectively bind-
ing to adenylate cyclase-coupled ADP receptors on the platelet surface. Furthermore,
by blocking the ADP receptor, clopidogrel inhibits the binding of ﬁbrinogen to
the glycoprotein GP IIb/IIIa receptor.
89
DIURETICS
90
MANNlTOL
Name: Mannitol
Availability: It is available in 100 ml bottles containing 20% mannitol (20 g/100ml).
Mechanism of action: It is a hyperosmolar drug (1500 mOsm/L) and acts as an osmotic diu-
retic. It increases plasma osmolality and initially draws fluid into the intravascular compart-
ment. The plasma volume increases and then diuresis ensues.
Uses, dose and route: It is used as a diuretic in the following situations:
Raised intracranial pressure, as after head injury, neurosurgery
Patients with brain tumours
To protect kidneys after mismatched blood transfusion
Prophylaxis of hepatorenal syndrome
Forced diuresis.
It is given intravenously. The dose is 0.25 to 1 g/kg.
Duration: Eight hours when given intravenously.
Elimination: It is eliminated unchanged by kidneys.
Adverse effects:
Hypovolaemia
Electrolyte imbalance such as hypokalaemia and hyponatraemia
Pulmonary oedema and congestive cardiac failure
Intracranial bleed, in the elderly and neonates where meningeal vessels may be very deli-
cate.
Initial transient hyperkalaemia is known to occur with mannitol bolus. The mechanism be-
hind this is that mannitol like glucose, draws water and potassium from intracellular and
interstitial compartments to intravascular compartments. This results in initial hyperkalae-
mia and hypervolaemia. However, unlike glucose, mannitol is not taken up by cells and is
excreted unchanged by kidneys. Hence, subsequently, along with mannitol both water and
potassium get excreted through kidneys resulting in hypovolaemia and hypokalaemia.
However, one must remember that in patients receiving massive blood transfusion and
mannitol, sudden significant and life threatening hyperkalaemia may occur.
Caution:
Mannitol should be used cautiously in patients with lower ejection fraction or renal impair-
ment as sudden increases in plasma volumes may not be well tolerated in these patient popu-
lation.
Remember: Dose of IV mannitol 0.25 g/kg—1 g/kg

Dose of IV frusemide 0.25 mg/kg—1mg/kg
91
FRUSEMIDE
Name: Frusemide
Availability: It is available in 2 ml ampoules containing 10 mg/ml.
Mechanism of action: It is a loop diuretic. It inhibits the Na+/K+/2Cl- ATPase in the cells of the
ascending limb of the loop of Henle inhibiting chloride absorption. This prevents movement of
water out of the tubule and diuresis ensues.
Uses, dose and route: It is used as a diuretic in the following situations:
It is life-saving in the treatment of cardiogenic pulmonary oedema
To treat acute hypervolaemia
Raised intracranial pressure, as after head injury, neurosurgery
Protection of kidneys after mismatched blood transfusion
Prophylaxis of hepatorenal syndrome
Forced diuresis
It may also be used as an antihypertensive agent.
It is given intravenously in emergency situations. It may be given orally in chronic users.
The intravenous dose of frusemide is 0.25-1 mg/kg. But up to 2 mg/kg may be used to treat
pulmonary oedema, especially in patients with renal impairment. It is used in a dose of I mg/
kg bolus followed by an infusion of 1 mg/ min for six hours, to convert oliguric renal failure to
nonoliguric renal failure.
Duration: Six hours when given intravenously.
Elimination: It is eliminated unchanged by kidneys.
Adverse effects: Hypovolaemia, electrolyte imbalance. It can cause ototoxicity in large doses.
FORCED ALKALINE DIURESIS:
Used for treatment of acidic drug poisoning (ex: salicylate)
Intravenous fluids + sodium bicarbonate and frusemide / mannitol is used to flush the kidneys
and keep the urine alkaline.
92
BRONCHODILATORS
93
SALBUTAMOL
Name: Salbutamol hydrochloride
Availability: In an metered dose inhaler (MDI) form, canister containing 100 µg/puff. It is also
available in solution form for nebulisation, containing 5 mg/ml.
Mechanism of action: It stimulates the β2 receptors, increases activity of adenylate cyclase,
increases intracellular cyclicAMP and causes bronchodilatation.
It is used mainly as a bronchodilator.
It may be used in the treatment of hyperkalaemia.
It is occasionally used to relax a pregnant uterus (tocolytic), either during cervical encirclage
or during manual removal of placenta.
Onset: Five minutes
Side-effects: It can cause tachycardia, tremors, hypokalaemia, uterine relaxation.
TERBUTALINE
Terbutaline is another β2 agonist that is available as 0.5 mg/ml ampoule. It is used s/c in the
treatment of asthma.
94
IPRAVENT
Name: Ipratropium bromide
Availability: In an MDI form, canister containing 18 µg/puff. It is also available in solution form
for nebulisation, containing 0.5 mg/ml.
Mechanism of action: It inhibits muscarinic (M1,2,3) receptors, increases anticholinergic effect
and causes bronchodilatation. However, it must be remembered that inhibition of M2 recep-
tors can inadvertently trigger bronchospasm. Tiotropium is a drug that selectively inhibits only
the M1 and M3 receptors and stimulates the M2 receptors. Hence, this is the best anticholiner-
gic bronchodilator available.
Uses, dose and route: It is used as a bronchodilator. It may cause dryness.
Onset: Five minutes
Side-effects: It can cause dryness, can also precipitate paradoxical bronchospasm
Caution: To be used with caution in patients with narrow-angle glaucoma
95
AMINOPHYLLINE
Name: Aminophylline hydrochloride
Mechanism of action: It is a phosphodiesterase inhibitor, increases intracellular cyclicAMP by
reducing its breakdown and causes bronchodilatation.
Uses, dose and route: It is used mainly as a bronchodilator. It is used in a dose of 5 mg/kg in-
travenous bolus followed by infusion at the rate of 0.5 – 0.9 mg/kg/h. It should be diluted in
5% dextrose only.
Onset: Five minutes
Side-effects:
Tachycardia
Increased inotropy
Diuresis
Increased diaphragmatic contraction.
Interaction with halothane can give rise to ventricular arrhythmias.
It has a very narrow therapeutic range (10 – 20 µg/ml). When this level is exceeded, seizures,
heart blocks and cardiac arrest can occur. Overdose is treated with activated charcoal and sup-
portive treatment.
Caution: In patients with liver or renal pathology, pregnancy and in patients on digitalis ther-
apy the dose needs to be reduced. In patients on enzyme stimulators and in smokers, the dose
of aminophylline needs to be increased.
96
DERIPHYLLINE
Name: Theophylline and etophylline hydrochloride
Availability: It is available in 2 ml ampoules containing 25 mg/ml of theophylline and 84 mg/ml
of etophylline. It is also available as 100 mg and 200 mg tablets.
Mechanism of action: It is a phosphodiesterase inhibitor, increases intracellular cyclic AMP by
reducing its breakdown and produces bronchodilatation.
Uses, dose and route: It is used as a bronchodilator. In case of bronchospasm this can be ad-
ministered in a dose of 2 ml slow IV bolus, IM or s/c.
Onset: Five minutes
Side-effects: Mild gastric irritation may occur with tablets. Therefore it should not be taken on
empty stomach.
97
HYDROCORTISONE
Name: Hydrocortisone hemisuccinate
Availability: It is available in vials containing 100 mg in powder form for reconstitution.
Mechanism of action: Hydrocortisone produces bronchodilatation by reducing mucosal in-
flammation (anti-inflammatory effects help in reducing the oedema of the airway thus contrib-
uting to relief of bronchospasm). It is a glucocorticoid with mild mineralocorticoid effects.
As a bronchodilator, it is used in a dose of 100 mg bolus given 8th hourly.
It may also be used for steroid replacement in patients who have been on steroids in the
preceding six months. These patients might be having adrenocortical suppression and may
not be able to respond to the stress of surgery. This could result in refractory hypotension
and cardiovascular collapse. This is called adrenal crisis / hypothalamo-pituitary-adrenal
axis suppression (HPA suppression). This can be avoided by exogenous steroid supplemen-
tation. Hydrocortisone is usually used for this purpose and is given in a bolus dose of 25 mg
followed by 100 mg either as continuous infusion or in divided doses over 24 h.
It is also used in the treatment of allergic reactions, anaphylaxis, septic shock with acute
respiratory distress syndrome and thyrotoxic crisis (prevents peripheral conversion of T4 to
T3).
Recommendations for hydrocortisone use in septic shock—Consider (<300 mg/d) when
the septic shock is not responsive to adequate fluids and inotropes / vasopressors. Steroid
therapy may be weaned once the patient is off inotropes / vasopressors.
Onset: One hour
Side-effects: Hyperglycaemia, fluid retention, infections, hypokalaemia, hypertension, muscle
weakness (especially in critically ill patients) on long term use. It may also cause gastric ero-
sions and concurrent use of H2 blockers or proton pump inhibitors is recommended with ster-
oid therapy.
METHYLPREDNISOLONE SODIUM SUCCINATE:

Availability: Manufactured and distributed as a white amorphous powder. The drug is avail-
able in several strengths and packages for intravenous or intramuscular administration as 40
mg, 125 mg, 500 mg and 1g Act-O-Vial System (Single-Dose Vials) as well as 500 mg and 1 g
vials for infusion. It is anti-inflammatory steroid with greater potency than prednisolone (Each
4 mg of methylprednisolone is equivalent to 5 mg of prednisolone in its anti-inflammatory po-
tency). In addition, it has less propensity to induce salt and water retention than predisolone.
It has been specifically recommended as steroid of choice for the management of early adult
respiratory distress syndrome (ARDS) and following spinal cord injury / inflammation.
Caution: Once reconstituted, the contents should be used within next 48 h.
Dose of methylprednisolone:
For spinal cord injury / inflammation: it can be used as a loading dose of 30 mg/kg adminis-
tered over 30 minutes and then as an infusion at 5.4 mg/kg/h for 24 h.
For early ARDS: 2 mg/kg loading dose, 0.5 mg/kg 6-8 h for 1-2 weeks depending on the re-
sponse.
98
Contra-indications: Methylprednisolone is contraindicated for use in premature infants as its
diluents contains benzyl alcohol which can precipitate the life-threatening ‘gasping syndrome’.
It is also contra-indicated in patients with systemic fungal diseases as this may flare up the dis-
ease process.
BUDESONIDE
Name: Budesonide
Availability: In an MDI form, canister containing 200 µg/puff.
Mechanism of action: Similar to hydrocortisone.
Uses, dose and route: It is used as a bronchodilator. It is used in a dose of 2 puffs (MDI) three
times a day. It may also be nebulised.
Onset: Five minutes
Side-effects: It is important to rinse the patient’s mouth after steroid nebulisation as it tends
to deposit around the oral structures and cause candidial infection (oral thrush).
Long term use of inhaled steroids even at recommended doses may result in adrenocortical
suppression. This is more likely to occur with flucatisone than with budesonide.
Special precaution while using metered dose inhalers: When using MDI in patients with arti-
ficial airway such as endotracheal tube / tracheostomy tube, 6-10 puffs need to be adminis-
tered each time as only one third to one quarter of the administered drug reaches the tra-
cheobronchial tree. Rest of the drug usually is lost in the artificial airway.
99
ANTIEMETICS
100
ONDANSETRON
Name: Ondansetron hydrochloride
Mechanism of action: It is a strong inhibitor of serotonin (5-HT3) receptors in the chemorecep-
tor trigger zone of the medulla (5 HT3 receptor antagonist).
Uses, dose and route: It is used as an antiemetic only. It may be given orally, intramuscularly
or intravenously. The dose is 0.1 mg/kg.
Onset: Five minutes
Duration: Eight hours
Central nervous system: Normally it has no effect on the central nervous system except for the
anti-emetic effect. It does not cause extrapyramidal reactions or cause oculogyric crisis.
Table showing various receptors involved in the stimulation of chemoreceptor trigger zone
and the vomiting centre and the effects of various antiemetics:
D2 M3 H1 5HT3
Scopolamine 0 ++++ + 0
Promethazine + ++ +++ 0
(Phenergan)
Metoclopramide + 0 + ++
Ondansetron 0 0 0 ++++
Prochlorperazine ++++ 0 0 0
(Avomine)
+ mark indicates inhibition of that receptor while ++++ indicates strong inhibition of the re-
ceptors.
101
METOCLOPRAMIDE
Name: Metoclopramide hydrochloride
Availability: It is available in 2 ml ampoules containing 5 mg/ml. It is also available as 10 mg
tablets.
Mechanism of action: It inhibits the dopamine (D2) and 5-HT3 receptors in the chemoreceptor
trigger zone of the medulla and by decreasing afferent activity from viscera to vomiting cen-
tre.
Uses, dose and route: It may be used as an antiemetic or a prokinetic agent. It may be given
orally, intramuscularly or intravenously. The dose is 10 mg.
Onset: Five minutes after intravenous administration
Central nervous system: Normally it has no effect on the central nervous system except for the
anti-emetic effect. Occasionally, it can cause extrapyramidal reactions and even cause ocu-
logyric crisis. This can be treated with promethazine (phenergan) which in itself is an antie-
metic. Promethazine acts through histamine (H1) and muscarinic (M3) receptors and the dose
is 0.25 mg/kg slow IV.
102
DEXAMETHASONE
Name: Dexamethasone
Mechanism of action: It is a steroid and exerts its antiemetic effect by acting on receptors in
the chemoreceptor trigger zone of the medulla.
Uses, dose and route: It may be used as an antiemetic agent. It may also be used to reduce
cerebral oedema, laryngeal oedema and tissue oedema. It may be given intramuscularly or
intravenously. The dose is 0.1 to 0.5 mg/kg. May also be used for thyrotoxic crisis (prevents
peripheral conversion of T4 to T3), addisonian crisis, bronchospasm.
Onset: Five minutes
It exerts the same effects as any other steroid on the body. It may stimulate gluconeogenesis
and produce hyperglycaemia, particularly in diabetics. Prolonged use may cause myopathies,
especially in critically ill patients. It may cause hypokalaemia. It may predispose patients to
infection. It can also cause gastric / peptic ulcers and upper gastro-intestinal tract bleeding.
103
INTRAVENOUS FLUIDS
104
POTASSIUM CHLORIDE
Name: Potassium chloride
Availability: It is available as 10 ml ampoules, containing 2 mmol/ml of potassium (1.5 g/10
ml). It is also available as an oral preparation, 15 ml of syrup containing 20 mmol of potassium.
Uses: To treat hypokalaemia, and also to supplement daily requirement of potassium in pa-
tients who are nil per oral.
Normal serum potassium concentration: 3.5 – 5.3 mmol/L (extracellular concentration).
Potassium is the most abundant intracellular cation, with a concentration of approximately
140 mmol/L.
HYPOKALAEMIA
Causes of hypokalaemia may be: a) reduced intake b) increased losses - vomiting, diarrhoea,
enterocutaneous fistulae, diuretics or due to c) shift of intravascular potassium to intracellular
compartment - insulin therapy, salbutamol therapy, alkalosis d) long term use of steroids e)
following aggressive dialysis in patients with renal failure.
Symptoms and signs of hypokalaemia: Muscle weakness, tremors, fatigue. It can also be a
cause of adynamic intestinal obstruction (ileus) and persistent gastric distention. The ECG may
show T wave inversion / flattening, appearance of ‘U’ wave, ventricular ectopics and in ex-
treme cases, can precipitate ventricular tachycardia and ventricular fibrillation.
Treament of hypokalaemia: The daily requirement of potassium is 1 mmol/kg. If the patient
can tolerate oral/enteral feeds, this can be given orally. Other sources of potassium such as
tender coconut water, fresh fruit juices must also be taken into account. Periodic check of se-
rum potassium levels will be needed when patients, especially critically ill, those in renal fail-
ure are administered potassium.
Intravenous administration of potassium must be done with more diligence. Potassium is
preferably given through a central venous line if it is in place since it can be irritant to veins.
When given through the peripheral line, it is recommended not to exceed 10 mmol/h and
when administered through central venous line, the dose can be increased the dose to 20-40
mmol/h. It may be given in a dose not exceeding 0.5 mmol/kg/h and not more than 200
mmol/day. Intravenous potassium administration must be done under continuous monitoring
for electrocardiogram, urine output and at least 4 h monitoring for serum potassium levels.
Oral potassium is irritant to the stomach.
Potassium is mainly an intracellular ion and the intravenously administered potassium goes to
the extracellular compartment. Even if the intracellular compartment deficit of potassium is
high, it takes time for the intravascularly administered potassium to cross the cell membranes
and enter the cells. If potassium is given at a faster rate, there is a possibility of hyperkalaemia
with serious consequences.
Because the potassium is predominantly an intracellular ion, a serum potassium of < 3mEq/L
means an approximate intracellular deficit of 200-400 mEq of potassium in an adult. This
needs to be corrected slowly over 24-48 h unless significant associated cardiovascular instabil-
ity is observed.
Resistant hypokalaemia may need treatment of alkalosis or even treatment of associated hy-
pomagnesaemia. Unless these are treated, it may be difficult to treat hypokalemia.
105
HYPERKALAEMIA
Causes of hyperkalaemia may be: a) Increased intake b) reduced losses – renal failure or due
to c) shift of intracellular potassium to intravascular compartment – acidosis, succinylcholine
in susceptible patients, e.g., burns, denervation as in hemiplegia, paraplegia etc d) rhabdo-
myolysis e) malignant hyperthermia.
Symptoms and signs of hyperkalaemia: The ECG shows tall peaked T waves, disappearance of
P wave, appearance of widening of QRS complex, sine wave pattern and can precipitate ven-
tricular arrest in diastole.
Treament of hyperkalaemia:
Immediate effect: Calcium chloride 10 ml of 10% solution IV stat if cardiac arrest is antici-
pated or has occurred. In other situations when ECG manifestations such as tall T waves or
sine wave pattern is found with acceptable haemodynamics, it can be administered slowly
over 5 – 10 minutes. Calcium is a physiological antagonist of potassium and so counters
the electrophysiological effect of potassium on the heart. It does not lower the serum po-
tassium levels.
Effect in about 15 minutes: Alkalosis drives potassium into the cells. Sodium bicarbonate,
1 mmol/kg may be given to induce metabolic alkalosis or counter metabolic acidosis and
hyperventilation induces respiratory alkalosis. Nebulisation of salbutamol also has a simi-
lar effect.
Effect in 15 – 30 minutes: 100 ml of 50% dextrose with 10 units of insulin may be given
over 20 – 30 minutes. Insulin drives the potassium into the cells along with glucose.
Effect over hours: Frusemide in doses of 0.5-1 mg/kg may induce diuresis and bring about
reduction in the total body potassium.
Dialysis, particularly haemodialysis is a definite way of lowering serum potassium concen-
tration.
Sodium-potassium exchange resins: These could be given to ‘mop up’ potassium by ex-
changing it with sodium.
106
SODIUM BICARBONATE
Name: Sodium bicarbonate
Availability: It is available as 7.5% containing 0.9 mmol/ml of bicarbonate. It is also available
as 8.4%, containing 1 mmol/ml of bicarbonate.
This is calculated as follows:
The molecular weight of sodium bicarbonate is 84. (Na = 23, H = 1, C = 12, O3 = 16 x 3).
84 g is a mole (1000 mmol).
Each ml of 8.4% sodium bicarbonate contains 84 mg of sodium bicarbonate, i.e., 1 mmol.
Uses:
To treat metabolic acidosis, when the pH is < 7.1 in diabetics and < 7.2 in general popula-
tion. The dose is usually 1 mmol/kg but is better given as follows: 0.3 x body weight x base
deficit. Half of this volume is given along with correction of factors that led to the acidosis.
It may be repeated, if repeat assessment demonstrates its requirement.
To treat hyperkalaemia, by inducing metabolic alkalosis or countering metabolic acidosis.

As a component of forced alkaline diuresis.
Adverse effects:
Increased sodium load, hypernatraemia
Sodium bicarbonate 7.5% has a serum osmolarity of 1400 mOsm/L. Therefore, it draws fluid
into the intravascular space and can cause volume overload.
Alkalosis can shift oxygen dissociation curve to the left; oxygen affinity of haemoglobin is
increased.
Alkalosis causes hypokalaemia
Sudden increase in intravascular space can cause intracranial haemorrhages in neonates.
It is irritant to veins.
107
50 % DEXTROSE
Uses:
This preparation of dextrose contains 50 g in 100 ml of water. Each gram of glucose provides
approximately 4 Kcal of energy. Therefore, 100 ml 50% dextrose will have 50 g which would
provide 200 Kcal.
It can also be used to provide partial parenteral nutrition.
To treat hypoglycaemia
As a high calorie source during total parenteral nutrition and
Along with insulin, to treat hyperkalaemia.
Adverse effects:
Irritant to veins and they get thrombosed easily.
If given rapidly, it can cause significant hyperglycemia.
It can also cause osmotic diuresis.
On metabolism in the body, this glucose can lead to significant production of carbon dioxide
which might necessitate an increase in the ventilatory requirements of the patient.
108
CALCIUM
Name: Calcium chloride / calcium gluconate
Availability: It is available as 10 ml ampoules, containing 100 mg/ml of calcium chloride. It is
also available as 10% calcium gluconate. Each ml of 10% calcium chloride contains 27.2 mg of
elemental calcium whereas each ml of calcium gluconate contains 9 mg of elemental calcium.
Uses:
To treat hypocalcaemia
To treat life-threatening hyperkalaemia
To counter the effect of calcium channel blockers
To treat citrate toxicity after massive transfusion
Normal serum calcium concentration: The normal total serum calcium level is 9 – 11 mg%.
Approximately half of this is bound to albumin and the rest circulates as free ionized calcium.
The total calcium level may decrease with hypoalbuminaemia. It is the ionized calcium that is
electrophysiologically important. Ionised calcium may be expressed in mmol/L (normal 1 –
1.25 mmol/L). Therefore, if hypoalbuminaemia is associated with hypocalcemia, the total cal-
cium value must be corrected by correcting for hypoalbuminaemia using the following rule of
thumb: for every gram/dl decrease in serum albumin from 3.5 g/dl, add approximately 1 mg%
to serum calcium levels. After this correction, if the total serum calcium is still below 9 mg/dl,
only then it needs to be corrected. Alternatively, ionized calcium estimation and correction
may be done as necessary.
HYPOCALCAEMIA
Causes of hypocalcaemia may be: a) reduced intake b) hypoparathyroidism c) renal failure d)
Vitamin D deficiency e) alkalosis (shift of Ca into the cell) f) massive blood transfusion causing
citrate toxicity and hypocalcaemia due to chelation of calcium and g) acute pancreatitis.
Symptoms and signs of hypocalcaemia: Muscle weakness, tremors, fatigue. It is one of the
causes of postoperative stridor after thyroidectomy (where parathyroids have been removed).
Classically two signs have been described in hypocalcaemia:
Trousseau’s sign – When a blood pressure cuff tied around the arm is inflated for a sustained
period, the ipsilateral hand goes into spasm (carpopedal spasm).
Tapping in front of the tragus of the ear causes masseter spasm. The ECG shows QT wave pro-
longation ventricular ectopics and in extreme cases, can precipitate ventricular tachycardia
and ventricular fibrillation.
Treament of hypocalcaemia: The daily requirement of calcium is 0.5 mmol/kg.
If the patient can tolerate oral/enteral feeds, this can be given orally.
Intravenous administration of calcium may be given in a dose of 10 ml of 10 % calcium glucon-
ate, if given prophylactically as in massive blood transfusion. In an emergency such as in hy-
perkalaemic cardiac arrest, 10 ml of 10% calcium chloride should be given. If unavailable, 30
ml of calcium gluconate will need to be given to give the same amount of elemental calcium.
In cardiac arrest situations, it is preferable to use calcium chloride as calcium gluconate needs
to metabolized in the liver to release calcium and the action is delayed.
109
HYPERCALCAEMIA
Causes of hypercalcaemia may be hyperparathyroidism, tumour lysis in cancer patients
Symptoms and signs of hypercalcaemia: If the serum calcium has been elevated chronically,
they may manifest with abdominal pain, kidney stones, joint pains and psychiatric distur-
bances. The ECG shows shortening of QT interval.
Pharmacologic treament of hypercalcaemia:
Frusemide: 20 – 40 mg frusemide may induce diuresis with loss of calcium.
110
CRYSTALLOIDS:
These are solutions of simple sugars or electrolytes in water. When infused, these solutions
tend to get distributed through the entire water compartments, both intra and extracellular.
5 % dextrose: Each 100 ml contains 5 g of dextrose. It may be used to replace insensible free
water loss. Once the dextrose is metabolized, only water remains. Hence it is called a hypo-
tonic solution. It may be used to dilute inotropes, vasopressors, inodilators, sodium nitroprus-
side, aminophylline etc. It may be used as part of glucose-insulin-potassium solution. One litre
of 5% dextrose will provide 200 Kcal of energy.
Normal saline: This is a misnomer. This term is usually used for 0.9% saline, which contains
154 mmol each of sodium and chloride per litre of solution. This may be used as replacement
solution. However large amounts of saline infusion can cause hyperchloraemic metabolic aci-
dosis. Its osmolarity is 308 mOsm/L. This does not provide any energy.
Ringer lactate: Also called as balanced salt solution as this is a solution of electrolytes in wa-
ter, with a composition very similar to extracellular fluid. This is the solution of choice to re-
place third space losses. It contains Na+ 131 mmol/L, K+ 5 mmol/L, Ca++ 2 mmol/L , chloride
111 mmol/L and lactate 29 mmol/L which gets converted to bicarbonate in the body. This
does not provide any calories. Osmolarity is around 270-278 mOsm/L and hence is marginally
hypo-osmolar.
1.6%, 3% and 5% saline: These stronger saline olutions are available for treatment of hypona-
traemia as required. They contain 273, 514 and 855 mmol/L of sodium respectively. They may
also be used for hypertonic fluid resuscitation. 16% saline is used as a scolicidal agent in the
management of hydatid cyst excision.
COLLOIDS
These are suspensions of large molecules in water or saline. They have a high colloidal osmotic
pressure, remain in intravascular space for a longer period and produce better and longer du-
ration of plasma volume expansion. Colloids synthesized from animal origin (haemaccel,
gelofusine) tend to have higher allergic tendencies than those derived from plant origin
(tetrastarch, pentastarch or hetastarch).
Hetastarch: These are solutions containing starch molecules of various sizes. Its duration of
action is around four hours. The amount of substitution on each molecule determines its dura-
tion of action – called tetrastarch, pentastarch or hetastarch. It is removed from plasma by
reticulo-endothelial system where it may be retained for days. Hetastarch may cause coagula-
tion abnormalities when given in excess of 15 ml/kg. Formulations with less substitution seem
to be safer and may be given up to 50 ml/kg. Caution must be exercised in patients with renal
failure. The incidence of anaphylaxis is 1:15000.
Haemaccel: This is succinylated gelatin, derived from bovine collagen. It is similar to starch
preparations. The incidence of anaphylaxis is 1:3-4000. A succinylated version of this gelatin,
marketed as gelofusine is safer and the incidence of allergic reactions is similar to starch
preparations.
Dextran: This is available as Dextran 40, 70 and 110, based on the average molecular weight of
the molecules at 40,000, 70,000 or 110,000. Dextran 110 is no longer used, Dextran 70 is used
as a plasma expander whereas Dextran 40 is used to improve blood rheology as it reduces its
viscosity and platelet aggregation. Dextran 40 is commonly used to maintain blood flow to vas-
cular pedicle flaps.
111
CORRECTION OF SODIUM LEVELS IN TRUE HYPONATRAEMIA:
Conventional method:
Na requirement = (Desired Na+ - Actual Na+) x TBW
If [Na+] = 110 mmol/l, and the desired [Na+] is 125 mmol/L, weight is 50 kg,
Na requirement = (125 – 110) x 0.6 x 50 = 15 x 30 = 450 mmol.
Alternative (newer) method:
This calculates change in serum concentration for a given infusate. For a given target of
change in sodium concentration, this formula can directly calculate the volume of selected Na
containing fluid.
Change in serum Na concentration = Infusate Na/L – Serum [Na+] /Total body water (L) + 1
If [Na+] = 110 mmol/l, weight is 50 kg and 3% saline {[Na+] = 513 mmol/L} is to be used, TBW =
0.6 x 50 = 30 L;
(513 – 110)/30 + 1 = 403/31 = 13 mmol/L.
If the sodium concentration is to be raised by 4 mmol/L in the first four hours
13 mmol/L - 1000 ml
4 mmol/L - ?;
4 x 1000/13 = 307 ml; 307/4 = 76.75 ml/h.
Solution [Na+] mmol/L

0.45% 70
0.9% 154
1.6% 273
3% 513
112

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PHARMACOLOGY VIVA FOR THE

Serial Chapter Page No

DRUG AFFINITY FOR PLASMA PROTEINS

EXTRACTION RATIO: This is a measure of effectiveness of an organ to remove or process a

Elimination: It is metabolized by conjugation to glucuronide and sulphate by liver. It also un-

PROPOFOL INFUSION SYNDROME

It should also be avoided in patients known to have sulpha drug allergy

Ketamine can produce hallucinations and an increase in secretions. Hence, administration of

Name: Midazolam hydrochloride

It is a competitive benzodiazepine antagonist.

It is available as vials containing 0.3 mg. It is given in 100 µg boluses, to a total of 1 mg as

Onset: Two minutes

Name: Diazepam hydrochloride

Environmental temperature for Ether 35°C

Table showing physical properties of inhalation anaesthetics.

Boiling point (°C)

SVP (mmHg) 243 238 160 668 59

MAC (in oxygen)

LIQUID VOLATILE AGENT USED PER HOUR:

MAC: It is the minimum alveolar concentration of an inhaled anesthetic required to prevent

Blood-gas solubility coefficient: The solubility of an anaesthetic agent in blood is indicated by

Sevoflurane anaesthesia may result in fluoride concentration above the nephrotoxic

When sevoflurane is used with soda lime, the following is recommended:

2% solution for intravenous use, as an antiarrhythmic agent or to blunt responses to en-

With preservative (methyl paraben):

2% viscous solution for gargling, 2% jelly for mucosal analgesia

As an antiarrhythmic agent for the treatment of ventricular arrhythmias, it is given in a

Name: Bupivacaine hydrochloride

TREATMENT OF LOCAL ANAESTHETIC TOXICITY

Bupivacaine, unlike lignocaine, is very cardiotoxic. It is described as a ‘slow-in, slow-out’ agent.

Bupivacaine toxicity may be treated as follows:

The incidence of severe pseudocholinesterase deficiency (with no detectable enzyme activity,

Name: Rocuronium bromide

DRUGS METABOLISED BY ESTERASES

Succinyl choline, and mivacurium are metabolized by pseudocholinesterase.

Esmolol is metabolized by red cell esterases.

Remifentanyl is metaboised by non-specific plasma esteraces.

Pyridostigmine: It is the only anticholinesterase that is available as an oral preparation. It is

Based on their action on opioid receptors, they can be classified into

Opioid receptors are classified as

Cardiovascular system: It causes bradycardia, hypotension and decrease in cardiac output.

100% oxygen. Take care of airway and breathing.

Adrenaline, 50—100 µg boluses intravenously as required. If an intravenous access is not

Chlorpheniramine maleate, 10 mg, intravenously

Hydrocortisone 100 mg, IV

Salbutamol nebulisation for bronchospasm

Adrenaline infusion to maintain circulation.

Dopexamine hydrochloride is a synthetic catecholamine, structurally related to dopamine,

Discontinue nitroprusside administration

IV Sodium thiosulphate: Available as a 25% or a 50% solution. 150-200 mg/kg. Thiosul-

Methylene blue: 1-2 mg/kg IV over several minutes to treat methaemoglobinaemia, if it

Haemodialysis is not effective in removing cyanide.

SODIUM NITROPRUSSIDE AND NITROGLYCERINE

It is usually given intravenously as an infusion, in a dose range of 0.5 to 5 µg/kg/min. It is avail-

Absolute / relative contraindications for the use of any β blockers:

Absolute / relative contraindications for the use of any β blockers:

Can you name any other indication for beta blockers?

If the patient is on chronic beta blocker therapy, continue it.

Do not use beta blockers to treat tachycardia during surgery.

Adverse effects/ contra-indications:

Overdose: The effects are easily remembered as follows:

Remember: Dose of IV mannitol 0.25 g/kg—1 g/kg

FORCED ALKALINE DIURESIS: