Local anesthetics (LAs) prevent or relieve pain by

interrupt- ing nerve conduction. They bind to specific

receptor sites on the sodium (Na+) channels in nerves

and block the movement of ions through these pores

Electric potential of
60-70mV

Mechanical,chemical thermal stimuli

Miniscule electric current
Electric potential become less negative
Threshold potential Achieved
Action potential results
-sudden influx of Na ions
depolarization
-depolarization generates the current that
-depolarizes the adjacent segment of NV
Thus occur sequential polarization

Repolarization
Na permeability decreases
K permeabiliy increases

LAs prevent the generation and conduction of nerve

impulse by binding to the alpha sub unit of voltage gate
sodium channel and preventing the influx of Na ions

Block duration is JUST related to protein binding

Extend of period to which local anaesthetic remain in

vicinity of nerve

-lipid solubility

-vascularity of tissue

- presence of vasoconstrictors

pKa

The pH at which 50% of the drug is ionized and 50% is

base

The closer the pka to body pH ,fastest is the onset

The degree of protein binding of a particular LA is

influenced by the pH

The binding decreases from 95% to 70% with acidosis,

the amount of free drug bupivacaine increases from 5% to
30%

Acidosis renders the drug more toxic

Short acting(45-90 minutes)

-2-chloroprocaine

Intermediate acting(90-180 MINUTES)

-lidocaine
,mepivacaine

Long acting(4-18 HOURS)

-BUPIVACAINE
LEVOBUPIVACINE

ROPIVACAINE

Smaller nv fibers are more susceptible to the action

of LA than large fibers

Myelinated are easily blocked than unmyelinated

C fibers ,small in diameter, unmyelinated are most

resistant to block

Loss of pain sensation

Cold
Warmth
Touch
Deep pressure
Motor function

NV BLOCK RECOVERY

NV BLOCK ONSET
B
A DELTA
A GAMMA
A BETA
A ALPHA
C

Is proportional to concentration of LA in
circulation
Which depends on

dose of drug administered

Rate of absorption of drug
-site injected.
Vasoactivity of drug.
vasoconstrictors
Biotransformation and elimination of drug in
circulation

Short acting ester linked local anaesthetic are

inherently safer with respect to systemic toxicity due

to their clearance by pseudo cholinesterase

Appparent stimulaqtion
followed by depression
of neuronal activity

No current monitoring method can prevent systemic toxicity.

cases have been reported despite (1) negative aspiration
for

blood, (2) the use of recommended dosages, and (3) the

observation of local anesthetic spread in a tissue plane and

not intravascularly

Thus constant vigilance and preparation for treatment is essential

during all regional

anesthetic procedures.

Lidocaine

onset of seizures 10 to 12 g/mL

respiratory depression (20-25 g/mL)

Bupivacaine,

4 g/mL result in seizures,

4 - 6 g/mL cardiac toxicity.

This is reflective of a much lower therapeutic index for

bupivacaine compared with lidocaine in terms of cardiac toxicity.

The symptoms of CNS toxicity associated with LAs are a

function of their plasma level

Toxicity is typically first expressed as stimulation of the

CNS, producing restlessness,disorientation, and tremor

central stimulation is followed by depression and

respiratory failure, culminating in coma

However, rapid systemic administration of a LA may

produce death with no, or only transient, signs of CNS
stimulation

occurs at high systemic concentration than required for CNS

toxicity

Predominantly CNS signs may or may not occur prior to

cardiac symptom

Due to action on pacemaker cell

Bupivacaine causes
Progressive Prolongation of ventricular conduction,

widening of QRS COMPLEX,VF

Bupivacaine, which is four times more potent than

lidocaine in blocking nerves, is also four times more

potent in depressing cardiac contractility.

PLASMA CONCENTRATION of AAG is decreased

in pregnancy and newborns

Increases the free fraction of bupivacaine thus more

cardio toxic

No current monitoring method can prevent systemic oxicity

Midazolam-0.050.1mg/kg

Propofof0.51mg/kg

Ventilation wih 100% oxygen

If ventilation inadequate than intubation with aid of a

muscle relaxant

Cardiotoxicity-cardiac resuscitative measure

Act as lipid sink; that draws drug out of the solution

Its possible role in overriding the inhibition of
mitochondrial carnitine-acylcarnitine translocase, thereby
providing the myocardium with fatty acid for fuel

Hydrolyzed at ester linkage by

LIVER[dealkylation]

Allergic reaction due to

pseudocholine esterase

Hydrolysis lead to formation

of PABA(POTENTIAL OF

PABA as preservative

ALLERGIC RECTION)

ESTER LINKED

AMIDE LINKED

Short acting ester linked local anaesthetic are

inherently safer with respect to systemic toxicity due

to their clearance by pseudo cholinesterase

Leaves of coca shrub

local vasoconstrictor

Only LA THAT inhibit uptake of norepinephrne and do

not produce sensitization to catecholamine

Mydriatic

Use topical anaesthesia

vasocostrictor

INFILTERATION ANAESTHESIA

Chlorine derivative of procaine

Rapid break down

Most toxic

Used in combination with lidocaine as

super caine

Prilocaine is an intermediate-duration amino amide LA with a

pharmacologic profile similar to that of lidocaine

. The primary differences are a lack of vasodilatation.

methemoglobinemia, an effect of metabolism of the aromatic

ring to o-toluidine

IV administration of methylene blue (1-2 mg/kg). Prilocaine is

used infrequently in peripheral nerve blockade

Etidocaine

Etidocaine is a long-acting amino amide introduced in

1972.

profound motor blockade outlasts sensory blockade.

not used for peripheral nerve blockade.

introduction in 1963,
commonly used in regional and infiltration anesthesia.
producing prolonged anesthesia and analgesia
. At least part of the cardiotoxicity of bupivacaine may be
mediated centrally because direct injection of small quantities of

bupivacaine into the medulla can produce malignant ventricular

arrhythmias.

Bupivacaine-induced cardiotoxicity can be difficult to treat.

S-enantiomer of 1-propyl-2', 6'-pipecolocylidide

The S-enantiomer, has a lower toxicity than the R-enantiomer.

. Ropivacaine undergoes extensive hepatic

. Ropivacaine is slightly less potent than bupivacaine

reduced CNS toxicity and cardiotoxic potential

For these reasons, ropi- vacaine has become one of the most commonly

used long acting LAs in peripheral nerve blockade.

Levobupivacaine

Levobupivacaine contains a single enantiomer of

bupivacaine hydrochloride, and is less cardiotoxic than

bupivacaine

The addition of a vasoconstrictor to a LA delays its

vascular absorption, increasing the duration of drug
contact with nerve tissues. The net effect is

prolongation of the blockade by as much as 50% and a

decrease in the systemic absorption of LA.

opioid receptors are present in the substantia gelatinosa

of the spinal cord.
successfully used in neuraxial blockade to both
enhance the blockade and prolong analgesia.
However, in peripheral nerves, similar receptors are
absent.
For this reason, opiates do not have a significant
clinical role in peripheral nerve blockade.
Clonidine.FENTANYL,MORPHINE

Mixing of Local Anesthetics

. Unfortunately, when LAs are mixed, their onset,

duration, and potency become much less predictable,

and the end result is far from expected

results in little clinical advantage.

 0.5%
2%

is 5mg /ml

is 20mg/ml

 EMERGENCY

DRUGS

There is limited evidence to suggest that one particular

inotrope is better than another.

Dobutamine is predominantly a 1 agonist and

therefore increases cardiac contractility and heart rate.

It also acts at 2 receptors causing vasodilatation and

decreasing afterload.

Because of this vasodilatation, and to ensure adequate MAP is

achieved, it may be necessary to administer dobutamine in

combination with a vasopressor (eg, noradrenaline).

side effects
increased heart rate,
arrhythmias
raised myocardial oxygen demand.

These can cause myocardial ischaemia.

Dobutamine is not a vasopressor but rather a inotrope

that causes vasodilation

increasea inotropy and chronotropy and

reduces LV filling pressure

Dopamine is a complicated inotrope

it has dose-dependent pharmacological effects

. Low-dose dopamine (25g/kg/min) exerts mainly

dopaminergic effects

medium doses (510g/kg/min) the 1 inotropic effects

high doses (1020g/kg/min) a1 vasoconstriction

predominates.

Epinephrine also serves as a marker of intravenous

injection of local anesthetic. An increase in heart rate of

20 bpm or greater and/or an increase in systolic blood

pressure of 15 mmHg or greater after a dose of 15 mg

of epinephrine is

should raise a suspicion of

intravascular injection.

For postoperative analgesia (often in concert with

general anesthesia) do not require a high concentration

of LA.

Ropivacaine 0.2% is usually sufficient to provide

excellent sensory analgesia but spare any motor

blockade.

 In

1903, Braun suggested using

adrenaline as a chemical tourniquet to

prolong the duration of local anesthetics

Phenylephrine has purely Alpha-adrenergic agonist

activity and therefore results in vasoconstriction with
minimal cardiac inotropy or chronotropy. MAP is

augmented by raising SVR

Isoproterenol
is also primarily an inotropic and chronotropic agent
rather than a vasopressor.[ Beta-1]

Utility limited to hypotensive patients, where

hypotension results from bradycardia.

Norepinephrine

acts both on Alpha-1 and Beta-1 adrenergic receptors,

thus producing potent vasoconstriction as well as a less

pronounced increase in CO.

A reflex bradycardia ususally occurs in response to

increased MAP

Most commonly used in septic shock.

Route: IVDosage: For acute myocardial infarction 6 mg IV bolus followed by 54

mg within the first hour, followed by 20 mg/hour for 2 hours for a total dose of 100
mg.

Patients <65 kg should receive a total of 65 mg.

Alternatively: 15 mg IV bolus then 50 mg IV over 30 minutes, followed by 35 mg

over 60 minutes ("front loading" regimen).

Anistreptase (Eminase, Iminase)

Route: IV
Dosage: For acute myocardial infarction 30
units IV over 2-5 minutes

Atenolol (Tenormin, Atenil, Atenolan, Betatop, and others)

Route: IV
Dosage: Following acute myocardial infarction, 5 mg IV over 5 minutes

every 10 minutes for a total IV dose of 10 mg.

Oral atenolol therapy should be initiated immediately after the second IV

bolus with 50 mg, followed by another 50 mg oral dose 12 hours later. Oral

maintenance therapy is continued with 100 mg daily for at least 10 days.

Route: IV
Hyperkalemia
Magnesium intoxication:.
Hypocalcemic tetany:
Calcium channel blocker overdosage:
5-10 mL (6.8-13.6 mEq) of 10% calcium chloride
10-20 mL (4.65-9.3 mEq) of 10% calcium gluconate IV
over 5 minutes.
Repeat after 1-2 minutes as necessary.

Magnesium sulphate
Route: IV, IM
Dosage: Seizure prevention and control in pre-

eclampsia or eclampsia:

4-5 gm of 50% solution IM every 4 hours.

Metoprolol (Lopressor, Betaloc, Arbralene, Beprolo, and

others)
Route: IV, PO
Dosage: Following acute myocardial infarction, 5 mg IV push
every 2 minutes for a total IV dose of 15 mg.
Oral metoprolol at a dose of 50 mg every 6 hours should be
started 15 minutes after the last IV bolus dose and continued for
48 hours.
The maintenance dose is 100 mg twice daily for at least 3
months.

Streptokinase (Kabikinase, Streptase)

Route: IV
Dosage: For acute myocardial infarction 1.5 million

units IV over 1 hour

Vasopressin (Pitressin)
Route: IV

Dosage: For bleeding oesophageal varices (unlabeled

use in U.S.), 0.2 units/minute initially.

The infusion rate may be increased by 0.2 units/minute

every hour if bleeding continues and up to 1

unit/minute,

Verapamil
Route: IV

Dosage: For Supraventricular tachyarrhythmias 5-10 mg

IV push over 2 minutes.

A second bolus dose of 10 mg may be administered after

30 minutes