Pharmacology lecture for MBBS students

1. 10/5/2013RK 1

2. • Anesthesia literally means “no
sensation”
• Derived from the Greek verb for “to
perceive” : Oliver Wendell Holmes, 1846
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3. LOCAL ANAESTHESIA
• Loss of sensory perceptions by reversibly
inhibiting the propagation of signals
along nerve pathways in a specific area of
the body.
• LAs block generation and conduction of
impulse at all parts of neurons where they
come in contact.
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4. HISTORY
• Cocaine :
• First local anaesthetic
• Discovered by German, Albert Niemann (1860)
• Isolated from the leaves of coca
• First clinical use in 1884 by Sigmund Freud
and Karl Kollar in ophthalmology as a topical
ointment
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5. INJECTABLE
• Low potency & short duration
• Procaine
• Chloroprocaine
• Intermediate potency & duration
• Lignocaine
• Prilocaine
• High potency & long duration
• Tetracine
• Bupivacaine
• Ropivacaine
SURFACE
• Soluble
• Cocaine
• Lignocaine
• Tetracaine
• Insoluble : Benzocaine
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6. GENERAL STRUCTURE
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7. • Lignocaine
• Mepivicaine
• Prilocaine
• Bupivacaine
More intense and longer
lasting anaesthesia
• Cocaine
• Procaine
• Tetracaine
• Chlorprocaine
• Benzocaine
Short DOA, less intense
analgesia
Esters Amides
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8. • These get metabolized
in the liver to inactive
agents
• Binding to amides is
provided by alpha 1
glycoprotein in plama
• No allergies associated
with amides
• Hydrolysed in the
plasma by a pseudo
cholinesterase
• One by-product of this
reaction Para-Amino
Benzoic Acid (PABA)
• Allergic reaction are
associated with PABA
Esters Amides
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9. MECHANISM OF ACTION
• Inhibits sodium influx through sodium-specific ion
channels in the nerve cytoplasm
• Sodium ions cannot flow in, so potassium ions cannot
flow out, thereby preventing the depolarization of the
nerve
• Rate of rise of AP and depolarisation decreases with
increase in concentration of LAs
• To do this the anaesthetic molecules must actually enter
through the cell membrane of the nerve. This is where
the differences in the time of onset and duration of the
various local anaesthetics lies.
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11. FACTORS THAT AFFECT ACTION OF LOCAL
ANESTHETICS
• pH
• Cationic form binds to receptor site. The
uncharged form penetrates membrane .
Efficacy of drug can be changed by
altering extracellular or intracellular pH
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12. FACTORS THAT AFFECT ACTION OF LOCAL
ANESTHETIC
• Lipophilicity
• Main determinant of
anesthetic potency.
• Compounds with high
lipophilicity penetrate the
nerve membrane easily.
• This means less molecules
are needed to inhibit the
blockade of sodium ions.
This leads to enhanced
potency.
Lipid solubility and potency
Drug Relative
potency
Lipid
solubility
Procaine =1 100
Prilocaine 1.8 129
Lignocaine 2 366
Bupivicaine 8 3420
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13. • Blood absorbs the unused anesthetic. In order to
slow down this process many anesthetics are
administered with a vasoconstrictor.
• These constrict the vessel and slow down the
absorption of the anesthetic, by allowing less
blood to enter/leave the site
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14. ADVANTAGES OF LIGNOCAINE ADRENALINE
COMBINATION
• Decrease systemic toxicity (uptake by up to 1/3)
• Prolong local anesthesia (by ~50%)
• Decrease local bleeding (improve visualization of
surgical field
DIS ADVANTAGES:
• Makes injection more painful
• Increases chances of local injury and necrosis.
• May raise BP and promote arrhythmias in
susceptible individuals
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15. PROGRESSION OF LOCAL
ANESTHESIA
• Loss of:
• 1. Pain
• 2. Cold
• 3. Warmth
• 4. Touch
• 5. Deep pressure
• 6. Motor function
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16. PHARMACOLOGICAL ACTIONS
• CNS :
• All can produce CNS stimulation followed by depression.
• Cocaine:
• Euphoria-excitement-mental Confusion-tremors-
muscle Twitching-convulsions- Unconciousness -
resp. Depression.
• Procaine, Lignocaine: safe at clinical doses
• CVS :
• Cardiac depressant at iv doses
• Antiarrhythmic action (procainamide)
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17. TECHNIQUES OF ADMINISTRATION
• Topical Anesthesia
• Infiltration
• Conduction block
Field block
Nerve block
• Peridural
• Spinal anesthesia
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18. TOPICAL ANESTHESIA
• Done by the administering the anesthetic
to mucous membranes or skin. Relieves
itching, burning and surface pain, i.e.
sunburns.
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19. INFILTRATION
• Occurs by directly injecting a local
anesthetic to block the nerve endings under
the skin or in the subcutaneous tissue.
Used mainly for surgeries, i.e. cavities
being filled.
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20. CONDUCTION BLOCK
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21. • This is accomplished
by injecting a local
anesthetic into the
peridural space, a
covering of the spinal
cord
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22. • Here, the local
anesthetic is injected
into the subarachnoid
space of the spinal
cord
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23. TOXICITY
• CNS Toxicity:
• Systematic absorption can lead to excitement (tremors,
shivering, convulsions),
• If absorbed in even higher amounts can lead to
depression (coma, respiratory arrest and death)
• Cardiovascular toxicity:
• If absorbed in excess systematically can lead to
depression of the cardiovascular system
• Hypersensitivity: Rashes to anaphylaxis
• Local reactions: Combination with vasoconstrictor
(combination should be avoided-feet, fingers, toes, pinna, penis)
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24. Cocaine
 Ester, tendency to cause allergy
 Cardiovascular and CNS stimulant
 Addictive
 Used in ENT as a vasoconstrictor
 Metabolised by plasma esterases
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