Pharma LT: Local Anesthetics

Question 1

Local anesthetic use

Answer 1

Cause reversible loss of sensation in a specific area of the body.

When used in specific nerve pathways ie nerve block—> reversible analgesia and paralysis

Question 2

Local anesthetics

Mechanism of action

Answer 2

MOA:

Bind to voltage gated Na channels to prevent intracellular increase of Na

Question 3

Primary afferent fibers

Answer 3

1. C-fibers which are small and unmyelinated
2. As-fibers which are fine myelinated and are involved in noxious and temperature transmission
3. AB-fibers which are myelinated ajd relay touch sensation

Question 4

The order in which local anesthetics block transmission

Answer 4

1. AS (small myelinated)
2. C-fibers (non myelinated)
3. AB (large myelinated) and motor axons
   * all LA cause a certain degree of paralysis)

Question 5

Classification of Local Anesthetics

Answer 5

Lipophilic aromatic ring linked to a hydrophilic tertiary amine side chain by either an:
A. Ester bond
B. Amide bond

Question 6

Prototype of esters

Answer 6

Procaine

Question 7

Prototype of amide

Answer 7

Lidocaine

Question 8

Amides

Answer 8

LIDOCAINE
PRILOCAINE
Mepivacaine
Dopivacaine
Etidocaine

Question 9

Esters

Answer 9

PROCAINE
BENZOCAINE
Cocaine
Tetracaine

Question 10

The speed of tissue penetration and DOA of LA depends on

Answer 10

pKa
Lipid solubility
Protein binding

Question 11

pKa of LA and its clinical significance

Answer 11

LA= weak bases (pKa 8-9)

Clinical Significance: in inflammation, the environment is acidic—> resistant to LA

Question 12

The relationship of molecular structure and its solubility and protein binding

Answer 12

More lipid soluble—> readily penetrates the cell membrane—>more potent…eg bupivacine > lidocaine

More protein bound—> longer duration of action—> longer duration of side effects …eg bupivacine > lidocaine

Question 13

Metabolism of ester linked agents

Answer 13

Procaine, Benzocaine||

Rapidly hydrolyzed and inactivated by “non specific esterases” in PLASMA AND TISSUES—> t1/2=1-2 hrs

Question 14

Hydrolysis products of esters clinical significance

Answer 14

Some products cause unwanted effects

Eg|

Procaine is hydrolyzed—> Para-aminobenzoic acid (PABA)—> allergic reactions in some ppl + INHIBITS SULPHONAMIDE (antibiotic)

Question 15

Amide linked LA metabolism

Answer 15

Mainly metabolized in liver—> pharmacologically active metabolites there4 longer t1/2 and more stable

Enzyme: N-dealkylation

Question 16

Surface administration of LA

Answer 16

ie into nose mouth bronchial tree cornea and urinary tract

Question 17

Infiltration method of administering LA

Answer 17

Ie direct injection into tissues that blocks nerve branches and terminals

Used for minor surgery

Question 18

Regional IV administration administration of LA

Answer 18

1. Apply pressure cuff to arrest blood flow
2. Inject IV “distal” to pressure cuff

! Effective until circulation is restored
Used for limb surgery
! Dangerous if cuff released before 20 min—> systemic toxicity

Question 19

Nerve block administration of LA

Answer 19

Injected close to nerve trunks like brachial plexus or dental nerves—>peripheral loss of sensation

!used in surgery, dentistry, analgesia

Question 20

Spinal administration of LA

Answer 20

Injected in subarachnoid space to act on spinal roots and sc

!used as an alternative to general anesthetic in abdomen, leg of pelvis surgery

Question 21

Epidural administration of local anesthetic

Answer 21

Injected into epidural space to block spinal root

!spinal anesthesia and painless childbirth

Question 22

The use of vasoconstrictors with LA

Answer 22

Adrenaline (vasoconstrictor) as an adjunct decreases rate of absorption of LA—> increase duration of action and reduces toxicity

BUT| systemic vasoconstriction leads to hypoxia and delayed wound healing

Question 23

Cns Side effects of LA

Answer 23

Caused by LA seeping into systemic circulation

CNS:
1. Restlessness 
2. Tremor
3. Convulsions
At high dose—>cns depression—> resp depression

Question 24

Cv side effects of LA

Answer 24

Myocardial depression and vasodilation—> sudden life threatening drop in BP

Question 25

Immune side effects of LA

Answer 25

Hypersensitivity (allergic dermatitis)

Cocaine—> mucosal irritation therefore damage of sputum