Pharma LT: Local Anesthetics Flashcards
Local anesthetic use
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
Local anesthetics
Mechanism of action
MOA:
Bind to voltage gated Na channels to prevent intracellular increase of Na
Primary afferent fibers
- C-fibers which are small and unmyelinated
- As-fibers which are fine myelinated and are involved in noxious and temperature transmission
- AB-fibers which are myelinated ajd relay touch sensation
The order in which local anesthetics block transmission
- AS (small myelinated)
- C-fibers (non myelinated)
- AB (large myelinated) and motor axons
* all LA cause a certain degree of paralysis)
Classification of Local Anesthetics
Lipophilic aromatic ring linked to a hydrophilic tertiary amine side chain by either an:
A. Ester bond
B. Amide bond
Prototype of esters
Procaine
Prototype of amide
Lidocaine
Amides
LIDOCAINE PRILOCAINE Mepivacaine Dopivacaine Etidocaine
Esters
PROCAINE
BENZOCAINE
Cocaine
Tetracaine
The speed of tissue penetration and DOA of LA depends on
pKa
Lipid solubility
Protein binding
pKa of LA and its clinical significance
LA= weak bases (pKa 8-9)
Clinical Significance: in inflammation, the environment is acidic—> resistant to LA
The relationship of molecular structure and its solubility and protein binding
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
Metabolism of ester linked agents
Procaine, Benzocaine||
Rapidly hydrolyzed and inactivated by “non specific esterases” in PLASMA AND TISSUES—> t1/2=1-2 hrs
Hydrolysis products of esters clinical significance
Some products cause unwanted effects
Eg|
Procaine is hydrolyzed—> Para-aminobenzoic acid (PABA)—> allergic reactions in some ppl + INHIBITS SULPHONAMIDE (antibiotic)
Amide linked LA metabolism
Mainly metabolized in liver—> pharmacologically active metabolites there4 longer t1/2 and more stable
Enzyme: N-dealkylation
Surface administration of LA
ie into nose mouth bronchial tree cornea and urinary tract
Infiltration method of administering LA
Ie direct injection into tissues that blocks nerve branches and terminals
Used for minor surgery
Regional IV administration administration of LA
- Apply pressure cuff to arrest blood flow
- Inject IV “distal” to pressure cuff
! Effective until circulation is restored
Used for limb surgery
! Dangerous if cuff released before 20 min—> systemic toxicity
Nerve block administration of LA
Injected close to nerve trunks like brachial plexus or dental nerves—>peripheral loss of sensation
!used in surgery, dentistry, analgesia
Spinal administration of LA
Injected in subarachnoid space to act on spinal roots and sc
!used as an alternative to general anesthetic in abdomen, leg of pelvis surgery
Epidural administration of local anesthetic
Injected into epidural space to block spinal root
!spinal anesthesia and painless childbirth
The use of vasoconstrictors with LA
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
Cns Side effects of LA
Caused by LA seeping into systemic circulation
CNS: 1. Restlessness 2. Tremor 3. Convulsions At high dose—>cns depression—> resp depression
Cv side effects of LA
Myocardial depression and vasodilation—> sudden life threatening drop in BP
Immune side effects of LA
Hypersensitivity (allergic dermatitis)
Cocaine—> mucosal irritation therefore damage of sputum
