Local anesthetics Flashcards
Local Anesthetics (LAs)
MOA?
Pharmacological effects?
Therapeutic uses?
MOA:
- Reversibly block voltage-gated sodium channels and therefore block impulse conduction along nerve axons and other excitable membranes
Pharmacological effects:
- Inhibit perception of sensation (Nociception)
- Paralysis
Therapeutic uses:
- Localized topical pain
- Dental care
- Pain control during surgery/obstetric procedures
Local anesthetic block conduction in what order?
1) Small myelinated axons (e.g. those carrying nociceptive impulses)
2) Unmyelinated axons
3) Large myelinated axons
Ester-linked LAs metabolism?
Metabolized by pseudocholinesterases in plasma and tissue
- Patients with pseudocholinesterase deficiency will show decreased metabolism of LAs
Amide-linked LAs metabolism
Mostly metabolized in liver by P450s
- Excreted by kidneys
Some drugs metabolized in lungs or kidneys
PABA (para-aminobenzoic acid)
Known allergen; found in many sunscreens; metabolite of many LAs (allergic reactions)
- Competitively inhibits synthesis of essential metabolite in folate biosynthesis
- Reduces effectiveness of sulfonamides
- Can exacerbate bacterial infections
- Used to treat IBS
- OTC dietary supplement
Procaine
Short acting; ester linked Low hydrophobicity - Rapid removal; little sequestration Therapeutic uses: - Infiltration anesthesia - Dental procedure - 2-chloroprocaine sometimes used as epidural right before delivery Adverse effects: - PABA is a metabolite FDA regulation: - 2004 all formulations of GH3 banned - Procaine/novocaine discontinued in US market
Tetracaine
Long acting; highly potent; ester linked Highly hydrophobic: - Long duration of action Rapidly hydrolyzed by esterases, but released slowly from binding site so effectively longer metabolism Therapeutic uses: - Spinal and topical anesthetic - Ophthalamology
Cocaine
Naturally occurring LA Medium potency Medium duration of action Therapeutic uses: - Ophthalmic analgesia - Topical formulation TAC (tetracaine, adrenaline, cocaine) Adverse effects: - Significant vasoconstriction - Cardiotoxic
Benzocaine
Ester-linked Therapeutic effects: - OTC throat lozenges - Relieving ear conditions such as Otitis Media and swimmers ear - Prevent premature ejaculation Adverse effects - Methemoglobinemia - PABA allergic reactions - Decreased gag reflex
Lidocaine
Most commonly used LA Amide-linked, moderate hydrophobicity - Rapid onset of action Medium duration of action (1-2 hours) - Often given with epinephrine Moderately potent Therapeutic effects - Infiltration - Peripheral nerve block - Epidural, spinal and topical anesthesia - Class I antiarrhymic Adverse effects: - Drowsiness, tinnitus, twitching, seizures
Prilocaine
Similar to lidocaine
Does have vasoconstricive activity
- No need for Epi
Therapeutic uses:
- In conjunction with lidocaine for topical application (EMLA)
- For use with patients where EPI is contraindicated
EMLA (eutectic mixture of local anesthetic)
- Higher concentration of LA per drop than standard preparations
- Especially useful in children
-Therapeutic uses:
- Venipuncture, arterial cannulation, lumbar
punture, dental procedures
Bupivcaine
Amide linked, highly hydrophobic, highly potent
- Long duration of action
More effect on nociception than locomotion
Therapeutic uses:
- Spinal, epidural, infiltration anesthesia
- Peripheral nerve block
Racemic mixture (R- and S-) with different affinities
Adverse effects
- cardiotoxic (S- entaniomer is less toxic)
- Levobupivacaine
- Ropivacaine (structural homologue)
Articaine
Unique structural properties minimize potential
- Metabolized by plasma cholinesterases and in the liver
- 1/2 life ~ 20 minutes
Therapeutic uses:
- Dentistry
- More to come
Dyclonine
Used in oral preparations
Pramoxine
Used for mile irritations (sunburn, poison ivy)
Sometimes combined with dibucaine in hemorrhoid preparations
