[PF] LOCAL ANESTHETICS Flashcards
_________ provide anesthesia & analgesia by blocking the transmission of pain sensation along nerve fibers
Local anesthetics
The key target of local anesthetics is the _________. The binding is _________ and is mediated by hydrophobic interactions.
voltage-gated sodium channel
intracellular
The degree of nerve blockade depends on both _________ and _________.
drug concentration and volume
Efficacy for clinical use of local anesthetics may be increased by addition of:
- epinephrine
- opioids
- ⍺2-adrenergic agonists
The rate of local anesthetic system absorption depends on:
- the site of injection
- the dose
- the drug’s intrinsic pharmacokinetic properties
- the addition of vasoactive agent
Cocaine is also known as:
Coca shrub (Erythroxylon coca)
First isolated in 1860, numbing of tongue
Albert Niemann
Cocaine’s physiological actions
Sigmund Freud
Topical anesthetic for ophthalmological surgery 1884
Carl Koller
Infiltration and conduction block anesthesia
Halstead
Amides
- BUPIVACAINE
- LEVOBUPIVACAINE
- ETIDOCAINE
- LIDOCAINE
- MEPIVACAINE
- PRILOCAINE
- ROPIVACAINE
Esters
- BENZOCAINE
- CHLOROPROCAINE
- COCAINE
- PROCAINE
- TETRACAINE
Block conduction by _______ or ________ permeability to Na+
decreasing or preventing
No propagation of ________ = nerve conduction fails
action potential
The degree of block depends on how the nerve has been _______ and on its __________.
stimulated
resting membrane potential
_________ frequency of stimulation and _______ membrane potential cause a greater degree of anesthetic block
Higher
More positive
Local anesthetic gains access to its binding site within the pore only when the Na+ channel is in an _________.
open state
Pain
Unmyelinated C fibers
Temperature
Myelinated Aδ fibers
Touch
Myelinated A (gamma) fibers
Deep pressure
Myelinated Aβ fibers
Motor function
Myelinated A (alpha) fibers
Epinephrine is a?
Vasoconstrictor
Epinephrine acts by _________ the rate of absorption, it localizes the anesthetic at the desired site.
decreasing
It allows the rate at which it is destroyed in the body to keep pace with the rate at which it is absorbed into the circulation.
Epinephrine
Reduces systemic toxicity
Epinephrine
Sympathomimetic amines: =
↑ O2 consumption of tissue + vasoconstriction
Sympathomimetic amines: ↑ O2 consumption of tissue + vasoconstriction =
hypoxia, local tissue damage
Regions with limited collateral circulation could produce:
irreversible hypoxic damage, tissue necrosis, gangrene
Central nervous system:
- Restlessness
- Tremor
- Clonic convulsion
- Depression
- Death
The myocardium ________ in electrical excitability, conduction rate, & force of contraction
decreases
*seen only after high systemic concentrations are attained & effects on the CNS are produced
Bupivacaine side effects:
Ventricular tachycardia & fibrillation
Inadvertent IV administration
Bupivacaine
Undesired effects in GIT
depress contractions in the intestines
Undesired effects in vascular and bronchial smooth muscles
relaxation
Undesired effects in sympathetic nervous system
paralysis
Undesired effects in uterine muscle
Increase resting tone
Decrease contraction
Undesired effects in intrapartum:
uterine contractions not depressed
Local anesthetics block ________.
nicotinic Ach receptors
Hypersensitivity manifest as:
allergic dermatitis or a typical asthmatic attack
Esters are hydrolyzed as:
Plasma cholinesterase
Esters
- Benzocaine
- Chloroprocaine
- Cocaine
- Procain
- Tetracaine
Amides:
- Lidocaine
- Prilocaine
- Bupivacaine
- Ropivacaine
Initially hydrolysis forming o-toluidine metabolite – Methemoglobinemia
Prilocaine
Hepatic cyps
N-dealkylation then hydrolysis
Amides are extensively bound to ___________.
⍺1-acid glycoprotein
↑ ⍺1-acid glycoprotein:
- cancer
- surgery
- trauma
- MI
- smoking
- uremia