Pharmacology Local and MR Flashcards
Ester-linked Local Anesthetic drugs
- cocaine
- procaine
- benzocaine
- tetracaine
local anesthetic mechanism of action
votalge-gated Na+ channel blocker
- decrease rate of depolarization
- increase threshold for electrical excitability
Nociception
- opioids = morphine
- voltage-gated = local anesthetics
- a2 agonists = dexmedetomidine
Susceptibility factors of local anesthetics
- fiber diameter
- myelination
- fiber position
- firing frequency
Myelination and local anesthetics
myelinated nerves are blocked before unmyelinated
fiber position and local anesthetics
outer nerves in a bundle are blocked more readily than inner nerves
Firing frequency and local anesthetics
LA have a higher affinity for the active Na+ channels compared to resting
- Rapidly firing neurons are more readily blocked by local anesthetics when compared to slowly firing neurons
Ionizable group of local anesthetics
most LA are weak bases
- LA must be unpronated and neutral to permeate cellular membranes
- Protonated LA are more potent than their unprotonated counterpart
Ester-Linked Local Anesthetics
rapidly hydrolyzed
- have a shorter half life
- have a lower Vd
- are less likely to elicit systemic side effects
“local” adverse effects of LA
tissue damage
- stinging sensation due to acidic nature
- hypoxia due to co-administration of vasoconstrictor
Large doses of which 3 LA may cause metheglobinemia?
prilocaine, benzocaine, lidocaine
Vasoconstrictors and LA
epinephrine or Levonordefrin
- limits escape of LA from site of administration
- decreases the potential for systemic toxicity
- increases the duration of action at target site
3 classifications of muscle relaxants
- neuromuscular blockers
- spasmolytics
- antispasmodics
Neuromuscular blockers
- exert effects on periphery
- do not cross the BBB
Spasmolytics
used to reduce spasticity assoicated with neuromuscular disorders
- mostly exert effects within the CNS
Antispasmodics
Used to treat musculoskeletal conditions such as back bain and fibromyalgia
- exert their effect within the CNS
Neuromuscular blocker mechanism of action
bidns to and blocks nicotinic cholinergic receptors (NM) located at the NMJ
- interferes with acetylcholine action
Nicotinic cholinergic receptors are ____ and ____
ligand-gated receptors and sodium channels
Structure of Nicotinic receptors
- Made from 5 types of homologous subunits
- NN located at ganglia
Acetylcholine binding sites on nicotinic receptors
2 (alpha2)
Describe the “pore” of nicotinic receptors
M2 region within each of the 5 subunits forms the pore that is selective for Na+
- 3 negatively charged amino acid rings pull Na+ through
- Leucine ring is important in channel desensitization
Succinylcholine
Depolarizing MR
- at low concentrations, acts like ACh and depolarizes membrane
- large doses cause muscle paralysis
- rapid onset (1-1.5 min)
- short duration (5-10 minutes)
Black box warning on Succinylcholine
acute rhabdomylosis with hyperkalemia in children with undiagonsed musclar dystrophies
Malignant Hyperthermia
drugs induce massive Ca2+ discharge through a defective mucle cell ryanodine receptor (RyR)
Dantrolene
RYR-1 calcium channel antagonist
- prevents Ca2+ release from the SR
- blocks movement of myosin and actin
Isoquinolone NDMR
atracurium, cisatracurium, tubocurarine
Steroid NDMR
rocuronium, vecuronium, pancuronium
NDMR
competitive antagonist at NM
AChE inhibitors for MR reversal
neostigmine or pyridosigmine
Sugammadex
selective relaxant binding drug
- chelates steroid-derived NMB and facilitates urinary excretion
