Conductive Tissue/Muscle/NMJ Physiology Flashcards
Mechanism of action of local anesthetics
Block fast Na channels in axons (block action potentials) by binding inside the channels
***Exception: Benzocaine (a topical LA), binds outside of the Na channel rather than inside.
- Drug needs to be lipid soluble to penetrate membrane*
- Drugs with higher lipid solubility tend to be more potent*
Ester versus amide local anesthetic metabolism
Ester local anesthetics are quickly degraded by serum esterases → short half-life, shorter-acting
Amide local anesthetics can only be metabolized in the liver, which takes a long time → longer-acting
Ester local anesthetics
Procaine, Tetracaine (Pontocaine)
Amide local anesthetics
Lidocaine (Xylocaine)
Bupivacaine (Marcaine)
Mepivacaine (Carbocaine)
- Good for old people and cardiac pts bc can be administered w/o epinephrine
***All of these have two “i’s” in thier name
Differential sensitivity of nerve fibers
Using differential sensitivity allows these drugs to be applied to block pain but not affect sensory and/or motor fibers
CNS and cardiovascular side effects of local anesthesia
Adverse reactions occur primarily in the central nervous and cardiovascular systems because these tissues are also composed of excitable membranes.
Cardiovascular effects
- Conduction failure
- Ventricular arrhythmias or fibrillation
- Both effects are worse in the presence of epinephrine
- Hypotension as a result of a combination of vasodilation effects from local anesthetics and negative inotropic forces (Which weaken the force of muscular contraction)
- Spillage of excessive amounts of local anesthetic into general circulation can be caused by excessive local injections or tourniquet failure.
CNS effects
- Low doses affect only excitatory neurons, causing sedation and drowsiness
- High doses affect both excitatory and inhibitory interneurons, causing convulsions
Cross-bridge cycle
Clinical uses and mechanism of action of botulinum toxin
Mechanism of action: blocks acetylcholine release from presynaptic terminals (results in total blockade of neuromuscular transmission)
Clinical uses: used to treat Upper Motor Neuron Disease and for chewing problems, swallowing problems, muscle spasms, hair loss, twitching of the eyelids, and excessive sweating
Clinical uses and mechanism of action of curare
Mechanism of action: competes with acetylcholine for nicotinic receptors on motor end plate (decreases size of end plate potential)
Clinical uses:
- D-tubocurarine is used to relax skeletal muscles during anesthesia
- α-bungarotoxin is used experimentally to measure the density of acetylcholine receptors on the motor end plate
Clinical uses and mechanism of action of acetylcholinesterase inhibitors
Mechanism of action: prolong and enhance action of acetylcholine at motor end plate by preventing its degradation
Clinical uses: used to treat myasthenia gravis
Subunits of troponin and their actions
Troponin blocks myosin binding sites during rest but when calcium binds to troponin (C) it exposes myosin binding site and allows for contraction.
- Troponin C: binds to calcium leading to conformational change
- Troponin T: binds to tropomyosin to form troponin-tropomyosin complex
- Troponin I: binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place
Locations and functions of dihydropyridine receptor and ryanodine receptor in skeletal muscle fiber
Dihydropyridine Receptor: Voltage Sensitive Protein activated by AP from sarcolemma
- Location: T-Tubules
- Function: Activates ryanodine receptors
Ryanodine Receptor: Ca2+ Release Channel
- Location: sarcoplasmic reticulum
- Function: Enables muscle contraction by increasing intracellular Ca2+
Exitation contraction coupling in smooth muscle
Excitatory versus inhibitor neurotransmitters
Excitatory:
- Glutamate: the major excitatory neurotransmitter in the CNS
Inhibitory:
- Glycine
- GABA (gamma-aminobutyric acid)
- Nitric Oxide
