Musculoskeletal: Skeletal Muscle Relaxants

Front 1

Cholinoreceptors and main ones in skeletal muscle

Back 1

Nicotinic (ligand gated ion channels) - Nm - SNS - NMJ and Nn - ANS ganglia

Muscarinic - G protein coupled. M1 - Neural, M2 Heart, M3 glands, SM, EC, M4 - CNS (Gi), M5 CNS (Gq)

Muscles use Nm at junction and Nn at ANS ganglion. Acetycholine is the neurotransmittor. Nicotine will also stimulate them. Dose dependent and stay open as long as NT available

Front 2

Nm excitatory neurotransmitters and inhibitory ones

Back 2

Excitatory - AcH, nicotine, glutamate

Inhibitory - (via Cl- channel), Glycine, GABA

Needs 2 AcH to open and stays open as long as there

Front 3

Neuromuscular Nm Blockers Depolarizing vs Non Depolarizing and role

Back 3

Produce muscle paralysis (surgery, respirator, etc). Local action at postsynaptic terminal of motor neuron (unlike antispasmolytics at central)

Depolarizing - Succinylcholine causes continuous depolarization (Phase I) followed by desensitization (Phase II) and muscle twitches, AChE inhibitors potentiate Phase I effects

Nondepolarizing - Tubocurarine, atracurium, pancuronium compete with AcH for Nm receptors, AChE inhibitors reverse block

Front 4

Ganglionic Blockers MOA and common ones

Back 4

competitive Nn receptor blockers, Hexamethonium (lowers BP), Trimethaphan (IV HTN emergency), Mecamylamine

Shuts down PNS and SNS so rarely used.

Front 5

Spasmolytics categories and where act on chain

Back 5

Antispasticity - baclofen (spinal cord), dantrolene (direct acting on smooth muscle) - SPINAL CORD

Antispasm - cyclobensaprine, metaxalone, methocarbamol (central acting via spinal reflex) - BRAIN

Motor nerve blocking drugs - botulinum toxin (blocks Ach release) - MOTOR NERVE

Front 6

Cholingergic transmission process. AChE process

Back 6

Choline transportor (rate limiting step) brings in choline from outside cell with Na

Choline ester transferase makes AcH

Vesicular amine transportor and VAMPs ready it and release it

Acetylcholine esterase breaks down to stop transmission (butyrylcholinesterase in plasma)

AChE cleaves to choline and acetylated enzyme complex. AEC is hydrolyzed to acetate and free AChE

Front 7

What 2 things release contraction normally

Back 7

ACh depletion (in cleft or stores), receptor desensitization

Front 8

Succinylcholine MOA, Role, depolarization and repolarization time

Back 8

Depolarizing Nm blocker (NMJ), LOCAL

AChE inhibitors potentiate Phase I

Induces paralysis in muscles, often given IV for systemic SHORT surgeries b/c risks, endotracheal intubation

Structure: 2 AcH joined, AChE can't break down so longer half life b/c must be broken down by butyrylcholinesterase, only systemic b/c CANT" CROSS BBB

MOA: Phase I: prolonged Nm acitvation, initial fasciculations followed (Phase I) then Phase II flaccid paralysis. This continuous depolarization desensitizes the membrane. Can be reversed if ACh present

ACh is rapid depolarization and repolarization. Succinylcholine is rapid depolar and persistent depolarization for paralysis

Front 9

Tubocurarine MOA, Role, Reversal, uses

Back 9

(Trimethaphan, Mecamylamine, pancuronium, atracurium, vecuronom, mivacurium)

Nondepolarizing Nm blocker, LOCAL that competes with ACh for Nm receptors. High ACh can reverse

Induces paralysis in muscles, often given IV for systemic

Structure: very large and physically block AChReceptor, polar so CAN"T CROSS BBB, only systemic

NO AGONISM, ONLY PARALYSIS, can be reversed with ACh. long half life,

Reversal: AChE inhibitor to increase ACh levels (neostigimine, pyridostigimine, edrophonium)

USE: long half life, RESPIRATOR

Front 10

Succinylcholine Risks and Uses

Back 10

Uses: Short surgery, endotracheal intubation

Risks: increases cellular K efflux, hyperkalemia could cause arrythmia or arrest

combination with halothan or gas anasthetics can cause malignant hyperthermia (dantrolene reversal)

MG pts are hypersensitive to Phase II part

Also activates Nn and cardiac receptors M2

Front 11

Uses and Risks of Tubocurarine

Back 11

Uses: Respirator pts, b/c long half life

Risks: kidney excretion so NO if renal impaired, USE ATRACURIUM;

GANGLIONIC BLOCKADE and His release to lower BP and up HR

Front 12

Age differences for Succinylcholine vs Tubocurarine

Back 12

Succinycholine is less potent in neonates than tubocurarine

Front 13

Renal impaired pt can't use tubocurarine

Back 13

Try atracurium, same MOA, hepatic metabolism

Front 14

Inhaled anesthetics effect on Nm blockers. Ca and K effect on Tubocurarine

Back 14

Succinylcholine - halothane can cause malignant hyperthermia from Ca++ release block. Dantrolene reverse

Tubocurarine potentiated by anesthetics and low K or Ca++, Elevated K or Ca counteracts

Front 15

Burn pt med

Back 15

Not succinylcholine, use Tubocurarine

Front 16

Pancuronium risks

Back 16

mixed agonist/antagonist of M2 and blocked NE reuptake couldb cause arrythmia, tachycardia, HTN, doesn't cause His release like other nondepolarizing (tubocurarine) though

Front 17

How to reverse postoperative residual curarization

Back 17

Pt can't breathe well. Sux I block will recover with short half life. Phase II can use AChE inhibitor

Nondepolarizors (Tubocurarine, Pancuronium) - use AChE plus Muscarinic receptor blocker (to prevent PNS ACh diarrhea)

Front 18

Spasticity commonly caused from what

Back 18

Hyperexcitability of alpha motor neurons causing a loss of normal inhibition or imbalance of excitatory and inhibitory neurotransmitters

Front 19

Baclofen MOA, Role, ASE

Back 19

Antispasticity drug acts on SPINAL CORD by binding GABAb receptor to decrease excitatory NT release. Inhibits motor neuron activity and spinal reflexes

MOA: binds presynaptic spinal interneurons, hyperoplarizes, decreases Ca++ in and lowers glutamate and aspartate release (excitatory NT)

Crosses BBB, mild liver metabolism, kidney excretion

ASE: drowsiness, dizziness, fatigue, hypotension

Front 20

Diazepam MOA, Role, ASE

Back 20

Antispasm drug/Antispasticity drug acts on Brain and spinal cord via GABAa receptors to decrease spinal reflexes

Front 21

Tizanidine MOA, Role

Back 21

Acts on Alpha 2 adrenoreceptors to decrease reflexes of spine

Front 22

Dantrolene MOA, Role, ASE

Back 22

Antispasm drug - spinal cord, local acting by INHIBITING RYANODINE RECEPTOR CALCIUM RELEASE, direct acting

Used to reverse malignant hyperthermia (Succinylcholine + halothane)

ASE: muscle weakness, diarrhea, drowsiness, seizures, hepatotoxicity if chronic use

Front 23

Cyclobenzaprine, Methocarbamol, Metaxalone MOA, role

Back 23

Antispasm drugs for muscle cramping and hyperactivity, DO NOT act on motor neuron or muscle but BRAIN and reflexes. May induce sedation.

Front 24

Botulinum Toxin role

Back 24

Blocks ACh release from motor neurons by interfering with synaptic proteins. Causes 3 month paralysis

ASE: weakness, double vision, loss of bladder control .