L18 Flashcards
clonus
reduced ability to lower calcium between stimulations due to increased frequency of stimulation leads to incomplete relaxation
tetanic contraction
no appreciable reducing in [Ca2+] between stimuli leads to physiological muscle contraction
2 classifications of neuromuscular relaxant drugs
- non-depolarizing agents (Curare)
2. depolarizing agents (succinylcholine)
non-depolarizing drugs mechanism of actions
competitive antagonist at nicotinic Ach receptors. Prevents opening of nicotinic receptor ion channel thus preventing membrane depolarization and end-plate potentials
non-depolarizing drugs can be cover come by
excessive Ach through:
- tetanic stimulation
- cholinesterase inhibitors
T1/2 of non-depolarizing drugs depends on
route of elimination kidney>liver>plasma cholinesterase
Pancuronium (mechanism, uses, and excretion and duration)
non-depolarizing neuromuscular relaxant - blocks muscle nicotinic receptors.
used for adjuvant in surgica anesthesia, abdominal wall relaxation and orthopedic procedures
primarily renal excretion
durations 30-60 min
Vecuronium
non-depolarizing neuromuscular relaxant
liver and renal excretion
mivacurium
non-depolarizing neuromuscular relaxant
good for intubation bc it is fast acting and short lived
excretion: plasma cholinesterases
Rocuronium (mechanism, uses, excretion, and duration)
non-depolarizing neuromuscular relaxant
excretion: liver
uses: intubation, muscle relaxation during surgery or ventilation
duration: ~25min
receptor reserve and curare compounds
due to the receptor reserve a very high percentage of receptors must be occupied by an antagonist to inhibit contraction (even at 75% occupancy a full strength muscle concentration) therefore even with a long half life the duration of action is short
order of effect of non-depolarizing neuromuscular agents
Fine muscles before large limbs before respiratory muscles
extraoccular, hand and feet, head and neck, abdomen and extremities, diaphragm-respiratory muscles
recovery is in the reverse order
clinical uses for non-depolarizing neuromuscular agents
Clinical Uses of Non-depolarizing NM relaxants
Adjuvant to anesthesia during surgery (choice depends on length of surgery and liver/renal function) Relaxation of larynx for endotracheal intubation (rocuronium and mivacuronium) Relaxation of chest during mechanical ventilation (choice depends on liver and renal function)
Side Effects of non-depolarizing neuromuscular agents
Not analgesic (all) Apnea (all)
inhaled anesthetics affects on non-depolarizing neuromuscular drugs
enhance their effects making the duration unpredictable
antidote to non-depolarizing neuromuscular agents
cholinesterase inhibitors- neostigmine
muscarinic blockers - (to minimize the effects of cholinesterase inhibitors) glycopyrrolate
depolarizing blocking drugs mechanism of action
agonists ie Succinylcholine
2 phases
phase 1: ion channels are opened depolarizing the membrane. the membrane remains depolarized preventing further APs. Results in a flaccid paralysis. Cholinesterase inhibitors augment block (further prevent repolarization)
phase 2: membrane becomes repolarized
Receptor becomes insensitive to Ach (and other agonists). can be overcome by cholinesterase inhibitors
succinyl choline is metabolised by
plasma cholinesterase
Depolarizing Agents (Succinylcholine) pharmacokinetics
More rapid onset than non-depolarizing agents
Metabolized by plasma cholinesterase
Action terminated by diffusion away from synapse
Genetic variant of cholinesterase can
prolong T1/2 of Succ
Depolarizing Agents (Succinylcholine) clinical uses
Clinical Uses
Endotracheal intubation
Suppression of muscle contraction during ECST
electro-convulsive shock therapy
Side effects of Depolarizing Agents (Succinylcholine)
Side Effects
Not analgesic (all)
Apnea (all)
Muscle pain (fasciculations)
Intraocular pressure/intragastric pressure
Stimulation of ganglionic nicotinic receptors (arrhythmia and hypertension)
Stimulation of muscarinic receptors, sinoatrial node
* Hyperkalemia (K+ release from motor endplate)
immediately after burns
several days after widespread tissue injury
chemical antidote for Depolarizing Agents (Succinylcholine)
phase I- none
phase II- cholinesterase inhibitors
contraindications of Depolarizing Agents (Succinylcholine)
family history of malignant hyperthermia,
burns,
Spasmolytic Drugs indications
heightened skeletal muscle tone due to:
- release from inhibitory supraspinal control
- increased activity of facilitory pathways
- increased excitability of α and γ motor systems
Goal of spasmolytic therapy is:
reduce 1a afferent-mediated stretch reflex.
enhance activity of inhibitory internuncial neurons
Baclofen mechanism of action, uses, side effects
GABA agonists
reduced calcium influx and therefore reduces the release of excitatory transmitters
used for spinal spasticity or spasticity due to multiple sclerosis
side effect: drowsiness
Benzodiazepines (Diazepam and clonazepam) (mechanism, uses, and side effects)
facilitate GABA mediated presynaptic inhibition.
used for spinal spasticity and multiple sclerosis
side effects: sedation and drowsiness
Tizanidine (mechanism, uses, and side effects)
alpha 2 adrenergic agonist (promotes pre and post synaptic inhibition in the spinal cord.
used for multiple sclerosis and spinal spasticity
side effects: drowsiness, hypotension
dantrolene (mechanism, uses, and side effects)
blocks calcium release from sarcoplasmic reticulum in muscle
used for spasticity and malignant hyperthermia
side effects: muscle weakness and sedation
