Muscle spasticity is a characteristic of many clinical conditions, including trauma, myositis, muscular and ligamentous sprains and strains, intervertebral disc disease, tetanus, strychnine poisoning, neurologic disorders, and exertional rhabdomyolysis. An increase in tonic stretch reflexes originates from the CNS with involvement of descending pathways and results in hyperexcitability of motor neurons in the spinal cord. Skeletal muscle relaxants alleviate muscle spasms by modifying the stretch reflex arc or by interfering with the excitation-coupling process in the muscle itself. Centrally acting muscle relaxants block interneuronal pathways in the spinal cord and in the midbrain reticular activating system. Some drugs also have sedative effects, which are beneficial to animals that are anxious or in pain. The hydantoin derivatives have a direct action on muscle.
Skeletal Muscle Relaxants
Methocarbamol is a centrally acting muscle relaxant chemically related to guaifenesin. Its exact mechanism of action is unknown, and it has no direct relaxant effect on striated muscle, nerve fibers, or the motor endplate. It also has a sedative effect. In dogs, cats, and horses, methocarbamol is indicated as adjunct therapy for acute inflammatory and traumatic conditions of skeletal muscle and to reduce muscle spasms. Because methocarbamol is a CNS depressant, it should not be given with other drugs that depress the CNS. Overdosage is generally characterized by CNS depression, but emesis (small animals), salivation, weakness, and ataxia may be seen.
Methocarbamol is metabolized via dealkylation and hydroxylation followed by conjugation to form glucuronides and sulfates. Only after oral administration of methocarbamol, guaifenesin is detectable in equine plasma and urine, indicating that first-pass metabolism is necessary for guaifenesin to be produced as a metabolite. Because of their sedative effects, methocarbamol and guaifenesin are regulated by equine sports organizations, and withdrawal periods must be respected.
Guaifenesin (glyceryl guaiacolate) is a centrally acting muscle relaxant believed to depress or block nerve impulse transmission at the internuncial neuron level of the subcortical areas of the brain, brain stem, and spinal cord. It also has mild analgesic and sedative actions. Guaifenesin is given intravenously to induce muscle relaxation as an adjunct to anesthesia for short procedures. It relaxes laryngeal and pharyngeal muscles, allowing easier intubation; however, it has little effect on the diaphragm and respiratory function. It may cause transient increases in cardiac rate and decreases in blood pressure. It is also used in treatment of horses with exertional rhabdomyolysis and in dogs with strychnine intoxication. Overdose results in apneustic breathing, nystagmus, hypotension, and contradictory muscle rigidity. Treatment of overdose is with supportive care until the drug is cleared to nontoxic levels.
Benzodiazepines, such as diazepam, affect polysynaptic reflexes at the supraspinal level, act as a spinal cord depressant at the interneuronal level, and inhibit presynaptic acetylcholine release. Clinically, diazepam is administered as an adjunct to anesthesia, in management of clinical signs of tetanus, and in treatment of functional urethral obstruction and urethral sphincter hypertonus in cats.
Dantrolene, a hydantoin derivative, is structurally and pharmacologically different from other skeletal muscle relaxants. Dantrolene has a direct action on muscle, likely by interfering with the release of calcium from the sarcoplasmic reticulum. It has no discernible effects on respiratory and cardiac function but can cause dizziness and sedation. In veterinary medicine, dantrolene is used to treat malignant hyperthermia in various species, porcine stress syndrome, equine postanesthetic myositis, and equine exertional rhabdomyolysis. Because of its sedative effects, dantrolene is regulated by equine sports organizations, and withdrawal periods must be respected.
Baclofen is a centrally acting skeletal muscle relaxant used to control spasticity and pain in humans with multiple sclerosis and spinal disorders. Baclofen is structurally similar to the inhibitory neurotransmitter 4-aminobutyric acid (GABA). It acts as a GABA receptor B agonist to reduce calcium influx into presynaptic nerve terminals, thereby decreasing the amount of excitatory neurotransmitters released by primary afferent neurons in the spinal cord and brain. This action results in reduced muscle tone as well as pain associated with spasticity. Because of a very narrow safety margin, baclofen is not recommended for use in veterinary medicine. Rarely, it has been administered to treat dogs with tetanus and to reduce urethral resistance in treatment of urinary retention. Even at doses as low as 1.3 mg/kg, dogs may have clinical signs of vomiting, depression, and vocalization. With overdose, the severity of CNS signs can be substantial and may include dysphoria, lateral recumbency, or coma. Treatment of baclofen toxicity should include rapid and aggressive decontamination and intensive supportive care. Management of affected dogs may require positive-pressure ventilation as a result of severe obtundation, respiratory depression, and respiratory arrest or hypoventilation. Cyproheptadine, a serotonin antagonist, may be administered orally or rectally as needed to reduce vocalization or disorientation. Intravenous lipid emulsion has been useful to treat some dogs with baclofen toxicity.