PDF NMT150 PHARM, Wk 5 GABA derivatives and muscle relaxants Low Back Pain (1).pdf

NON-OPIOID ANALGESICS AND ANTI-INFLAMMATORIES PART 2 Dr. Adam Gratton NMT150 MSc ND February 9, 2023 LECTURE COMPETENCIES Describe the proposed mechanism of action of GABA derivatives for neuropathic pain Describe the adverse effects associated with GABA derivatives Describe the...

NON-OPIOID ANALGESICS AND ANTI-INFLAMMATORIES PART 2 Dr. Adam Gratton NMT150 MSc ND February 9, 2023 LECTURE COMPETENCIES Describe the proposed mechanism of action of GABA derivatives for neuropathic pain Describe the adverse effects associated with GABA derivatives Describe the mechanism of action of commonly used muscle relaxants Describe the adverse effects of commonly used muscle relaxants FOCUS ON LOW BACK PAIN Pharmacotherapeutic options depend on the timeline of pain The differential diagnosis for low back pain is extensive Focus on the drug options for acute low back pain of non- infectious, non-malignant, non-traumatic origin PHARMACOLOGIC OPTIONS Acetaminophen and NSAIDs (discussed previously) GABA derivatives Muscle relaxants Opioids (discussed in an upcoming lecture) GABA DERIVATIVES Pregabalin and Gabapentin Typically reserved for soft tissue and hyperalgesic pain Act centrally GABA DERIVATIVES Complicated mechanism of action that has yet to be fully explained Originally designed as GABA analogues and are classified as anticonvulsants Despite being structurally similar to GABA these drugs do not interact with GABA receptors VOLTAG E- G AT ED C A LC I UM C HA N N EL Chincholkar M. Analgesic mechanisms of gabapentinoids and effects in experimental pain models: a narrative review. Br. J. Anaesth 2018. 120(6):5- 34. doi: 10.1016/j.bja.2018.02.066 MECHANISM OF ACTION Bind α2δ1 receptors of voltage-gated calcium channels This specific subtype is present in the brain, skeletal, cardiac, and smooth muscle Most important area is the dorsal horn of the spinal column These receptors are upregulated as a response to pain Modifies calcium entry and reduces neurotransmitter release INDICATIONS Typically reserved for neuropathic pain Indicated or other disorders that will be discussed later ADVERSE EFFECTS Most common: sedation, ataxia, tremor, dizziness, dry mouth, weight gain May also cause GI upset, peripheral edema, and vision changes Cannot be abruptly discontinued – dose should be tapered over a minimum of 1 week to avoid withdrawal effects DOSING Gabapentin: Initial dose is 300 – 400 mg/day PO divided TID Can increase at weekly intervals to a maximum of 3600 mg/day divided TID Should not be taken with mineral supplements or antacids as this may decrease bioavailability DOSING Pregabalin: Initial dose is 50 – 150 mg daily PO divided BID May increase weekly by 50 – 150 mg/day to a maximum of 600 mg/day divided BID Does not have any significant interactions and is typically preferred as it is taken twice a day vs three times a day with gabapentin MUSCLE RELAXANTS A very broad term that includes drugs of a number of different drug classes Loosely differentiated into antispasmodics and antispastics All muscle relaxants are not recommended for those over the age of 65. ANTISPASMODICS Decrease muscle spasm associated with pain Further classified as benzodiazepines or non- benzodiazepines METHOCARBAMOL A non-benzodiazepine antispasmodic Actually has no effect on the contraction of muscle fibers, motor end plates, or nerve fibers Mechanism of action thought to be dependent on its CNS depressant activity by blocking spinal polysynaptic reflexes, decreasing nerve transmission, and prolonging the refractory period of muscle cells ADVERSE EFFECTS Can cause drowsiness, dry mouth, dizziness, fatigue, nausea, and constipation Combination with other CNS depressants or opioids can increase the risk of CNS depression DOSING 1 g QID PO ANTISPASTICS Reduce muscle rigidity/spasticity that interferes with therapy or function (as in cerebral palsy, for example) Mechanism of action is dependent on the actual drug as there are a number of drugs from various classes that fall into this category BACLOFEN A GABA receptor agonist specific for the beta subunit which is primarily expressed on pre- and post-synaptic neurons Binding causes an influx of potassium into the neuron causing hyperpolarization and decreased calcium influx at presynaptic nerve terminals Results in the reduced rate of action potentials and reduced activation of post-synaptic motor neurons that innervate muscle spindles ADVERSE EFFECTS Can cause sedation, muscle weakness, nausea, dizziness In rare cases can cause hepatotoxicity Potential additive CNS depression with other drugs like opioids and benzodiazepines Dose should be adjusted gradually to minimize adverse effects and tapered to avoid withdrawal symptoms DOSING Initial dose: 5 mg TID PO Increase gradually to a maximum of 20 mg TID LOW BACK PAIN Use of muscle relaxants for low back pain is controversial Mostly due to significant adverse effects Most guidelines caution against their use Despite that they are widely used, possibly given increased hesitancy to recommend opioids SAMPLE QUESTION Which of the following drugs is classified as a non- benzodiazepine antispasmodic? A. Gabapentin B. Baclofen C. Pregabalin D. Methocarbamol