NU 406 Relaxants and Opiods (1) PDF

CHAPTER 25 MUSCLE RELAXANTS NERVES AND MOVEMENT Constantly fluctuating sequence of muscle contraction and relaxation Regulated by spinal motor neurons Influences from higher-level brain activity in lower areas of the brain Basal ganglia Cerebellum Cerebral cortex TYPES O...

CHAPTER 25 MUSCLE RELAXANTS NERVES AND MOVEMENT Constantly fluctuating sequence of muscle contraction and relaxation Regulated by spinal motor neurons Influences from higher-level brain activity in lower areas of the brain Basal ganglia Cerebellum Cerebral cortex TYPES OF SPINAL REFLEXES Simple Involving an incoming sensory neuron and an outgoing motor neuron Complex Involving interneurons that communicate with the related centers in the brain REFLEX ARC SHOWING PATHWAY OF IMPULSES BRAIN CONTROL Pyramidal tract Controls precise intentional movement Extrapyramidal tract Modulates unconsciously controlled muscle activity Allows the body to make automatic adjustments in posture or position and balance NEUROMUSCULAR ABNORMALITIES Muscle spasms Often result from injury to the musculoskeletal system Thought to be caused by flood of sensory impulses coming to the spinal cord from the injured area Muscle spasticity Result of damage to neurons within the CNS May result from an increase in excitatory influences or a decrease in inhibitory influences within the CNS PROCESS OF MUSCLE CONTRACTION USE OF SKELETAL MUSCLE RELAXANTS ACROSS THE LIFESPAN  CENTRALLY ACTING SKELETAL MUSCLE RELAXANTS #1 Therapeutic actions Work in the CNS to interfere with the reflexes causing the muscle spasm Lyse or destroy spasm (spasmolytics) Exact mechanism of some is unknown, thought to alter spinal or subcortical neurons Indications Relief of discomfort associated with acute, painful musculoskeletal conditions Adjunct to rest, physical and occupational therapy, and other measures  CENTRALLY ACTING SKELETAL MUSCLE RELAXANTS #2 Pharmacokinetics Most are rapidly absorbed and metabolized in the liver Excreted in the urine Contraindications Known allergy Spasms resulting from rheumatic disorders Cautions Epilepsy Cardiac dysfunction Conditions marked by muscle weakness Hepatic or renal dysfunction Pregnancy and lactation  CENTRALLY ACTING SKELETAL MUSCLE RELAXANTS #3 Adverse effects Effects associated with CNS depression GI disturbances Hypotension and arrhythmias Urinary frequency, enuresis, feelings of urinary urgency Chlorzoxazone may discolor the urine Tizanidine associated with liver toxicity and hypotension in some patients  CENTRALLY ACTING SKELETAL MUSCLE RELAXANTS #4 Drug–drug interactions CNS depressants Alcohol  DIRECT-ACTING SKELETAL MUSCLE RELAXANTS #1 Therapeutic actions Enter the muscle to prevent muscle contraction directly Dantrolene: interferes with the release of calcium from the muscle tubules Botulinum toxins A and B: inhibit release of acetylcholine Indications Treatment of spasticity directly affecting peripheral muscle contraction Management of spasticity associated with neuromuscular diseases  DIRECT-ACTING SKELETAL MUSCLE RELAXANTS #2 Pharmacokinetics Dantrolene Slowly absorbed from the GI tract Metabolized in the liver T ½ 4 to 8 hours Excreted in the urine Crosses the placenta; embryotoxic Enters human milk Botulinum toxins Not generally absorbed systemically No pharmacokinetic information available  DIRECT-ACTING SKELETAL MUSCLE RELAXANTS #3 Contraindications Dantrolene: Known allergy; spasticity that contributes to locomotion, upright position, or increased function; active hepatic disease; lactation Botulinum toxins: Known allergy Cautions Dantrolene: Female patients; age over 35 years; history of liver disease or previous dysfunction; respiratory depression; cardiac disease; pregnancy Botulinum toxins: Peripheral neuropathic disease; neuromuscular disorders; pregnancy and lactation; cardiovascular disease  DIRECT-ACTING SKELETAL MUSCLE RELAXANTS #4 Adverse effects Dantrolene: effects related to CNS depression; GI disturbances; hepatocellular damage, hepatitis; some unusual adverse effects Botulinum toxins: anaphylactic reactions; headache, dizziness, muscle pain, paralysis; redness and edema; adverse effects specific to cosmetic use Drug–drug interactions Dantrolene and estrogen Botulinum toxins and drugs that interfere with neuromuscular transmission; aminoglycosides CHAPTER 26 OPIOID AGONISTS, OPIOID ANTAGONISTS, AND ANTIMIGRAINE AGENTS PAIN Sensory and emotional experience associated with actual or potential tissue damage One of hardest sensations for patients to cope with Acute or chronic Drugs used to relieve pain Work in the CNS to alter the way pain impulses are processed Opium derivatives used to treat many types of pain Antimigraine drugs reserved for the treatment of migraine headaches NEURAL PATHWAYS OF PAIN PAIN IMPULSE TRANSMISSION AND PERCEPTION Unpleasant stimuli transmitted from point of initial injury to the brain via nociception fibers: A- delta and C fibers Larger A fibers transmit sensations associated with pressure, stretch, vibration Spinothalamic tracts form synapses with various nerve cells that transmit information to the cerebral cortex Gate control theory The transmission can be modulated or adjusted. Along spinal cord interneurons act as “gates” by blocking ascending transmission of pain impulses. Theory is that gates can be closed by stimulation of A fibers and by descending impulses coming down the spinal cord from higher levels. PAIN RECEPTORS Opioid receptors found: In CNS On nerves in the periphery On cells in the gastrointestinal (GI) tract Endorphins and enkephalins normally modulate pain information coming into the brain USE OF OPIOIDS ACROSS THE LIFESPAN OPIOID AGONISTS #1 Drugs that react with opioid receptors Cause analgesia, sedation, or euphoria Potential for physical dependence Classified as controlled substances Rising problem of addiction OPIOID AGONISTS #2 Therapeutic actions Act at specific opioid receptor sites in the CNS Produce analgesia, sedation, and a sense of well-being Indications Relief of severe acute or chronic pain Analgesia during anesthesia Specific individual indications depending on receptor affinity When deciding which to use, it is important to consider all aspects of patient’s condition; select drug that will be most effective with fewest adverse effects OPIOID AGONISTS #3 Pharmacokinetics IV fastest way to achieve therapeutic response IM and sub-q offer varying rates of absorption Undergo hepatic metabolism Generally excreted in the urine and bile Cross the placenta and enter human milk OPIOID AGONISTS #4 Contraindications Known allergy Diarrhea caused by toxins Some: presence of GI obstruction Cautions Respiratory dysfunction, asthma, or emphysema Recent GI or GU surgery and acute abdomen or inflammatory bowel disease Head injury Alcohol use disorder Delirium tremens Cerebral vascular disease Pregnancy, labor, or lactation OPIOID AGONISTS #5 Adverse effects Most common relate to effects on various opioid receptors Respiratory depression Orthostatic hypotension GI effects Neurologic effects Drug–drug interactions Barbiturate general anesthetics, other CNS depressants, some phenothiazines and MAOIs Tapentadol: SSRIs, MAOIs, TCAs, St. John’s wort Anticholinergic agents Antihypertensive agents QUESTION #1 Identify a reason an opioid agonist may be prescribed? A. Relief of minor pain B. Analgesia during anesthesia C. Analgesia during sleep D. Relief of moderate acute pain ANSWER TO QUESTION #1 B. Analgesia during anesthesia Rationale: Opioid agonists are indicated for relief of severe pain, preoperative medication, analgesia during anesthesia, and specific individual indications depending on receptor affinity. OPIOID AGONISTS–ANTAGONISTS #1 Therapeutic actions Act as partial agonists at the mu-opioid receptors and antagonists at the kappa-opioid receptor in the CNS to produce analgesia, sedation, euphoria, and hallucinations Indications Treatment of moderate to severe pain Some can be used to treat opioid use disorder OPIOID AGONISTS–ANTAGONISTS #2 Pharmacokinetics Readily absorbed after IM administration; reach peak levels rapidly when given IV Metabolized in the liver excreted in urine or feces Cross placenta and enter human milk OPIOID AGONISTS–ANTAGONISTS #3 Contraindications Known allergy Nalbuphine: Allergy to sulfites Cautions Physical dependence on opioids COPD and other respiratory dysfunction Acute MI, documented CAD, or hypertension Renal or hepatic dysfunction Pregnancy and lactation OPIOID AGONISTS–ANTAGONISTS #4 Adverse effects Respiratory depression with apnea and suppression of cough reflex Nausea, vomiting, constipation, and biliary spasm Light-headedness, headache, dizziness, psychoses, anxiety, fear, hallucinations, impaired mental processes GU effects Sweating and dependence less likely than with opioid agonists Drug–drug interactions Barbiturate general anesthetics Physical dependence on opioid agonists OPIOID ANTAGONISTS #1 Therapeutic actions Block opioid receptors and reverse effects of opioids Indications Reversal of the adverse effects of opioid use Treatment of opioid overdose OPIOID ANTAGONISTS #2 Pharmacokinetics Widely distributed in the body Hepatic metabolism; excreted in the urine Contraindications Known allergy Cautions Pregnancy and lactation NARCOTIC ANTAGONISTS #3 Adverse effects Most common: Acute opioid abstinence syndrome CNS excitement and reversal of analgesia especially common after surgery CV effects Drug–drug interactions Larger doses may be needed to reverse effects of buprenorphine, butorphanol, nalbuphine, pentazocine QUESTION #2 Identify one indicator for an opioid antagonist to be prescribed. A. Treatment of alcohol independence B. Reversal of bronchoconstriction C. Treatment of opioid overdose D. Reversal of tachycardia ANSWER TO QUESTION #2 C. Treatment of opioid overdose Rationale: These agents are indicated for reversal of the adverse effects of opioid use, including respiratory depression and sedation, and for treatment of opioid overdose. MIGRAINE HEADACHES Due to activation of trigeminal nerve that causes inflammation within the meningeal blood vessels Often cause severe, throbbing headaches on one side of head Pain can cause widespread disturbances: GI, CNS Three times more likely to occur in females Classifications Common Classic USE OF ANTIMIGRAINE AGENTS ACROSS THE LIFESPAN ERGOT DERIVATIVES #1 Cause constriction of cranial blood vessels and decrease the pulsation of cranial arteries, reducing the hyperperfusion of the basilar artery vascular bed Dihydroergotamine (Migranal, D.H.E. 45) Ergotamine (Ergomar) ERGOT DERIVATIVES #2 Therapeutic actions Block alpha-adrenergic and serotonin receptor sites in the brain to cause constriction of cranial vessels, decrease in cranial artery pulsation, decrease in hyperperfusion of basilar artery bed Indications Prevention or abortion of migraine or vascular headaches ERGOT DERIVATIVES #3 Pharmacokinetics Rapidly absorbed from many routes Onset of action ranges 15–30 minutes Metabolized in the liver; primarily excreted in the bile ERGOT DERIVATIVES #4 Contraindications Known allergy CAD, hypertension, or peripheral vascular disease Impaired liver function Pregnancy or lactation Cautions Pruritus Malnutrition ERGOT DERIVATIVES #5 Adverse Effects CNS effects CC effects GI effects Ergotism Drug–drug interactions Beta-blockers Triptans QUESTION #3 Which is an action of ergotamine? A. Decreases hyperperfusion of basilar artery vascular bed B. Increases hyperperfusion of basilar artery vascular bed C. Increases hypoperfusion of basilar artery vascular bed D. Decreases hypoperfusion of basilar artery vascular bed ANSWER TO QUESTION #3 A. Decreases hyperperfusion of basilar artery vascular bed Rationale: The ergot derivatives block alpha-adrenergic and serotonin receptor sites in the brain to cause a constriction of cranial vessels, a decrease in cranial artery pulsation, and a decrease in the hyperperfusion of the basilar artery bed. TRIPTANS #1 Therapeutic actions Bind to selective serotonin receptor sites to cause vasoconstriction of cranial vessels Indications Treatment of acute migraine Not used for prevention of migraines Sumatriptan also used for cluster headaches in adults TRIPTANS #2 Pharmacokinetics Rapidly absorbed from many sites Metabolized in the liver Primarily excreted in the urine Cross the placenta and enter human milk TRIPTANS #3 Contraindications Known allergy Pregnancy CAD Cautions Older adult patients Patients with risk factors for CAD Lactation Renal or hepatic dysfunction TRIPTANS #4 Adverse effects CNS effects GI effects CV effects Almotriptan reported to have fewer side effects than other triptans Drug–drug interactions Ergot-containing drugs QUESTION #4 An 8-year-old patient has been diagnosed with acute migraines. Which triptan does the nurse expect the provider to prescribe? Eletriptan (Relpax) Almotriptan (generic) Rizatriptan (Maxalt, Maxalt-MLT) Naratriptan (Amerge) ANSWER TO QUESTION #4 C. Rizatriptan (Maxalt, Maxalt-MLT) Rationale: Rizatriptan is indicated for use in adults and children aged 6– 17 years. Eletriptan and naratriptan are indicated for use in adults. Almotriptan is indicated for use in adults and teens aged 12–17 years.  CALCITONIN GENE–RELATED PEPTIDE (CGRP) INHIBITORS AND SEROTONIN AGONIST #1 Therapeutic actions CGRP inhibitors: Inhibit CGRP, a potent vasodilator chemical released during migraine headache attacks Serotonin agonist: Has selective action on a specific serotonin receptor Indications Prevention of migraine headaches Galcanezumab also indicated for cluster headaches Lasmiditan: treatment of acute migraine with or without aura  CALCITONIN GENE–RELATED PEPTIDE (CGRP) INHIBITORS AND SEROTONIN AGONIST #2 Pharmacokinetics Gepants CGRP inhibitors and lasmiditan absorbed via GI tract Monoclonal antibodies that are CGRP inhibitors injected Lasmiditan: absorbed quickly, metabolized in and outside liver, eliminated renally Gepants CGRP inhibitors: proteins metabolized, eliminated through bile and feces Monoclonal antibodies have long half-lives No human data of effects on pregnancy  CALCITONIN GENE–RELATED PEPTIDE (CGRP) INHIBITORS AND SEROTONIN AGONIST #3 Contraindications Signs of allergy to the medication Cautions Pregnancy Adverse effects Lasmiditan: dizziness, fatigue, paresthesia, sedation CGRP inhibitors: risk of hypersensitivity reactions Gepant substances: nausea Monoclonal antibodies: injection site reactions  CALCITONIN GENE–RELATED PEPTIDE (CGRP) INHIBITORS AND SEROTONIN AGONIST #4 Drug–drug interactions Lasmiditan: CNS depressants, heart rate lowering medications, other serotonergic medications Gepant CGRP inhibitors: CYP3A4 inducers and inhibitors Both lasmiditan and the gepant CGRP inhibitors: Pgp and BCRP