PAIN DRUGS HANDBOOK TABLE
OF CONTENTS
About the
Author
About
the Handbook
Acknowledgments
Forward
to 2rd Edition
Forward
to 1st Edition
DRUGS (Alphabetical Order)
TOPICAL AGENTS
Amitriptyline
Baclofen
Clonidine
Cyclobenzaprine
2-deoxy-d-glucose
Dexamethasone
Dextromethorphan
Diclofenac
Doxepin
DMSO
Gabapentin
Ketamine
Ketoprofen
NEUROLYTIC AGENT
Phenol
APPENDICES
Appendix 1: World Health Organization
Three-step Ladder
Appendix 2: Drug Tables
Appendix 3: Infusion Tables
Appendix 4: Relative Potencies of
Opioids Effects
Appendix 5: Relative Potencies of Steroids
Appendix 6: Intravenous PCA
Standard Orders
Appendix 7: Patient Controlled Analgesia Flow Sheet
Appendix 8: Relative Potencies of Opioids
Appendix 9: Epidural Analgesia Monitoring Orders
Appendix 10: Pain Rating Scales
Appendix 11: Multiplication Factors for Converting the
Daily Dose of a Prior Opioid to the Daily Dose of Oxycontin
Appendix 12: CPR Algorithms
Appendix 13: Pediatric CPR Algorithms
Appendix 14: Trade Name Table
BIBLIOGRAPHY
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Sota
Omoigui's
Pain Drug Handbook
2nd Edition:
Amoxapine
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SECTION
ONE:
Class,
Uses, Dosing,
Elimination
SECTION TWO:
Preparation, Pharmacology, Pharmacokinetics
SECTION THREE:
Interactions, Toxicity
Guidelines/Precautions
Principal Adverse Reactions
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Class
(TRICYCLIC ANTIDEPRESSANT)
Uses
treatment of neurotic and endogenous depression, migraine prophylaxis,
adjunct treatment of neuropathic pain syndromes including diabetic neuropathy, post herpetic neuralgia, tic doloureux, cancer pain, anxiety disorders, phobias, panic disorders, enuresis, eating disorders.
Dosing
Pain Syndromes Initial PO 50 -150 mg (1-3 mg/kg) daily at bedtime.
Titrate dose upward every three-four weeks by
increments of 25-50 mg as necessary.
Maintenance PO 50-300 mg (1-6 mg/kg) daily at bedtime.
Doses should be decreased if unacceptable side effects occur.
Serum levels should be determined if there are signs of toxicity.
Higher end of the dose range may be required in the management of
painful diabetic neuropathy.
Depression: Initial PO 100-150 mg (2-3 mg/kg) daily in one to three divided doses.
Maintenance PO 100-400 (2-8 mg/kg) mg daily in one to three divided doses. Doses that exceed 300 mg should be administered in two to
three divided doses.
Doses for pain are generally smaller than those used for treatment of affective disorders. Medication should be administered on a fixed schedule and not p.r.n. Administration of the entire daily dose at bedtime may reduce daytime sedation. After symptoms are controlled, dosage should be gradually reduced to the lowest level that will maintain relief of symptoms. Analgesia may be enhanced by addition of opioid analgesics (see front matter for drug combinations), non-steroidal anti-inflammatory drugs (NSAID) and use of non-drug therapies e.g. TENS. In geriatric patients, and patients with decreased renal or hepatic function, decrease doses by one-third to one-half and do not exceed 300 mg daily. The possibility for suicide is inherent in depression and may persist until significant remission occurs. The quantity of drug dispensed, should reflect such consideration.
Elimination
hepatic, renal.
Preparation
Amoxapine (Amoxapine, Asendin)
Tablets: 25 mg, 50 mg, 100 mg, 150 mg
Pharmacology
A dibenzoazepine derivative and a secondary amine tricyclic antidepressant. Amoxapine is a metabolite of loxapine an antipsychotic agent. Antidepressant activity may be partly due to inhibition of amine-pump uptake of norepinephrine and serotonin at the presynaptic neuron. Like loxapine, amoxapine has substantive neuroleptic activity, blocks the effects of dopamine on dopamine receptors, may cause extrapyramidal side effects and has been associated with development of neuroleptic malignant syndrome. Amoxapine is moderately sedating and has little anticholinergic activity. Compared with amitriptyline or imipramine, amoxepin may have a more rapid onset of action. Amoxapine does not inhibit the monoamine oxidase (MAO) system. The analgesic effects of amoxapine (and other antidepressants) may occur partly through the alleviation of depression, which may be responsible for increased pain suffering, but also by mechanisms that are independent of mood effects. Serotonin and norepinephrine activity may be increased in descending pain inhibitory pathways. Activation of these pathways decreases the transmission of nociceptive impulses from primary afferent neurons to first order cells in laminae I and V of the spinal cord dorsal horn. Amoxapine may also potentiate the analgesic effect of opioids by increasing their efficacy of binding to opioid receptors. Amoxapine has varying degrees of efficacy in different pain syndromes and may be better at relieving the burning, aching and dyesthetic component of neuropathic pain. The drug is seldom useful in the management of lancinating, shooting paroxysmal pain. Patients with low norepinephrine levels may respond better to amoxapine (and the other secondary amines) compared with serotonin deficient patients. Amoxapine does not have addiction liability and its use is not associated with drug seeking behavior. Withdrawal symptoms including sleep disruption with vivid dreams may be precipitated by acute withdrawal. Tolerance develops to the sedative and anticholinergic effects, but there are no reports of tolerance to the analgesic effects. Toxic manifestations of amoxapine differ significantly from those of the other tricyclic antidepressants, with CNS effects particularly grand mal seizures occurring more frequently in the absence of serious cardiovascular effects. Amoxapine crosses the placenta and is excreted in breast milk . Usage in pregnant or nursing mothers should occur only if the potential benefit justifies the potential risk.
Pharmacokinetics
ONSET OF ACTION: Analgesic effect: PO < 5 days Antidepressant effect PO 4-7 days
PEAK EFFECT: Antidepressant effect PO 2-4 weeks
DURATION OF ACTION: Antidepressant effect PO variable
Interactions
increased risk of hyperthermia with concomitant administration of anticholinergics e.g. atropine, phenothiazines, thyroid medications; serum levels and toxic effects of amoxapine increased by concomitant methylphenidate, fluoxetine, cimetidine, phenothiazines and haloperidol; ventilatory and circulatory depressant effects of CNS depressant drugs and alcohol potentiated by amoxapine; amoxapine increases the pressor and cardiac effects of sympathomimetics e.g. isoproterenol, phenylephrine, norepinephrine, epinephrine, amphetamine; amoxapine decreases serum levels and pharmacologic effects of levodopa and phenylbutazone; amoxapine increases serum levels and toxic effects of dicumarol; onset of therapeutic effects shortened and adverse cardiac effects of amoxapine increased with concomitant administration of levothyroxine and liothyronine; fatal hyperpyretic crisis or seizures with concomitant use of MAO inhibitors; uptake dependent efficacy of IV regional bretylium decreased by amoxapine..
Toxicity
Toxic Range:
Not routinely monitored.
Manifestations:
Chronic - dream and sleep disturbances, akathisia, anxiety, chills, coryza, malaise, myalgia, headache, dizziness, nausea and vomiting.
Acute - In addition to above symptoms, CNS stimulation with grand mal seizures, excitement , delirium, hallucinations, hyperreflexia, myoclonus, extrapyramidal symptoms including tardive dyskinesia, hyperpyrexia, then CNS depression with drowsiness, areflexia, hypothermia, respiratory depression, cyanosis, hypotension, coma; Peripheral anticholinergic symptoms including urinary retention, dry mucous membranes, mydriasis, constipation, adynamic ileus; Sinus tachycardia; Metabolic and/or respiratory acidosis, polyradiculoneuropathy, rhabdomyolysis, acute tubular necrosis, acute renal failure, vomiting, ataxia, dysarthria, bullous cutaneous lesions and pulmonary consolidation.
Antidote:
None
Management:
Discontinue or reduce medication
Correction of fluid, electrolyte and acid-base disturbances
Airway protected - ipecac syrup (30 mls or 0.5 mls/kg) induced emesis or gastric lavage (with drug ingestion) followed by administration of activated charcoal (PO 50-100 grams or 1-2 gram/kg). These should be performed even if several hours have elapsed after ingestion because the anticholinergic effects may delay gastric emptying and the drug may also be secreted into the stomach.
Prophylactic anticonvulsants
Control seizures. IV benzodiazepines (e.g. Diazepam IV 0.05-0.2 mg/kg, Midazolam IM 0.2 mg/kg or IV 0.025-0.1 mg/kg) are the first choice as IV barbiturates (e.g. Thiopental Sodium IV 0.5-2 mg/kg) may enhance respiratory depression. However IV barbiturates may be useful in refractory seizures.
Support ventilation and circulation (Patent Airway, Oxygen, IV Fluids, Vasopressors)
Treat renal impairment
Control hyperpyrexia with ice packs, cooling sponge baths e.t.c.
Physostigmine (Slow IV 1-3 mg) may be used in the treatment of life threatening anticholinergic toxicity. Routine use of physostigmine is not advisable due to its serious adverse effects e.g. seizures, bronchospasm and severe bradyarrhythmias
Hemodialysis or Peritoneal dialysis are ineffective as the drug is highly protein bound.
Symptomatic treatment
Consider the possibility of multiple drug involvement
Counseling prior to and after discharge for patients who have attempted suicide.
Guidelines
(1) To avoid withdrawal symptoms, the medication should be tapered down over a couple of weeks and not discontinued abruptly.
(2) Use with caution in patients with cardiovascular disease, thyroid disease, seizure disorders and those in whom excessive anticholinergic activity may be harmful e.g. patients with benign prostatic hypertrophy, a history of urinary retention, increased intraocular pressure. The drug should be used in close angle glaucoma only when the glaucoma is adequately controlled by drugs and closely monitored.
(3) Amoxapine is contraindicated in patients receiving MAO inhibitors (concurrently or within the past two weeks) and those with demonstrated hypersensitivity to amoxapine. Cross sensitivity with other tricyclic antidepressants may occur.
(4) Neuroleptic malignant syndrome, a rare but potentially fatal side effect, may manifest with hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability ( irregular pulse or blood pressure, tachycardia, diaphoresis, arrhythmias). Discontinue amoxapine, treat symptomatically and with dantrolene or bromocriptine (PO 2.5-10 mg tid).
(4) Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery. Persisting daytime drowsiness may be decreased by administering a lower dose, administering the dose earlier in the evening or substituting with a less sedating alternative..
Adverse
CVS: postural hypotension, sinus tachycardia
PULM: respiratory depression
CNS: confusion, disorientation, extrapyramidal symptoms
GI: hepatic dysfunction, jaundice, nausea, vomiting, constipation, decrease in lower esophageal sphincter tone
GU: acute tubular necrosis
EYE: blurred vision, mydriasis, increased intraocular pressure
DERM: pruritus, urticaria, petechiae, photosensitivity
HEMATOLOGIC: leukopenia, thrombocytopenia, eosinophilia, agranulocytosis, purpura
ENDOCRINE: increased or decreased libido, impotence, gynecomastia, SIADH
OTHER: hyperthermia, neuroleptic malignant syndrome
Reactions
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