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:
Desipramine
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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, adjunct treatment of
neuropathic pain syndromes including diabetic neuropathy, post herpetic
neuralgia, tic doloureux, cancer pain, anxiety disorders, phobias, panic
disorders, enuresis, eating disorders, attention deficit disorders.
Dosing
Pain Syndromes Initial PO 50-100 mg (1-2 mg/kg) daily in the morning or at bedtime. Titrate dose upward every three-four weeks by increments of 25-50 mg as necessary.
Maintenance PO 50-200 mg (1-4 mg/kg) daily in the
morning or 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 75-100 mg daily in one to four divided doses.
Maintenance PO 50-300 mg daily in one to four divided doses .
Doses greater than 200 mg daily are not recommended for
outpatients.
IM 100 mg daily in divided doses. Replace with oral
medication as soon as possible. Do
not administer intravenously
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. 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
Desipramine HCL (Norpramin, Desipramine)
Tablets: 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
Injection: 12.5 mg/ml
Pharmacology
A dibenzazepine derivative and a secondary amine tricyclic antidepressant. Desipramine is the active metabolite of imipramine. Antidepressant activity may be partly due to inhibition of the amine-pump uptake of norepinephrine and serotonin at the presynaptic neuron and down regulation of beta receptor sensitivity. Desipramine has fewer side effects e.g. orthostatic hypotension and may be used in patients who cannot tolerate the ‘parent’ drug imipramine or some of the other tricyclic antidepressants e.g. amitriptyline or doxepin. Desipramine has a low incidence of anticholinergic or antihistaminic effects. It is not sedating for most patients and may even stimulate some. Thus it may be given in the morning. Although blockade of neurotransmitter uptake may occur immediately, the initial antidepressant response may take a week. Desipramine may have a more rapid onset of action than imipramine. Like other secondary amines, patients with low norepinephrine levels respond better to desipramine compared with serotonin deficient patients. Desipramine does not inhibit the monoamine oxidase (MAO) system. The analgesic effects of desipramine 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. Desipramine may also potentiate the analgesic effect of opioids by increasing their efficacy of binding to opioid receptors. Desipramine 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. The seizure threshold may be lowered. Therapeutic doses do not affect respiration but toxic doses may lead to respiratory depression. The direct quinidine-like effects may manifest at toxic doses and produce cardiovascular disturbances e.g. conduction blockade. Desipramine does not have addiction liability and its use is not associated with drug seeking behavior. Withdrawal symptoms including nausea, headache and malaise 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. Desipramine 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 2-5 days
PEAK EFFECT: Antidepressant effect PO 2-3 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 desipramine increased by concomitant methylphenidate, fluoxetine, cimetidine, phenothiazines and haloperidol; ventilatory and circulatory depressant effects of CNS depressant drugs and alcohol potentiated by desipramine; desipramine increases the pressor and cardiac effects of sympathomimetics e.g. isoproterenol, phenylephrine, norepinephrine, epinephrine, amphetamine; desipramine decreases serum levels and pharmacologic effects of levodopa and phenylbutazone; desipramine increases serum levels and toxic effects of dicumarol; onset of therapeutic effects shortened and increased adverse cardiac effects of desipramine 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 desipramine..
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Toxicity
Toxic Range:
Not routinely monitored. Blood and urine levels may not correlate with the degree of intoxication and are not reliable guides for clinical management.
Manifestations:
Chronic - dreams and sleep disturbances, akathisia, anxiety, chills, coryza, malaise, myalgia, headache, dizziness, nausea and vomiting.
Acute - In addition to above symptoms, CNS stimulation with excitement , delirium, hallucinations, hyperreflexia, myoclonus, choreiform movements, parkinsonian symptoms, seizures, 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; Cardiac irregularities including tachycardia, QRS prolongation; Metabolic and/or respiratory acidosis, polyradiculoneuropathy, 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.
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 or phenytoin may be useful in refractory seizures.
Support ventilation and circulation (Patent Airway, Oxygen, IV Fluids, Vasopressors)
Continuous EKG monitoring
Treat cardiac arrhythmias with IV lidocaine or propranolol. Digoxin, quinidine, procainamide and diisopyramide should be avoided as they may further depress myocardial conduction and/or contractility.
Temporary pacemakers may be necessary in patients with advanced A-V block, severe bradycardia, and/or life threatening ventricular arrhythmias unresponsive to drug therapy.
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 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) Contraindicated in patients receiving MAO inhibitors (concurrently or within the previous two weeks) , patients in the acute recovery phase following myocardial infarction and those with demonstrated hypersensitivity to desipramine. Cross sensitivity with other tricyclic antidepressants may occur.
(4) The drug may cause exacerbation of psychosis in schizophrenic patients.
(5) 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, arrhythmias, conduction disturbances, hypertension, sudden death
PULM: respiratory depression
CNS: confusion, disorientation, extrapyramidal symptoms
GI: hepatic dysfunction, jaundice, nausea, vomiting, constipation, decrease in lower esophageal sphincter tone
GU: urinary retention, paradoxical nocturia, urinary frequency
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
Reactions
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