Phenytoin

Nutrients Depleted: Biotin, Calcium, Folic Acid, Vitamin B1, Vitamin B12, Vitamin D, Vitamin K

U.S. Brand Names: Dilantin®; Diphenylan Sodium®

Use: Manangement of generalized tonic-clonic (grand mal), simple partial and complex partial seizures; prevention of seizures following head trauma/neurosurgery; ventricular arrhythmias, including those associated with digitalis intoxication, prolonged Q-T interval and surgical repair of congenital heart diseases in children; also used for epidermolysis bullosa.

Pregnancy Risk Factor and Implications: D; Enters breast milk/use caution.

Contraindications: Hypersensitivity to phenytoin, other hydantoins, or any component; heart block, sinus bradycardia.

Dietary Considerations:

Alcohol: Additive CNS depression has been reported with hydantoins
Alcohol (chronic use): Stimulates metabolism of phenytoin; avoid or limit use
Folic Acid: Low erythrocyte and CSF folate concentrations. Phenytoin may decrease mucosal uptake of folic acid; to avoid folic acid deficiency and megaloblastic anemia, some clinicians recommend giving patients on anticonvulsants prphylactic doses of folic acid and cyancobalamin.
Calcium: Mypocalcemia has been reported in patients taking prolonged high-dose therapy with an anticonvulsant. Phenytoin may decrease calcium absorption. Monitor calcium serum concentration for bone disorders (eg, rickets, ostemalacia). Some clinicians have given an additional 4,000 Units/week of vitamin D (especially in those receiving poor nutrition and getting no sun exposure) to prevent hypocalcemia.
Fresh fruits containing vitamin C: Displaces drug from binding sites, resulting in increased urinary excretion of hydantoin. Educate patients regarding the potential for a decreased anticonvulsant effect of hydantoins with consumption of foods high in vitamin C.
Vitamin D: Phenytoin interferes with vitamin D metabolism and osteomalacia may result; may need to supplement with vitamin D.
Glucose: Hyperglycemia and glycosuria may occur in patients receiving high-dose therapy. Monitor blood glucose concentration, especially in patients with impaired renal function.
Tube feedings: Tube feedings decrease phenytoin bioavailability; to avoid decreased serum levels with continuous NG feeds, hold feedings for 2 hours prior to and 2 hours after phenytoin administration, if possible. There is a variety of opinions on how to administer phenytoin with interal feedings. BE CONSISTENT throughout therapy.

Warnings/Precautions: May increase frequency of petit mal seizures; I.V. form may cause hypotension, skin necrosis at I.V. site; avoid I.V. administration in small veins; use with caution in patients with porphyria; discontinue if rash or lymphadenopathy occurs; use with caution in patients with hepatic dysfunction, sinus bradycardia, S-A block, A-V block, or hepatic impairment; elderly may have reduced hepatic clearance and low albumin levels, which will increase the free fraction of phenytoin in the serum and, therefore, the pharmacologic response.

Adverse Reactions: I.V. effects: Hypotension, bradycardia, cardia arrhythmias, cardiovascular collapse (especially with rapid I.V. use), venous irritation and pain, thrombophlebitis.

Effects not related to plasma phenytoin concentrations: Hypertrichosis, gingival hypertrophy, thickening of facial features, carbohydrate intolerance, folic acid deficiency, peripheral neuropathy, vitamin D deficiency, osteomalacia, systemic lupus erthematosus.

Dose-related effects: Nystagmus, blurred vision, diplopia, ataxia, slurred speech, dizziness, drowsiness, lethargy, coma, rash, fever, nausea, vomiting, gum tenderness, confusion, mood changes, folic acid depletion, osteomalacia, hyperglycemia.

Related to elevated concentration:
>20 mcg/ml: Far lateral nystagmus
>30 mcg/ml: 45 degree lateral gaze nystagmus and ataxia
>40 mcg/ml: Decreased mentation
>100 mcg/ml: Death

Less than 10% experience:
Central nervous system: Psychiatric changes, slurred speech, dizziness, drowsiness
Gastrointestinal: Constipation, nausea, vomiting, gingical hyperplasia
Neuromuscular & Skeletal: Trembling

1% to 10% experience:
Central nervous system: Headache, insomnia
Dermatologic: Rash
Gastrointestinal: Anorexia, weight loss
Hematologic: Leukopenia
Hepatic: Hepatitis
Renal: Increase in serum creatinine

Less than 1% experience:
Hypotension, bradycardia, cardia arrhythmias, cardiovascular collapse, confusion, fever, ataxia, thrombophlebitis, peripheral neuropathy, paresthesia, diplopia, nystagmus, blurred vision, SLE-like syndrome, lymphadenopathy, hepatitis, Stevens-Johnson syndrome, blood dyscrasis, dyskinesias, pseudolymphoma, lymphoma, venous irritation and pain.

Overdose/Toxicology: Symptoms of overdose include unsteady gait, slurred speech, confusion, nausea, hypothermia, fever, hypotension, repiratory depression, coma. Treatment is symptomatic.

Carbamazepine (Anticonvulsant)

Nutrients Depleted: Biotin, Folic Acid, Vitamin D

U.S. Brand Names: Carbatrol®; Epitol®; Tegretol®; Tegretol®-XR

Use: Prophylaxis of generalized tonic-clonic, partial (especially complex partial), and mixed partial or generalized seizure disorder; pain relief of trigeminal neuralgia.

Pregnancy Risk Factor and Implications: C; Enters breast milk/compatible.

Contraindications: Hypersensitivity to carbamazepine or any component; may have cross-sensitivity with tricyclic antidepressants; should not be used in any patient with bone marrow suppression, MAO inhibitor use; the oral suspension should not be administered simultaneously with other liquid medicinal agents or diluents.

Dietary Considerations:
Food: Drug may cause GI upset, take with large amount of water or food to decrease GI upset. May need to split doses to avoid GI upset.
Sodium: SIADH and water intoxication; monitor fluid status; may need to restrict fluid.

Warnings/Precautions: MAO inhibitors should be discontinued for a minimum of 14 days before carbamazepine is begun; administer with caution to patients with history of cardiac damage or hepatic disease; potentially fatal blood cell abnormalities have been reported following treatment; early detection of hamatologic change is important; advise patients of early signs and symptoms including fever, sore throat, mouth ulcers, infections, easy brusing, petechial or purpuric hemorrhage; carbamazepine is not effective in absence, myoclonic or akinectic seizures; exacerbation of certain seizure types have been seen after initiation of carbamazepine therapy in children with mixed seizure disorders. Elderly may have increased risk of SIADH-like syndrome.

Adverse Reactions:

Dermatologic: Rash; but does not necessarily mean the drug should not be stopped

Less than 10% experience:
Central nervous system: Sedation, dizziness, fatigue, ataxia, confusion
Gastrointestinal: Nausea, vomiting
Ocular: Blurred vision, nystagmus

1% to 10% experience:
Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
Endocrine & metabolic: Hyponatremia, SIADH
Gastrointestinal: Diarrhea
Miscellaneous: Diaphoresis

Less than 1% experience:
Edema, congestive heart failure, syncope, bradycardia, hypertension or hypotension, A-V block, arrhythmias, slurred speech, mental depression, hypocalcemia, hyponatremia, urinary retention, sexual problems in males, neutropenia (can be transient), aplastic anemia, agranulocytosis, eosinophilia, leukopenia, pancytopenia, thrombocytopenia, bone marrow suppression, hepatitis, peripheral neuritis, diplopia, swollen glands, hypersensitivity.

Overdose/Toxicology: Symptoms of overdose include dizziness, ataxia, drowsiness, nausea, vomiting, tremor, agitation, nystagmus, urinary retention, dysrhythmias, coma, seizures, twitches, respiratory depression, and neuromuscular disturbances. Activated charcoal is effective at binding certain chemicals and this is especially true for carbamazepine. Other treament is supportive and symptomatic.

Valproic Acid and Derivatives (Anticonvulsant)

Nutrients Depleted: Carnitine, Folic Acid

U.S. Brand Names: Depacon®; Depakene®; Depakote®

Use: Managment of simple and complex absence seizures; mixed seizure types; myoclonic and generalized tonic-clonic (grand mal) seizures; may be effective in partial seizures, infantile spasms, bipolar disorder; prevention of migraine headaches

Pregnancy Risk Factor and Implications: D; Enters breast milk/compatible.

Contraindications: Hypersensitivity to valproic acid or derivatives or any component; hepatic dysfunction

Dietary Considerations:

Alcohol: Additive CNS depression, avoid or limit alcohol
Food:
Valproic acid may cause GI upset; take with large amount of water or food to decrease GI upset. May need to split doses to avoid GI upset. Food may delay but does not affect the extent of absorption.
Coated particles of divalproex sodium may be mixed with semisolid food (ed applesauce or pudding) in patients having difficulty swallowing; particles should be swallowed and not chewed
Valproate sodium oral solution will generate valproic acid in carbonated beverages and may cause mouth and throat irritation; do not mix valproate sodium oral solution carbonated beverages
Milk: No effect on absorption; may take with milk
Sodium: SAIDH and water intoxication; monitor fluid status. May need to restrict fluid.

Warnings/Precautions: Hepatic failure resulting in fatalities has occurred in patients; children less than 2 years of age are at considerable risk; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting; may cause severe thrombocytopenia, bleeding; hepatoxicity has been reported after 3 days to 6 months of therapy; tremors may indicate overdosage; use with caution in patients receiving other anticonvulsants.

Adverse Reactions:

1% to 10% experience:
Endocrine & metabolic: Change in menstrual cycle
Gastrointestinal: Abdominal cramps, anorexia, diarrhea, nausea, vomiting, weight gain

Less than 1% experience:
Drowsiness, ataxia, irritability, confusion, restlessness, hyperactivity, headache, malaise, alopecia, erythema multiforme, hyperammonemia, pancreatitis, thrombocytopenia, prolongation of bleeding time, transient increased liver enzymes, liver failure, tremor, nystagmus, spots before eyes

Overdose/Toxicology: Symptoms of overdose include coma, deep sleep, motor restlessness, and visual hallucinations. Supportive treatment is necessary. Naloxone has been used to reverse CNS depressant effects, but may block the action of other anticonvulsants.

Desipramine (Antidepressant)

Nutrients Depleted:Coenzyme Q10, Vitamin B2

U.S. Brand Names: Norpramin®

Use: Treatment of various forms of depression, often in conjuction with psychotherapy, analgesic adjunct in chronic pain.

Pregnancy Risk Factor and Implications: C; Enters breast milk/not recommended.

Contraindications: Hypersensitivity to desipramine (cross-sensitivity with other tricyclic antidepressants may occur); patients receiving MAO inhibitors within past 14 days; narrow-angle glaucoma; use immediately postmyocardial infarction.

Dietary Considerations:
Alcohol: Additive CNS effects, avoid use

Warnings/Precautions: Use with caution in patients with cardiovascular disease, conduction disturbances, urinary retention, seziures disorders, hyperthyroidism or those receiving thyroid replacement; do not discontinue abruptly in patients receiving long-term high-dose therapy.

Adverse Reactions:

Less than 10% experience:
Central nervous system: Dizziness, drowsiness, headache
Gastrointestinal: Xerostomia, constipation, increased appetite, nausea, unpleasant taste, weight gain
Neuromuscular & skeletal: Weakness

1% to 10% experience:
Cardiovascular: Arrhythmias, hypotension
Central Nervous System: Confusion, delerium, hallucinations, nervousness, restlessness, parkinsonian syndrome, insomnia
Gastrointestinal: Diarrhea, heartburn
Genitourinary: Dysuria, sexual dysfunction
Neuromuscular & skeletal: Fine muscle tremors
Ocular: blurred vision, eye pain
Miscellanous: Diaphoresis (excessive)

Less than 1% experience:
Anxiety, seizures, alopecia, photosensitivity, breast enlargement, galactorrhea, SIADH, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux, testicular edema, agranulocytosis, leukopenia, eosinophila, cholestatic jaundice, increased liver enxymes, increased intraocular pressure, tinnitus, allergic reactions.

Overdose/Toxicology:Symptoms of overdose include agitation, confusion, hallucinations, hyperthermia, urinary retention, CNS depression, cyanoisis, dry mucous membranes, cardia arrhythmias, and seizures. Treatment is supportive. Ventricular arrhythmias and EKG changes (eg, QRS widening) often respond with concurrent systemic alklinization (sodium bicarbonate 0.5-2 mEq/kg I.V. or hyperventilation). Arrhythmias unresponsive to phenytoin 15-20 mg/kg (adults) may respond to lidocaine. Physostigmine (1-2 mg I.V. slowly for adults) may be indicated for reversing life-threatening cardiac arrhythmias.

Nortriptyline (Antidepressant)

Nutrients Depleted: Coenzyme Q10, Vitamin B2

U.S. Brand Names: Aventyl® Hydrochloride; Pamelor®

Use: Treatment of various forms of depression, often in conjuction with psychotherapy. Maximum antidepressant effect may not be seen for 2 or more weeks after initiation of therapy; has also demonstrated effectiveness for chronic pain.

Pregnancy Risk Factor and Implications: D; Enters breast milk/contraindicated.

Contraindications: Narrow-angle glaucoma, avoid use during pregnancy and lactation, hypersensitivity to tricyclic antidepressants.

Dietary Considerations:
Alcohol: Additive CNS effect, avoid use.

Warnings/Precautions: Use with caution in patients with cardiac conduction disturbance, history of hyperthyroid; should not be abruptly discontinued in patients receiving high doses for prolonged periods; use with caution with renal or hepatic impairment.

Adverse Reactions:

Less than 10% experience:
Central nervous system: Dizziness, drowsiness, headache
Gastrointestinal: Xerostomia, constipation, increased appetite, nausea, unpleasant taste, weight gain
Neuromuscular & skeletal: Weakness

1% to 10% experience:
Cardiovascular: Postural hypotension, arrhythmias, tachycardia, sudden death
Central nervous system: Confusion, delirium, hallucinations, nervousness, restlessness, parkinsonian syndrome, insomnia
Endocrine & metabolic: Sexual dysfunction
Gastrointestinal: Diarrhea, heartburn, constipation
Genitourinary: Dysuria, urinary retention
Ocular: Blurred vision, eye pain, increased intraocular pressure
Neuromuscular & skeletal: Fine muscle tremors
Miscellaneous: Diaphoresis (excessive)

Less than 1% experience:
Anxiety, seizures, alopecia, photosensitivity, breast enlargement, galactorrhea, SIADH, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux, testicular edema, leukopenia, rarely agranulocytosis, eosinophilia, increased liver enzymes, cholestatic jaundice, increased intraocular pressure, tinnitus, allergic reactions

Overdose/Toxicology: Symptoms of overdose include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, seizures, and ventricular tachycardia. Treatment is symptomatic and supportive. Alkalinization by sodium bicarbonate and/or hyperventilation may limit cardiac toxicity.

Amitriptyline (Antidepressant)

Nutrients Depleted: Coenzyme Q10, Vitamin B2

U.S. Brand Names: Elavil®; Enovil®

Use: Treatment of various forms of depression, often in conjuction with psychotherapy; analgesic for certain chronic and neuropathic pain, prophylaxis against migrane headaches.

Pregnancy Risk Factor and Implications: D; Enters breast milk/not recommended.

Contraindications: Hypersensitivity to amitriptyline (cross-sensitivity with other tricylics may occur); patients receiving MAO inhibitors within past 14 days; narrow-angle galucoma; avoid use during pregnancy and lactation.

Dietary Considerations:
Alcohol: Additive CNS effect, avoid use.

Warnings/Precautions: Amtriptyline should not be abruptly discontinued in patients receiving high doses for prolonged periods. Use with caution in patients with cardiac conduction disturbances; an EKG prior to initiation of therapy is advised; use with caution in patients with a history of hyperthyroidism, renal or hepatic impairment. The most anticholinergic and sedating of the antidepressants; pronounced effects on the cardiovascular system (hyptension), hence, many psychiatrists agree it is best to avoid in the elderly.

Adverse Reactions:
Anticholinergic effects may be pronounced; moderate to marked sedation can occur (tolerance to these effects usually occurs)

Less than 10% experience:
Central nervous system: Dizziness, drowsiness, headache
Gastrointestinal: Xerostomia, constipation, increased appetite, nausea, unpleasant taste, weight gain
Neuromuscular & skeletal: Weakness

1% to 10% experience:
Cardiovascular: Hypotension, postural hypotension, arrhythmias, tachycardia, sudden death
Central nervous system: Nervousness, restlessness, parkinsonian syndrome, insomnia, sedation, fatigue, anxiety, impaired cognitive function, seizures have occured occasionally, extrapyramidal symptoms are possible
Gastrointestinal: Diarrhea, heartburn
Genitourinary: Sexual dysfunction, urinary retention
Ocular: Blurred vision, eye pain, increased intraocular pressure
Neuromuscular & skeletal: Tremor
Ocular: Eye pain, blurred vision
Miscellaneous: Diaphoresis (excessive)

Less than 1% experience:
Alopecia, photosensitivity, breast enlargement, galactorrhea, rarely SIADH, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux, testicular edema, leukopenia, rarely agranulocytosis, cholestatic jaundice, increased liver enzymes, increased intraocular pressure, tinnitus, allergic reactions

Overdose/Toxicology: Symptoms of overdose include agitation, confusion, hallucinations, urinary retention, hypothermia, hypotension, ventricular tachycardia, and seizures. Treatment is symptomatic and supportive. Alkalinization by sodium bicarbonate and/or hyperventilation may limit cardiac toxicity.

Doxepin (Antidepressant)

Nutrients Depleted: Coenzyme Q10, Vitamin B2

U.S. Brand Names: Adapin® Oral; Sinequan® Oral; Zonalon® Topical Skin Product

Use:
Oral: Treatment of various forms of depression, often in conjuction with psychotherapy; Treatment of anxiety disorders.
Unlabeled Use: Analgesic for certain chronic and neuropathic pain
Topical: Short-term (no more than 8 days) management of moderate pruritus in adults with atopic dermatitis or lichen simplex chronicus

Pregnancy Risk Factor and Implications: C; Excretion in breast milk unknown/not recommended.

Contraindications: Hypersensitivity to doxepin or any component (cross-sensitivity with other tricylic antidepressants may occur); narrow-angle galucoma.

Dietary Considerations:
Alcohol: Additive CNS effect, avoid use.

Warnings/Precautions: Use with caution in patients with cardiovascular disease, conduction disturbances, seizure disorders, urinary retention, hyperthyroidism, or those receiving thyroid replacement; avoid use during lactation; use with caution in pregnancy; do not discontinue abruptly in patients receiving chronic high-dose therapy.

Adverse Reactions:

Less than 10% experience:
Central nervous system: Sedation, drowsiness, dizziness, headache
Gastrointestinal: Xerostomia, constipation, increased appetite, nausea, unpleasant taste, weight gain
Neuromuscular & skeletal: Weakness

1% to 10% experience:
Cardiovascular: Hypotension, arrhythmias
Central nervous system: Confusion, delirium, hallucinations, nervousness, restlessness, parkinsonian syndrome, insomnia,
Gastrointestinal: Diarrhea, heartburn
Genitourinary: Sexual dysfunction, dysuria
Ocular: Blurred vision, eye pain, increased intraocular pressure
Neuromuscular & skeletal: Fine muscle tremors
Ocular: Blurred vision, eye pain
Miscellaneous: Diaphoresis (excessive)

Less than 1% experience:
Anxiety, seizures, alopecia, photosensitivity, breast enlargement, galactorrhea, SIADH, trouble with gums, decreased lower esophageal sphincter tone may cause GE reflux, urinary retention, testicular edema, leukopenia, agranulocytosis, leukopenia, eosinophilia, hepatitis, cholestatic jaundice and increased liver enzymes, increased intraocular pressure, tinnitus, allergic reactions

Overdose/Toxicology: Symptoms of overdose include confusion, hallucinations, seizures, urinary retention, hypothermia, hypotension, tachycardia, and cyanosis. Following initiation of initial overdose management, toxic symptoms should be treated symptomatically.

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