Drugs And Pregnancy Part 30

0.

0.

0.

2.7.1.1016 h after overdose 10.0.

2.0.

3.2.4.1.1624 h after overdose 4.1.3.1.2.1.1.0.

Nonnarcotic a.n.a.lgesic overdoses Total 24.1.5.1.5.5.12.2.Adapted from Riggs et al., 1989.

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Drug overdoses during pregnancy Table 14.7 Case reports of aspirin overdose during pregnancy Amount EGA Case reports of aspirin overdose during pregnancy Amount EGA (weeks) Treatment Outcome Fetal Author ingested Maternal 100 5 grain 24.300 ml mg citrate Tinnitus, hyperventilated state Stillborn, anomalies Rejent and Baik, 1985 8 365 mg daily 37.Not mentioned Not mentioned Tachypnea, compensated Ahlfors et al., 1982 for several days metabolic acidosis up to delivery Megadose First trimester Not mentioned Not mentioned Metanephric adenoma Bove et al., 1979 Unknown 32.Not mentioned Uncomplicated Generalized hypertonia, Lynd, 1976 increased reflex, irritability 56 g daily 040 Not mentioned Abruptio placenta; C-section Unremarkable Levy et al., 1975 1518 g 40.Exchange Not mentioned Hyperpnoea, intercostal Earle, 1961 and suprasternal retractions present EGA, estimated gestation age.

Nonnarcotic a.n.a.lgesic overdoses 263.

Table 14.8 Recommended treatment of aspirin overdose Management Recommended treatment of aspirin overdose Management Early management Adult: >120 mg/kg: give 50 g activated charcoal.

Child: for >120 mg/kg give activated charcoal.

Consider charcoal even for late-presenting patients; peak absorption may be delayed up to 12 h postingestion especially with enteric coated tablets.

Adults only: > 500 mg/kg.

Consider gastric lavage followed by 50 g activated charcoal, if patient presents within 1 h.

Contact National Poison Information Service (NPIS) in the UK on 0870 600 6266 and in the US on 1-800-222-1222 Maintenance management Check salicylate concentration 4 h postingestion, then every 23 h until peak concentration achieved and is falling consistently. If history is reliable for an ingestion >120 mg/kg and tablets are enteric coated, consider measuring levels for minimum 12 h postingestion even if no salicylate is detected initially. Monitor and correct urine and electrolytes, arterial blood gases and pH, blood sugar, prothrombin time.

Rehydrate with oral or IV fluids; large volumes may be necessary to correct dehydration (care required with the elderly or those with cardiac disease). Moderate or severe cases may require central venous pressure monitoring particularly patients with cardiac disease or elderly people Repeat doses of activated charcoal (RAC) (adult, 2550 g; child, 1 g/kg) every 4 h until salicylate level has peaked and is consistently falling. RAC is effective in preventing excessive delayed absorption.

Urinary alkalinisation For salicylate level 500700 mg/L in adults or salicylate level 350600 mg/L in children/elderly where patients have moderate clinical effects. In the presence of alkaline urine (optimum pH 7.58.5), renal elimination of salicylate is enhanced (10- to 20-fold with an increase from a urine pH of 5 to 8). Forced alkaline diuresis is not recommended.

Adult: 1 L of 1.26 percent sodium bicarbonate (isotonic) + 40 mmol pota.s.sium IV over 4 h and/or 50 mL boluses of 8.4 percent sodium bicarbonate IV (ideally via a central line).

Child: 1 ml/kg 8.4 percent sodium bicarbonate saline infused at 23 mL/kg.h 1 mmol/kg pota.s.sium diluted in 10 mL/kg hypokalemia prevents urinary excretion of alkali so must be corrected. Check urinary pH hourly aiming for pH 7.58.5, the rate of bicarbonate administration alone (avoiding hyperkalemia) may need to be increased if pH remains <>

Check urine and electrolytes every 24 h and keep pota.s.sium between 4.0 and 4.5.

From Kamanyire, 2002.

conclusion as acetaminophen overdoses: early therapy antidote (activated charcoal, lavage, bowel irrigation) is a.s.sociated with better outcomes (Table 14.8).

Naproxen One case of naproxen overdose during pregnancy was published in detail. An estimated 8 h after maternal ingestion of 5 g of naproxen at 35 weeks of gestation, nonspecific and supportive antidote therapy was initiated because no specific antidote is available.

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Drug overdoses during pregnancy Following nonspecific therapy, spontaneous labor ensued and a preterm infant was delivered. The newborn had severe hyponatremia and water retention. Subsequently the infant recovered with no apparent sequelae at follow-up. The mother recovered with no evidence of hepatotoxicity or other adverse effects (Alon-Jones and Williams, 1986).

In contrast to the pharmac.o.kinetics of salicylate elimination, high doses of naproxen (14 g) result in a disproportionate increase in renal excretion of the drug without apparent saturation of the excretory mechanism or metabolic pathway (Erling and Strand, 1977; Runkel et al et al., 1976). Increase in renal elimination may contribute to a lower incidence of acute toxicity compared with salicylate overdose.

Ibuprofen Ibuprofen overdose during pregnancy has not been described in case studies and no specific antidote exists. Therefore, nonspecific antidote and supportive therapy should be given. Symptoms of ibuprofen toxicity include nausea, epigastric pain, diarrhea, vomiting, dizziness, blurred vision, and edema. The half-life of ibuprofen is 0.92.5 h in the post-absorptive period (Baselt, 1978). Among 67 cases of ibuprofen overdose, 36 percent occurred among children. Fifty reports of ibuprofen overdose during pregnancy have been reported, with mothers and infants suffering no untoward effects (i.e., hepatorenal failure, etc.) among those followed prospectively (Barry et al et al., 1984).

NUTRITIONAL SUPPLEMENT OVERDOSES.

Prenatal vitamins The course of pregnancy and infant outcome following prenatal vitamin overdoses has not been published. Since there is no specific antidote to prenatal vitamins, nonspecific and supportive antidote therapy should be given. It is reasonable to think that most cases of vitamin overdose would probably result in little, if any, risk to either mother or fetus. However, the retinoic acid content of the vitamins should be determined to estimate the total exposure. It is possible that megadose vitamin A may be involved, in which case Chapter 13, Use of dermatologics during pregnancy, should be consulted.

Iron The clinical course following iron overdose during pregnancy has been reported for six cases (Table 14.9). Notably, adverse outcomes were a.s.sociated with nonspecific treatment. The dangers of iron overdose vary according to the amount ingested. Iron poisoning is a.s.sociated with gastrointestinal hemorrhage, physiological shock, acidosis, hepatic failure, and coagulopathies (Table 14.10). Death is usually the result of liver failure or cardiac collapse. The highest serum iron concentrations are likely to occur within 4 h of ingestion, with serum levels in excess of 500 g/100 mL being more likely to be a.s.sociated with severe poisoning (James, 1970). Thus, these patients should be treated aggressively.

The specific antidote to iron overdose is deferoxamine. From clinical experience, it is clear that early administration of the antidote is essential if therapy is to be efficacious.

Table 14.9 Cases of iron overdose during pregnancy Amount Cases of iron overdose during pregnancy Amount EGA Treatment Outcome Fetus Author (weeks) Maternal 50 Ferrous gluconate tablets 27 Lavage, Deferoxamine Uncomplicated Uncomplicated Tran et al., 1998 40 Ferrous sulfate tablets 25.Deferoxamine Uncomplicated Uncomplicated Schauben et al., 1990 5 g Elemental iron (25 g 36.Deferoxamine Hepatic necrosis, coma and Uncomplicated Olenmark et al., 1987 ferrous sulfate) subsequent expiration in cardiac failure 50 300 mg Ferrous sulfate 15.Deferoxamine Temporary abdominal Uncomplicated Blanc et al., 1984 (3050 mg/kg Elemental tenderness and mild metabolic iron) acidosis Unknown amount, along 34.Deferoxamine Brief episodes of vomiting Uncomplicated Rayburn et al., 1983 with prenatal vitamins and mild pain Unknown amount 34.Deferoxamine ?.

Uncomplicated Rayburn et al., 1983 Nutritional supplement overdoses 95 tablets of Fer-In-Sol 14.Deferoxamine Died on the third day; pulmonary Spontaneous abortion Strom et al., 1976 edema and hypotension 90 325 mg Ferrous 16.Deferoxamine Metabolic acidosis, depressed Spontaneous abortion Manoguerra, 1976 sulfate capsules mental status; subsequent death 80 h postadmission 46 g Elemental iron with 10.DPTA.

Brief episode of abdominal pain, Uncomplicated Dugdale and Powell, 15 Sodium amytal, drowsiness, a systolic BP fall to 1964.

6 g Aspirin 60 mmHg EGA, estimated gestation age; DPTA, diethylenetriaminepentaacetic acid.

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Drug overdoses during pregnancy Table 14.10 Time course of iron overdose Time course of iron overdose Phase Time to onset Symptoms I.

03 h Vomiting, hemetemesis, abdominal pain, diarrhea, lethargy, restlessness II.

up to 12 h Quiescent period, symptoms subside III.

1248 h Shock, acidosis, hepatic necrosis, renal tubular necrosis, increasing lethargy, coma, seizures, hypotension, cyanosis, pulmonary edema, hypoglycemia, coagulopathies IV.

24 weeks Gastric scarring, gastric/pyloric strictures Adapted from Friedman, 1987.

Total iron-binding capacity and liver function should be routinely monitored in the patient with an iron overdose, as should thrombin and prothrombin times. Essentially, the gravida with an iron overdose should be managed similarly to the nonpregnant adult, as is described in detail elsewhere (Friedman, 1987). Guidelines for treatment according to ingested dose (if known) are given in Table 14.11. In a report of 49 pregnancies in which iron overdose occurred, there were 43 live births. Three infants had congenital anomalies, but they were exposed to the iron overdose and deferoxamine after the first trimester. Hence, the relationship appears not to be causal. The authors urge aggressive treatment of iron overdose with the specific antidote to prevent maternal death or organ toxicity (McElhatton et al et al., 1991a). Review of 61 pregnancies indicated that in iron poisoning during pregnancy (1) peak maternal serum iron levels are a.s.sociated with iron toxicity, and (2) deferoxamine should be administered without hesitation (Tran et al et al., 2000).

Table 14.11 Sequelae of iron overdose based on amount ingested Amount Sequelae of iron overdose based on amount ingested Amount Risk of toxicity Less than 20 mg/kg Minimal risk, no action required 2060 mg/kg Moderate risk, monitor for symptoms, induce vomiting More than 60 mg/kg High risk, requires treatment, gastrointestinal decontamination, chelation Adapted from Friedman, 1987.

Following unpublished animal studies that suggest deferoxamine may cause significant fetal effects in animals, clinical experience has not shown this to be true in the human. Iron-overdose-a.s.sociated pathophysiological effects on the mother seem to be the cause of adverse fetal outcomes, and not the direct result of iron overdose or antidote. No abnormalities have been reported among infants whose mothers consumed high doses of iron during pregnancy (Lacoste et al et al., 1992; Tenenbein, 1989). It appears as though the placenta acts as a partial barrier to iron (Olenmark et al et al., 1987; Rayburn et al et al., 1983; Richards and Brooks, 1966). Chemical properties of the deferoxamine molecule strongly suggest that it would not cross the placenta in large amounts because it is a large molecule (molecular weight, 657) and is highly polarized.

Hypnotic and sedative overdoses 267.

ANXIOLYTIC OVERDOSES.

Benzodiazepines Benzodiazepines are the most frequently used psychotropic medication in suicide gestures. The US Food and Drug Administration (FDA) approved a benzodiazepine receptor antagonist, flumazenil, in 1992 for the management of benzodiazepine overdose (The Flumazenil in Benzodiazepine Intoxication Multicentre Study Group, 1992; J Clin Pharmacol, 1992). Several investigators have shown the efficacy of flumazenil in revers-ing the clinical signs and symptoms of a benzodiazepine overdose (Krisanda, 1993; L'Heureux et al et al., 1992; Spivey et al et al., 1993). Flumazenil can cause complications (e.g., seizures) among patients with clinically high, but subtoxic, antidepressant poisoning or those who are taking benzodiazepines to therapeutically control seizures (The Flumazenil in Benzodiazepine Intoxication Multicentre Study Group, 1992; L'Heureux et al et al., 1992). One case study reported on the reversal of fetal benzodiazepine intoxication using flumazenil (Stahl et al et al., 1993). A 36-weeks, 22-year-old primipara ingested between 50 and 60 5 mg diazepam tablets. The patient was intravenously given two small doses (0.3 mg) of flumazenil. No adverse effects or withdrawal symptoms were noted in the patient or in the infant, who was born spontaneously 2 weeks later. The 'floppy infant syndrome' has been described, showing that benzodiazepines (1) cross the placenta and (2) have a depressive effect on the fetus. Warnings signs of complications in benzodiazepine overdoses in pregnancy are bradycardia and other symptoms of the drugs' depressive physiologic effects on mother and fetus.

Hydroxyzine The clinical courses of pregnancies after hydroxyzine overdoses have not been published. Hypersedation and hypotension are the most frequently observed abnormalities with hydroxyzine overdose in nonpregnant adults. Hydroxyzine counteracts epinephrine's pressor effect. Therefore, hydroxyzine overdose-a.s.sociated hypotension should not be treated with epinephrine. Intravenous fluids and other pressor agents (levarterenol or metaraminol) should be used instead to treat hypotension. Between 1 and 2 g of hydroxyzine pamoate commonly produces drowsiness and lethargy that may progress to a coma (Magera et al et al., 1981). Elimination half-life of hydroxyzine is 2.53.4 h, with a single dose of the drug and given that no more is taken (Baselt, 1978).

No specific antidote to hydroxyzine is available. Therefore, nonspecific and supportive antidote therapy should be given.

HYPNOTIC AND SEDATIVE OVERDOSES.

Phen.o.barbital and secobarbital The course of pregnancy following barbituric-acid-derivative overdoses during gestation has not been published. Barbituric acid derivatives have no specific antidote. Therefore, nonspecific and supportive antidote therapy is indicated. Barbituric acids cross the placenta and these drugs may induce fetal hepatic enzymes. No congenital anomalies have 268 268 Drug overdoses during pregnancy Box 14.2 Phen.o.barbital overdose stages Stage I: Awake, competent, and mildly sedated. Average blood level of 3.5 mg/100 mL. Awake, competent, and mildly sedated. Average blood level of 3.5 mg/100 mL.

Stage II: Sedated, deep tendon reflexes (DTRs) present, prefers sleep, answers questions when aroused, does not cerebrate properly. Average blood level of 4.4 mg/100 mL. Sedated, deep tendon reflexes (DTRs) present, prefers sleep, answers questions when aroused, does not cerebrate properly. Average blood level of 4.4 mg/100 mL.

Stage III: Comatose, DTRs present. Average blood level of 6.5 mg/100 mL. Comatose, DTRs present. Average blood level of 6.5 mg/100 mL.

Stage IV: Comatose, no DTRs obtainable. Average blood level of 10.0 mg/100 mL. Comatose, no DTRs obtainable. Average blood level of 10.0 mg/100 mL.

Stage V: Comatose, no DTRs obtainable, and with circulatory and/or respiratory difficulty. Comatose, no DTRs obtainable, and with circulatory and/or respiratory difficulty.

Half-lives of phen.o.barbital and secobarbital range from 2 to 6 days and 22 to 29 h, respectively (Baselt, 1978).

been observed in several studies of children born to women treated with phen.o.barbital during pregnancy (Bertollini et al et al., 1987; Heinonen et al et al., 1977). Five clinical stages of intoxication have been described in adults with acutely toxic (i.e., in nontolerant individuals) levels of phen.o.barbital (Sunshine, 1957), as shown in Box 14.2.

Pyrilamine No reports of pregnancy following pyrilamine overdoses have been published. No specific antidote to pyrilamine is available. Therefore, nonspecific and supportive antidote therapy should be given.

NARCOTIC a.n.a.lGESIC OVERDOSES.

Opioid narcotics Opioid narcotics are either derived from opium or are synthetics, and include morphine, codeine, oxycodone, and hydromorphone. These drugs are metabolized to monoacetyl-morphine. Approximately 6 percent of suicide gestures in one study involved opioid a.n.a.lgesic preparations (Rayburn et al et al., 1984) and 2.5 percent in another (Flint et al et al., 2002).

An opioid-specific antidote, naloxone, is available. It compet.i.tively binds to opioid receptors and opioid a.n.a.lgesics and blocks uptake. Opioid a.n.a.lgesics are eventually excreted.

If the patient is addicted to opioids, naloxone will cause an almost immediate onset of withdrawal symptoms. Most narcotic a.n.a.lgesic preparations also contain other substances, such as acetaminophen and aspirin. When an opioid overdose is doc.u.mented, naloxone should be given according to directions in the Physicians' Desk Reference Physicians' Desk Reference (PDR). Opioids cross the placenta freely and affect the fetus, as will the antidote. (PDR). Opioids cross the placenta freely and affect the fetus, as will the antidote.

Therefore, it follows that treatment of maternal overdose will also treat the fetal overdose. Nalmefene has an 11-h half-life and was found to have potential benefits over naloxone (Kaplan and Marx, 1993), which has a shorter duration of action (12 h half-life). Nalmefene produces a longer period of withdrawal in opioid-dependent patients because of its long half-life (Anonymous, 1995; Kaplan and Marx, 1993). Importantly, overdose of other nonopioid const.i.tuents (e.g., acetaminophen) must be considered in Antihistamine and decongestant overdoses Antihistamine and decongestant overdoses 269.

devising the antidote regimen and treatment plan because they may have serious hepatic and renal toxicities that need immediate attention. Half-lives in the post-absorptive period are: morphine, 1.36.7 h; codeine, 1.93.9 h; oxycodone, 4.05.0 h; and hydromorphone, 1.53.8 h (Baselt, 1978).

Propoxyphene and pentazocine Propoxyphene and pentazocine are synthetic narcotic preparations; however, naloxone and nalmefene are not antidotes to either of them. The minimum lethal dose of propoxyphene has been estimated at 500800 mg (Baselt, 1978). Whole-blood concentrations of 1 mg/L indicate serious toxicity and 2 mg/L or more of propoxyphene are a.s.sociated with death (Baselt, 1978). Fatalities due to pentazocine overdose generally occur with blood concentrations in the 15 mg/L range, with brain concentrations often exceeding blood levels except in cases of intravenous administration (Baselt, 1978).

The course of pregnancy following propoxyphene or pentazocine overdose has not been published. Nonspecific and supportive antidote therapy should be given because the effectiveness and safety of nalmefene for narcotic overdose have been demonstrated only in a pilot study. It is known that significant amounts of these synthetic narcotic drugs cross the placenta to reach the fetus. Narcotics may stimulate fetal hepatic maturation, inducing enzymatic activity, but effects of a potentially toxic dose are unknown.

Among adult males, the half-lives of propoxyphene and pentazocine in the post-absorptive period are 824 h and 2.13.5 h, respectively (Baselt, 1978).

ANTIBIOTIC OVERDOSES.

Cephalexin, amoxicillin, and trimethoprim sulfamethoxazole In one study two decades ago, antibiotics were used in 7 percent of suicide gestures during pregnancy. The course of pregnancy following antibiotic overdoses has not been published. Nonspecific and supportive antidote therapy should be given because no specific antidote to antibiotic overdoses is available. Appreciable amounts of these drugs cross the placenta and expose the fetus to high drug doses, but the effects of potentially toxic doses on the fetus are unknown. In one study two decades ago, antibiotics were used in 7 percent of suicide gestures during pregnancy. The course of pregnancy following antibiotic overdoses has not been published. Nonspecific and supportive antidote therapy should be given because no specific antidote to antibiotic overdoses is available. Appreciable amounts of these drugs cross the placenta and expose the fetus to high drug doses, but the effects of potentially toxic doses on the fetus are unknown.

ANTIHISTAMINE AND DECONGESTANT OVERDOSES.

Six percent of attempted suicides by pregnant women included large doses of antihistamines and/or decongestants in one study (Table 14.1), but not another (Table 14.2). One pregnancy following antihistamine overdose, diphenhydramine (35 Benadryl pills), in a suicide gesture at 26 weeks estimated gestation age (EGA) has been published. In the emergency room with palpable contractions, preterm labor was successfully treated with intravenous magnesium as tocolysis. Diphenhydramine overdose was treated with activated charcoal slurry because no specific antidotes are available. After 3 days the patient was released from the hospital in good health.

Preterm labor was attributed to the oxytocin-like effects of diphenhydramine (not listed in the Physicians' Desk Reference Physicians' Desk Reference) (Brost et al et al., 1996).

270.

Drug overdoses during pregnancy Hence, nonspecific and supportive antidote therapy should be given. It is known that considerable amounts of these drugs cross the placenta to reach the fetus. However, the effects of a potentially toxic dose are unknown.

ANTIPSYCHOTIC OVERDOSES.

Thioridazine and trifluoperazine Approximately 3 percent of pregnant women who attempted suicide during pregnancy used antipsychotic preparations (Flint et al et al., 2002; Rayburn et al et al., 1984). One case report is published regarding overdose of trifluoperazine (including misoprostol) during pregnancy (Bond and Van Zee, 1994). Fetal death was the final outcome, but the authors noted misoprostol as the probable cause of fetal death.

Antipsychotic overdose therapy includes nonspecific supportive therapy because there is no specific antidote. These drugs cross the placenta and achieve a near-therapeutic fetal concentration. Large doses of these drugs cause hypersedation in the nonpregnant adult and would be expected to have the same effect on the gravid woman and fetus.

The effects of a potentially toxic dose during pregnancy have not been published.

Thioridazine and trifluoperazine half-lives in the post-absorptive period are 2636 h and 718 h, respectively (Baselt, 1978).

ANORECTIC OVERDOSES.

Sympathomimetic amines, phenylpropanolamine In one study, anorectic agents were used by approximately 2 percent of pregnant women in suicide gestures (Table 14.1). The course of pregnancy following anorectic agent overdoses has not been published. Therapy consists of nonspecific antidote and supportive therapy. The drugs cross the placenta and reach near therapeutic levels in the fetus. Oral doses of 5075 mg produce anxiety, agitation, dizziness, and hallucinations (Dietz, 1981). Higher doses (85400 mg) are a.s.sociated with severe headaches, hypertensive crisis, and occasionally vomiting (Frewin et al et al., 1978; Horowitz et al et al., 1979; Ostern, 1965; Salmon, 1965; Teh, 1979).

Potentially toxic dose effects on the fetus are unknown. The half-life of phenylpropanolamine is unknown.

HORMONAL AGENT OVERDOSES.

Corticosteroids and oral contraceptives An estimated 2 percent of pregnant women used large doses of hormonal agents in their suicide attempt (Rayburn et al et al., 1984). The course of pregnancy following hormonal agent overdoses has not been published. Nonspecific supportive therapy should be given because no specific antidote to hormonal agents is available. Near-therapeutic amounts of these drugs cross the placenta and can be detected in the fetus. The effects of a poten-Anticonvulsant overdoses 271.

tially toxic dose of hormonal agents are unknown, but fetal adrenal suppression should be antic.i.p.ated based upon known pharmacology and physiology.

One overdose of misoprostol and trifluoperazine has been reported (Bond and Van Zaa, 1994). Signs of toxicity included hypertonic uterine contraction with fetal death, hyperthermia, rhabdomyolysis, hypoxemia, respiratory alkalosis, and metabolic acidosis. The clinical impression was that misoprostol was being used as an illegal abortifacient.

ANTIDEPRESSANT OVERDOSES.

Doxepin and amitriptyline Approximately 2 percent of pregnant women used antidepressants in suicide gestures in two studies (Flint et al et al., 2002; Rayburn et al et al., 1984). The clinical details of the course of pregnancy following antidepressant agent overdoses have not been reported and therapy is mostly supportive. The toxic systemic effects (tachycardia, dry mouth, dilated pupils, and urinary retention) as well as the central nervous system effects (agitation, hallucinations, and hyperpyrexia) are anticholinergic in nature (Burks et al et al., 1974). For this reason, physostigmine (an anticholinesterase) has been used in the diagnosis and antidotal therapy of poisoning with amitriptyline and other tricyclic antidepressants (Burks et al et al., 1974; Slovis et al et al., 1971). Large doses of antidepressants are a.s.sociated with coma in nonpregnant adults and cardiac toxicity has been reported with acute ingestion of high doses of these drugs. Although these drugs cross the placenta to reach the fetus, the effects of a potentially toxic dose are unknown. Half-lives in the post-absorptive period for doxepin and amitriptyline are 825 h and 851 h, respectively (Baselt, 1978).

ANTICONVULSANT OVERDOSES.

Phenytoin and carbamazepine An estimated 2 percent of pregnant women who attempted suicide used large doses of anticonvulsants (Rayburn et al et al., 1984). Pregnancy outcome following anticonvulsant agent overdoses has been published in one isolated case report. A case of carbamazepine megadose in attempted suicide with more than 10 g of carbamazepine during early pregnancy resulted in a fetus with a large meningomyelocele and frontal lobe necrosis that was electively aborted. The mother recovered without complication following nonspecific therapy and coma for 5 days (Little et al et al., 1993). This is a cautionary anecdote regarding overdoses of anticonvulsants. Damage to the embryo or fetus is probable because the two anticonvulsants listed (phenytoin, carbamazepine) are known human teratogens. Anticonvulsant agents have no specific antidote, and supportive therapy should be given.

Near-therapeutic amounts of these drugs cross the placenta and achieve significant concentrations in the fetus. It is known that phenytoin may induce fetal hepatic enzymes, but the effects of a potentially toxic dose are unknown. Phenytoin's half-life ranges from 860 h and is dose dependent because each individual has a threshold plasma concentration beyond which the drug exhibits zero-order kinetics (Arnold and 272 272 Drug overdoses during pregnancy Gerber, 1970; Kostenbauder et al et al., 1975). Carbamazepine half-life after a single dose is 1865 h (Baselt, 1978).

OVERDOSES OF OTHER DRUGS.

Miscellaneous other drugs (Bendectin, docusate, cimetidine, methyldopa) were used by about 6 percent of pregnant women in their suicide gestures (Table 14.1). Details of the clinical course of pregnancy after overdoses of any of these agents have not been published. No specific antidotes to any of these agents are available. It is known that significant amounts of these drugs cross the placenta to reach near-therapeutic levels in the fetus. Megadose effects on mother or fetus are unknown.

OVERDOSES OF NONDRUG CHEMICALS.

An estimated 2 percent of pregnant women who attempted suicide used nondrug chemicals in one study (Rayburn et al et al., 1984).

Camphorated oil Camphor, a gastrointestinal irritant and central nervous system stimulant, was used in four suicide attempts during pregnancy that have been published (Blackmon and Curry, 1957; Jacobziner and Raybin, 1962; Riggs et al et al., 1965; Weiss and Catalano, 1973).

Uniformly, maternal seizures occurred and should apparently be expected with camphor ingestion. Three of the four infants survived with no obvious abnormalities. The fourth pregnancy was compromised by preeclampsia, abruptio placenta, and other serious complications, and the infant died less than 1 h after delivery. Clearly, the death cannot be directly attributed to megadose camphor oil.