Phenobarbital overdose

Palmer BE. Effectiveness of hemodialysis in the extracorporeal therapy of phenobarbital overdose. Am JKidney Dis. 2000 36 640-643... 

Pond SM, Olson KR, Osterloh JD, et al. Randomized smdy of the treatment of phenobarbital overdose with repeated doses of activated charcoal. JAMA 1984 251 3104-3108. 

Obviously severe or critical intoxication with a deteriorating condition despite maximal supportive care (eg, phenobarbital overdose with intractable hypotension). 

Palmer BF Effectiveness of hemodialysis in the extracorporeal therapy of phenobarbital overdose. Am J Kidney DIs 2000 36(3) 640-643. [PMID 10977799] (Use of a high-etficiency hemodialysis machine resulted in high clearance values and dramatic improvement after a life-... 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

Forced diuresis is occasionally useful. It may cause volume overload or electrolyte disturbances. Forced diuresis is useful for phenobarbital, bromides, lithium, salicylate, or amphetamines overdoses. Do not use for tricyclic antidepressants, sedative-hypnotics, or highly protein-bound medications. The most common agents employed are furosemide and osmotic diuretics with mannitol. 

RPC has found use in the analysis of barbiturates including the determination of drugs taken in an overdose (332). Thiopental was determined using a mobile phase comprised of methanol-0.1% sodium citrate buffer, pH 6.5 (45 55) (333). Hydantoins, along with other species which have anticonvulsant activity, have been determined with barbiturates. These include phenytoin in the presence of phenobarbital and primidone (334,335) and the related anticonvulsants ethosuximide and carbamazepine (336). 

Historically, alcohol has been used as an anxiety-reducing agent, both casually and in professional medical settings. In 1903, barbital was introduced as the first barbiturate to treat anxiety, and phenobarbital followed a few years later. Barbiturates have many side effects and addictive properties, and overdose can lead to coma and death. For these reasons, they are rarely used today, except to treat some forms of epilepsy. This class of drugs was eventually replaced by the benzodiazepines (see Chapter 4). 

Phenobarbital, mephobarbital and metarbital are the only oral anticonvulsants which are effective at sub-hypnotic levels. Many barbiturates are classified as Schedule II, III, or IV due to their high potential for overdose and dependence. Abrupt withdrawal may cause seizures, restlessness, trembling, and insomnia and may be fatal. Phenobarbital is used as an anticonvulsant for the treatment of epilepsy and in some combination medications for the relief of irritable bowel syndrome. 

Changes in plasma pH may also affect the distribution of toxic compounds by altering the proportion of the substance in the nonionized form, which will cause movement of the compound into or out of tissues. This may be of particular importance in the treatment of salicylate poisoning (see chap. 7) and barbiturate poisoning, for instance. Thus, the distribution of phenobarbital, a weak acid (pKa 7.2), shifts between the brain and other tissues and the plasma, with changes in plasma pH (Fig. 3.22). Consequently, the depth of anesthesia varies depending on the amount of phenobarbital in the brain. Alkalosis, which increases plasma pH, causes plasma phenobarbital to become more ionized, alters the equilibrium between plasma and brain, and causes phenobarbital to diffuse back into the plasma (Fig. 3.22). Acidosis will cause the opposite shift in distribution. Administration of bicarbonate is therefore used to treat overdoses of phenobarbital. This treatment will also cause alkaline diuresis and therefore facilitate excretion of phenobarbital into the urine (see below). 

Other nervous system depressants that could trigger a GHB overdose reaction are benzodiazepines (mild tranquilizers such as Valium and Xanax), phenothiazines (potent tranquilizers like Thorazine and Stellazine), various painkillers (barbiturates and opiates), anticonvulsants (Dilantin and phenobarbital), and even many over-the-counter allergy and sleep remedies. 

The effect of urinary pH on drug ionization also has toxicological implications. For example, in cases of phenobarbital (a weak acid barbiturate) overdose the urine can be alkalinized (the pH elevated) by administering sodium bicarbonate to the patient. The resultant increase in pH shifts the dissociation equilibrium for this weak acid to the right, producing an increase in the proportion of the ionized form, less reabsorption in the kidneys, and more rapid elimination. Conversely, acidifying the urine with ammonium chloride will increase the excretion rate of drugs that are weak bases since they will be more protonated (ionized) and less reabsorbed (more polar, less lipophilic). 

Activated charcoal Carbamazepine Lamotrigine Phenobarbital Phenytoin Valproate With some drugs can be exploited to reduce drug concentrations in overdose Sequestration in the gastrointestinal tract... 

The basis of clinical management is supportive care. The airway should be secured and protected as needed. Symptomatic patients should have intravenous access and cardiac monitoring. Accidental ingestions exceeding 500-800 mg, and all intentional overdoses, should be treated with oral activated charcoal if patients present within 60 min of exposure. Seizures should be treated with benzodiazepines, or phenobarbital if refractory. Hypotension should be treated with intravenous fluids and vasopressors (dopamine or norepinephrine) if needed. Hemodialysis or hemoper-fusion may enhance elimination of both the parent compound and metabolites, but the clinical value of... 

The majority of a dose is excreted in the urine as PEMA 15% as phenobarbital. The plasma elimination half-lives of primidone, PEMA, and phenobarbital are 8-10, 24-36, and 100 h, respectively. The metabolism of primidone is enhanced with chronic therapy, with a reduced half-life of 4-7 h. An elimination half-life of 6.2 h has been documented following overdose. 

Ebid A-H-I, Abdel-Rahman HM. Pharmacokinetics of phenobarbital during certain enhanced elimination modalities to evaluate their clinical efficacy in management of drug overdose. Ther Drug Monit 2001 23 209-16. 

Phenobarbital is dangerous in overdose, producing coma and respiratory and circulatory failure and consequently is not much used nowadays. 

In terms of the amount of literature developed, biochemical separations have been largely ignored by those in the field of LEM-mediated separations. One application that has enjoyed some experimental scrutiny is that of the use of LEMs in drug delivery and overdose prevention systems. They have been used to separate or release several different types of drugs including acetylsalicyclic acid (18), phenobarbital (19), and several barbiturates (20,21). 

A patient is admitted to the emergency room 2 hours after taking an overdose of phenobarbital. The plasma level of the drug at time of admission is 100 mg/L, and the apparent volume of distribution, half-life, and clearance of phenobarbital are 35 L, 4 days, and 6.1 L/d, respectively. The ingested dose was approximately... 

---