Phenobarbital Benzodiazepines

Use cimetidine with caution in >50 year olds w/kidney or liver failure Little plasma protein binding, little metabolism. Cimetidine T levels of many drugs (see notes ) by inhibiting liver P450 enzymes. Oral anticoagulants, theophylline, caffeine, phenytoin, phenobarbital, benzodiazepines, propranolol. 

Valerian Valeriana officinalis Restlessness, sleep disorders Rare if used as directed. May interact with the barbiturates (eg, phenobarbital), the benzodiazepines (eg, diazepam) and the opiates, (eg, morphine). 

Major malformations occur in 4% to 6% of the offspring of women taking benzodiazepines, carbamazepine, phenobarbital, phenytoin, or valproic acid. 

Following acute exposure to cyclodiene organochlorine pesticides, seizures and respiratory depression may occur (Ellenhom 1988 Proctor et al. 1988). Benzodiazepines (e.g., diazepam or lorazepam) or other anticonvulsant medications (e.g., phenobarbital) have been commonly used to control seizures (Ford 1993). Organochlorines may sensitize the myocardium to the proarrhythmic effects of adrenergic amines, potentially resulting in initiation of ventricular fibrillation (TOMES 1994). 

Barbiturates. The first barbiturate, barbital, was introduced at the turn of the 20th century. Hundreds of others, including phenobarbital and pentobarbital, were later developed. The barbiturates were a highly successful class of medications as it became clear that they treated not only alcohol withdrawal but seizure disorders, anxiety, and insomnia as well. By the 1960s, however, the barbiturates were largely surpassed by the benzodiazepines. The newer benzodiazepines act in a similar fashion and provide much the same therapeutic benefit but are significantly safer and easier to tolerate. 

The sedative hypnotic ethchlorvynol has approximately the same activity and toxicity as phenobarbital however, its hypnotic effect develops and dissipates qnicker. It is nsed mnch less than benzodiazepines in treating insomnia for a nnmber of reasons. 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

Drugs that may interact with clozapine include caffeine, SSRIs, benzodiazepines, risperidone, CYP1A2 induces/inhibitors, CYP3A4 inhibitors, phenobarbital, and ritonavir. 

St. John s wort, rifamycins, and ritonavir. Drugs that may be affected by efavirenz include phenytoin, phenobarbital, carbamazepine, itraconazole, ketoconazole, methadone, ritonavir, amprenavir, benzodiazepines, clarithromycin, ethinyl estradiol, indinavir, nelfinavir, saquinavir, and warfarin. 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

The anticonvulsant activity of diazepam, assessed by its protection against pentylenetetrazole-induced tonic convulsions, was strongly reduced in ai-(HIOIR) mice compared to wild-type animals (Rudolph et al. 1999). Sodium phenobarbital remained fully effective as anticonvulsant in ai(HlOlR) mice. Thus, the anticonvulsant activity of benzodiazepines is partially but not fuUy mediated by ai receptors. The anticonvulsant action of zolpidem is exclusively mediated by ai receptors, since its anticonvulsant action is completely absent in ai(HlOlR) mice (Crestani et al. 2000). 

Type II Multiple actions enhance GABAergic inhibition, reduce T-calcium currents, and possibly block SRF Valproic acid Benzodiazepines Phenobarbital Primidone... 

Valproic acid causes hair loss in about 5% of patients, but this effect is reversible. Transient gastrointestinal effects are common, and some mild behavioral effects have been reported. Metabolic effects, including hyperglycemia, hyperglycinuria, and hyperammonemia, have been reported. An increase in body weight also has been noted. Valproic acid is not a CNS depressant, but its administration may lead to increased depression if it is used in combination with phenobarbital, primidone, benzodiazepines, or other CNS depressant agents. 

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). 

Different sites on the same receptor (e.g., diazepam and phenobarbital both bind to the GABA-A receptor, but at different sites benzodiazepine site versus barbiturate site). 

Figure 4.12 The GABA-A channel functions as a receptor for many multiple different drug classes, including benzodiazepines (e.g., diazepam) and barbiturates (e.g., phenobarbital). There is also a steroid-binding site on the GABA-A channel which may be useful in the future design of general anesthetics.

For patients who do not respond to phenytoin, phenobarbital can be given in large doses 100-200 mg intravenously to a total of 400-800 mg. Respiratory depression is a common complication, especially if benzodiazepines have already been given, and there should be no hesitation in instituting intubation and ventilation. 

Schedule IV - This class represents medications considered to be of low abuse potential with the possibility of limited dependence especially when compared to the previous schedules. Examples are phenobarbital, chloral hydrate, the benzodiazepine tranquilizers, propoxyphene and meprobamate (all are sedatives). 

Phenobarbital was covered with the barbiturates and diazepam is a benzodiazepine tranquilizer. 

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