Phenobarbital antiepileptic

Fig. 1 Reflectance scan of a blank (A) and of a mixture of antiepileptics with 500 ng substance per chromatogram zone (B). Start (1), primidone (2), carbamazepine (3), phenytoin (4), phenobarbital (5), ethosuximide (6), hexobarbital (7) and solvent front (8).

Drug-induced osteoporosis may result from systemic corticosteroids (prednisone doses greater than 7.5 mg/day), thyroid hormone replacement, some antiepileptic drugs (e.g., phenytoin, phenobarbital), depot medroxyprogesterone acetate, and other agents. 

A, adult AED, antiepileptic drug C, child Co, combination therapy M, monotherapy PB, phenobarbital VD, volume of distribution. 

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. 

Epilepsy, monotherapy Indicated for conversion to monotherapy in adults with partial seizures who are receiving treatment with carbamazepine, phenytoin, phenobarbital, primidone, or valproate as the single antiepileptic drug (AED). 

The apparent clearance of lamotrigine is affected by the coadministration of AEDs. Lamotrigine is eliminated more rapidly in patients who have been taking hepatic enzyme inducing antiepileptic drugs (ElAEDs), including carbamazepine, phenytoin, phenobarbital, and primidone. 

Pharmacology Primidone s mechanism of antiepileptic action is not known. Primidone and its 2 metabolites, phenobarbital and phenylethylmalonamide (PEMA) have anticonvulsant activity. 

Sullivan, F.M. and McElhatton, P.R. (1975) Teratogenic activity of the antiepileptic drugs phenobarbital, phenytoin, and primidone in mice. Toxicol Appl Pharmacol 24 271—282. 

Concentrations of lipoprotein(a) were measured in 51 patients taking long-term carbamazepine, phenobarbital, phenytoin, or valproate and 51 age- and sex-matched controls (133). Lipoprotein(a) concentrations were above 450 pg/ml in 11 patients compared with only 4 controls, and the mean serum lipoprotein(a) concentrations were 330 and 169 pg/ml respectively. The epileptic patients also had a thicker intima media of the common carotid artery. These results suggest that patients taking antiepileptic drugs may be at a higher risk of atherosclerosis. 

Phenobarbital is the oldest antiepileptic drug in common use and has a solid efficiency record for the control of seizure. However, due to some side effects (hypertension, depression, dizziness, rash, memory lapses) and drug interactions (primarily other anticonvulsants), phenobarbital is now generally used as a second-line treatment. 

Actions Phenobarbital (see p. 94) has antiepileptic activity, limiting the spread of seizure discharges in the brain and elevating the seizure threshold. Its mechanism of action is unknown but may involve potentiation of the inhibitory effects of y-aminobutyric acid (GABA)-mediated neurons. Doses required for antiepileptic action are lower than those that cause pronounced CNS depression. 

DISOPYRAMIDE ANTIEPILEPTICS- BARBITURATES, PHENYTOIN Disopyramide levels are 1 by phenobarbital and primidone Phenobarbital and primidone induce the hepatic metabolism of disopyramide Watch for poor response to disopyramide check serum levels if necessaiy... 

OXCARBAZEPINE 1. BARBITURATES-phenobarbital 2. PHENYTOIN t levels of these antiepileptics Uncertain Watch for early features of toxicity... 

VIGABATRIN 1. BARBITURATES-phenobarbital, primidone 2. PHENYTOIN i levels of these antiepileptics Possibly induction of metabolism Watch for poor response to these antiepileptics... 

CARMUSTINE ANTIEPILEPTICS -PHENOBARBITAL 1 plasma concentrations of carmustine and 1 anti-tumour effect in animal experiments Attributed to induction of liver metabolizing enzymes of carmustine by phenobarbitone, particularly with long-term therapy Avoid concurrent use. As this study did not show any interaction with phenytoin, phenytoin may be a suitable alternative antiepileptic... 

ETOPOSIDE ANTIEPILEPTICS - PHENYTOIN, PHENOBARBITAL Significantly i plasma concentrations of etoposide (clearance may be >170%) and considerable risk of loss of therapeutic efficacy Due to potent induction of the hepatic microsomal enzymes that metabolize etoposide Do not co-administer. Consider use of alternative antiepileptics that do not induce hepatic microsomal enzymes, e.g. valproic acid... 

LOMUSTINE ANTIEPILEPTICS-PHENOBARBITAL 1 plasma concentrations of lomustine and risk of inadequate therapeutic response Phenobarbital induces the metabolism of lomustine by the CYP450 isoenzymes Avoid concurrent use. If necessaiy, t dose of lomustine and monitor therapeutic effects... 

PACLITAXEL 1. ANTIBIOTICS-rifampicin 2. ANTIDEPRESSANTS-St John s wort 3. ANTIEPILEPTICS -carbamazepine, phenobarbital, phenytoin 1 plasma concentration of paclitaxel and 1 efficacy of paclitaxel Due to induction of hepatic metabolism of paclitaxel by the CYP isoenzymes Monitor for clinical efficacy and need to T dose if inadequate response is due to interaction... 

PROCARBAZINE ANTIEPILEPTICS-CARBAMAZEPINE, PHENOBARBITAL PHENYTOIN, VALPROIC ACID T risk of hypersensitivity reactions in patients with brain tumours Strong correlation between the therapeutic antiepileptic level and the hypersensitivity reactions Consider using non-enzyme-inducing agents... 

TAMOXIFEN ANTIEPILEPTICS -CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL i plasma concentrations of tamoxifen and risk of inadequate therapeutic response Due to induction of metabolism of tamoxifen by the CYP3A isoenzymes by phenytoin Avoid concurrent use if possible. Otherwise monitor for clinical efficacy of tamoxifen by t dose of tamoxifen... 

CORTICOSTEROIDS ANTIEPILEPTICS -CARBAMAZEPINE, PHENYTOIN, PHENOBARBITAL 1 plasma concentrations of corticosteroids and risk of poor or inadequate therapeutic response, which would be undesirable if used for e.g. cerebral oedema Due to induction of the hepatic metabolism by the CYP3A4 isoenzymes Closely monitor therapeutic response - clinically, by ophthalmoscopy and radiologically - and t dose of corticosteroids for desired therapeutic effect... 

OPIOIDS ANTIEPILEPTICS 1. Barbiturates T sedative effects of opioids 2.1 efficacy of fentanyl and methadone with carbamazepine, phenobarbital, phenytoin or primidone 3. Carbamazepine l tramadol levels 4. Risk of pethidine toxicity 1. Additive sedative effect 2. t hepatic metabolism of fentanyl and methadone, and possibly an effect at the opioid receptor 3. Carbamazepine T metabolism of tramadol 4. Phenytoin induces metabolism of pethidine, which causes T level of a neurotoxic metabolite 1. Monitor respiratoiy rate and conscious levels 2. Be aware that the dose of fentanyl and methadone may need to be t 3. Watch for poor effect of tramadol. Consider using an alternative opioid 4. Co administer with caution the effect may be i by administering pethidine intravenously... 

Antiepileptics. Large doses of vitamin B6 can reduce serum levels of phenytoin and phenobarbital, and thus cause loss of control of epilepsy. Vitamin B6 in excess of 10 mg a day should be avoided. The antiepileptics phenytoin, phenobarbital and primidone can cause folate deficiency (resulting in... 

Also, if concomitant enzyme-inducing antiepileptic drugs such as carbamazepine, phenobarbital, phenytoin, and primidone are discontinued after lamotrigine dose is stabilized, then the lamotrigine dose should be maintained for 1 week following discontinuation of the other drug and then reduced by half over 2 weeks in equal decrements each week... 

---