Barbiturates urinary excretion

Table VI lists several drugs Inducing hepatic microsomal enzymes (5). These enzymes can metabolize the drug as well as other substrates. Barbiturates, grlseofulvln, and glutethlmlde Induce enzymes which metabolize coumarln and phenlndlone derivatives and thus reduce their anticoagulant activity. Dlphenylhydantoln and phenylbutazone stimulate cortisol hydroxylase activity and Increase the urinary excretion of B-hydroxy cortisol and decrease the concentration of cortisol In the plasma.

Barbiturates such as phenobarbital are weak acids. The toxicity of the barbiturate is mainly the result of the effects on the central nervous system. Only the nonionized form of the drug will distribute into the central nervous system. The proportion ionized will depend on the pKa and the pH of the blood. By increasing the pH of the blood using sodium bicarbonate administration to the poisoned patient, ionization of the barbiturate will be increased and distribution to tissues such as the brain will be decreased. Urinary excretion of the barbiturate will also be increased because the urinary pH will be increased. 

The inactive metabolites are excreted in the urine. The administration of bicarbonate enhances the urinary excretion of barbiturates that have a pK of 7.4 (phenobarbital and thiopental). This generalization is not true of other barbiturates. The long-term administration of barbiturates activates the cytochrome P-450 drug-metabolizing system. 

CARBONIC ANHYDRASE INHIBITORS ANTIEPILEPTICS- BARBITURATES, PHENYTOIN Risk of osteomalacia Barbiturates and phenytoin have a small risk of causing osteomalacia this may be t by acetazolamide-induced urinary excretion of calcium Be aware... 

There are examples of weak acids reabsorbed by simple nonionic diffusion which urinary excretion is not influenced by changes in urine pH. It is the case if the pKa is above or close to the upper limit of urine pH, as it is the case for barbital (pKa = 7.8), and a few other barbiturates. Also, if the pKa value is very low, such as it is the case for 2-nitroprobenecid (pKa=1.3), the acid remains mainly unionized in the physiological range of urine pH [15], and its excretion remains independent of fubular urine pH. 

Mannitol may be used alone or in combination with other diuretic agents to promote urinary excretion of toxins such as salicylates, barbiturates, lithium, and bromides. 

Effects of pH on urinary drug elimination may have important applications in medical practice, especially in cases of overdose. For example, one can enhance the elimination of a barbiturate (a weak acid) by administering bicarbonate to the patient. This procedure alka-linizes the urine and thus promotes the excretion of the now more completely ionized drug. The excretion of bases can be increased by making the urine more acidic through the use of an acidifying salt, such as ammonium chloride. 

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). 

Uncertain. Mild osteomalacia induced by antiepileptics is a recognised phenomenon (see also Vitamin D substances + Phenytoin and Barbiturates , p.l291). It seems that this is exaggerated by acetazolamide, which increases urinary calcium excretion, possibly by causing systemic acidosis, which results from the reduced absorption of bicarbonate by the kidney. The changes in the antiepileptic levels are not understood. 

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