Nifedipine lithium

Cummings JL, Miller B, Hill MA, et al Neuropsychiatric aspects of multi-infarct dementia and dementia of the Alzheimer type. Arch Neurol 44 389-393, 1987 Cundall RL, Brooks PW, Murray LG A controlled evaluation of lithium prophylaxis in affective disorders. Psychol Med 2 308-311, 1972 Cutler NR, Haxy J, Kay AD, et al Evaluation of zimeldine in Alzheimer s disease cognitive and biochemical measures. Arch Neurol 42 744-748, 1985 Czyrak A The effect of chronic nifedipine and ECS in the forced swimming test in rats. PolJ Pharmacol 45 191-195, 1993... 

Gengo F, Timko J, D Antonio J, et al Prediction of dosage of lithium carbonate use of a standard predictive method. J Clin Psychiatry 41 319-321, 1980 Geoffroy M, Mogilnicka E, Nielsen M, et al Effect of nifedipine on the shuttlebox escape deficit induced by inescapable shock in the rat. Eur J Pharmacol 154 277-283, 1988... 

Other reported potentially significant drug interactions include the combination of verapamil or nifedipine with CBZ, which, at times, can lead to toxicity secondary to increases in CBZ levels, and neurotoxic reactions when verapamil or diltiazem is combined with lithium. 

A 30-year-old man required a reduction in lithium dosage from 1500 to 900 mg/day to maintain his serum lithium concentration in the target range shortly after he started to take nifedipine 60 mg/day (645). 

Bruun NE, Ibsen H, Skott P, Toftdahl D, Giese J, Holstein-Rathlou NH. Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension. Clin Sci (Lond) 1988 75(6) 609-13. 

Pinkofsky HB, Sabu R, Reeves RR. A nifedipine-induced inhibition of lithium clearance. Psychosomatics 1997 38(4) 400-1. 

Noninterfering acetaminophen, N-acetylprocainamide, amikacin, amitriptyline, amlodi-pine, carbamazepine, cefotaxime, ceftazidime, chloramphenicol, ciprofloxacin, cisapride, clindamycin, clonidine, codeine, cyclosporine, digoxin, diphenhydramine, disopyramide, ethosuximide, fluconazole, gentamicin, gentamicin, heparin, labetalol, levothyroxine, li-docaine, lithium, methotrexate, metronidazole, minoxidil, nafcillin, nifedipine, phenobar-bital, phenobarbital, phenytoin, phenytoin, primidone, procainamide, propranolol, quini-dine, ranitidine, salicylic acid, theophylline, tobramycin, tobramycin, valproic acid, warfarin... 

A woman taking lithium carbonate developed signs of lithium toxicity (ataxia, dysarthria, tremor, confusion) within 2 to 3 weeks of starting to take enalapril 20 mg daily. After 5 weeks her plasma-lithium levels had risen from 0.88 to 3.3 mmol/L, and moderate renal impairment was noted. No toxicity occurred when the enalapril was later replaced by nifedipine. Lithium toxicity following the use of enalapril, and associated in some cases with a decrease in renal function, has been seen in another 5 patients, " and a reduced lithium dosage was found adequate in another patient. Enalapril 5 mg daily for 9 days had no effect on the mean serum-lithium levels of 9 healthy male subjects. However, one subject had a 31% increase in lithium levels. "... 

The concurrent use of lithium and verapamil can be uneventful, but neurotoxicity (ataxia, movement disorders, tremors) with unchanged lithium levels has been reported in a few patients. Reduced and increased lithium levels have also occurred with verapamil. An acute parkinsonian syndrome and marked psychosis has been seen in at least one patient taking lithium and diltiazem. Reduced lithium clearance, and one possible case of increased lithium levels have been reported with nifedipine. 

In a study of patients with essential hypertension, two doses of nifedipine 20 mg did not affect single-dose lithium clearance, but nifedipine 40 to 80 mg daily for 6 and 12 weeks was found to decrease single-dose lithium clearance by 30%.A man, on lithium carbonate 1.5 g daily with a level of 0.8 mmol/L, developed ataxia and dysarthria 7 days after starting nifedipine 30 mg daily for 48 hours, then 60 mg daily. His lithium dose was reduced by 40%, but his serum-lithium level first increased to 1.1 mmol/L (about 2 weeks after starting the nifedipine), before restabilising at 0.9 mmol/L. In contrast, a patient taking lithium, who developed dysarthria and ataxia after verapamil was added to her treatment (see fcj below), was subsequently well controlled on lithium and nifedipine 40 mg daily... 

The neurotoxic adverse reactions cited above for lithium and verapamil contrast with two other case reports describing uneventful concurrent use.i2 i3 Variable reports of altered serum-lithium levels have also occurred. This unpredictability emphasises the need to monitor the effects closely where it is thought appropriate to give lithium and verapamil. Only a couple of isolated reports of neurotoxicity have been reported with lithium and diltiazem, and their general relevance is uncertain, but bear them in mind in the event of an unexpected response to treatment. Some limited data suggest that nifedipine may slightly reduce lithium clearance, and the clinical relevance of this is again uncertain. 

A 79-year-old woman on lithium (as well as fosinopril, nifedipine, oxazepam and haloperidol) had a rise in her trough serum-lithium levels... 

Non-linear pharmacokinetic behaviour, meaning that the blood concentration increases are not proportional to increasing dose. This may lead to toxic blood levels. Examples of active substances with non-linear pharmacokinetics include nitrates, nifedipine, fentanyl, theophylline, paclitaxel and lithium carbonate. Non-linear pharmacokinetic behaviour may be due to saturation of pre systemic enzymatic elimination mechanisms at increasing concentrations of the substrate. 

There is an extensive database describing surface and nanosolid Tm suppression [21-26]. For instance, a photoelectron emission study [27] confirmed that lithium (110) surface melting occurs 50 K below the bulk (454 K). A temperature-resolved XRD analysis revealed that the of nanometer-sized drugs (polymer) also drops (by 33 and 30 K for 7.5-nm-sized griseofulvin and 11.0-nm-sized nifedipine, respectively) in a 1/R fashion [28]. STM measurements of a reversible, temperature-driven structural surface phase transition of Pb/Si(lll) nanoislands indicates that the transition temperature decreases with inverse of domain size and the phase transition is independent of the processes of cooling or heating [29]. 

---