CNS & Analgesics

·         MPTP exposure depletes dopamine & causes Parkinsonism.

·         3 metabolic effect of Salycilates.

- Low Dose = 1º respiratory alkalosisà ¯pCO₂ à ­pH (7.51)

-2º Metabolic acidosis (compensation)= ¯CO₂ à¯HCO₃à­pH (7.42)

-Toxic Dose= ­CO₂, ¯HCO₃ à respiratory acidosis and metabolic acidosis è patient will be comatose/ obtunded.

·         Zidovudine may decrease serum phenytoin levels so that the patient now requires a higher dose to achieve therapeutic levels.

·         Phenytoin-induced skin eruption usually occur 7 to 21 days after initiation and almost always within the first 2 months of therapy. these reactions may proceed to fatal reactions, like toxic epidermal necrolysis and drug should be stooped if this occurs.

·         Anticonvulsant is known to cause a skin rash : Lamotrigine,( which may lead to Stevens-Johnson syndrome) especially with rapid dose escalation. Phenytoin, carbamazepine, and phenobarbital are all first-generation anticonvulsants that also may cause a rash.

·         Anticonvulsants are also FDA-approved for migraine prophylaxis are Divalproex or valproic acid and topiramate.

·         Autoinduction of carbamazepine's metabolism begins 3 to 5 days after dosing and is complete in about 1 month. (might a patient be at risk for loss of seizure control secondary to carbamazepine's induction of its own metabolism.)

·         Total phenytoin serum concentration causing nystagmus  >20 µg/mL.

Ataxia and diplopia frequently occur with levels >30 µg/mL

seizures and coma at concentrations >40 µg/mL.

·         Ropinirole is used to control motor fluctuations in Parkinson's disease is also beneficial in the treatment of restless legs syndrome.

·         Aripiprazole is a partial agonist at D2 and 5-HT1A receptors and a potent antagonist at 5-HT2A receptors.

·         CNS side effects may occur with metronidazole at high doses (>1.5 g) Peripheral neuropathy and seizures are potential side effects.

·         Migraine or tension headaches during pregnancy:

Acetaminophen is the preferred agent. Nonsteroidal anti-inflammatory agents may be acceptable early in pregnancy but are contraindicated after 37 weeks of gestation.

·         Fluoxetin (not other SSRIs) may be stopped abruptly because it has a long half-life of 60 hours and will clear the body after 2 weeks without major risk of withdrawal side effects.

·         The risk of seizure with BUPROPION is dose-dependent, with increased risk at daily doses >450 mg. Bupropion is contraindicated in patients with a history of seizures, bulimia or anorexia secondary to increased seizure risk.

·         The anxiolytic effects of buspirone take several days to develop, obviating its use for acute severe anxiety.

·         Antipsychotic drugs as long-acting depot preparations:

Two conventional antipsychotics available are haloperidol given every 28 days and fluphenazine given as fluphenazine decanoate every 2 to 4 weeks or fluphenazine enanthate every 1 to 2 weeks. Risperidone is the only second-generation antipsychotic available as a long-acting injection given every 2 weeks, but it has a 3-week lag time to full effect, requiring 3 weeks of concurrent oral antipsychotics.

·         Olanzapine and clozapine have the highest incidence of weight gain followed by quetiapine. This is usually most significant during the first 12 weeks of treatment, with a 3- to 15-lb weight gain.

Ziprasidone and aripiprazole have a low tendency to promote weight gain.

·         Fatalities have been reported when fluoxetine and MAO inhibitors (MAOIs) such as tranylcypromine have been given simultaneously. The MAOIs should be stopped at least two weeks before the administration of fluoxetine or paroxetine.

·         If Aspirin is not tolerable in prophylaxis of TIA, Ticlopidine > Dipyridamole should be given.

·         BarbiDURATe (↑DURATion).

·         FREnzodiazepines (↑FREquency)

·         Ergotism or “St. Anthony’s fire” : Overdose of ergot alkaloids causes prolonged vasospasm resulting in gangrene and amputation, hallucinations, dementia and abortion ·         About 3 months of continuous or intermittent treatment with neuroleptics is needed before the risk of tardive dyskinesia increases.

·         Two of the important types of MAO are: (1) MAO-A, which metabolizes norepinephrine and serotonin and other biogenic amines, and is the predominant hepatic form of the enzyme; and (2) MAO-B, which metabolizes dopamine and other monoamines in the brain. Selegiline is a selective inhibitor of MAO-B.

·         High or frankly toxic serum levels of meperidine can cause seizures, hypertension, and a psychosis-like state, in addition to typical morphine-like effects

·         Serotonin is already present in increased amounts in synapses because of blockade of its reuptake by the SSRIs. When sumatriptan (or other triptans used for migraine therapy; they are 5-HT1B/2D agonists) is added, rapid accumulation of serotonin and/or the triptan in the brain can occur.

The risk of the serotonin syndrome in SSRI–treated patients is much higher when MAO inhibitors are used concomitantly. Nonetheless, such severe reactions from an SSRI–triptan interaction have been reported. In addition, do not forget that MAO inhibitors can also cause an acute and potentially fatal hypertensive crisis when coadministered with tricyclic/tetracyclic antidepressants (e.g., imipramine); such combined use should be avoided.

·         livedo reticularis, is characteristically associated with amantadine.

·         phenytoin must be diluted before injection, but it is physically incompatible with glucose-containing solutions that so often are used as a vehicle for many IV drugs

·         Whether you have learned or read about this specifically in a pharmacology class or text, for medicolegal and societal (and board-related?) reasons you should be aware of the growing problem of illicit “meth labs” that use pseudoephedrine (“pseudo”) as the starting point for a rather easy chemical synthesis of this highly addictive and dangerous CNS stimulant methamphetamine. None of the other drugs listed can be synthesized using this common indirect-acting sympathomimetic as a starting point.

·         Vigabatrin (γ-vinyl GABA) is useful in partial seizures. It is an irreversible inhibitor of GABA aminotransferase, an enzyme responsible for the termination of GABA action. This results in accumulation of GABA at synaptic sites, thereby enhancing its effect. Vigabatrin can induce psychosis. It is recommended that it not be used in patients with preexisting depression and psychosis. None of the other drugs listed are associated with this phenomenon.

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·         RESERPINE causes parkinsonism & suicidal tendency as it is nonselective, so withdrawn.

·         Lorazepam, Oxazepam, Temazepam are metabolized in liver by CONJUGATION only…not by OXIDATION, so safe in liver dz.