Methamphetamine and Parkinson’s Disease.

Methamphetamine and Parkinson’s disease.

Parkinsons Dis. 2013; 2013: 308052
Granado N, Ares-Santos S, Moratalla R

Parkinson’s disease (PD) is a neurodegenerative disorder predominantly affecting the elderly. The aetiology of the disease is not known, but age and environmental factors play an important role. Although more than a dozen gene mutations associated with familial forms of Parkinson’s disease have been described, fewer than 10% of all cases can be explained by genetic abnormalities. The molecular basis of Parkinson’s disease is the loss of dopamine in the basal ganglia (caudate/putamen) due to the degeneration of dopaminergic neurons in the substantia nigra, which leads to the motor impairment characteristic of the disease. Methamphetamine is the second most widely used illicit drug in the world. In rodents, methamphetamine exposure damages dopaminergic neurons in the substantia nigra, resulting in a significant loss of dopamine in the striatum. Biochemical and neuroimaging studies in human methamphetamine users have shown decreased levels of dopamine and dopamine transporter as well as prominent microglial activation in the striatum and other areas of the brain, changes similar to those observed in PD patients. Consistent with these similarities, recent epidemiological studies have shown that methamphetamine users are almost twice as likely as non-users to develop PD, despite the fact that methamphetamine abuse and PD have distinct symptomatic profiles. HubMed – drug

Call-fleming syndrome (reversible cerebral artery vasoconstriction) and aneurysm associated with multiple recreational drug use.

Case Rep Neurol Med. 2013; 2013: 729162
Drazin D, Alexander MJ

Drug abuse represents a significant health issue. Evidence suggests that recreational drug use has a direct effect on the cerebral vasculature and is of greater concern in those with undiagnosed aneurysms or vascular malformations. The authors report a case of thunderclap headache with a negative head CT and equivocal lumbar puncture after a drug-fueled weekend. The patient underwent diagnostic cerebral angiogram which demonstrated multisegmental, distal areas of focal narrowing of the middle, anterior, posterior, and posterior inferior cerebral artery and an incidental aneurysm. It is often difficult to determine the exact origin of symptoms; thus we were left with a bit of a chicken or the egg debate, trying to decipher which part came first. Either the aneurysm ruptured with associated concomitant vasospasm or it is a case of Call-Fleming syndrome (reversible cerebral artery vasoconstriction) with an incidental aneurysm. The authors proposed their management and rationale of this complex case. HubMed – drug

The use of intravenous neostigmine in palliation of severe ileus.

Case Rep Gastrointest Med. 2013; 2013: 796739
Kasi PM

Neostigmine is a parasympathomimetic drug that acts as a reversible acetylcholinesterase inhibitor. Clinically it is used in patients with acute colonic pseudo-obstruction (ACPO or Ogilvie’s syndrome, which is a gastrointestinal motility disorder characterized by marked dilatation of the colon in the absence of mechanical obstruction), postoperative ileus, urinary retention, myasthenia gravis, and in anesthesia to reverse the effects of nondepolarizing muscle relaxants. Both bolus and infusion are noted to be effective and lead to prompt evacuation of flatus or stool with a reduction in abdominal distention on physical examination. Median duration is noted to be 4-30 minutes in some trials. Here we present our experience of using 2?mg of intravenous neostigmine to help relieve the severe abdominal distention and ileus in a patient with severe fecal impaction when all conservative measures had been futile. The most frequent side effect of the drug is abdominal pain/cramping, which was noted in our patient as well. Other complications include bradycardia which is very infrequently symptomatic to require atropine. Overall, the drug is a simple, safe, and effective strategy; and as pointed out in the previous studies, the drug appears to be underused in patients who do not have a true contraindication to its use. HubMed – drug

Comparative cytochrome p450 in vitro inhibition by atypical antipsychotic drugs.

ISRN Pharmacol. 2013; 2013: 792456
Gervasini G, Caballero MJ, Carrillo JA, Benitez J

The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC = 9.5? M), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1′-hydroxybufuralol (IC range, 3.5-25.5? M). Olanzapine inhibited CYP3A-catalyzed production of 1′, and 4′-hydroxymidazolam (IC = 14.65 and 42.20? M, resp.). In contrast, risperidone (IC = 20.7? M) and levomepromazine (IC = 30? M) showed selectivity towards the inhibition of midazolam 1′-hydroxylation reaction, and haloperidol did so towards 4′-hydroxylation (IC of 2.76? M). Thioridazine displayed a of 1.75? M and an inhibitory potency of 1.57 on CYP2D6, suggesting a potential to induce interactions. However, with this exception, and given the observed values, the potential of the assayed antipsychotics to produce clinically significant inhibitions of CYP450 isoforms seems limited. HubMed – drug