Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.1.8 (cholinesterase)
 12,691 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously reported that the angiotensin system in the anterior hypothalamic area (AHA) is enhanced in spontaneously hypertensive rats (SHR) and that this enhancement is involved in hypertension in SHR. In addition, acetylcholine (ACh) release is increased in the rostral ventrolateral medulla (RVLM) of SHR, which has also been shown to be involved in hypertension in SHR. In this study, we examined whether the enhanced angiotensin system in the AHA of SHR is related to the increase in cholinergic inputs to the RVLM. Electrical stimulation in the AHA produced a pressor response and an increase in firing rate of RVLM barosensitive neurons. These responses were inhibited and enhanced by RVLM application of the muscarinic receptor antagonist scopolamine and the cholinesterase inhibitor physostigmine, respectively. AHA stimulation also produced release of ACh in the RVLM. Microinjections of angiotensin II and carbachol into the AHA produced pressor responses. The pressor response to angiotensin II was inhibited by scopolamine microinjected into the RVLM, although this produced no effect on the response to carbachol. In SHR, although not in Wistar-Kyoto rats, microinjection of losartan into the AHA inhibited pressor responses to physostigmine. However inhibition was not observed in response to the directly acting muscarinic receptor agonist carbachol, injected into the RVLM. These findings demonstrate that angiotensin receptor activation or electrical stimulation in the AHA produce a pressor response via an increase in ACh release in the RVLM. In addition, the present study suggests that the enhanced angiotensin system in the AHA of SHR increases cholinergic inputs to the RVLM, which leads to increases in blood pressure.
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PMID:Activation of hypothalamic angiotensin receptors produces pressor responses via cholinergic inputs to the rostral ventrolateral medulla in normotensive and hypertensive rats. 1238 57

The issue of drug-drug interactions is particularly relevant for geriatric patients with epilepsy because they are often treated with multiple medications for concurrent diseases such as cardiovascular disease and psychiatric disorders (e.g., dementia and depression). The antidepressants with the least potential for altering antiepileptic drug (AED) metabolism are citalopram, escitalopram, venlafaxine, duloxetine, and mirtazapine. The use of established AEDs with enzyme-inducing properties, such as carbamazepine, phenytoin, and phenobarbital, may be associated with reductions in the levels of drugs such as donepezil, galantamine, and particularly warfarin. Carbamazepine, phenytoin, and phenobarbital have been reported to decrease prothrombin time in patients taking oral anticoagulants, although with phenytoin, an increase in prothrombin time has also been reported. Drugs associated with increased risk of bleeding in patients taking oral anticoagulants include selective serotonin reuptake inhibitors (especially fluoxetine), gemfibrozil, fluvastatin, and lovastatin. Other drugs affected by enzyme inducers include cytochrome P450 3A4 substrates, such as calcium channel blockers (e.g., nimodipine, nilvadipine, nisoldipine, and felodipine) and the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors atorvastatin, lovastatin, and simvastatin. Although there have been no reports of AEDs altering ticlopidine metabolism, ticlopidine coadministration can result in carbamazepine and phenytoin toxicity. Also, there is a significant risk of elevated levels of carbamazepine when diltiazem and verapamil are administered. In addition, there are case reports of phenytoin toxicity when administered with diltiazem. Drugs with a lower potential for metabolic drug interactions include (1) cholinesterase inhibitors (although the theoretical possibility of a reduction in donepezil and galantamine levels by enzyme-inducing AEDs should be considered) and the N-methyl-D-aspartate receptor antagonist memantine and (2) antihypertensives such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, hydrophilic beta-blockers, and thiazide diuretics. There is a moderate risk that enzyme-inducing AEDs will decrease levels of lipophilic beta-blockers. Newer AEDs have a lower potential for drug interactions. In particular, levetiracetam and gabapentin have not been reported to alter enzyme activity. In summary, there is a significant potential for drug interactions between AEDs and drugs commonly prescribed in geriatric patients with epilepsy.
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PMID:Risk and predictability of drug interactions in the elderly. 1743 28