Hypertension: Focus on Olmesartan Medoxomil

Hypertension is the leading cause of stroke, heart failure, and ischemic heart disease. One of the key regulators of blood pressure is the renin-angiotensin aldosterone system (RAAS). Olmesartan medoxomil, an angiotensin receptor blocker (ARB), counteracts some of the primary effects of the RAAS by selectively and irreversibly binding to the type 1 angiotensin II receptor (AT1-R). The pharmacokinetic profile of this ARB allows for the convenience of one a day dosing. The pharmacodynamic profile of olmesartan is favorable because it is neither metabolized by, induces, nor inhibits the CYP450 isozyme system. The metabolism of the prodrug to the active form occurs in the gut by the enzyme arylesterase. No further metabolism and a lack of interaction with the CYP450 isozyme system leads to very few drug interactions with olmesartan medoxomil. Numerous studies have been conducted to evaluate the efficacy, safety, and tolerability of olmesartan medoxomil. Studies have been conducted to compare olmesartan medoxomil to other angiotensin receptor blockers. The efficacy of olmesartan medoxomil has been compared to other classes of antihypertensive agents. Results of all trials have proven non-inferiority of olmesartan medoxomil to other antihypertensive agents; some studies have shown superior blood pressure control provided by olmesartan medoxomil when starting dosages are evaluated. Overall, olmesartan medoxomil has the potential to facilitate the achievement of blood pressure goals, enhance compliance with a once daily dosing regimen, and is associated with minimal side effects. Olmesartan medoxomil has been proven to be a safe and effective antihypertensive drug when compared to other ARBs and other antihypertensive agents.

Antidepressant Drug Interactions

Second-generation antidepressants are more selective in their pharmacological mechanisms and offer fewer side effects and a safer toxicological profile than cyclic antidepressants and monoamine oxidase inhibitors. While the risk for pharmacodynamic interactions is more limited than with older agents with broader receptor effects, the risks for pharmacokinetic interactions is greater. The capacity of selective serotonin reuptake inhibitors to inhibit the metabolic activity of cytochrome P450 isozyme system has spurred over a decade of intense psychopharmacological and pharmacogenetics research to better the understanding of the significance of these interactions. Clinicians have had to increase their knowledge and understanding of drug interaction potential to better manage patients receiving these newer antidepressants. The following is a review of both pharmacodynamic and pharmacokinetic drug-drug interactions with antidepressants.

Pharmacological treatment strategies in mood, panic and obsessive compulsive disorders

SummarySince the introduction of the monoamine oxydase inhibitors and the first tricyclic antidepressant (TCA) imipramine in the late fifties, the treatment of depressive disorders has been changed dramatically. Althought a great variety of antidepressants such as TCA's, selective serotoninte-re-uptake inhibitors (SSRI's) mianserin, trazodone, mirtazapine, moclobemide and venlafaxine has become available, the exact mode of action is not revealed as yet, and classification should be done according to the interference of antidepressants with central monoaminergic processes.As to the potential of causing interactions, special attention has to be given to the SSRI's because of their interference with the CYP450 isozyme system. Therapeutic monotoring is recommended for the TCA's. The choiseforan antidepressant should be based on various factors like symptomatology and severity of the depression, potential interactions and somatic and/or psychiatric comorbidity.Extensive clinical research has demonstrated that TCA's are the most effective for major depression with melancholia (vital depression) and depressive disorders in the elderly.

Pollen Parent Effect on the Selective Abscission of `Mauritius' and `Floridian' Lychee Fruitlets

Fruit produced by adjacent blocks of `Mauritius' and `Floridian' lychee (Litchi chinensis Sonn.) were sampled at four different stages of development and the embryos were analyzed for pollen parentage by phosphoglucose isomerase (PGI; EC 5.3.1.9) isozyme system. Hybrid percentage increased significantly from ≈5 weeks after fruit set to maturity as follows: from 29.5% to 76.3% in `Mauritius' and from 74.2% to 92.5% in `Floridian'. These findings clearly indicate selective abscission of selfed fruitlets. In `Mauritius', yield was not related to the distance from the pollenizer block or hybrid percentage. In `Floridian', yield of trees adjacent to the `Mauritius' pollenizer was higher by 36% than that of trees at a distance of 24 m. The correlation between `Flordian' yield and hybrid percentage tended toward significance (r= 0.64, P = 0.08). In addition, in both cultivars, fruit and seed weights were affected by the pollen parent: outcrossed fruit were heavier and contained heavier seeds than selfed ones.

Pharmacogenetics of Agents Acting on the Central Nervous System

This article will review the various agents affecting the central nervous system (CNS) such as the analgesics, antidepressants, anticonvulsants, antipsychotics, and benzodiazepines. Most of the research in pharmacogenetics with the CNS agents have been conducted in the antidepressants. The cytochrome 450 IID6 isozyme system has been shown to influence the disposition of the antidepressants and antipsychotics. Amitriptyline metabolism to nortriptyline and nortriptyline conversion to its 10-OH metabolite were shown to be influenced by the IID6 isozyme. Interestingly, imipramine metabolism to desipramine is only partially related to the IID6 isozyme. Biotransformation of imipramine to its 2-OH metabolite was shown to be affected by the IID6 isozyme, but its metabolism to the 10-OH remains to be investigated. Of the antipsychotic drugs, haloperidol and thioridazine are two agents most studied. Haloperidol is converted to a reduced metabolite via a ketone reductase enzyme. The reduced metabolite is oxidized back to Haloperidol. This oxidation pathway was reported to be affected by the IID6 isozyme. Thioridazine metabolism to mesoridazine and conversion of codeine to morphine appear to be also influenced by CP-450 IID6. Other 450 isozymes are reported to be involved with other CNS agents.

DETERMINATION OF THE POLLEN PARENT AND ITS EFFECT ON LYCHEE FRUIT CHARACTERISTICS BY ISOZYMIC ANALYSIS.

Fruits produced in two commercial lychee (litchi chinensis Sonn.) orchards consisting of adjacent blocks of `Floridian' and `Mauritius' were analyzed for pollen parentage by phosphoglucose isomerase (PGI) isozyme system. 'Mauritius' and `Floridian' were found to possess distinguishable homozygous isozyme phenotypes in PGI, thus allowing the unequivocal identification of their progenies as originating from self- or cross-pollination. The rates of hybrids produced in the two orchards were 69% and 87% for `Floridian' and 17% and 65% for `Mauritius'. In both cvs a significant correlation was found between pollen parent and the weights of fruits and seeds. Fruits originating from cross-pollination were heavier and contained heavier seeds than selfed fruits. The most pronounced effect of the pollen parent on seed weight was found in `Floridian, which appears to exhibit inbreeding depression.

Developmental expression of the creatine kinase isozyme system of Xenopus: maternally derived CK-IV isoform persists far beyond the degradation of its maternal mRNA and into the zygotic expression period

The differential expression of the multilocus CK isozyme system throughout development of the two Xenopus species X. laevis and X. borealis was investigated. A cDNA containing the nearly complete coding sequence of the CK-IV subunit of X. laevis was isolated and sequenced. Early development of X. laevis proceeds with a stock of maternally derived CK-IV/IV isozyme. While the mRNA declines rapidly after fertilization and disappears before neurulation, maternal CK-IV/IV isozyme is active far beyond the onset of zygotic expression and is still detectable when tadpoles start feeding. Zygotic expression of CK-IV begins after neurulation, at stage 22/24, and seems to start simultaneously with that of another gene, CK-III. Modulation in the expression of these two genes and the appearance of two other isoforms, the CK-I and CK-II/III isozymes, take place during development in a tissue-specific manner. During metamorphosis, the CK phenotypes of eyes and skeletal musculature undergo additional changes. The final adult pattern only appears several weeks after metamorphosis. The presumed orthologous CK isozymes of X. borealis show a developmental profile similar to that of X. laevis, except that CK-II/II is equally present in oocytes and during early development, in addition to CK-IV/IV isozyme. These results show that the expression of each of the four CK genes of Xenopus is under differential developmental control.