Natural Erectile Dysfunction Treatment
The analysis of the active components of ginseng using HPLC combined with UV or MS detection has been extensively studied. Harkey et al. analyzed 25 commercial ginseng products available in the USA for the presence of marker compounds using HPLC-MS-MS. They concluded that although all products were labeled correctly and marker compounds were found in all preparations, there were wide variations in the concentrations of marker products, suggesting poor quality control and standardization in manufacturing such products.44 Bonfill et al. described a reversed-phase HPLC assay for the simultaneous quantitative determination of several ginsenosides, Rb(1), Rb(2), Rc, Rg(1), Re and Rf, in ginseng products. Chromatographic separation can be achieved in less than 20 min using a diol column and UV detection at 203 nm.45 Another method employed HPLC combined with negative ion electrospray MS for determination of three ginsenosides Rb(1), Rc, and Re in six different samples of ginseng, including...
Summary (provided by applicant) Ginseng is an herb widely used by humans to treat lack of stamina, loss of appetite and cachexia, and impotence. In Asian medicine, ginseng is a common component in herbals used in treatment of cancer, including breast cancer. There is recent scientific evidence that ginseng and its ginsenoside components are effective in inhibiting breast cancer cell proliferation in vitro and tumor growth in vivo. Consequently, many patients may be taking ginseng supplements during treatment with standard chemotherapy and hormonal therapy regimens in an effort to enhance therapeutic results as well as ameliorate side effects of the cancer chemotherapeutic drugs. However, there is no information on how adjuvant ginseng use could influence the efficacy of the cancer therapeutic drugs. This R21 proposal will address the following questions. Will the adjuvant use of ginseng aid in or interfere with standard breast cancer chemo- or hormonal therapy Will adjuvant ginseng...
Promoted to improve vitality and well-being 200 mg PO daily. Ginsana 2 caps PO daily or 1 cap PO bid. Ginsana Sport 1 cap PO daily. Preliminary evidence of efficacy for erectile dysfunction. Efficacy unclear for improving physical or psychomotor performance, diabetes, herpes simplex infections, cognitive or immune function. American College of Obstetrics and Gynecologists and North American Menopause Society recommend against use for postmenopausal hot flashes. Not by prescription. 2- - GINSENG SIBERIAN (Eleutherococcus senticosus, Ci-wu-jia) Does not appear effective for improving athletic endurance, or chronic fatigue syndrome. May interfere with some digoxin assays. Not by prescription.
Asian Ginseng Root Processed (Cultivated Processed Red) Radix Ginseng Rubra Pinyin Hong shen, hong ren shen Red Asian ginseng is the prepared root of the yuan sheng, cultivated Asian ginseng (Panax ginseng) (PPRC 2000). It is prepared by steaming, which turns the root red. The root of red ginseng is anatomically identical to unprepared (white) Panax ginseng root except for the virtual absence of starch granules. Steam processing turns the starch granules into gelatinous masses that give the parenchyma cells a swollen appearance. Red ginseng is thought to have increased activity as an energizing tonic over the unprocessed roots.
The secondary xylem of P. ginseng consists mostly of parenchyma, whereas that of O. horridus consists primarily of fibers. Overall, the wood of O. horridus has a much denser and more regular appearance (compare photomicrographs of the root transverse section of each species). In addition, the secretory ducts of P. ginseng are considerably smaller in diameter (up to 120 im) compared to those of O. horridus (up to 200 m).
Approximately 10 of the adult male population in industrialized countries suffers from erectile dysfunction, provoked mainly by psychosocial stress. Erection is a complex physiological event characterized by vasodilation, increased blood vessel permeability and edema. PGEi has been identified as an important mediator in this process due to its vasodilative properties. Thus, it represents a target for therapeutic intervention. Recently, these findings have been clinically applied in the diagnosis and treatment of erectile dysfunction by means of intracavenous injection of PGEt (Alprostadil) 221 , Besides PGEi, other potent vasodilators acting via local prostaglandin modulation (papaverin and phentolamine) or combinations of these three drugs are in use 222 .
Indications pulmonary arterial hypertension erectile dysfunction (section 7.4.5) Cautions hypotension (avoid if systolic blood pressure below 90 mmHg) intravascular volume depletion left ventricular outflow obstruction cardiovascular disease autonomic dysfunction pulmonary veno-occlusive disease anatomical deformation of the penis, predisposition to priapism bleeding disorders or active peptic ulceration consider gradual withdrawal interactions Appendix 1 (sildenafil) Revatio (Pfizer) TA Tablets, f c, sildenafil (as citrate), 20 mg, net price 90-tab pack 373.50 Injection, sildenafil (as citrate), 800micrograms mL, net price 50-mL vial 45.28 Viagra (Pfizer) A D Section 7.4.5 (erectile dysfunction)
There are three main groups of ginseng that are classified based on their geographic origin (Hughes et al. 2004). These are Asian ginseng, American ginseng, and Siberian ginseng, with the pharmacologically active ingredient in ginseng being ginsenosides (Hughes et al. 2004, Leak 1999, Kaye et al. 2000). Asian and American ginsengs have been used to increase resistance to environmental stress, promote diuresis, stimulate the immune system, and aid digestion (Ng et al. 1987, Jellin et al. 2003). Further, while Asian ginseng has shown promise in improving cognition when combined with the herbal agent Ginkgo, American ginseng has been studied for its potential to stimulate human tumor necrosis factor-a (TNF-a) production in cultured human white blood cells (Jellin et al. 2003, Zhou and Kitts 2002). American ginseng may also possess hypoglycemic activity (Jie et al. 1984, Sotaniemi et al. 1995). Such effects have been observed in both normal and diabetic subjects and may be attributed to...
Dysfunction (section 7.4.5) Cautions hypotension (avoid if systolic blood pressure below 90 mmHg) aortic and mitral valve disease pericardial constriction congestive cardiomyopathy left ventricular dysfunction life-threatening arrhythmias coronary artery disease uncontrolled hypertension pulmonary veno-occlusive disease predisposition to priapism anatomical deformation of the penis hereditary degenerative retinal disorders interactions Appendix 1 (tadalafil) Contra-indications acute myocardial infarction in past 90 days history of non-arteritic anterior ischaemic optic neuropathy avoid concomitant use of nitrates Tablets, f c, tadalafil 20 mg (orange), net price 56-tab pack 491.22
It is not uncommon for large companies to suddenly establish a direction through serendipitous discoveries. Alexander Fleming discovered penicillin as a result of serendipity. Although many of the drugs that are in use today have been discovered in this way, it is a difficult route for the pharmaceutical industry to follow and breaks are few and far between. More recently, the discovery that the phosphodiesterase type 5 inhibitor (originally tested as antihypertensive agents) can be a good candidate for male erectile dysfunction has changed the focus of research at Pfizer, and as a result, at several other companies.
A number of syntheses targeting commercially available drugs have been reported, which demonstrate the utility and effectiveness of supported reagents for the rapid and efficient preparation of drug-like scaffolds. The introduction of Sildenafil45 4 for the treatment of male erectile dysfunction has been incredibly successful, resulting in it becoming one of the largest selling globally marketed prescription drugs.46 Sildenafil acts by inhibiting the phosphodiesterase enzyme PDE5, which is the main phosphodiesterase present in the smooth muscle of the corpus cavernosum. Upon sexual stimulus, nitric oxide is released from nerve terminals in the corpus cavernosum. The nitric oxide activates guanylate cyclase to produce cyclic guanosine monophosphate (cGMP), causing the intracellular levels of cGMP within the smooth muscle cells of the penis to increase. In healthy tissue, the elevated cGMP is returned to basal levels by the action of the PDE5 enzyme. Inhibition of the PDE5 enzyme...
Nitrovasodilators (see Chapter 31) produce vasodilation by NO-dependent elevation of cyclic GMP in vascular smooth muscle. The pharmacologic effects of sildenafil, tadalafil, and vardenafil result from inhibition of the type 5 cyclic nucleotide phosphodiesterase (PDE5) that hydrolyzes cyclic GMP to 5'GMP in the vasculature. Thus, coadministration of an NO donor (e.g., nitroglycerin) with a PDE5 inhibitor can cause potentially catastrophic hypotension.
The relation between prostate cancer risk and the occurrence of the aforementioned valine to leucine mutation at codon 89 in the SRD5A2 gene, a polymorphism that is associated with reduced 5a-reductase activity, was examined by Febbo et al. 175 and Lunn et al. 153 . Febbo et al. 175 , who conducted a nested case-control study using the Physician's Health Study cohort, found the valine-leucine and leucine-leucine genotypes in 50 of cases and 51 of controls and these were not associated with elevated prostate cancer risk as compared with the valine-valine genotype. Lunn et al. 153 confirmed these findings in a case-control study that employed prostate cancer patients from urology clinics in North Carolina. Controls, not matched to cases, were drawn from BPH and impotence patients from the same clinics. Most men were European American and 5-11 were African American. The valine-leucine and leucine-leucine genotypes were found in 56 of cases and 49 of controls and were not associated with...
Apomorphine is a drug used to treat impairments in motor function (tremor, slow movement, and difficulty walking and speaking) in Parkinson's patients. It is sometimes used for erectile dysfunction. In larger doses, it has emetic effects and was used in aversion therapies. It is a nonspecific dopamine agonist with actions at several subtypes of dopamine receptors, both presynaptic and postsynaptic. As a pharmacological tool for probing the function of dopamine receptors, it has been largely replaced by more selective substances. It does not have morphine-like effects and does not interact with opioid receptors.
Traditional herbal medicines encompass an extremely diverse group of preparations, and originate from many different cultures. Many herbal medicines have emerged from healing traditions around the world. Digitalis (from the dried leaf of Digitalis purpurea L.) and quinine (from the bark of the cinchona tree, Cinchonapubescens Vahl) are well-known examples of valuable therapeutic products of botanical origin. Some herbal products in current use in many parts of the world, such as ginseng (e.g., from Panax ginseng C.A. Mey) and valerian (e.g., from Valeriana officinalis L.), have long standing for their modest efficacy and few side-effects. Some, however, such as ephedra (e.g., from Ephedra sinica Stapf) have been imported from traditional healing systems and then used for indications (weight loss, athletic performance enhancement) never contemplated in the traditions from which they emerged.
Epi is used in many surgical procedures in the nose, throat, and larynx to shrink the mucosa and improve visualization by limiting hemorrhage. Simultaneous injection of Epi with local anesthetics retards the absorption of the anesthetic and increases the duration of anesthesia ( see Chapter 14). Injection of a agonists into the penis may be useful in reversing priapism, a complication of the use of a receptor antagonists or PDE5 inhibitors (e.g., sildenafil) in the treatment of erectile dysfunction. Both phenylephrine and oxymetazoline are efficacious vasoconstrictors when applied locally during sinus surgery.
SILDENAFIL (Revatio) Pulmonary arterial hypertension 20 mg PO tid. Contraindicated with nitrates. Coadministration is not recommended with ritonavir, potent CYP3A inhibitors, or other phosphodiesterase-5 inhibitors. Teach patients to seek medical attention for vision loss, hearing loss, or erections lasting longer than 4 h. Trade only (Revatio) Tabs 20 mg. LK 2B TADALAFIL (Adcirca) Pulmonary arterial hypertension 40 mg PO daily. Contraindicated with nitrates. Coadministration is not recommended with potent CYP3A inhibitors (itraconazole, ketoconazole), potent CYP3A inducers (rifampin), other phosphodiesterase-5 inhibitors. Caution with ritonavir, see PI for specific dose adjustments. Teach patients to seek medical attention for vision loss, hearing loss, or erections lasting longer than 4 h. Trade only (Adcirca) Tabs 20 mg. L 2B
Especially pertinent is the identification of significant persons in the patient's life and how the pain has influenced relationships with those persons. For example, pain patients and their significant others can experience loss in intimacy and sexual dissatisfaction because of the impact of pain on sexual functioning.
Nitric oxide activates heme-containing guanylate cyclase by forming an NO-heme complex (8). Elevations in 3',5'-cyclic guanosine monophosphate (cGMP) result in vascular smooth muscle and this increases cerebral blood flow (CBF) (43). However, cGMP-dependent mechanisms may only be operational in cells adjacent to those generating NO because intracellular calcium levels sufficient to activate NOS inhibit guanylate cyclase. Blood vessels may provide an example (8,44). Vasodilatory neuromediators like acetylcholine or bradykinin raise intracellular calcium and stimulate endothelial NOS activity to release NO from endothelial cells. NO, in turn, enhances cGMP synthesis in smooth muscle cells. Nitrovasodilators such as nitroglycerin, nitroprusside, or 3-morpholinosy-nonimine (SIN-1) raise cGMP in vascular smooth muscle by directly liberating or donating NO (8,45). Under physiological conditions guanylate cyclase is a key mediator of cerebral arterial relaxations to NO. Platelet inhibition,...
Controversy in the management of insomnia revolves around two issues pharmacological versus nonpharmacological treatment and the use of short-acting versus long-acting hypnotics. The side effects of hypnotic medications must be weighed against the sequelae of chronic insomnia, which include a fourfold increase in serious accidents. Two aspects of the management of insomnia traditionally have been underappreciated a search for specific medical causes and the use of nonpharmacological treatments. In addition to appropriate pharmacological treatment, management of insomnia should correct identifiable causes, address inadequate sleep hygiene, eliminate performance anxiety related to falling asleep, provide entrainment of the biological clock so that maximum sleepiness occurs at the hour of attempted sleep, and suppress the use of alcohol and OTC sleep medications.
Adequate control of anxiety in patients with anxiety disorders often produces adequate resolution of the accompanying insomnia. Sedative use in the anxiety disorders is decreasing because of a growing appreciation of the effectiveness of other agents, such as adrenergic receptor antagonists (see Chapter 10) for performance anxiety and serotonin reuptake inhibitors for obsessive-compulsive disorder and perhaps generalized anxiety disorder. The profound insomnia of patients with acute psychosis owing to schizophrenia or mania usually responds to dopamine-receptor antagonists (see Chapter 18) benzodiazepines, often used adjunctively in this situation to reduce agitation, will result in improved sleep.
Assessment of toxic effects of each drug. Decreased libido and impotence were associated with both drugs (carbamazepine 13 , phenytoin 11 ). Between carbamazepine and valproic acid, carbamazepine provides superior control of complex partial seizures. Overall, data demonstrate that carbamazepine and phenytoin are preferable for treatment of partial seizures, but phenobarbital and valproic acid are also efficacious. Control of secondarily generalized tonic-clonic seizures does not differ significantly with carbamazepine, phenobarbital, or phenytoin, and val-proic acid is as effective as carbamazepine. Since secondarily generalized tonic-clonic seizures usually coexist with partial seizures, these data indicate that among drugs introduced before 1990, carbamazepine and phenytoin are the first-line drugs here.
Codonopsis is one of the primary energy tonics used in traditional Chinese medicine. For this purpose it is specifically used to enhance digestive powers, is considered similar in activity to Panax ginseng, and is often used as a lower cost alternative to ginseng. According to the Chinese pharmacopoeia (2005), Radix Codonopsis may consist of the roots of Codonopsis pilosula (Franch.) Nannf. or Codonopsis tangshen Oliv.
It has been reported for many years that the stimulation of 5-HT2C receptors alters behaviors per se in rodents including penile erection, grooming, stereotypes, oral dyskinesia, decrease in impulsivity, locomotor activity and feeding behavior, and increase in anxiety (Jones and Blackburn 2002 Giorgetti and Tecott 2004 Millan et al. 2005). Interestingly, some authors, using new agonists, have reported that 5-HT2C receptors may also display anxiolytic antidepressant properties (Rosenzweig-Lipson et al. 2007), underscoring a possible existence of multiple and opposite behavioral outputs induced by 5-HT2C drugs of a similar pharmacological class. The stimulation of 5-HT2C receptors has also been shown to alter behaviors associated with perturbations of central DA transmission. In particular, 5-HT2C receptor stimulation decreases the effects on locomotor hyperactivity and self-administration associated with drugs of abuse (Grottick et al. 2000 Tomkins et al. 2002). However, 5-HT2C...
To this list must be added a number of herbs, the extracts of which have not yet been characterized but that look promising, These include Ganoderma lucidum spore oil, Ginkgo biloba, ginseng, green tea, huperzine, Nerium indicum flowers, panax, polygonum, stepholidine, and Tripterygium wilfordii hook 132 .
Severe zinc deficiency has been observed in experimental human zinc deple-tion,16 in adults and children on total parenteral nutrition solutions lacking zinc17,18 and in patients with acrodermatitis enteropathica - a rare autosomal recessive disorder of zinc uptake associated with mutations in an intestinal zinc transporter gene.19 The clinical manifestations of severe zinc deficiency in humans include slowing or cessation of growth and development, delayed sexual maturation and impotence, characteristic skin rashes, alopecia, chronic and severe diarrhea, immune system deficiencies, impaired wound healing, diminished appetite, impaired taste sensation, night blindness, corneal changes and behavioral disturbances.8,20 Although not a useful indicator of mild zinc deficiency, plasma zinc concentrations, which normally range from 75 to 120 mg dL (11.5-18.5 mmol L), have been found to fall below 70 mg dL with experimental zinc depletion.
We have become very interested in exploring this promising field that has great potential in providing effective protection against aging-and exercise- associated oxidative damage. Recently we conducted a study wherein antioxidant properties of North American Ginseng (Panax Quinquefolium.) were investigated in young and old rats fed a ginseng-supplemented diet for a period of 4 months (Fu and Ji, 2003). Female Fischer 344 rats at 4 or 22 months of age were randomly divided into three groups, fed either a AIN-93G formula-based control diet, or a diet containing 0.5 g kg (low-dose) or 2.5 g kg (high-dose) dry ginseng power for 4 months. Oxidant generation, measured with DCFH, was significantly lowered with ginseng feeding in the homogenates of heart, soleus, and DVL muscle in both young and old rats, and the effects were dose-dependent. SOD activity was elevated in heart, DVL and soleus muscle with high and low dose of ginseng feeding, respectively. Rats fed with high-dose ginseng diet...
Although dopamine has received little attention in biological research on depression, as compared with other monoamines such as serotonin and noradrenaline, current research on the dopaminergic system is about to change this situation. It is now well established that disturbances of mesolimbic and nigrostriatal DA function are involved in the pathophysiology of depression (Fibiger 1995 Brown and Gershon 1993). Moreover, stress promotes profound and complex alterations involving DA release, metabolism, and receptor densities in the mesolimbic system (Puglisi-Allegra et al. 1991 Cabib and Puglisi-Allegra 1996). It seems that exposure to unavoidable uncontrollable aversive experiences leads to inhibition of DA release in the mesoaccumbens DA system as well as impaired responding to rewarding and aversive stimuli. These alterations could elicit stress-induced expression and exacerbation of some depressive symptoms in humans (Cabib and Puglisi-Allegra 1996). Thus, in view of the hypothesis...
Impotence Gynecomastia, impotence structurally similar to diethylstilbestrol. A study in 1981 -1983 of 39 DAS workers reported low testosterone in 37 of men tested, as well as impotence 116 . A follow-up study found significantly reduced testosterone (both total and free) in both current and former DAS-exposed workers compared to unexposed controls 117 . Thus, it is clear that at the high levels present in the work place, a variety of EDCs have the capacity to alter significantly male reproductive function.
Fibric acid compounds usually are well tolerated. Side effects, most often Gl-related, may occur in 5-10 of patients but most often are not sufficient to cause drug discontinuation. Other infrequent side effects include rash, urticaria, hair loss, myalgias, fatigue, headache, impotence, and anemia. Minor increases in liver transaminases and alkaline phosphatase have been reported. Clofibrate, bezafibrate, and fenofibrate reportedly can potentiate the action of oral anticoagulants by displacing them from their binding sites on albumin thus, monitoring of the prothrombin time and reduction in anticoagulant dosage may be appropriate.
As discussed throughout this chapter, the cyclic nucleotide phosphodiesterases constitute a group of enzymes that catalyze the hydrolysis of various cyclic nucleotides including cAMP and cGMP. The contractility of all muscle types is regulated primarily by reversible phosphorylation of the protein myosin. The phosphorylation of myosin allows it to interact with actin, which results in muscle contraction. Through different mechanisms, cAMP and cGMP interfere with the ability of myosin to be phosporylated and or interact with actin. This, in turn, results in muscle relaxation. Agents that interfere with the degradation of the cyclic nucleotide have usefulness in treating hypertension, erectile dysfunction, etc. Phosphodiesterase type 5 (PDE5) is responsible for the catalytic hydrolysis of cGMP in the smooth muscle of the arteries in the penis and lungs. Inhibitors of this particular phos-phodiesterase have been shown to relax arteries in the penis, thus allowing the corpus cavernosum to...
Fucoidan, a sulfated polysaccharide isolated from the brown algae Fucus evanescens, stimulated phagocytic and bactericidic activity of murine peritoneal neutrophils 201 . Neutrophil phagocytosis was also activated by polysaccharides isolated from Panax ginseng (panaxanes) 164 , polysaccharides isolated from Lemna minor (lemnan) 202 , arabinogalactans from S. vulgaris 180 , a-1,4-d-galacturonan from Bergenia crassifolia (bergenan) 131 and polysaccharides purified from G. lucidum 203 .
While NO is often considered a cytotoxic compound, it can also function as an antioxidant in cells by its reaction with other radical molecules, thereby breaking the chain of free radical propagation (Wink et al., 1993 Halliwell et al., 1999). Several reports of NO as a protectant against senescence and oxidative stress in plants have appeared. In a variety of both climacteric and non-climacteric fruits and flowers, of vegetables and legume species, NO emission decreases with maturation and during senescence (Leshem and Haramaty, 1996 Leshem et al., 1998). Moreover, exogenous application of NO markedly delays senescence and maturation of these tissues (Leshem et al., 1998). NO is thought to delay senescence both by down-regulating ethylene emission and by acting as an antioxidant. NO can, therefore, be regarded as a naturally occurring plant growth effector. More recently, the same authors (Leshem et al., 1998) have shown that NO fumigation can be advantageously replaced, in the case...
The available, nonselective, 5-HT2C agonists elicit various alterations of motor responses including grooming, penile erection, hypolocomotor activity, forms of stereotypies, and purposeless oral movements. This latter response is interesting because it is observed at low doses of agonists and, at variance with some of the other behaviors evoked above, is only dependent on 5-HT2C receptors. Stewart and colleagues (1989) observed an increase in purposeless oral movements elicited by the nonselective 5-HT agonists mCPP and TFMPP (Stewart et al. 1989). The oral bouts consisted of vacuous chewing, jaw tremor, and tongue darting occurring without any physical object. The intensity of oral bouts induced by the 5-HT agonist was dose dependent and decreased when very high doses of mCPP were used
In triterpenoidal saponins, the aglycone is a triterpene. Most aglycones of triterpenoidal saponins are pentacyclic compounds derived from one of the three basic structural classes represented by a-amyrin, b-amyrin and lupeol. However, tetracyclic triterpenoidal aglycones are also found, e.g. ginseno-sides. These glycosides occur abundantly in many plants, e.g. liquorice and ginseng roots contain glycyrrhizinic acid derivatives and ginsenosides, respectively. Most crude drugs containing triterpenoid saponins are usually used as expectorants. Three major sources of triterpenoidal glycosides along with their uses are summarized below. Ginseng Panax ginseng
Finasteride (propecia) inhibits the type II isozyme of 5a-reductase, the enzyme that converts testosterone to dihydrotestosterone (see Chapter 58). The type II 5a-reductase is found in hair follicles. Balding areas of the scalp are associated with increased dihydrotesterone levels and smaller hair follicles than nonbalding areas. Orally administered finasteride (1 mg day) has been shown to variably increase hair growth in men over a 2-year period, increasing hair counts in the vertex and the frontal scalp. Finasteride is approved for use only in men. Pregnant women should not be exposed to the drug because of the potential for inducing genital abnormalities in male fetuses. Adverse effects of finasteride include decreased libido, erectile dysfunction, ejaculation disorder, and decreased ejaculate volume. Each of these occurs in
Estrogen replacement therapy (ERT) may positively affect sexual function in a number of ways. Estrogens rapidly restore the superficial cell layer of the vaginal epithelium, reestablish elasticity, restore the balance in vaginal pH, improve mood, and increase blood flow to enhance lubrication. Short-term studies of estrogen replacement therapy have confirmed a benefit in some postmenopausal women with sexual dysfunction. However, not all studies have demonstrated positive results, possibly because women most likely to respond are those with symptoms of hypoestrogenism. Any short-term positive effect of oral estrogen may diminish in long-term use because of increasing sex hormone binding globulin (SHBG) levels, which lead to reduced estrogen and androgen bioavail-ability, and consequent decreased desire and activity. The increase in SHBG appears to be less significant in women who use non-oral delivery system for ERT. Vaginal estrogen is highly effective for treating genitourinary...
Halbreich and Kahn 3 proposed that many of the clinical adverse consequences of HPRL could be accounted for by its effects on the HPG axis. HPRL is associated with suppression of gonadotropin pulsatile release, which in turn inhibits the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary leading to suppression of ovarian and testicular function in turn leading to hypogonadism 3, 27 . This potentially further led to a range of menstrual disorders, reduced fertility in both sexes, decreased sexual function in men and women including decreased libido, increased risk of cardiovascular disorders, galactorrhoea, anxiety and depression. Halbreich and Kahn 3 also postulated that adverse events such as an increased risk of breast cancer were possibly associated with HPRL. This hypothesis is supported by Harvey et al. 6 who identified that PRL has a direct action on breast tissue where it can act as a mitogen in the mammary gland. Furthermore, PRL...
In the United States, the issues of herbal purity and adulteration have been neglected for years. Because herbs are not regulated in the United States the same way they are in other countries, the pressure to ensure lot-to-lot standardization and to screen out plant adulterants has been less than optimal. Instances have been reported in the literature11 in which several bottles of an herb purchased in the same location possessed different concentrations of active ingredient. Ephedra and ginseng are notable examples. Another example is echinacea. This herb is occasionally adulterated with a plant that looks very similar to Echinacea angustifolia but has none of the activity of echinacea. Plant parts, insect parts, soil, etc. can all be adulterants. Fortunately, pressure on the herb-producing industry has caused a markedly increased effort to screen and standardize herbs for trade. Possibly, simple high-performance liquid chromatography (HPLC) methods could be used to verify the herb's...
Paimleaf Raspberry Fruit is the dried fruit of Rutin* chtngii Ilu (Fam. Rosaceae). Action To benefit the kidney, and arrest seminal discharge and excessive urination. Indications Enuresis, frequent urination. impotence, premature ejaculation, seminal emission and spermatorrhea in de-Jiiitmy syndrome of the kidney. Dosage 12g.
Salicylates may reduce the tubular secretion and decrease the diuretic efficacy of spironolactone, and spironolactone may alter the clearance of cardiac glycosides. Owing to its effects on other steroid receptors, spironolactone may cause gynecomastia, impotence, decreased libido, and menstrual irregularities. Spironolactone also may induce diarrhea, gastritis, gastric bleeding, and peptic ulcers (the drug is contraindicated in patients with peptic ulcers). CNS adverse effects include drowsiness, lethargy, ataxia, confusion, and headache. Spironolactone may cause rashes and, rarely, blood dyscrasias. Whether therapeutic doses of spironolactone can induce malignancies remains an open question. Strong inhibitors of CYP3A4 (see Chapter 3) may increase plasma levels of eplerenone such drugs should not be administered to patients taking eplerenone, and vice versa. Other than hyperkalemia and GI disorders, the rate of adverse events for eplerenone is similar to that of placebo.
Devil's club is native to North America and is abundant in old-growth forests of Oregon, Washington, and many parts of Canada and Alaska. Among Native Americans, it is considered a sacred and very powerful medicine both physically and ritualistically. It is a member of the ginseng Araliaceae family and is considered by many to have adaptogenic properties similar to Panax species plants, though substantiation for this is lacking.
Because of their adjuvant effects and additional bioactivities described above, as well as their low toxicity, botanical polysaccharides have been proposed to be ideal adjuvants for use in modern cancer therapy 299 . Indeed, Shin and co-workers 300 demonstrated a synergistic antitumour effect of polysaccharides isolated from Korean red ginseng (P. ginseng C.A. Meyer) and paclitaxel in mice transplanted with Sarcoma-180 tumour cells, resulting in increased life span of treated animals. The augmented antitumour effect of paclitaxel was proposed to be the result of the immunomodulating antitumour effect of the polysaccharide, which was shown to exhibit B-cell-specific mitogenic activity and also induced secretion of IL-6 by spleen cells 300 .
The definition of atypical drugs often includes low capacity to elevate prolactin levels. An increase in prolactin secretion, usually associated with treatment by typical antipsychotics, results in galactorrhea, menstrual changes in women, and impotence in men.20 Clozapine, olanzapine, sertindole, and quetiapine either produce transient increase or no elevation in prolactin levels and, therefore, can be considered atypical by this criterion.12 In contrast, sulpiride, amisulpiride, remox-ipride, and risperidone, while deemed atypical by the more narrow standard, produce dose-dependent elevation in prolactin secretion and, thus, should be classified as typical by this extended
NO plays a role in penile erection, in controlling blood clotting by inhibition of platelet aggregation, and in the immune response, wherein it is produced by macrophages. NO is a very reactive, shortlived species which is deactivated with a halflife of less than a minute.1
Erectile dysfunction is a frequently encountered problem whose risk factors parallel those of coronary artery disease. Thus, many men desiring therapy for erectile dysfunction already may be receiving antianginal therapy The phosphodiesterase 5 (PDE5) inhibitors sildenafil (viagra), tadalafil (cialis), and vardenafil (levitra) have been developed and widely used for therapy of erectile dysfunction. In the presence of a PDE5 inhibitor, nitrates cause profound increases in cyclic GMP and can dramatically reduce blood pressure. Thus, all three PDE5 inhibitors are contraindi-cated in patients taking organic nitrate vasodilators, as indicated by a black box warning on product labeling. In the event that patients develop significant hypotension following combined administration of PDE5 inhibitor and a nitrate, fluids and a adrenergic receptor agonists, if needed, should be used for support.
Ashwagandha is among the most highly regarded herbal tonifiers in ayurvedic herbalism. It is considered a tonic, nervine, and adaptogen. In modern research, it has been compared to Panax ginseng for its endurance-enhancing properties. Three primary chemotypes of ashwagandha are traded. Because only one chemotype was used for this characterization, the other chemotypes may differ microscopically from the sample used.
ADVERSE EFFECTS AND PRECAUTIONS Many patients experience annoying and even intolerable adverse effects with these drugs. Sedation and xerostomia are prominent. The latter may be accompanied by dry nasal mucosa, dry eyes, and parotid gland swelling and pain. Postural hypotension and erectile dysfunction are prominent in some patients. Clonidine may produce a lower incidence of dry mouth and sedation when given transdermally, perhaps because high peak concentrations are avoided. Less common CNS side effects include sleep disturbances with vivid dreams or nightmares, restlessness, and depression. Cardiac effects related to the sympatholytic action of these drugs include symptomatic bradycardia and sinus arrest in patients with dysfunction of the sinoatrial node and AV block in patients with AV nodal disease or in patients taking other drugs that depress AV conduction. Some 15-20 of patients who receive transdermal clonidine may develop contact dermatitis.
Eleuthero Root and Rhizome (Siberian Ginseng) Eleuthero, more commonly known as Siberian ginseng, is a member of the ginseng family Araliaceae and was once botanically classified as Acanthopanax or thorny ginseng. It continues to be cited as Acanthopanax throughout most of Asia. Like Panax species plants, eleuthero is used as an adaptogenic tonic and is one of the most widely researched adaptogens in the world. Eleuthero may be used interchangeably with a number of the other 34 species of Eleutherococcus (aka Acanthopanax e.g., E. gra-cilistylus syn. Acanthpanax gracilistylus pin yin wu jia pi) or adulterated with the potentially toxic Chinese silk vine (Periploca sepium). Analytical reviews suggest that the chemistry of a number of these species is similar and that roots of different species can be mixed in trade. A number of pharmacopoeial references (e.g., British Herbal Pharmacopoeia, 1996 European Pharmacopoeia, 2005 Pharmacopoeia of the People's Republic of China, 2005, and...
Howes et al. 28 investigated the relationship between sexual function and gonadal hormones. Although this study showed high rates of sexual dysfunction and high rates of hypogonadism (92 women and 28 men) there was no correlation between sexual function and gonadal hormones which indicated that this is not the main aetiological factor in these cases. Costa et al. 54 reported no differences in sexual function between patients treated with the atypical antipsychotic olanzapine and conventional antipsychotics but they did show differences in the rate of normalisation of hormone levels. This illustrates that sexual function is a complex multi-factorial activity controlled by many different neurotransmitters and not just PRL.
Several herbal supplements, including several Chinese medicines, have digoxin-like immu-noreactivity because some components have structural similarity to digoxin. Digoxin immunoassays available commercially may use either a monoclonal antibody specific to di-goxin or polyclonal antibodies. In general, assays that employ polyclonal antibodies against digoxin, such as the fluorescence polarization immunoassay (rabbit polyclonal antibody) and microparticle enzyme immunoassay (both marketed by Abbott Laboratories), are subject to more interference by Chinese medicines than other digoxin immunoassays based on monoclonal antibodies. Several Chinese medicines such as chan su, lu-shen-wan, danshen and Asian and Siberian ginseng interfere with various digoxin immunoassays.28-35 McRae reported a case where ingestion of Siberian ginseng was associated with an elevated digoxin level in a 74-year-old man. In this patient, the serum digoxin level had been maintained between 0.9 and 2.2 ng mL_1...
American Ginseng Root American ginseng has been a staple of North American herbalism for several hundred years. It was traditionally used by Native American tribes throughout the very broad growing range of the plant. Among the Cherokee, it was among the most highly regarded of medicinal plants. Economically, it has been an internationally traded commodity since the days of Daniel Boone. The majority of wild-harvested and cultivated American ginseng is exported to Asia, where it is as highly regarded as, and sometimes more highly regarded than, Asian Panax ginseng. There are three primary forms wild, grown in woods, and cultivated. Microscopically, the tissues of these forms are identical. For a comparison of the microscopy of American ginseng, tienchi ginseng (Panax pseudo ginseng), and Asian ginseng (P. ginseng), see the entry for Asian ginseng.
Previous studies have utilized nonselective treatments focused on enhancing 5-HT neurotransmission, such as L-tryptophan (Fletcher et al. 2004 McGregor et al. 1993) and fluoxetine (Carroll et al. 1990 Fletcher et al. 2004 Richardson and Roberts 1991), which were shown to reduce self-administration of cocaine and amphetamine. It was suggested that this occurred due to stimulation of 5-HT2C receptor in the VTA (Fletcher et al. 2004). However, nonselective treatments typically have more side effects. While the selective 5-HT2C agonist R0600175 inhibits the VTA dopamine pathway, R0600175 has also been shown to cause significant side effects in rats such as hypophagia, hypolocomotion, penile erection, motor functional suppression, and anxiety (Alves et al. 2004 Grottick et al. 2000 Higgins and Fletcher 2003 Wood 2003). Although PTEN inhibitors may reduce the dephosphorylation effects of PTEN on 5-HT2C receptor to suppress the rewarding effects of abused drugs, the role of PTEN as a tumor...
We lack medications to relieve suffering that are as effective as opioids in relieving pain. There is, however, an equally serious issue to face. The best medical approach to suffering is not always aggressive action. Although medicine prefers action and thrives on problem-solving, sometimes little or nothing can be done. Surgeon Sherwin B Nuland writes, The diagnosis of disease and the quest for overcoming it with his intellect are the challenges that motivate every specialist who is any good at what he does. He is fascinated with pathology. When faced by the certainty of his own impotence to treat it, the would-be healer too often turns away.''103 This is unfortunate, but not surprising. When medical practice becomes preeminently an arena of action, inaction is usually misinterpreted as failure. Yet sometimes suffering will run its terrible course regardless of any intervention. In such cases, there is great value in openly discussing the role of witness.
The first report ofCIDT dates back to 1846, when Dubrunfast uncovered the mutarotation of D-glucose 14c - In recent years, CIDT has been attracting much attention as a green technique and is used in several manufacturing processes for chiral drugs, such as the NK1 receptor antagonist aprepitant 14d and the PDE5 inhibitor tadalafil 14e (Figure 9.7). The CIDT-based process for aprepitant
Yohimbe bark is native to western Africa, where it was traditionally used as a sexual stimulant, primarily for men, and for the treatment of impotence. It is rich in the alkaloid yohimbine, which has been used for erectile dysfunction in medicine for more than 100 years.
Another example of a useful side effect comes from the Viagra development story. Viagra (trade name for sildenafil) was originally developed as a drug for hypertension. When the researchers discovered that the drug target was prevalent in vascular muscle walls, the project shifted the goal from a hypertension treatment to an angina treatment. When the drug entered human clinical trials, it became clear almost immediately that it was less effective than the existing nitroglycerin treatments. In the course of those initial clinical trials, the hospital staff noted that one side effect was an improvement in erectile dysfunction. This observation was taken seriously, and eventually lead to Viagra, which is now a blockbuster drug, meaning that sales have grossed over a billion dollars.
It is surprising to learn that occupational exposures to potential EDCs at effective concentrations apparently have not been eliminated from the workplace. A series of publications from about 1990 to 1996 presented documentation of sexual impotence in chemical factory workers exposed to a DES-like stilbene derivative. The National Institute of Occupation Safety and Health conducted two studies in response to complaints of impotence and decreased libido among male workers involved in the manufacture of 4,4'-diaminostilbene-2,2' -disulfonic acid (DAS), a key ingredient in the synthesis of dyes and fluorescent whitening agents. Both current and former workers had lower serum testosterone levels 63 and reduced libido 64 as compared to control workers. In addition, duration of employment was negatively correlated with testosterone levels. These studies replicated the observations reported by Quinn et al. 65 who reported low levels of serum testosterone and problems with impotence in male...
Citalopram is a selective serotonin reuptake inhibitor (SSRI). It is commonly used in the treatment of depression and some of the more severe anxiety disorders (e.g., obsessive-compulsive disorder, panic disorder, social anxiety disorder). As with other SSRIs, the most troublesome side effect of citalopram is sexual dysfunction (dysorgas-mia and erectile dysfunction) mild side effects include drowsiness, headache, and nausea. Escitalopram, the S-enantiomer of racemic citalopram, is also marketed as an antidepressant.
The chronic mild stress assay is commonly considered to be among the most predictive models of antidepressant action in the rat. The regimen of chronic unpredictable stress, which is essential to produce the anhedonic behavior on which the paradigm is based, also results in a 5-HT2C-mediated increase in penile erection (Berendsen and Broekkamp 1997). Isolation rearing in the rat has also been demonstrated to produce changes that can be likened to symptoms of depression specifically the model is characterized by increased behavioral and hormonal responses to stress. An increased responsiveness to metachlorophenylpiperazine (mCPP) on anxiety-like behavior and plasma corticosterone levels following isolation rearing suggests an increase in sensitivity of 5-HT2C receptors (Fone et al. 1996). These observations implicate 5-HT2C receptors in the mediation of the depression-like symptoms exhibited by these models, just as they are implicated in the changes brought about by the selective...
The 5-HT2C receptor has been implicated as a potential therapeutic target in a wide variety of conditions including obesity, anxiety, depression, obsessive-compulsive disorder, schizophrenia, migraine, and erectile dysfunction. The 5-HT2 receptor family currently accommodates three receptor subtypes, 5-HT2A, 5-HT2B and 5-HT2C receptors, which are similar in terms of their molecular structure, pharmacology, and signal transduction pathways. Because the binding properties of 5-HT toward the The involvement of 5-HT2C receptors in psychiatric disorders has been hypothesized based largely on pharmacological and clinical studies. A number of atypical and typical antipsychotic agents, including clozapine, loxapine, and chlorpromazine, have a relatively high affinity for 5-HT2C binding sites as well as 5-HT2A. Some conventional and atypical antidepressants (e.g., tricyclics, doxepin, mianserin, and trazodone) also exhibit a similar binding affinity (Canton et al. 1990, 1996 Roth and...
The starting point in the drug history is the documentation of current prescription drug use. It often is very helpful for patients to bring all current medications with them to the clinical encounter. Specific prompting is required to elicit the use of over-the-counter drugs and herbal supplements. Similarly, information about medications that are used only sporadically (e.g., sildenafil for erectile dysfunction) may not be volunteered. With cognitively impaired patients, it may be necessary to include caregivers and pharmacy records in the drug history process. Adverse reactions to drugs should be documented with specifics regarding severity. It is revealing to ask whether patients or their physicians have discontinued any medications in the past. A review of current drug profile and list of adverse effects are required for each patient encounter, both during hospital rounds and during outpatient visits, to maximize effectiveness and safety of treatment.
Whereas the chemical libraries of drug-like compounds can be readily screened to yield chemically novel compounds, the road to taking these leads to useful drugs remains a challenge. The off-patent and old drugs should not be shelved, as they offer a remarkable opportunity for newer uses for example, apomorphine, now used to treat nausea, finds a role in treating erectile dysfunction. These older drugs can be useful in generating genomic databases. Genomics involves sequencing of genomes and leads to the derivation of theoretical information from the analysis of such sequences with computational tools. In contrast, functional genomics defines the transcriptome and proteome status of a cell, tissue, or organism under a prescribed set of conditions. The term transcriptome describes the transcription (mRNA) profile, whereas proteome describes the translation (protein) complement derived from a genome, including post-translational modifications (PTM) of proteins. The proteome information...
After local exposure to vapors or aerosols or after their inhalation, ocular and respiratory effects generally appear first. Ocular manifestations include marked miosis, ocular pain, con-junctival congestion, diminished vision, ciliary spasm, and brow ache. With acute systemic absorption, miosis may not be evident due to sympathetic discharge in response to hypotension. In addition to rhinorrhea and hyperemia of the upper respiratory tract, respiratory effects include tightness in the chest and wheezing due to bronchoconstriction and increased bronchial secretion. GI symptoms occur earliest after ingestion and include anorexia, nausea and vomiting, abdominal cramps, and diarrhea. With percutaneous absorption of liquid, localized sweating and muscle fasciculations in the immediate vicinity are generally the earliest symptoms. Severe intoxication is manifested by extreme salivation, involuntary defecation and urination, sweating, lacrimation, penile erection, bradycardia, and...
A patent is a grant by the government of exclusive rights for a limited time with respect to a new and useful invention, rights to prevent others from making or selling the invention in a limited territory as defined by the patent-issuing authority. A patent is not a right to sell the invention. The word patent means open, and the words, letter patent, mean an announcement made to all that the inventor has been awarded rights to the invention. Open here means without having to break any seal, as was the custom in the decrees issued in the past by the sovereign governments. Note that letters patent are not restricted to inventions, as even today these are issued to appoint judges in the United Kingdom. Historically, patents were issued on elaborate stationary, as they still are to some extent. The point about the rights to exercise an invention, vis-a-vis to prevent others from practicing, needs further elaboration. The new chemical entity patent for sildenafil citrate expired in March...
Yohimbine readily enters the CNS, where it acts to increase blood pressure and heart rate it also enhances motor activity and produces tremors. Yohimbine also is an antagonist of 5-HT. In the past, yohimbine was used to treat male sexual dysfunction, although efficacy never was clearly demonstrated yohimbine also may be useful for diabetic neuropathy and in the treatment of postural hypotension.
Examination reveals myelin loss with relative axonal preservation.103 HIV is not always found in diseased tissues. MRI changes in the spinal cord include atrophy with diffuse, intramedullary, non-enhancing lesions on T2-weighted imaging. One study of nine patients showed that L-methionine, 3 g twice a day for 6 months, may result in improved strength and bladder and sexual function, and in improved somatosensory evoked potential changes.104
Fatigue, poor memory, hallucinations, anorexia, impotence and muscular pain in the lower extremities. This is followed by speech disorders, clumsiness in movements and loss of facial expressions. Finally, muscular rigidity, staggering gait and tremor of the upper limbs occur.26 The affinity of manganese to the basal ganglia in the brain suggests that this mineral might have a role in the pathogenesis of hepatic encephalopathy.27 Another effect of prolonged exposure might be impotence, as sperm motility and sperm counts were reduced in mice given high manganese doses.28
Fluoxetine is a selective serotonin reuptake inhibitor (SSRI). One of the earliest of these drugs to be developed, it is widely perceived in the popular culture to be paradigmatic of the class. It is commonly used in the treatment of depression and the more severe anxiety disorders (e.g., obsessive-compulsive disorder, panic disorder). Fluoxetine is also approved for the treatment of bulimia nervosa, anorexia nervosa, and premenstrual dysphoric disorder. A distinguishing pharmacokinetic feature of the drug is its long elimination half-life (up to 4-6 days during long-term use and up to 2 weeks for the major active metabolite norfluoxetine). As with other SSRIs, the most common troublesome side effect of fluoxetine is sexual dysfunction (dysorgasmia and erectile dysfunction) mild side effects include drowsiness, headache, and nausea. Some patients develop a syndrome of psychomotor activation upon starting the drug, which has been characterized as similar to akathisia.
Treating the target symptom (e.g., ondansetron for nausea, lorazepam for insomnia). More troublesome and persistent are sexual adverse effects, including anorgasmia, decreased libido, ejaculation disturbances, and erectile dysfunction. Transient adverse effects are likely the result of acute stimulation of postsynaptic serotonin receptors however, efforts to link these symptoms to specific receptor subtypes are speculative. Table 8 lists common adverse effects associated with SSRIs, and options for clinical management. increases, sildenafil (Viagra), or change to another antidepressant, bupropion
Consider again the 3 ' ,5 ' -cyclicGMP phosphodiesterase inhibitor sildenafil, the structure of which is shown below. Sildenafil's absolute bioavailability of 40 and its mean steady-state volume of distribution of 105 L are consistent with its general distribution into nearly all tissues. Sildenafil's molecular weight of 474.2 is clearly below the 500-Da molecular-mass limit indicated in Lupinski's Property-1. Its logi0 P value of 6.1 for the neutral species, which satisfies Property-2, is consistent with the pendant lipophilic groups (e.g., methyl-, ethyl-, propyl-, phenyl- groups). As regards Property-3, the following speculative drawing of the hydrated structure suggests there are likely to be a greater number of solvent hydrogen bonds as well as an intramolecular H-bond (hydrogen shown in blue), the latter likely to reduce the rate of sildenafil's transmembrane adsorption
Until 1882,5 several drugs were monographed and described in the United States Pharmacopoeia (USP). Ginseng, for example, was clearly characterized as a drug and could be labeled and described to patients as such. Today, the Food and Drug Administration (FDA) calls ginseng, legally, a food for beverage use. Outside the United States, it is common to find ginseng recommended for many different medical conditions.6 At the time of the 1882 USP and into the early 1900s, pharmacists were well trained in the use, preparation, and dispensing of herbals and could advise patients on their herbal selection. This is not always the case today.
Proteins, cardiovascular agents, describe the role various chemical entities play in controlling cardiovascular diseases. This chapter describes the agents used in the treatment of angina, cardiac arrhythmias, hypertension, erectile dysfunction, hyperlipidemias, and disorders of blood coagulation. For pharmacists to be good practitioners, it is necessary that they understand the pathophysiology of cardiovascular diseases and the agents used to treat these syndromes.
Cocaine Cocaine, molecular weight C17H2iNO4, is a white crystalline tropane alkaloid found mainly in coca plant. It is a potent central nervous system (CNS) stimulant and appetite suppressant. For its euphoretic effect, cocaine is often used recreationally, and it is one of the most common drugs of abuse and addiction. Cocaine is also used as a topical anaesthetic in eye, throat and nose surgery. Possession, cultivation and distribution of cocaine is illegal for non-medicinal and non-government sanctioned purposes virtually all over the world. The side-effects of cocaine include twitching, paranoia and impotence, which usually increase with frequent usage. With excessive dosage it produces hallucinations, paranoid delusions, tachycardia, itching and formication. Cocaine overdose leads to tachyarrhythmias and elevated blood pressure, and can be fatal.
The toxic effects of busulfan are related to its myelosuppressive properties prolonged throm-bocytopenia may occur. Occasional patients experience nausea, vomiting, and diarrhea. Long-term use leads to impotence, sterility, amenorrhea, and fetal malformation. Rarely, patients develop asthenia and hypotension. High-dose busulfan causes VOD of the liver in up to 10 of patients, as well as seizures, hemorrhagic cystitis, alopecia, and cataracts. The coincidence of VOD and hepatotoxicity is increased by its coadministration with drugs that inhibit CYPs, including imidazoles and metronidazole, possibly by inhibition of the clearance of busulfan and or its toxic metabolites.
Among the plants known by humans since ancient times, the hemp Cannabis sativa has been widely used both for therapeutic, ritual, and recreational purposes. According to Chinese legend, the emperor Sheng Nung discovered the medicinal properties of three plants ephedra, ginseng, and cannabis. The Chinese pharmacopoeia already described, in 200 B.C., the beneficial effects of cannabis for human health as well as the psychotropic properties of abuse. However, the isolation of the psychoactive ingredient of the plant, A9-tetrahydrocannabinol abbreviated here as THC, and
Of metastatic or progressive prostate cancer at a usual initial dose of 10-16 mg kg daily in 3 or 4 divided doses. Following oral administration, at least 75 of a dose of estramustine is absorbed from the GI tract and rapidly dephosphorylated. Estramustine is found in the body mainly as its oxidized 17-keto analog isomer, estromustine both forms accumulate in the prostate. Some hydrolysis of the carbamate linkage occurs in the liver, releasing estradiol, estrone, and the normustine group. Estramustine and estromustine have plasma t1 2 of 10-20 hours, respectively, and are excreted with their metabolites, mainly in the feces. In addition to myelosuppression, estramustine also possesses estrogenic side effects (gynecomastia, impotence, and elevated risk of thrombosis, and fluid retention) and is associated with hypercalcemia, acute attacks of porphyria, impaired glucose tolerance, and hypersensitivity reactions including angioedema.
Typically, data derived from clinical studies estimate sexual disability attributed to SRIs to be less than 20 , whereas in clinical practice the incidence appears to be significantly higher, perhaps as high as 40 . This side effect clearly has an adverse effect on medication adherence, partly because discussion of sexual issues is difficult for patients and clinicians alike. Although all SRIs and venlafaxine have been associated with male and female sexual dysfunction, there is a prevailing view among clinicians that this side effect might be more problematic with paroxetine, although few controlled data are available to address this issue. In a comparison study of 200 subjects treated with paroxetine, fluoxetine, fluvoxamine, or sertraline, paroxetine treatment was associated with higher rates of anorgasmia or difficulty with ejaculation and impotence in both men and women (Montejo-Gonzalez et al. 1997). Significant differences among the four drugs were not noted with respect to...
Phytopharmaceuticals in cancer chemoprevention 308 20.4.3 GINSENG Ginseng is the most thoroughly studied plant with the longest history of traditional use for cancer and other ailments.82 The Asian variety called Panax ginseng is the center of ginseng research and the most sought after herb in Chinese medicine. In Chinese tradition, ginseng is considered as a tonic that gives vital energy to the body. Its usage in Western medicine was picked up after scientists described ginseng as an adaptogen, something that normalizes bodily functions.83 Ginseng sales peaked during the 1990s. Ginsenosides are a major group of saponins in ginseng other constituents include eleutherosides, phenolics, flavonoids, polyacetylenic compounds, alkaloids and polysaccharides, etc. The proponents of ginseng considered it to be one of the promising agents for cancer treatment.84 It exhibited anticarcinogenesis in animal models.85 In a case control study of 1987 pairs of human patients from Korea Cancer Center...
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