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Anxiety is height- Counseling and evaluation of the drug-exposed pregnant patient 15 ened because the mother frequently feels guilt purchase danazol 50mg fast delivery, believing she may have damaged her baby through some action of her own cheap danazol 50mg with visa. Cultural beliefs regarding the causes of congenital anomalies differ from scientific explanations generic 50mg danazol free shipping, placing blame on the mother. Other fac- tors, such as the patient’s educational background, socioeconomic status, and ethnic- specific folklore, may also pose an obstacle to communication during counseling. These influences come into play when counseling patients exposed to potential teratogens. Rapport with the patient is important, assuring confidentiality and establishing a basis for the patient’s trust. The counselor must convey to the patient his or her under- standing of the patient’s concerns, and explain that the purpose of the consultation is to deal directly with those concerns by ascertaining the magnitude of the risk for an adverse pregnancy outcome arising from the drug exposure. General principles of counseling Many patients are not satisfied with the counseling they receive for exposure to poten- tial teratogens during pregnancy. Dissatisfaction stems largely from two major issues that both cause patient anxiety. First, the physician is frequently unable to obtain ade- quate information to make meaningful statements regarding the medical risks of whether the pregnancy was adversely affected by the drug exposure. Second, most patients do not understand the difference between an embryo and a fetus. Consequently, patients may not be able to grasp the importance of the concept of ‘critical periods’ unless they have been given a proper briefing during the consultation. It is our policy to explain that there are two distinct phases involved in the growth of a baby, as shown in Fig. The first phase is the embryonic development, and it is dur- ing this period that the structure or architecture for the baby is laid down. Embryonic age should be differentiated from menstrual age, which is 2 weeks greater than embryonic age. Briefly, we explain to our patients that organs take shape and the body assumes the form it will have thereafter by day 58 postconception. All major structures, such as the heart, brain, liver, kidneys, and limbs, have formed by this time. Fetal development dur- ing the remainder of pregnancy, the second phase of development, is primarily devoted to the growth of these organs and structures, and to augmenting their function. It is through this heuristic approach to counseling that the patient understands that most congenital anomalies are caused by early exposures, often before the pregnancy was recognized. This component is included early in the consultation; patients then understand why certain questions are important and having such knowledge increases their cooperation and rapport. Preconceptional counseling Ideally, all counseling regarding drug or medication use during pregnancy should occur before conception, because the opportunity to prevent possible adverse effects is then optimal. Preconceptional counseling should include all the components of a consultation during the pregnancy, with one exception. Recommendations regarding medication or drug use during pregnancy will be prospective for a preventive purpose, and only med- ically indicated drugs and medications known to be safe will be recommended for con- tinued use while attempting to conceive. The concept of background risk for major congenital anom- alies should be explained in a manner tailored to the patient’s level of understanding. This concept is especially important because it conveys to the patient that, even if the drug exposure is harmless, no guarantee can be given that the fetus she carries will not have a congenital anomaly. Notwithstanding other risk factors, the risk for major con- genital anomalies is approximately 3. Other identified risks are generally considered to be additive to background risk. A usual component of counseling is the determination of exactly what drugs were taken, the dosage, the timing and duration of the exposure(s), the patient’s health history and present state of health.

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Pharmacology Topiramate appears to have several mechanisms by which it exerts its antiseizure effects discount 200mg danazol otc. First purchase danazol 100 mg otc, topiramate reduces currents through voltage-gated Na+ channels and may act on the inactivated state of these channels similarly to phenytoin order danazol 200 mg overnight delivery, thus reduc- ing the frequency of repetitive firing action potentials. Lastly, topiramate has been shown to function as a weak carbonic anhydrase inhibitor (70,71). This unique phenomenon may lead to nonlinear changes in serum concentration until red cell binding sites have become saturated. Topiramate dosage adjustments should be based upon therapeutic response as no defined therapeutic range has been established. Hepatic metabolism involves several pathways including hydroxylation, hydrolysis, and glucuronidation. These include fatigue, somnolence, dizzi- ness, ataxia, confusion, psychomotor retardation, and difficulty concentrating. Visual disturbances such as diplopia and blurred vision and acute closed-angle glaucoma have also been reported (74). Antiepileptic Drugs 109 Side effects related to carbonic anhydrase inhibition include paresthesias and neph- rolithiasis. This weight loss typically begins within the first 3 mo of therapy and peaks between 12 and 18 mo of use. Higher degrees of weight loss tend to occur in patients with higher pretreatment weight (70). Lastly, some users of topiramate report difficulty with word finding while talk- ing. This has been attributed to the effects on psychomotor function and is not a speci- fic effect on language or speech (74). No significant metabolic, hematologic, or hepatic effects have been attributed to the use of topiramate. Contraindications and Precautions Topiramate has demonstrated various teratogenic effects in animal models. Patients with impaired renal function may be at risk of toxicity due to accumula- tion of topiramate and should be monitored appropriately. Other potent enzyme inducing drugs such as phenytoin or phenobarbital may exhibit similar effects. It should also be noted that dose adjustments would be necessary upon discontinuation of an enzyme- inducing drug while continuing the topiramate (75). Chemistry Tiagabine is a nipecotic acid derivative synthesized by linking nipecotic acid to a lipophilic anchor compound. The addition of this anchor compound facilitates transfer of the nipecotic acid moiety across the blood–brain barrier. Tiagabine is sparingly solu- ble in water and practically insoluble in most organic solvents. Absorp- tion is linear with maximum plasma concentrations occurring between 45 and 90 min after administration in the fasting state and after a mean of 2. Though food may delay the absorption of tiagabine, the extent of absorption is unaf- fected. It is recommended by the manufacturer that tiagabine be administered with food to avoid side effects associated with high plasma concentrations (78,79). Though no therapeutic range for tiagabine has been established, because of the risk of drug interactions the manufacturer suggests that monitoring concentrations of tiagabine before and after the addition or discontinuation of interacting drugs may be useful (76). The half-life of tiagabine ranges from 5 to 8 hours in patients receiving monotherapy but may be reduced to 2–3 h in patients taking enzyme-inducing medications (80). This extended elimination may be due to enterohepatic recycling of tiagabine metabolites (80). Adverse Reactions Side effects that occur more commonly with tiagabine than placebo include dizzi- ness, asthenia, nervousness, tremor, diarrhea, and depression (Table 1). More severe side effects such as ataxia, confusion, and itching or rash have been reported although rarely and should resolve upon discontinuation of tiagabine (81).

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It is also valuable when there is dribbling of urine buy danazol 50mg amex, loss of control from paralysis of the sphincter purchase danazol 100 mg with mastercard, perhaps order danazol 100mg with amex, in the aged, where urinary incontinence is present, with severe coughs, lack of control when coughing or sneezing. Sometimes in severe cases of nocturnal eneuresis, it is accompanied with belladonna or rhus aromatica with good results. In old men with chronic prostatitis, with constant dribbling of the urine, this agent is valuable. It tones the muscular structure of the bladder and exercises a desirable influence over the mucous structures of the entire urinary apparatus. It also stimulates secretion within the tubules of the kidneys by its direct influence. Where there is irritability of the bladder from the presence of uric acid, or Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 436 other precipitates in the urine, or where there is chronic rheumatism or gout, the agent is serviceable. The agent is useful in urethral caruncle, and as a remedy for gleet, when granular urethritis is present. The remedy is valuable in the treatment of disorders of the mucous lining of the bronchial tubes. It is beneficial in ulcerative forms of sore throat, where the secretions are fetid in character. It may be inhaled in chronic bronchitis, bronchorrhea; bronchitis, with offensive discharge; chronic nasal catarrh. A number of cases of spermatorrhea have been cured since our previous report on this remedy. It is beneficial when the urine seems to burn or scald in the passing, when there is local soreness in the urethra or neck of the bladder, when the bladder tolerates but little urine at a time, and the patient must rise frequently during the night. Homeopathists give thuja where the rectum is diseased; where there is a slimy discharge streaked with blood with dark blotches on the adjoining tissues; where there is itching and constant inclination without power to expel feces; sharp sticking pains in the rectum. In cases of verucca on the genitalia or rectum, this agent is advantageously used, especially if preceded by a mild escharotic. In prolapsus of the rectum, especially in cases depending upon paralysis, this agent, may be diluted and injected. The injection of thuja into nevi that are of a non-pulsating character, or those not too venous in structure, has been recently practiced. One case was cured in three weeks, where the nevus looked like a ring worm, and was of a fiery red color. One physician cured a case of ulcerated stomach with thuja in four-drop doses, alternated with sub-nitrate of bismuth every two hours. Anything warm produced great Ellingwood’s American Materia Medica, Therapeutics and Pharmacognosy - Page 437 distress. Another physician advised the agent in pruritus, whether of the anus or vulva, especially when accompanied by fissures. Another physician reports a case of extreme prolapsus of the bowel in a child which he cured with a five per cent solution of thuja. A wet dressing was applied and a small quantity of the remedy was injected into the bowel. A greatly enlarged and relaxed uterus in a woman of fifty with severe metrorrhagia was treated with injections of thuja. A doctor reports the cure of a urinary fistula by giving two drops of thuja internally every four hours. The use of the oil of thuja in confluent smallpox given internally and applied externally was advised by Dr. Thuja will prove an excellent remedy for all forms of sore mouth, especially if combined with echinacea and a mild antiseptic astringent. Gibbs reports a case where a number of varicose enlargements about the ankle of an old washer woman broke down. He made a 50 per cent solution of thuja and applied it freely with bandages, covering the whole with roller bandages, and produced a cure.

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Vitamins Vitamin D Many vitamin D analogues have demonstrated effects on epidermal cells and fibroblasts and they have achieved quick acceptance in treatment of psoriasis buy 200mg danazol mastercard. As some of their properties resemble those of retinoids 100mg danazol for sale, modulation of epidermal differentiation is possible and should be investigated in photoaging danazol 200 mg visa. Vitamin C As with claims for retinol in cosmetic products, the claims made for topical vita- min C are still more cosmetic than documented pharmaceutical. Vitamin E Vitamin E is an antioxidant in many systems and has been proposed, studied, and promoted for a large number of diverse systemic and skin conditions (33). On a theoretical basis, the concept of utility of the antioxidant effect of vitamin E is appealing, but, although the literature is voluminous, it is not completely convincing of a pharmaceutical effect in most conditions including skin disease, photoprotection, or photoaging. A 10-day study by the same investigators claimed Photoaging 29 enhanced skin smoothness with topical vitamin E. In a pilot study, a 25% increase in skin thickness was noted, comprised of both epidermal and dermal contributions. Increased acid mu- copolysaccharides, improvement in elastic fiber quality, and increase in collagen density were also noted (35). A 22-week double-blind study confirmed utility of both 8% glycolic and 8% lactic acid in treatment of photodamaged skin in overall appearance and in specific parameters of mottled pigmentation, sallowness, and roughness (36). The beta-hydroxy acid, salicylic acid, has been studied for its effects on photodamage in a large number of women during a home-use trial versus a propri- etary glycolic acid cream and was observed to be superior on global improvement of appearance (37). Hydroquinones These agents, as weak depigmenting agents, may occasionally be of some utility in treatment of the epidermal pigmentary irregularities associated with pho- toaging. Higher concentrations, better delivery systems, and combination with other active products may enhance their utility in treatment of pigmentary abnor- malities related to photoaging. Minerals The legends surrounding Cleopatra, the ancient Queen of Eygypt, are numerous. Frequently referenced in advertising of cosmetics, she is said to have claimed the rights to the Dead Sea’s mineral ingredients and, most naturally, these ingredi- ents have claimed numerous cosmetic properties (39). Some contain a high concentration of divalent cations, magnesium, and calcium and a lower concentration of mono- 30 Cunningham valent cations sodium and potassium as well as miscellaneous other cations and anions. Zinc and selenium have been frequently studied in dermatological condi- tions, most often inconclusively for true pharmacological effect, but these and other minerals unquestionably play major roles in normal physiology of the mam- malian organism. Most notably, their vital roles as cofactors in enzymatic pro- cesses means that they cannot be completely dismissed in spite of sometimes extravagant marketing claims. Much confirmatory work is needed to fully sub- stantiate cosmeceutically oriented claims of skin penetration, restoration of mois- ture because of hydroscopic characteristics, and, importantly, actual participation as cofactors in enzymatic regulation activities in the metabolism of healthy or photoaged skin. Hyaluronic Acid Hyaluronic acid plays a key role in both epidermis and especially dermis. Its water-holding properties are well established and, more recently, its involvement in control of cell growth, membrane receptor function, and adhesion have been demonstrated. A progressive reduction in electron-dense granules of hyaluronic acid has been observed with increasing age (40). Furthermore, application of topical tretinoin to photoaged skin has been demonstrated to increase both epidermal and dermal hyaluronic acid theoretically increasing water-holding capacity and possibly facilitating other intercellular transports (42). Natural Cartilage Polysaccharides Vivida, an oral formulation containing 500 mg/day of purified natural polysac- charides from cartilage of marine fish was compared with a placebo in a study of 30 women aged 40 to 50 years with sun-damaged skin (44). No changes were noted in the placebo group, but in the Vivida group, after 90 days, the epidermal thickness increased from 0. Imedeen, a different commercial preparation of natural cartilage polysac- charides containing 380 mg of active substance was compared to Vivida 500 mg/ Photoaging 31 day in a second study of 30 women aged 40 to 60 years (45). Confirmation of these results in larger, controlled multicenter studies, as well as explanation of how an oral preparation of polysaccharides would survive the digestive system and reach the systemic circulation and, therefore, the skin, is needed. The substances and products described above are at least partially clinically substantiated as having a cosmeceutical action in photoaging and in many cases have a theoretical basis for action.

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