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The physiology, mechanism of action, therapeutic use, effectiveness, potential risks, and noncontraceptive benefits of combination oral contraceptives (OCs) are reviewed with a discussion of patient considerations and management guidelines for common side effects. Modifications of the earlier combined (OCs) have both a lower estrogen and progestogen content. The contraceptive effects of estrogenic agents are related to modifications in ovulation, ovum transport, and implantation. The progestational agents act mainly by inhibiting ovulation and creating a hostile uterine environment. Biphasic and triphasic combined OCs are designed to deliver the hormones, throughout the menstrual cycle, in varying amounts that are similar to the natural physiologic quantities. Hte combined OC is the most effective method of birth control available with the exception of sterilization. If the low dose combined OCs are taken at approximately the same time each day, they are as effective as 50 mcg of estrogen in preventing pregnancy with a theoretical failure rate of less than .5/100 woman years. 3 longterm cohort studies of the risks of combined OC use are described. Although the primary focus of early research was on the adverse effects of combined OCs related to estrogen content, recent studies indicate that there are some noncontraceptive benefits associated with the use of the low dose combined OCs. In addition, the effects of progestogen content have been more closely examined in association with cardiovascular disease and metabolic effects. Guidelines for managing breadthrough bleeding and spotting, absence of withdrawal bleeding, nausea and vomiting, weight change, depression, and headaches are presented. Recommendations to be given to women who are beginning a combined OC regimen for the 1st time are outlined. Low dose combined OC given at the appropriate dose can provide relatively safe and very effective contraception for many women.
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PMID:Current perspectives on combination oral contraceptives. 638 84

Nitrates are potent relaxers of vascular smooth muscle and act by dilating veins, arteries, and arterioles (especially at high doses). Their clinical effects have been considered to be dominantly related to peripheral actions: systemic venodilatation and a decrease in systemic vascular resistance, reducing the preload and afterload of the heart. Considerable experimental work confirms potent salutary effects on the coronary circulation. These drugs are readily absorbed across mucosal surfaces; they are available in multiple formulations, including sublingual, buccal, oral, and topical delivery systems. Nitrate administration should begin with low doses and increased to doses that are often higher than previously recommended until a specific clinical end point or limiting side effects occur. Organic nitrate esters are effective in the treatment of stable angina pectoris, unstable angina, coronary vasospastic syndromes, and in vasodilator therapy in severe congestive heart failure. The pathophysiology of these syndromes is reviewed with respect to the clinical actions of nitrates on the central and peripheral circulations. The side effects of nitrates include headache, dizziness, and nausea. Nitrate tolerance, a controversial subject, does not appear to be an important clinical problem. Using the guidelines presented in this review, nitrate therapy provides effective, inexpensive, well-tolerated therapy for many patients with cardiovascular disease.
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PMID:Nitroglycerin and long-acting nitrates in clinical practice. 640 16

With the primary objective of examining the practice of prescribing oral contraceptives (OCs), a questionnaire was sent to 180 general practitioners and 45 community health doctors involved in family planning. 6 case histories were listed and doctors were asked to report their prescribing practice in 36 different hypothetical situations. They could choose 1 of 3 options--to prescribe the combined pill, the progestogen-only pill, or not prescribe OCs. They were also asked about changes in their prescribing practice, the 3 OCs prescribed most often, when a progestogen-only would pill be prescribed in preference to the combined pill, and views on the role of others in prescribing OCs. Completed questionnaries were returned by 124 (69%) general practitioners and 45 (80%) of family planning doctors. All were least likely to prescribe OCs in cases of hypertension or family history of ischemic heart disease. Diabetes and headache were each seen as less of a contraindication, and few doctors saw either age or fibrocystic disease of the breast as increasing the risk. Within each case history, smoking emerged as the most important contraindication. Almost all doctors reported changes in their prescribing practice; these related to enhanced understanding of the risks of OCs and to the availability of newer preparations. The 3 most commonly used OCs were the 30 mcg estrogen preparations (low and high progestogen) and the progestogen-only pill. Nearly all the doctors replied that they would prescribe the progestogen-only pill but not the combined pill in certain circumstances, the most commonly cited being when the woman was over age 35, was breastfeeding, had risk factors for cardiovascular disease, or smoked. The 2 groups of doctors showed different attitudes towards the role of other staff in prescribing OCs. Although 2/3 of the general practitioner group felt that prescribing should be limited to doctors, this view was shared by only 1/4 of the family planning group.
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PMID:Prescribing of oral contraceptives in Oxfordshire. 688 88

Pituitary adenomas are frequently encountered, benign intracranial tumours. Clinically classified according to their capacity to produce and secrete hormones, pituitary tumours are diagnosed from the clinical manifestations and biochemical findings of specific pituitary hormone overproduction or of impaired pituitary function due to pressure on normal pituitary cells, the pituitary stalk or the hypothalamus. Additionally, the tumour may result in neurological manifestations due to its effect as an intracranial space-occupying lesion. Pituitary adenomas may present acutely with pituitary apoplexy after intrapituitary haemorrhage or infarction. The subsequent hypofunction of the pituitary with concomitant neurological sequelae of an expanding intracranial mass are often associated with excruciating headache, diplopia and visual field defects. Gradually developing neurological deficits or secondary endocrine failure over several years may precede the recognition of non-secretory tumours (30-40% of pituitary adenomas) as well as some of the hormone-producing adenomas, especially when they expand beyond the confines of the sella turcica. Asymptomatic masses occur in the pituitary in 5-27% of unselected autopsy series. About 10-20% of pituitaries imaged as part of a brain study contain lesions 'consistent with a pituitary adenoma', with about half being pituitary adenomas ('incidentalomas'). Many advocate screening such cases for a wide spectrum of pituitary function abnormalities. Clinical judgement should be utilized to determine the extent of the work-up and the frequency of follow-up. Acromegaly, a clinical syndrome caused by excess growth hormone secretion, accounts for one-sixth of resected pituitary tumours. This disorder leads to chronic progressive disability and a shortened life span, with approximately 50% of untreated acromegalic patients experiencing premature death. The prevalence of acromegaly has been estimated to range from 50 to 70 per million, with the age of diagnosis usually between the third and fifth decades. Conditions associated with acromegaly include glucose intolerance, diabetes mellitus, lipid abnormalities, cholelithiasis, goitre, and hyperthyroidism, respiratory complications, hypertension, cardiovascular disease, and calcium metabolism abnormalities. An association between acromegaly and cancer, especially of the colon, is now recognized. Epidemiological series have indicated that cancer of the colon, breast and other types of malignancy are a cause of death with increased frequency in acromegalics compared with expected rates. Hypopituitary symptoms secondary to the mass effect of macroadenomas in acromegalic patients are common. Among premenopausal women, menstrual irregularities and galactorrhoea have been reported in 40-70%, while more than half of the men complain of impotence and decreased libido.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical features and differential diagnosis of pituitary tumours with emphasis on acromegaly. 762 86

A total of 4676 patients and 1759 patients were treated with lisinopril and nifedipine respectively in a post-marketing surveillance study conducted in general practice in the UK. Patients were followed up for 12 months. Most of the lisinopril patients had hypertension, but a small number (180) had heart failure. Most of the nifedipine patients had uncomplicated hypertension, but some (22.57%) had other cardiovascular disease with or without hypertension. Lisinopril and nifedipine were equally effective in reducing blood pressure. During the study, 1.5% of hypertensive patients assigned to lisinopril died compared with 1.8% of patients assigned to nifedipine, and 15.1% of lisinopril patients compared with 19.7% of patients in the nifedipine group withdrew because of adverse events. Cough, malaise and fatigue, nausea and vomiting were more frequent causes of withdrawal from lisinopril than nifedipine. Conversely, headaches, pallor and flushing, oedema and palpitations caused more frequent withdrawals from nifedipine. Anaemia was more often encountered on nifedipine treatment than on lisinopril. In hypertensive patients, the frequency of first-dose hypotension was similar on both treatments. Serious events occurred in 0.8% and 0.5% of patients given lisinopril and nifedipine respectively. Lisinopril was well tolerated by heart failure patients: 16 patients (8.88%) died and an incidence of 4.44% of serious adverse events was reported, a pattern to be anticipated in such patients; dizziness, giddiness, dyspnoea, cough, nausea and vomiting were the most frequent causes of withdrawal; the incidence of first-dose hypotension was low (2.22%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Post-marketing surveillance of lisinopril in general practice in the UK. 811 50

Despite advances in the delivery of hemodialysis, significant dialytic morbidity persists. Sodium modeling in older adults has been shown to decrease some dialytic symptoms, but clear benefits in young patients without coexisting diabetes or advanced cardiovascular disease have not been shown. The effects of sodium modeling were evaluated in 16 adolescent and young adult hemodialysis patients (16 to 32 yr of age) treated with conventional hemodialysis for a median of 11.5 months. The 8-wk study was divided into four 2-wk blocks. During each block, one of three sodium programs or a constant (control) dialysate sodium of 138 mEq/L was used. During each sodium program, the initial dialysate sodium of 148 mEq/L was decreased by an exponential, linear, or step program to 138 mEq/L. Treatments with sodium modeling were significantly better than those with constant sodium dialysate. When all sodium programs were grouped and compared with constant dialysate sodium, the odds of improvement in dialytic cramps, headaches, and nausea were 1.8, 2.1, and 3.9, respectively (P < 0.05). Sodium modeling also significantly decreased the frequency of postdialysis hypotension and interdialytic fatigue, dizziness, and muscle cramping (P < 0.05). No differences were seen among the sodium protocols in the incidence of symptomatic hypotension, the amount of normal saline administered, the degree of hemo-concentration during treatments, or the decrease in serum osmolality. There was no increase in pretreatment or posttreatment serum sodium concentrations, interdialytic thirst, weight gain, or hypertension. Sodium modeling dramatically decreases both intradialytic and interdialytic morbidity in young hemodialysis patients. There was no increase in adverse events associated with sodium modeling.
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PMID:Sodium modeling ameliorates intradialytic and interdialytic symptoms in young hemodialysis patients. 830 46

Women with many medical conditions need to plan their families with special care. For such women, the risk of complications with particular contraceptive methods is increased. Women with severe hypertension, a previous myocardial infarction or venous thromboembolism, or cerebrovascular stroke have a significant risk of problems in pregnancy, and should avoid the combined pill. The combined pill may increase the risk of cardiovascular disease in patients with diabetes mellitus and may worsen the severity of migrainous headaches in susceptible patients. Women with active hepatitis should wait for liver function tests to normalise before becoming pregnant or starting the combined pill or injectable progestogen. Control of epilepsy may deteriorate with use of the combined pill; this is probably because of the risk of drug interactions. Similarly, contraceptive control may also fail in women receiving rifampicin (rifampin) concurrently with contraceptive steroids. Intrauterine contraceptive devices should not be used in women who have experienced previous episodes of pelvic inflammatory disease, or with previous malignancy of the genital tract until complete cure is likely. Other conditions which may appear, become more common or worsen when the combined pill is prescribed include hepatic adenoma, gall bladder disease, ulcerative colitis, alopecia, hirsutism and acne. Some of these conditions are potentially hazardous to the woman's health, in which case combined pill use should be stopped. If the condition is unchanged then the combined pill may sometimes be reintroduced with caution.
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PMID:Contraceptive choice for women with 'risk factors'. 848 Dec 14

The newer progestogens gestodene, desogestrel and norgestimate were developed in an attempt to produce agents with more selective progestational activity that would improve cycle control and minimise metabolic changes and adverse events while effectively preventing pregnancy. In clinical practice, gestodene is combined with ethinylestradiol in monophasic or triphasic combined oral contraceptive preparations. The drug has pharmacokinetic advantages over the other new progestogens in that it is active per se (the others are prodrugs) and has high bioavailability (approximately 100%). The ability of gestodene-containing oral contraceptives to inhibit ovulation is similar to that of preparations containing other progestogens although the required dosage is lower. In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism. The effects of gestodene preparations on coagulation parameters, like those of desogestrel and levonorgestrel, are balanced by changes in the fibrinolytic system. Although the impact of these changes on clinical cardiovascular end-points has not been determined, the altered lipid profile is not likely to have significant clinical relevance because of the predominantly thrombogenic nature of cardiovascular disease in oral contraceptive users. Pregnancy rates and Pearl Indices with gestodene-containing preparations are low and similar to those with preparations containing other progestogens. Most pregnancies are attributable to user failure. Cycle control appears to be better with gestodene preparations than with levonorgestrel preparations, and available data suggest that cycle control may also be better with monophasic gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate-containing preparations, and better with triphasic gestodene- than with triphasic levonorgestrel- or norgestimate-containing preparations. However, differences between the new progestogen-containing preparations need to be confirmed in further large-scale trials. The most common adverse events with gestodene/ethinylestradiol are headaches and breast tension; the incidence of short term adverse events, including acne, is similar to that with preparations containing other progestogens. Changes in blood pressure and bodyweight are negligible. There are no comparative data on the incidence of cardiovascular events with gestodene-containing and other combined preparations. While the risk of breast cancer appears to be increased with long term combined oral contraceptive use in certain patient subgroups, this risk needs to be balanced against the noncontraceptive benefits of these preparations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Gestodene. A review of its pharmacology, efficacy and tolerability in combined contraceptive preparations. 852 63

Sumatriptan, a 5-hydroxytryptamine1, (5-HT1) receptor agonist is an effective abortive agent for migraine headaches. A common side effect in 3% to 7.9% of patients is chest pain. Although most cases of chest pain are not thought to be of cardiac origin, its mechanism is not entirely understood. Rare examples of electrocardiogram changes consistent with transient ischemia have been reported. Isolated instances of angina, arrhythmia, myocardial infarction, and death have been temporally associated with sumatriptan administration. In most cases, it is unclear whether underlying cardiovascular disease existed or contributed to this adverse event. We report the history of a 56-year-old female patient with migraine who experienced a myocardial infarction shortly after using sumatriptan, despite having had a normal cardiovascular evaluation. As she had a normal cardiac catheterization after the event, we find it probable that sumatriptan induced coronary vasospasm and myocardial infarction.
Headache 1996 May
PMID:Vasospasm-induced myocardial infarction with sumatriptan. 868 77

The safety profile of alfuzosin, a selective alpha 1-adrenergic antagonist, was assessed in a total of 13,389 patients (mean age 66.9 +/- 8.5 years) with symptomatic benign prostatic hypertrophy in two open, noncontrolled, multicentre, post-marketing surveillance studies, both conducted in France. Alfuzosin was prescribed at the recommended dose of 2.5 mg t.i.d., according to the current labelling recommendations, for a 3-month period. Clinical safety was assessed using spontaneous reporting of adverse events leading to discontinuation of treatment. Overall, 89.7% of the patients completed the treatment period. Drop outs were recorded in 10.3% of patients: 3.7% for intolerance; 1.5% for resolution of urinary symptoms; 2.1% for lack of efficacy, and 3.0% for loss to follow-up, noncompliance, and miscellaneous reasons. Two thirds of the adverse events leading to discontinuation were vasodilatory and occurred in 2.7% of the patients: vertigo/dizziness (1.4%); malaise (0.6%); hypotension (0.4%), and headache (0.4%). Other adverse events (predominantly gastrointestinal disorders) were recorded in < 1.2% of the patients. Three quarters of the adverse events occurred during the first week of therapy. As expected, adverse events were more frequent in the elderly (aged over 75 years) and in patients taking cardiovascular drugs or with concomitant cardiovascular disease. Overall, alfuzosin was very well tolerated and the adverse event profile was consistent with the cumulative experience of the drug. No unexpected or serious adverse events considered to be related to alfuzosin were recorded. Particular care must be taken when prescribing for very elderly patients and/or those with concomitant cardiovascular disease for which they are receiving therapy.
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PMID:Safety profile of 3 months' therapy with alfuzosin in 13,389 patients suffering from benign prostatic hypertrophy. 882 87


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