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Alprostadil is available as an intraurethral suppository and an injectable formulation purchase albendazole 400 mg online hiv infection timeline. In contrast to oral agents order generic albendazole on-line hiv infection rates by sexuality, alprostadil acts locally, which may reduce the occurrence of adverse effects. Mechanism of action Alprostadil causes smooth muscle relaxation by an unknown mechanism. As a result, protein kinase is activated, allowing trabecular smooth muscle relaxation and dilation of cavernosal arteries. Increased blood flow to the erection chamber compresses venous outflow, so that blood is entrapped and erection may occur. The onset of action of alprostadil is 5 to 10 minutes when given as a urethral suppository and 2 to 25 minutes when administered by injection. The resulting erection may last for 30 to 60 minutes, or longer, depending upon the particular patient. Adverse effects Since alprostadil is not systemically absorbed, adverse systemic effects are rare. Locally, adverse effects of alprostadil include penile pain, urethral pain, and testicular pain. Hematoma, ecchymosis, and rash are possible from alprostadil injection, although these adverse effects are also rare. Please refer to Chapter 7 for a discussion of α-blockers in the setting of hypertension. Mechanism of action α1A receptors are found in the prostate, α1B receptors are found in the prostate and vasculature, and α1D receptors are found in the vasculature. By blocking the α1A and α1B receptors in the prostate, the α-blockers cause prostatic smooth muscle relaxation, which leads to improved urine flow. Doxazosin, terazosin, and alfuzosin block α1A and α1B receptors, whereas tamsulosin and silodosin are more selective for the α1A receptor. Because doxazosin, terazosin, and alfuzosin block α1B receptors, these agents decrease peripheral vascular resistance and lower arterial blood pressure by causing relaxation of both arterial and venous smooth muscle. In contrast, tamsulosin and silodosin have less of an effect on blood pressure because they are more selective for the prostate-specific α1A receptor. When taken with food, the absorption of tamsulosin, alfuzosin, and silodosin is increased. Therefore, for best efficacy, these agents should be taken with food or after a meal, typically supper. Doxazosin, alfuzosin, tamsulosin, and silodosin are metabolized through the cytochrome P450 system. In general, the α-blockers have a half-life of 8 to 22 hours, with peak effects 1 to 4 hours after administration. Silodosin requires dosage adjustment in renal impairment and is contraindicated in patients with severe renal dysfunction. Adverse effects α-Blockers may cause dizziness, a lack of energy, nasal congestion, headache, drowsiness, and orthostatic hypotension. Because tamsulosin and silodosin are more selective for the α1A receptors found on the smooth muscle of the prostate, they have relatively minimal effects on blood pressure, although dizziness and orthostasis may occur. By blocking α receptors in the ejaculatory ducts and impairing smooth muscle contraction, inhibition of ejaculation and retrograde ejaculation have been reported. Several of these agents have a caution about “floppy iris syndrome,” a condition in which the iris billows in response to intraoperative eye surgery (ure 41. Because silodosin is a substrate for P-gp, drugs that inhibit P-gp, such as cyclosporine, may increase silodosin concentrations. In order for the 5-α reductase inhibitors to be effective, the prostate must be enlarged. Since it takes several months for 5-α reductase inhibitors to reduce the prostate size, it is appropriate to use these agents in combination with an α-blocker to provide relief of symptoms. Dutasteride and tamsulosin are available as a combination product for this indication. Pharmacokinetics Food does not affect the absorption of finasteride or dutasteride. The mean plasma elimination half-life of finasteride is 6 to 16 hours, while the terminal elimination half-life of dutasteride is 5 weeks once steady-state concentrations are achieved (which is typically after 6 months of therapy). Women who are pregnant or of childbearing age should not handle or ingest either agent, as this may lead to serious birth defects involving the genitalia in a male fetus. Avanafil has the quickest onset of action and may be taken 30 minutes before intercourse. Because of the α-blocking properties, terazosin commonly causes dizziness (this may be related to orthostatic hypotension). While most any drug may cause nausea and vomiting, terazosin is much more likely to cause dizziness. Terazosin must be taken with food, whereas tamsulosin can be taken on an empty stomach. Tamsulosin should be taken with food, while terazosin does not need to be taken with food. Because finasteride inhibits the conversion of testosterone to its active form, it may cause significant developmental defects in the male genitalia of a developing fetus. Unlike the α-blockers, the 5-α reductase inhibitors are not associated with hypotension. In addition to tamsulosin, he is also taking hydrochlorothiazide, testosterone, and vardenafil as needed before intercourse. Tamsulosin is appropriate in combination with a 5-α reductase inhibitor when the prostate is enlarged. Vardenafil is only prescribed as needed, and the two drugs do not have a pharmacokinetic interaction. Overview Anemia is defined as a below-normal plasma hemoglobin concentration resulting from a decreased number of circulating red blood cells or an abnormally low total hemoglobin content per unit of blood volume. General signs and symptoms of anemia include fatigue, palpitations, shortness of breath, pallor, dizziness, and insomnia. Anemia can be caused by chronic blood loss, bone marrow abnormalities, hemolysis, infections, malignancy, endocrine deficiencies, renal failure, and a number of other disease states. A large number of drugs cause toxic effects on blood cells, hemoglobin production, or erythropoietic organs, which, in turn, may cause anemia. Nutritional anemias are caused by dietary deficiencies of substances such as iron, folic acid, and vitamin B12 (cyanocobalamin) that are necessary for normal erythropoiesis. Individuals with a genetic predisposition to anemia, such as sickle cell disease, can benefit from pharmacologic treatment with actions beyond nutritional supplementation, such as hydroxyurea. Iron Iron is stored in the intestinal mucosal cells, liver, spleen, and bone marrow as ferritin (an iron–protein complex) and delivered to the marrow for hemoglobin production by transferrin, a transport protein. Iron deficiency, the most common nutritional deficiency, results from a negative iron balance due to depletion of iron stores and/or inadequate intake, such as acute or chronic blood loss, menstruating or pregnant women, or periods of accelerated growth in children. In addition to general signs and symptoms of anemia, iron deficiency anemia may cause pica (hunger for ice, dirt, paper, etc. Mechanism of action Supplementation with elemental iron corrects the iron deficiency.

This may be the result of an over‐vigorous logical purchase albendazole with a visa hiv infection impairs cell mediated immunity, but this is a debate between the definition of endometrial curettage affecting the basalis layer of the amenorrhoea and oligomenorrhoea cheap albendazole 400mg free shipping describe the hiv infection cycle. Women with sec­ endometrium or adhesions that may follow an episode ondary amenorrhoea must have a patent lower genital of endometritis. It is thought that oestrogen deficiency tract, an endometrium that is responsive to ovarian hor­ increases the risk of adhesion formation in breast­ mone stimulation and ovaries that have responded to feeding women who require a puerperal curettage for pituitary gonadotrophins. Typically, amenorrhoea is Secondary amenorrhoea is best classified according to not absolute, and it may be possible to induce a with­ its aetiological site of origin and can be subdivided into drawal bleed using a combined oestrogen/progestogen disorders of the hypothalamic–pituitary–ovarian–uter­ preparation. Intrauterine adhesions may be seen on an ine axis and generalized systemic disease. Alternatively, hysteroscopic inspec­ causes of secondary amenorrhoea are outlined in tion of the uterine cavity will confirm the diagnosis and Table 47. Following surgery, high‐ some women experience an intermittent return to men­ dose oral oestrogens are initially prescribed followed by ses, interspersed between variable periods of amenor­ a 3‐month course of cyclical progesterone/oestrogens. This occult ovarian failure, or contraceptive device for 2–3 months in order to prevent resistant ovary syndrome, is associated with the pres­ recurrence of adhesions. Pregnancies are sometimes Cervical stenosis achieved, although the ovaries are usually resistant to Cervical stenosis is an occasional cause of secondary exogenous gonadotrophins as they are to endogenous amenorrhoea. However, modern procedures, such as function rather than successes of treatment [23]. For women who are curettage of the uterus which inadvertently damages the predicted to develop ovarian failure as a result of steriliz­ endocervix. Ovarian causes of secondary amenorrhoea An alternative approach is the surgical removal of a Polycystic ovary syndrome whole ovary and transplantation of cryopreserved ovar­ See above. Live births have been achieved by all these methods, although Premature ovarian insufficiency the technology for oocyte cryopreservation is less effi­ Ovarian failure by definition is the cessation of periods cient than for embryo cryopreservation and ovarian tis­ accompanied by a raised gonadotrophin level prior to sue freezing is still in its infancy [23]. It may be particularly difficult cases go unrecognized, but estimates vary between 1 and for a young woman to accept the need to take oestrogen 5% of the female population. Adolescents who lose ovarian function soon after Younger women with premature loss of ovarian func­ menarche are often found to have a Turner mosaic tion have an increased risk of osteoporosis. However, orrhoea and the severity of the oestrogen deficiency the assay is expensive and not readily available in most rather than the underlying diagnosis, and was worse in units. It is therefore important to consider other autoim­ patients with primary amenorrhoea than in those with mune disorders and screen for autoantibodies to the thy­ secondary amenorrhoea. Approximately 5% of patients present with vis­ certain if the radiological improvement seen will actually ual field defects. The reason sellar extension and compression of the optic chiasma or for this is that even modern low‐dose combined oral invasion of the cavernous sinuses. The management of hyperprolactinaemia centres around the use of a dopamine agonist, of which bro­ Pituitary causes of secondary amenorrhoea mocriptine and cabergoline are the most widely used. Of Hyperprolactinaemia is the commonest pituitary cause course, if the hyperprolactinaemia is drug induced, stop­ of amenorrhoea. There are many causes of a mildly ele­ ping the relevant preparation should be commended. Serum ing pituitary adenoma or from a non‐functioning ‘dis­ prolactin concentrations must then be carefully moni­ connection’ tumour in the region of the hypothalamus or tored to ensure that they do not rise further. Most pituitary, which disrupts the inhibitory influence of patients show a fall in prolactin levels within a few days dopamine on prolactin secretion. Large non‐functioning of commencing bromocriptine therapy and a reduction tumours are usually associated with serum prolactin in tumour volume within 6 weeks. Longer‐term side effects include Raynaud’s phe­ prolactinaemia, the main symptoms are usually those of nomenon, constipation and psychiatric changes, espe­ oestrogen deficiency. Bromocriptine and cabergoline have been acterized by adequate oestrogenization, polycystic associated with pulmonary, retroperitoneal and pericar­ ovaries on ultrasound scan and a withdrawal bleed in dial fibrotic reactions and so echocardiography is recom­ response to a progestogen challenge test. Galactorrhoea mended before starting treatment in order to exclude may be found in up to one‐third of patients with hyper­ valvulopathy and this should be repeated after 3–6 prolactinaemia, although its appearance is correlated months and then annually, although young patients are neither with prolactin levels nor with the presence of a less at risk than older patients who may be prescribed 648 Menstruation (a) (b) (c) (d). The normal pituitary gland is hyperintense (bright) while the tumour is seen as a 4‐mm area of non‐enhancement (grey) in the right lobe of the pituitary, encroaching up to the right cavernous sinus. There is suprasellar extension with compression of the optic chiasm (small arrows). The tumour signal intensity on the T1 image and only part of the periphery of the tumour enhances. The carotid arteries have a low signal intensity (black arrows) due to the rapid flow within them and are deviated laterally and superiorly by the mass (C), which arises out of the pituitary fossa (P). If the serum prolactin is found to be elevated and the patient has a regular menstrual cycle, no treatment is Bromocriptine 2. Quinagolide 75–150 µg daily, at night Hypothalamic causes of secondary amenorrhoea Hypothalamic causes of amenorrhoea may be either pri­ higher doses for the management of Parkinson’s disease. Primary hypothalamic lesions the maintenance dose should be the lowest that reduces include craniopharyngiomas, germinomas, gliomas and prolactin to normal levels and is often lower than that dermoid cysts. Sheehan’s syndrome, the there is suprasellar extension of the tumour that has not result of profound and prolonged hypotension on the regressed during treatment with bromocriptine and a sensitive pituitary gland enlarged by pregnancy, may pregnancy is desired. It is essential to to resort to pituitary irradiation, which offers no advan­ assess the pituitary function fully in all these patients tages, and long‐term surveillance is required to detect and then instigate the appropriate replacement therapy. Furthermore, a chronic disease that leads bromocriptine therapy if there is continuing suprasellar to immobility, such as chronic obstructive airways dis­ expansion. These patients also require expert assessment ease, may increase the risk of amenorrhoea‐associated of their visual fields during pregnancy. Women 5–10 mm in diameter) together with a stroma of normal with chronic renal failure have a discordantly elevated density. Anorexia nervosa is at the extreme end of a spectrum Prolactin is also elevated in these women owing to failure of eating disorders and is invariably accompanied by of the normal inhibition by dopamine. Women with levels, thereby disrupting the normal feedback mecha­ anorexia nervosa should be managed in collaboration nisms. Metabolism of various hormones including tes­ with a psychiatrist, and it is essential to encourage weight tosterone are also liver‐dependent; both menstruation gain as the main therapy. Diabetes mellitus may result in functional hypotha­ significantly underweight patient is associated with a lamic–pituitary amenorrhoea. Furthermore, since three‐quarters of the underlying systemic problem and on preventing the cell divisions that occur during pregnancy do so dur­ complications of oestrogen deficiency. If fertility is ing the first trimester, it is essential that nutritional sta­ required, it is desirable to achieve maximal health and tus is optimized before conception. Weight can have profound effects on gonadotrophin Weight‐related amenorrhoea may also have profound regulation and release. Fat appears to before the normal age at which peak bone mass is be critical to a normally functioning hypothalamic– obtained (approximately 25 years) increases the likeli­ pituitary–gonadal axis. This level enables the extra‐ovarian cause of reduced reproductive ability, resulting in delayed aromatization of androgens to oestrogens and maintains pubertal growth and menarche in adolescents and infer­ appropriate feedback control of the hypothalamic–pitui­ tility in adults. Therefore, girls who are significantly conditions, has profound effects on fertility and fecun­ underweight prior to puberty may have primary amen­ dity.

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In response order albendazole visa infection cycle of hiv virus, Johnson & Johnson discount albendazole 400mg mastercard anti bullying viral video, the parent company for the contraceptive patch, provided research funds for three epidemiologic studies, comparing transdermal and oral contraception. The frst case-control study of nonfatal venous thrombosis used informa- tion derived from a very large database that records prescriptions and diag- noses longitudinally in managed health care plans. Sixty-eight cases of venous thrombosis and 266 controls were identifed and matched for year of birth and for the date of the thrombotic episode (thus providing comparable dates for exposure). A limitation of the study was the inabil- ity to confrm diagnoses in 100% of the cases through review of medical records (completed for 83% of the cases). A strength of the study was the thorough attempt to control for factors that infuence venous thrombosis. A strong point of both studies was a focus on new users, eliminating the problem known as attrition of susceptibles. Comparing new users, who are more likely to experience venous thrombosis, to old users would be com- paring two diferent groups of subjects. A postmarketing study compared the rate of venous thromboembolism in patch users and users of oral contraceptives containing levonorgestrel and 30 mg ethinyl estradiol. Comparing the two case-control studies, it is worth noting that the nega- tive report had about six times as many cases as the positive report, giving it more statistical power. Indeed, in the overall case-control analysis in the positive report, there were only 20 cases among transdermal users and 37 cases among oral contraceptive users, and the odds ratio of 2. Afer excluding cases and con- trols with high-risk factors, the odds ratio with 16 transdermal cases and 26 oral contraceptive cases achieved 2. Similarly, the cases in the postmarketing survey amounted to less than half of the number in the negative case-control study. At this point in time, it seems that if there is a diference in the risk of venous thrombosis comparing transdermal and oral contraception, the diference has to be very small. Bruni V, Pontello V, Luisi S, Petraglia binations of a nestorone progestogen/ F, An open-label, multicentre trial to ethinyl estradiol contraceptive vaginal evaluate the vaginal bleeding pattern of ring used on a bleeding-signaled regi- the combined contraceptive vaginal ring men, Contraception 72:46, 2005. Cagnacci A, Ferrari S, Tirelli A, Zanin lites of noregestimate in relation to its R, Volpe A, Route of administration of pharmacological properties, Contracep- contraceptives containing desogestrel/ tion 67:93, 2003. Szarewski A, High acceptability and sat- Group, Transdermal contraception: isfaction with NuvaRing use, Eur J Con- evaluation of three transdermal norel- tracept Reprod Health Care 7:31, 2002. Brucker C, Karck U, Merkle E, Cycle varied climates and conditions, Fertil control, tolerability, efficacy and accept- Steril 77(Suppl 2):S32, 2002. Veres S, Miller L, Burington B, A com- for the Ortho Evra™/Evra™ 008 Study parison between the vaginal ring and oral Group, Ortho Evra™/Evra™ versus oral contraceptives, Obstet Gynecol 104:555, contraceptives: follicular development 2004. Implantable, subdermal capsules that release proges- tins for several years are a response to this need. In many parts of the world, Jadelle has replaced the use of Norplant; however, Norplant is still used worldwide. Implanon difers from Norplant and Jadelle in many pivotal aspects, chiefy one rod instead of Norplant’s six capsules and Jadelle’s two rods, and a less androgenic progestin. Contraceptive implants are approved in more than 60 countries and used by approximately 11 million women. Because compliance does not require frequent resupply or instruction in use, as with oral contraception, the actual or typical use efec- tiveness is very close to the theoretical (lowest expected) efectiveness. Clinicians have a special responsibility to become skillful in the operations required to remove implants and to be available to women when those skills are required to terminate use. Disturbances of menstrual patterns and other side efects prompt many more questions from patients about these methods than about use of the familiar oral, intrauter- ine, and barrier contraceptives. It was approved in the United States in 1990, marketed in 1991, and withdrawn from the market in 2002. Norplant is a “sustained-release” system using silastic tubing permeable to steroid molecules to provide stable circulating levels of synthetic pro- gestin over years of use. The capsules are made of fexible, medical- grade silastic (polydimethylsiloxane and methylvinyl siloxane copolymer) tubing that is sealed shut with silastic medical adhesive (polydimethylsi- loxane). The six capsules contain a total of 216 mg levonorgestrel, which is very stable and remained unchanged in capsules examined afer more than 9 years of use. The thin, fexible Jadelle rods are wrapped in silastic tubing (the same material used by Norplant), 43 mm in length and 2. Whereas the levonorgestrel in Norplant is packed into the capsules in crystal form, the core of the Jadelle rod is a mixture of levonorgestrel and an elastic polymer (dimethylsiloxane/methylvinylsiloxane). Long-term clinical trials indicate that the performance and side efects are similar to Norplant, but removal is faster. In the discussion that follows, the more- studied product, Norplant, is ofen cited, but clinicians can assume that the fndings apply as well to Jadelle. Implanon is a single fexible rod, 4 cm long and 2 mm in diameter, that contains 68 mg of 3-keto desogestrel (etonogestrel, the active metabolite of desogestrel) dispersed in a core of ethylene vinyl acetate wrapped with Implant Contraception a 0. Side efects are similar to those with Norplant or Jadelle, except for less bleeding and a higher rate of amenorrhea with Implanon. Because multiple studies have failed to observe a signifcant impact on carbohydrate metabolism, implants, in our view, are particularly well suited for diabetic women. History of cardiovascular disease, including myocardial infarction, cerebral vascular accident, coronary artery disease, angina, or a previ- ous thromboembolic event. Concomitant use of medications that induce microsomal liver enzymes: Carbamazepine (Tegretol) Felbamate Lamotrigine Nevirapine Oxcarbazepine Phenobarbital Phenytoin (Dilantin) Primidone (Mysoline) Rifabutin Rifampicin (Rifampin) St. John’s wort Topiramate Vigabatrin Possibly valproic acid, ethosuximide, griseofulvin, and troglitazone We do not recommend the use of implants with any of the previously listed drugs because of a likely increased risk of pregnancy due to lower blood levels of the progestin. The progestin difuses from the implant into the surrounding tissues where it is absorbed by the circulatory system and distributed systemically, avoid- ing an initial high level in the circulation as with oral or injected steroids. Within 8 hours afer insertion of Implanon, plasma concentrations of etonogestrel are about 300 ng/mL, high enough to prevent ovulation. The 85 mg of hormone released by Norplant or the 100 mg released by Jadelle during the frst few months of use is about equiv- alent to the daily dose of levonorgestrel delivered by the progestin-only, minipill oral contraceptive, and 25% to 50% of the dose delivered by low- dose combined oral contraceptives. A Clinical Guide for Contraception Body weight afects the circulating levels of levonorgestrel; the greater the weight of the user, the lower the levonorgestrel concentrations at any time during Norplant or Jadelle use. The greatest decrease over time occurs in women weighing more than 70 kg (154 lb), but even for heavy women, the release rate is high enough to prevent pregnancy at least as reliably as oral contraceptives. In Implanon users, etonogestrel concentrations are afected very little by body weight, and failure rates did not increase with increasing body weight in the small numbers of overweight women in the clinical tri- als. Tere are three probable modes of action, which are similar to those attributed to the contracep- tive efect of the progestin-only minipills, but because daily dosing is not required, implants are more efective than oral methods. As determined by progesterone levels in many users over several years, approximately one third of all cycles in Norplant users are ovulatory. Implanon inhibits ovulation throughout a 3-year period, accounting for almost all of the contraceptive efect. The progestin suppresses the estradiol-induced cyclic maturation of the endometrium and eventually causes atrophy. Tese changes could prevent implantation should fertilization occur; however, no evidence of fertilization can be detected in Norplant users. Because this is a progestin-only method, it can be used by women who have contraindications for the use of estrogen-containing con- traceptives. The sustained release of low doses of progestin avoids the high initial dose delivered by injectables and the daily hormone surge associated with oral contraceptives.

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Because the kidney can lower potassium excretion to less than 25 mEq per day in response to potassium depletion buy generic albendazole canada hiv infection rates in african countries, decreased intake alone rarely causes hypokalemia albendazole 400mg amex antiviral genital herpes treatment, but it can enhance the severity of other causes of potassium depletion such as diuretic therapy. The transcellular hydrogen ion shifts accompanying metabolic and respiratory alkalosis obligate increased sequestration of potassium in cells. In general, this direct effect is relatively small because the plasma potassium concentration falls to less than 0. This phenomenon provides the rationale for the administration of sodium bicarbonate to treat the hyperkalemia of metabolic acidosis. Despite the fact that the direct effect of alkalemia is relatively small, hypokalemia is common in metabolic alkalosis. The major reason for this association is that the underlying cause (diuretics, vomiting, or hyperaldosteronism) leads to losses of both hydrogen and potassium ions. This effect is most prominent after the administration of insulin to patients with diabetic ketoacidosis or severe nonketotic hyperglycemia. The plasma potassium concentration can also be reduced in nondiabetic patients by a carbohydrate load. Thus, intravenous administration of potassium chloride in a dextrose-containing solution in an effort to correct hypokalemia can transiently further reduce the plasma potassium concentration and, possibly, lead to cardiac arrhythmias. As a result, transient hypokalemia can occur with stress-induced release of epinephrine, as in acute illness, coronary ischemia, theophylline intoxication, or alcohol withdrawal. This effect must be considered when diuretic therapy is used for the treatment of hypertension in patients receiving β-agonists for asthma or chronic lung disease. The hypokalemic response to epinephrine can be blocked by a nonselective β-blocker (such as propranolol), but a β1-selective agent (such as atenolol) offers no protection, at least at lower doses (<100 mg per day). Hypokalemic periodic paralysis is a rare disorder of uncertain cause characterized by potentially fatal episodes of muscle weakness or paralysis that can affect the respiratory muscles. Acute attacks—in which the sudden movement of potassium into the cells can lower the plasma potassium concentration to as low as 1. Hypokalemic periodic paralysis may be familial with autosomal dominant inheritance, or it may be acquired in patients (often, but not exclusively, Asian men) with thyrotoxicosis. Oral administration of 60 to 120 mEq of potassium chloride usually aborts acute attacks within 15 to 20 minutes. The presence of hypokalemia must be confirmed before therapy because potassium can worsen episodes caused by the normokalemic or hyperkalemic forms of periodic paralysis. Furthermore, excess potassium administration during an acute episode may lead to posttreatment hyperkalemia as potassium moves back out of the cells. An acute increase in hematopoietic cell production is associated with potassium uptake by the new cells and possible hypokalemia. This most often occurs after the administration of vitamin B12 or folic acid to treat a megaloblastic anemia or of granulocyte-macrophage colony-stimulating factor to treat neutropenia. This phenomenon has been described in patients with acute myeloid leukemia and a high white blood cell count. In these patients, the measured plasma potassium concentration may be less than 1 mEq per L (without symptoms) if the blood is allowed to stand at room temperature for a prolonged period before separation of the plasma from the cells. Accidental or induced hypothermia (as occurs during cardiac bypass) can accelerate potassium movement into the cells and lower the plasma potassium concentration to less than 3. In contrast, hyperkalemia in an individual with severe hypothermia usually signifies irreversible tissue necrosis. Barium sulfide, used in pesticides, radiologic imaging, and depilatory agents, has been reported to cause severe transient hypokalemia when ingested [35]. Loss of gastric or intestinal secretions from any cause (vomiting, diarrhea, laxatives, or tube drainage) is associated with potassium wasting and, possibly, hypokalemia. However, it should be emphasized that the concentration of potassium in gastric secretions is relatively low (5 to 10 mEq per L) and that the potassium depletion is primarily because of increased urinary losses. The metabolic alkalosis that results from loss of gastric secretions raises the plasma bicarbonate concentration and, therefore, the filtered bicarbonate load above its proximal tubular reabsorptive threshold. More sodium bicarbonate and water are thus delivered to the distal potassium secretory site in the presence of hypovolemia-induced aldosterone release. Secreted potassium combines with the negatively charged bicarbonate and is excreted in the final urine, leading to hypokalemia. The urinary potassium wasting seen with loss of gastric secretions is typically most prominent in the first few days; thereafter, proximal bicarbonate reabsorptive capacity increases, leading to a marked reduction in urinary sodium, bicarbonate, and potassium excretion. Urinary potassium excretion is mostly derived from potassium secretion in the distal nephron, particularly by the principal cells in the cortical collecting tubule. This process is primarily influenced by two factors: aldosterone and the distal delivery of sodium and water. The removal of cationic sodium makes the lumen relatively electronegative, thereby promoting passive potassium secretion from the tubular cell into the lumen through specific potassium channels in the luminal membrane. Any diuretic that acts proximal to the potassium secretory site, including carbonic anhydrase inhibitors and loop and thiazide diuretics, increases distal delivery and, via the induction of volume depletion, activates the renin–angiotensin–aldosterone system. Urinary potassium wasting is characteristic of any condition associated with primary hypersecretion of a mineralocorticoid, as occurs with an aldosterone-producing adrenal adenoma. Affected patients are usually hypertensive, and the differential diagnosis includes diuretic therapy (which may be surreptitious) in a patient with underlying hypertension and renovascular disease, in which increased secretion of renin leads to enhanced aldosterone release. The presence of nonreabsorbable anions in the filtrate draws increased amounts of sodium to the distal nephron where it is reabsorbed at the expense of potassium. Examples of nonreabsorbable anions include bicarbonate in vomiting-induced metabolic alkalosis, β-hydroxybutyrate in diabetic ketoacidosis, hippurate in toluene exposure (glue sniffing), and penicillin in patients receiving high-dose penicillin therapy. Both the resulting decrease in distal chloride delivery (limiting the ability of chloride reabsorption to dissipate the lumen-negative gradient) and the enhanced secretion of aldosterone promote potassium secretion. Increased urinary potassium losses can occur in several forms of metabolic acidosis by mechanisms similar to those already described. In diabetic ketoacidosis, for example, increased distal sodium and water delivery (because of the glucose-induced osmotic diuresis), hypovolemia-induced hyperaldosteronism, and β- hydroxybutyrate acting as a nonreabsorbable anion all can contribute to potassium wasting. In many cases, such as with diuretic therapy, vomiting, or diarrhea, there are concurrent potassium and magnesium losses. A direct effect of magnesium on tubular potassium transport is likely the mechanism by which hypomagnesemia promotes kaliuresis [37]. Diagnosis of concomitant hypomagnesemia is particularly important because the hypokalemia often cannot be corrected until the magnesium deficit is repaired. Occasionally, renal diseases associated with decreased proximal, loop, or distal sodium reabsorption can lead to hypokalemia via a mechanism similar to that induced by diuretics. This problem may arise in patients with Bartter’s syndrome or Gitelman’s syndrome, tubulointerstitial diseases, such as interstitial nephritis as a result of Sjögren’s syndrome or lupus, hypercalcemia, and tubular injury induced by lysozyme in patients with acute monocytic or myelomonocytic leukemia. Increased potassium uptake by the leukemic cells may also contribute to the fall in the plasma potassium concentration. In the presence of potassium depletion, healthy subjects can lower their urinary potassium concentration to 5 to 10 mEq per L.

By J. Spike. Slippery Rock University.