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It is thus contraindicated in the elderly diction potential of the opioids while retaining the anal- patient and those with renal or liver disease cheap cialis super active 20mg line erectile dysfunction beat. The use erally attributed to an interaction at the - and to a of sedatives in combination with propoxyphene can be lesser extent the -opioid receptor purchase 20mg cialis super active amex erectile dysfunction caused by ptsd. In addition, the metabolism of the drug is in- Interaction at the -receptor increases the sedative creased in smokers due to induction of liver enzymes. The euphoric effects are due to in- Thus, smokers may require a higher dose of the drug for teraction with the -receptor. Propoxyphene enhances the effects of both chotomimetic side effects of the drugs are attributed to warfarin and carbamazepine and may increase the tox- interaction at the -receptor. Other con- duce excitatory effects related to the sympathetic dis- traindications are similar to those for morphine. Similarly, it is contraindicated in epileptic Pentazocine patients because it decreases seizure threshold. In addi- Pharmacological Effects tion, in head trauma patients, it can increase intracranial Pentazocine (Talwin) is a potent analgesic with an- pressure and brain injury. It incom- with psychoses is contraindicated because of its psy- pletely blocks the effects of morphine in such patients chotomimetic side effects. To eliminate abuse of the drug via IV administration, pentazocine is com- Drug Interactions bined with naloxone (Talwin-NX). IV administration of The combination of pentazocine with the antihista- Talwin-NX will produce no analgesic or euphoric ef- mine tripelennamine results in a combination known to fects because naloxone blocks the pentazocine moiety. This combination pro- However, the drug will retain its analgesic potency duces heroinlike subjective effects, and heroin addicts when administered orally, since naloxone is not active use it in the absence of heroin. Pentazocine produces as much respiratory de- pentazocine in combination with alcohol or barbitu- pression as morphine but does not produce the same rates greatly enhances its sedative and respiratory de- degree of constipation or the biliary constriction ob- pressant effects. Unlike morphine, penta- Tolerance and Dependence zocine increases heart rate and blood pressure by re- Tolerance to the analgesic effects of pentazocine de- leasing norepinephrine. The onset of action occurs within approxi- Butorphanol (Stadol) is chemically related to levor- mately 15 minutes, and the half-life is 2 to 3 hours. As an opioid antagonist it is nearly 30 times as thus has a high first-pass effect following oral administra- potent as pentazocine and has one-fortieth the potency tion; its half-life differs considerably from patient to pa- of naloxone. Its potency is 7 gation to glucuronides in the liver terminates the effects times that of morphine and 20 times that of pentazocine of pentazocine. It produces exci- Pentazocine is indicated for relief of moderate pain tatory effects and sedation and precipitates withdrawal in patients not receiving large doses of opioids. Although generally ad- used as premedication for anesthesia and as a supple- ministered parenterally because of its low bioavailabil- ment to surgical anesthesia. The nasal spray is Adverse Effects indicated for the relief of postoperative pain and mi- The most common side effect of pentazocine is se- graine headache. Nasal administration of butorphanol decreases the Respiratory depression and increased heart rate, body onset of action to 15 minutes and decreases the first- temperature, and blood pressure accompany overdose. Naloxone is effective in reducing the respiratory de- Generally the patient sprays a set dose of 1 mg per hour pression but requires the use of higher doses than for for 2 hours. The convenience of such administration is a major 326 IV DRUGS AFFECTING THE CENTRAL NERVOUS SYSTEM advantage to patients requiring repeat dosing. The morphinelike, it does reduce the craving for morphine abuse potential following such administration has not and for the stimulant cocaine. Thus, buprenorphine is a been extensively studied, although it is thought to be potential new therapy for the treatment of addiction to small. Adverse effects, contraindications, and drug interac- Dezocine tions are similar to those for pentazocine and morphine. The onset of Nalbuphine activity and potency as an analgesic are comparable to Nalbuphine (Nubain) is a mixed agonist–antagonist that those of morphine. Although the drug requires glu- is similar in structure to both the antagonist naloxone curonidation during metabolism, patients with hepatic and the agonist oxymorphone. As an an- fects (analgesia, respiratory depression, sedation, and so tagonist, dezocine is more potent than pentazocine. As on) are similar to those produced by pentazocine, nal- an agonist, dezocine produces analgesia and respiratory buphine produces fewer psychotomimetic effects.

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Also purchase cialis super active 20 mg mastercard erectile dysfunction dr. hornsby, hypokalemia Insulin glargine (Lantus) is a long-acting insulin can follow acute insulin administration order cialis super active 20mg erectile dysfunction protocol scam, an effect that is analogue that does not use zinc or protamine to modu- due to the stimulation of Na –K –ATPase (adenosine late insulin solubility. The introduction of two positive triphosphatase) with its resultant redistribution of K to arginine residues at the carboxy terminus of the -chain the intracellular compartment. A thin, ac- Injection of insulin glargine forms microprecipitates in tive type I diabetic will have very different insulin re- subcutaneous tissue as the pH is raised from 4 to phys- quirements from those of a sedentary, obese type II di- iological. Hence, it is not possible to provide a cookbook site of injection mimics the basal secretion of insulin approach for designing all diabetes regimens. Other considerations, such as work it is necessary to maintain its acidic pH prior to injec- schedule and mealtimes, are important in determining tion, insulin glargine must not be mixed with any other the way the insulin is divided proportionally to cover form of insulin during injection. Although there is quite a bit of variation, most diabetics have about half to two-thirds of their insulin as a long-acting Adverse Reactions to Insulin Therapy preparation, and the rest is usually delivered as a rapid- The most common side effect associated with insulin or short-acting insulin. In many cases, diabetics product is 75/25 insulin, which contains 75% protamine are aware that hypoglycemia is developing, and prompt lispro and 25% lispro insulin. While these combination glucose or intramuscular glucagon is required to reverse products may be convenient for some patients and can the hypoglycemia. Some is due to increased caloric storage of arately mixing their rapid- or short-acting insulin with glucose by insulin, and some is due to renal sodium re- an intermediate- or long-acting insulin to arrive at a ra- tention resulting in fluid retention and edema. The pumps Other complications arising from insulin therapy are provide a basal rate of insulin between meals and can uncommon. Sometimes, diabetics treated with exoge- be manually adjusted to facilitate glycemic control at 67 Insulin and Oral Drugs for Diabetes Mellitus 771 mealtimes. Pumps are usually worn 2 to 3 Although their structural similarities to the sulfon- days before the tubing and needle are changed. ORAL AGENTS FOR TREATING Mechanism of Action DIABETES MELLITUS The primary mechanism of action of the sulfonylureas is Although insulin has the disadvantage of having to be direct stimulation of insulin release from the pancreatic injected, it is without question the most uniformly ef- -cells. Some milder fonylureas enhance the release of endogenous insulin, forms of diabetes mellitus that do not respond to diet thereby reducing blood glucose levels. At higher doses, management or weight loss and exercise can be treated these drugs also decrease hepatic glucose production, with oral hypoglycemic agents. The success of oral hy- and the second-generation sulfonylureas may possess poglycemic drug therapy is usually based on a restora- additional extrapancreatic effects that increase insulin tion of normal blood glucose levels and the absence of sensitivity, though the clinical significance of these phar- glycosuria. Because these drugs do not have to the number of viable -cells in these forms of diabetes be injected, oral agents enhance compliance in type II is small. These classes of drugs are not generally used to the sulfonylureas, possibly because of the insulin re- in type I diabetes. The Sulfonylurea Receptor Sulfonylureas The sulfonylurea receptor was identified as an adeno- Sulfonylureas are the most widely prescribed drugs in sine triphosphate (ATP) sensitive potassium (KATP) the treatment of type II diabetes mellitus. Less common adverse re- the -cell triggers insulin granule fusion to the -cell actions include muscular weakness, ataxia, dizziness, membrane and insulin release. The intracellular levels mental confusion, skin rash, photosensitivity, blood of ATP and adenosine diphosphate (ADP) modulate dyscrasias, and cholestatic jaundice. Occasionally, per- the activity of the KATP channel, depending on the avail- sons who display drug sensitivities to sulfa-containing ability of glucose. The activity of the KATP channels is modulated by In this situation, a nonsulfonylurea insulin secretagogue the direct binding of sulfonylureas to a specific subunit can be used (if desired), such as repaglinide or nateglin- of the KATP channel called SUR1. Four SUR1 subunits form a complex with Since diabetic patients with renal or hepatic disease four subunits from the Kir 6. A decrease in alcohol tolerance also has been closure of these KATP channels, lowering the threshold observed in some patients taking sulfonylurea com- for glucose-dependent insulin release. Since sulfonylureas are highly bound to plasma rect vasodilator discussed in Chapter 20) also binds to proteins and are extensively metabolized by microso- SUR1 but keeps the KATP channels open, raising the mal enzymes, coadministration of drugs capable of dis- threshold for glucose-stimulated insulin secretion and placing them from their protein binding sites or inhibit- sometimes causing hyperglycemia in patients. Sulfonylureas are readily absorbed from the gastroin- testinal tract following oral administration but undergo varying degrees and rates of metabolism in the liver First-Generation Sulfonylureas and/or kidney; some metabolites possess intrinsic hy- The first-generation sulfonylureas are not frequently poglycemic activity. Thus, the biological half-lives of the used in the modern management of diabetes mellitus sulfonylureas vary greatly, and a comparison of the because of their relatively low specificity of action, de- drug half-life with the observed duration of action does lay in time of onset, occasional long duration of action, not always show a good correlation. They also tend to have their metabolites are excreted either renally or in the more adverse drug interactions than the second-gener- feces. They are occasionally used in pa- tients who have achieved previous adequate control Clinical Uses with these agents. Sulfonylureas are generally effective in individuals with Acetohexamide (Dymelor) is the only sulfonylurea with uricosuric activity, an action that may be of benefit mild to moderate type II diabetes.

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Once a hormone binds to a receptor on or in a target Anterior cell order cialis super active 20mg with visa erectile dysfunction 40s, it affects cell activities buy generic cialis super active 20 mg erectile dysfunction shots, regulating pituitary the manufacture of proteins, changing the permeability of the membrane, or affecting metabolic reactions. Hormone Chemistry Thyroid Stimulates gland Chemically, hormones fall into two main categories: High level of thyroid Inhibits hormones inhibits ◗ Amino acid compounds. The anterior pitu- All hormones except those of the ad- itary releases thyroid stimulating hormone (TSH) when the blood level of thyroid hor- renal cortex and the sex glands fall mones is low. This is a typical example of the kind of self- also includes information on the effects of hypersecretion regulating system that keeps hormone levels within a set (oversecretion) or hyposecretion (undersecretion) of a normal range. That is, they produce substances that act on other Chapter 1, and the release of some hormones in the men- tissues, usually at some distance from where they are strual cycle, as described in Chapter 23. Hormones The pituitary is often called the master gland because The remainder of this chapter deals with hormones and it releases hormones that affect the working of other the tissues that produce them. By this circulatory “detour,” Ovaries some of the blood that leaves the hy- Testes pothalamus travels to capillaries in the anterior pituitary before returning to the heart. For example, the 248 ✦ CHAPTER TWELVE Table 12•1 The Endocrine Glands and Their Hormones GLAND HORMONE PRINCIPAL FUNCTIONS Anterior pituitary GH (growth hormone) Promotes growth of all body tissues TSH (thyroid-stimulating hormone) Stimulates thyroid gland to produce thyroid hormones ACTH (adrenocorticotropic hormone) Stimulates adrenal cortex to produce cortical hor- mones; aids in protecting body in stress situations (injury, pain) PRL (prolactin) Stimulates secretion of milk by mammary glands FSH (follicle-stimulating hormone) Stimulates growth and hormone activity of ovarian follicles; stimulates growth of testes; promotes development of sperm cells LH (luteinizing hormone); ICSH (interstitial Causes development of corpus luteum at site of cell-stimulating hormone) in males ruptured ovarian follicle in female; stimulates secretion of testosterone in male Posterior pituitary ADH (antidiuretic hormone) Promotes reabsorption of water in kidney tubules; at high concentration stimulates constriction of blood vessels Oxytocin Causes contraction of uterine muscle; causes ejection of milk from mammary glands Thyroid Thyroxine (T4) and triiodothyronine(T3) Increases metabolic rate, influencing both physical and mental activities; required for normal growth Calcitonin Decreases calcium level in blood Parathyroids Parathyroid hormone (PTH) Regulates exchange of calcium between blood and bones; increases calcium level in blood Adrenal medulla Epinephrine and norephinephrine Increases blood pressure and heart rate; activates cells influenced by sympathetic nervous system plus many not affected by sympathetic nerves Adrenal cortex Cortisol (95% of glucocorticoids) Aids in metabolism of carbohydrates, proteins, and fats; active during stress Aldosterone (95% of mineralocorticoids) Aids in regulating electrolytes and water balance Sex hormones May influence secondary sexual characteristics Pancreatic islets Insulin Needed for transport of glucose into cells; required for cellular metabolism of foods, especially glucose; decreases blood sugar levels Glucagon Stimulates liver to release glucose, thereby increasing blood sugar levels Testes Testosterone Stimulates growth and development of sexual organs (testes, penis) plus development of secondary sexual characteristics, such as hair growth on body and face and deepening of voice; stimulates maturation of sperm cells Ovaries Estrogens (e. In- uretic hormone, or ADH, and oxytocin) are actually pro- hibiting hormones suppress both growth hormone, duced in the hypothalamus and stored in the posterior pi- which stimulates growth and metabolism, and prolactin, tuitary. THE ENDOCRINE SYSTEM: GLANDS AND HORMONES ✦ 249 Table 12•2 Disorders Associated with Endocrine Dysfunction HORMONE EFFECTS OF HYPERSECRETION EFFECTS OF HYPOSECRETION Growth hormone Gigantism (children), acromegaly (adults) Dwarfism (children) Antidiuretic hormone Syndrome of inappropriate antidiuretic Diabetes insipidus hormone (SIADH) Aldosterone Aldosteronism Addison disease Cortisol Cushing syndrome Addison disease Thyroid hormone Graves disease, thyrotoxicosis Infantile hypothyroidism (cretinism) in chil- dren; myxedema in adults Insulin Hypoglycemia Diabetes mellitus Parathyroid hormone Bone degeneration Tetany (muscle spasms) Internal-external stimuli Neurotransmitters Hypothalamus 12 Releasing hormones secreted ADH Oxytocin Infundibulum Portal system Posterior pituitary Hormones feed back to anterior pituitary Anterior pituitary and hypothalamus Breast Oxytocin Thyroid TSH ADH Uterus Thyroid hormones ACTH Adrenal Kidney PRL FSH Ovary FSH GH Adrenocorticosteroids LH LH (ICSH) Estrogen Corpus Breast luteum Testes Bone and Progesterone soft tissues Testosterone Figure 12-3 The hypothalamus, pituitary gland, and target tissues. This ◗ Growth hormone (GH), or somatotropin (so-mah-to- type of diabetes should not be confused with diabetes TRO-pin), acts directly on most body tissues, promot- mellitus, which is due to inadequate amounts of in- ing protein manufacture that is essential for growth. Tumors of the Pituitary The effects of pituitary tu- ◗ Follicle-stimulating hormone (FSH) stimulates the devel- mors depend on the cell types in the excess tissue. A person who develops ovulation in females and sex hormone secretion in both such a tumor in childhood will grow to an abnormally tall males and females; in males, the hormone is sometimes stature, a condition called gigantism (ji-GAN-tizm) (see called interstitial cell–stimulating hormone (ICSH). FSH and LH are classified as gonadotropins (gon-ah- If the GH-producing cells become overactive in the do-TRO-pinz), hormones that act on the gonads to regu- adult, a disorder known as acromegaly (ak-ro-MEG-ah- late growth, development, and function of the reproduc- le) develops. The fingers resemble a spatula, and the face takes on a coarse appearance: the nose widens, the Hormones of the Posterior Lobe lower jaw protrudes, and the forehead bones may bulge. In hu- itary tries to compensate for decreased glucocorticoid levels mans, though, MSH levels are usually so low that its role as a by increasing POMC production. This is so because pituitary regulating pigmentation, women do produce more MSH dur- cells do not produce ACTH directly but produce a large pre- ing pregnancy and often have darker skin. Calcitonin works with parathyroid hor- exhibit signs of underactivity of other endocrine glands mone and with vitamin D to regulate calcium metabo- that are controlled by the pituitary, such as the ovaries, lism, as described below. Disorders of the Thyroid Gland A goiter (GOY- Evidence of tumor formation in the pituitary gland ter) is an enlargement of the thyroid gland, which may may be obtained by radiographic examinations of the or may not be associated with overproduction of hor- skull. Computed tomography (CT) and magnetic res- adenomatous (ad-eh-NO-mah-tus), or nodular, goiter onance imaging (MRI) scans are also used to diagnose pi- is an irregular-appearing goiter accompanied by tumor tuitary abnormalities. Underactivity of the thy- roid, known as hypothyroidism (hi-po-THI-royd-izm), The thyroid, located in the neck, is the largest of the en- shows up as two characteristic states related to age: docrine glands (Fig. The thyroid has two roughly oval lateral lobes on either side of the larynx (voice box) ◗ Infantile hypothyroidism, also known as cretinism connected by a narrow band called an isthmus (IS-mus). Iodine deficiency is rare now myxedema regains health easily, although treatment due to widespread availability of this mineral in iodized must be maintained throughout life. Hyperthyroidism is the opposite of hypothyroidism, Another hormone produced by the thyroid gland is that is, overactivity of the thyroid gland with excessive se- calcitonin (kal-sih-TO-nin), which is active in calcium cretion of hormone. A common form of hyperthyroidism is Graves disease, which is characterized by a goiter, a strained appearance of the face, intense nervousness, Epiglottis weight loss, a rapid pulse, sweating, tremors, and an ab- normally quick metabolism. Another characteristic symp- Thyroid gland Hyoid bone (right lobe) tom is protrusion (bulging) of the eyes, known as exoph- thalmos (ek-sof-THAL-mos), which is caused by swelling of the tissue behind the eyes (Fig. Treatment of Isthmus of Larynx thyroid gland hyperthyroidism may take the following forms: ◗ Suppression of hormone production with medication Trachea ◗ Destruction of thyroid tissue with radioactive iodine ◗ Surgical removal of part of the thyroid gland Figure 12-4 Thyroid gland (anterior view). The two lobes An exaggerated form of hyperthyroidism with a sud- and isthmus of the thyroid are shown in relation to other struc- den onset is called a thyroid storm. The secretion of these glands, parathyroid hormone (PTH), promotes calcium release from bone tissue, thus increasing the amount of calcium circulating in the bloodstream. The four and measuring the amount and distribution of radiation small parathyroid glands are embedded in the posterior surface that accumulates in the thyroid gland. THE ENDOCRINE SYSTEM: GLANDS AND HORMONES ✦ 253 In contrast, if there is excess production of PTH, as ◗ Increase in the heart rate may happen in tumors of the parathyroid glands, calcium ◗ Increase in the metabolic rate of body cells is removed from its normal storage place in the bones and ◗ Dilation of the bronchioles, through relaxation of the released into the bloodstream.

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