The drug has been evaluated in subjects with alcoholism purchase decadron 1mg with amex skin care now pueblo co, opioid addiction buy discount decadron 1mg on line acne nodule, and psychiatric disorders buy 1mg decadron with visa skin care mario badescu, including depression, anxiety, and obsessive-compulsive disorder. Salvia Salvia divinorum is a hallucinogenic herb native to southern Mexico and to Central and South America. Its primary psychoactive component is salvinorin A, a potent activator of kappa opioid receptors. The genus Salvia, a part of the mint family, is commonly known as sage—hence the colorful street names for S. Salvia is legal in some states, illegal in others, and not yet regulated under the Controlled Substances Act. Salvia is used extensively in the United States, primarily by teens and young adults. Among Mexican Indians, the traditional method is to chew the leaves or drink a liquid extract. In contrast, recreational users usually smoke the dried leaves, either in a pipe or rolled in a joint. When the smoke is inhaled, salvinorin A undergoes rapid absorption from the lungs. As a result, psychological effects begin quickly (in less than 1 minute) and then quickly fade (typically in 5–10 minutes). They may feel they are floating, traveling through time and space, or merging with or transforming into objects. There may be a sense of overlapping realities and of being in several places at once. Possible physical effects include chills, dizziness, nausea, incoordination, and bradycardia. However, we do know that Mexican Indians have used the drug for generations, with no apparent ill effects. Mescaline, a constituent of the peyote cactus, and psilocin and psilocybin, constituents of “magic mushrooms,” represent compounds found in nature. In addition, they can cause hallucinations and induce mental states that resemble psychosis. The use of psilocybin in patients with terminal cancer and obsessive-compulsive disorder is under investigation. The drug is structurally related to methamphetamine (a stimulant) and mescaline (a hallucinogen). These effects result from (1) blocking reuptake of serotonin and (2) promoting the release of serotonin, dopamine, and norepinephrine. With oral administration, effects begin in 20 minutes, peak in 2 to 3 hours, and persist 4 to 5 hours. The drug can elevate mood, increase sensory awareness, and heighten sensitivity to music. It can also facilitate interpersonal relationships: users report a sense of closeness with others, lowering of defenses, reduced anxiety, enhanced communication, and increased sociability. The drug can injure serotonergic neurons, stimulate the heart, and raise body temperature to a dangerous level. Treatment consists of rapid cooling, rehydration, and administering dantrolene [Dantrium], a drug that relaxes skeletal muscle, thereby reducing heat generation and the risk for rhabdomyolysis. Remarkably, the increases in heart rate and blood pressure equal those produced by maximal doses of dobutamine, a powerful adrenergic agonist (see Chapter 13). Inhalants The inhalants are a diverse group of drugs that have one characteristic in common: administration by inhalation. Anesthetics Provided that dosage is modest, anesthetics produce subjective effects similar to those of alcohol (euphoria, exhilaration, loss of inhibitions). The anesthetics that have been abused most are nitrous oxide (“laughing gas”) and ether. One reason for the popularity of these drugs is ease of administration: both agents can be used without exotic equipment. For nitrous oxide, ready availability also promotes use: small cylinders of the drug, marketed for aerating whipping cream, can be purchased without restriction. Organic Solvents A wide assortment of solvents have been inhaled to induce intoxication. These compounds include toluene, gasoline, lighter fluid, paint thinner, nail-polish remover, benzene, acetone, chloroform, and model-airplane glue. These agents are used primarily by children and the very poor—people who, because of age or insufficient funds, lack access to more conventional drugs of abuse. Administration Solvents are administered by three processes, referred to as “bagging,” “huffing,” and “sniffing. In addition, these compounds can cause visual hallucinations and disorientation with respect to time and place. Possible causes include anoxia, respiratory depression, vagal stimulation (which slows heart rate), and dysrhythmias. For example, chloroform is toxic to the heart, liver, and kidneys, and toluene can cause severe brain damage and bone marrow depression. Many solvents can damage the heart; fatal dysrhythmias have occurred secondary to drug-induced heart block. Anabolic Steroids Many athletes take anabolic steroids (androgens) to enhance athletic performance. Because of the massive doses that are employed, the risk for adverse effects is substantial. The basic pharmacology of androgens and their abuse by athletes are discussed in Chapter 50. U N I T I X Drugs that Affect the Heart, Blood Vessels, Blood, and Blood Volume O U T L I N E Chapter 34 Review of Hemodynamics Chapter 35 Diuretics Chapter 36 Drugs Acting on the Renin-Angiotensin- Aldosterone System Chapter 37 Calcium Channel Blockers Chapter 38 Vasodilators Chapter 39 Drugs for Hypertension Chapter 40 Drugs for Heart Failure Chapter 41 Antidysrhythmic Drugs Chapter 42 Prophylaxis of Atherosclerotic Cardiovascular Disease Drugs That Help Normalize Cholesterol and Triglyceride Levels Chapter 43 Drugs for Angina Pectoris Chapter 44 Anticoagulant and Antiplatelet Drugs Chapter 45 Drugs for Deficiency Anemias C H A P T E R 3 4 Review of Hemodynamics Laura D. Concepts introduced here reappear throughout the chapters on cardiovascular drugs, so we urge you to review these now. Because this is a pharmacology text, and not a physiology text, discussion is limited to hemodynamic factors that have particular relevance to the actions of drugs. Overview of the Circulatory System The circulatory system has two primary functions: (1) delivery of oxygen, nutrients, hormones, electrolytes, and other essentials to cells and (2) removal of carbon dioxide and metabolic wastes from cells. The circulatory system has two major divisions: the pulmonary circulation and the systemic circulation. The systemic circulation is also known as the greater circulation or peripheral circulation. Components of the Circulatory System The circulatory system is composed of the heart and blood vessels. The blood vessels have several functions: • Arteries transport blood under high pressure to tissues. As a result, small increases in venous pressure cause large increases in vessel diameter, which produce a large increase in venous volume. Distribution of Blood The adult circulatory system contains about 5 L of blood, which is distributed throughout the system. Within the systemic circulation, however, distribution is uneven: most (64%) of the blood is in veins, venules, and venous sinuses; the remaining 20% is in arteries (13%) and arterioles or capillaries (7%).
Probenecid competes with cidofovir for renal tubular secretion and thereby delays elimination buy 1mg decadron with amex acne 101e. Cidofovir has a prolonged intracellular half-life (17– 65 hours) buy decadron 0.5 mg with mastercard acne epiduo, and hence a long interval (2 weeks) can separate doses generic decadron 0.5mg amex acne 6 days after ovulation. Adverse Effects Nephrotoxicity The principal adverse effect is dose-dependent nephrotoxicity, manifesting as decreased renal function and symptoms of a Fanconi-like syndrome (proteinuria, glucosuria, bicarbonate wasting). Also, serum creatinine and urine protein should be checked within 48 hours before each dose, and, if these values indicate kidney damage, cidofovir should be withheld or the dosage reduced. Cidofovir is contraindicated for patients taking other drugs that can injure the kidney and for patients with proteinuria (2+ or greater) or baseline serum creatinine greater than 1. Other Adverse Effects Neutropenia develops in about 20% of patients, so neutrophil counts should be monitored. Ocular disorders—iritis, uveitis, or ocular hypotony (low intraocular pressure)—can also occur. In animal studies, cidofovir was carcinogenic and teratogenic and caused hypospermia. Preparations, Dosage, and Administration Cidofovir [Vistide] is supplied in solution (75 mg/mL) in 5-mL ampules. The dosage is 2 g given 3 hours before the infusion, 1 g given 1 hour after the infusion, and another 1 g given 8 hours after that. Ingesting food before each dose can decrease probenecid-induced nausea and vomiting. For patients who can tolerate it, 1 L more can be infused over 1 to 3 hours, beginning when the cidofovir infusion begins or as soon as it is over. Compared with ganciclovir, foscarnet is more difficult to administer, less well tolerated, and much more expensive. Unlike many other antiviral drugs, which must undergo conversion to an active form, foscarnet is active as administered. Pharmacokinetics Foscarnet has low oral bioavailability and must be administered intravenously. Between 10% and 28% of each dose is deposited in bone; the remainder is excreted unchanged in the urine. Because foscarnet is eliminated by the kidneys, dosages must be reduced in patients with renal impairment. Adverse Effects and Interactions In general, foscarnet is less well tolerated than ganciclovir. However, unlike ganciclovir, foscarnet does not cause granulocytopenia or thrombocytopenia. Nephrotoxicity Renal injury, as evidenced by a rise in serum creatinine, is the most common dose-limiting toxicity. The risk for nephrotoxicity is increased by concurrent use of other nephrotoxic drugs, including amphotericin B, aminoglycosides (e. Renal function (creatinine clearance) should be monitored closely, and the dosage should be reduced if renal impairment develops. B l a c k B o x Wa r n i n g : F o s c a r n e t [ F o s c a v i r ] Renal impairment has occurred. Seizures have occurred in relation to alterations in electrolytes and mineral composition in plasma. Electrolyte and Mineral Imbalances Foscarnet frequently causes hypocalcemia, hypokalemia, hypomagnesemia, and hypophosphatemia or hyperphosphatemia. Ionized serum calcium may be reduced despite normal levels of total serum calcium. Serum levels of calcium, magnesium, potassium, and phosphorus should be measured frequently. Special caution is required in patients with preexisting electrolyte, cardiac, or neurologic abnormalities. Other Adverse Effects Common reactions (occurring in 25%–50% of patients) include fever, nausea, anemia, diarrhea, vomiting, and headache. In addition, foscarnet can cause fatigue, tremor, irritability, genital ulceration, abnormal liver function tests, neutropenia, and seizures. Drugs for Hepatitis Viral hepatitis is the most common liver disorder, affecting millions of Americans. The disease can be caused by six different hepatitis viruses, labeled A, B, C, D, E, and G. All six can cause acute hepatitis, but only B, C, and D also cause chronic hepatitis. In most cases, acute hepatitis resolves spontaneously, so intervention is generally unnecessary. In contrast, chronic hepatitis can lead to cirrhosis, hepatocellular carcinoma, and life-threatening liver failure, and hence treatment should be considered. Transmission occurs primarily through exchange of blood, with injection drug use being the most common means. Rather than give detailed information about drugs that nonspecialist providers may never prescribe or encounter, our goal will be to provide a summary of information that will benefit health care providers who see these patients for other conditions. For years, dual therapy with pegylated interferon alfa (peginterferon alfa) plus ribavirin was the standard of care. Because the mechanisms of action are directed toward the virus, the drugs avoid the sometimes dangerous adverse effects associated with interferon therapy. To decrease the development of viral resistance and to increase the likelihood of successful outcomes, all of these drugs are used in combination therapy. Interferon Alfa Human interferons are naturally occurring compounds with complex antiviral, immunomodulatory, and antineoplastic actions. In the following discussion, these compounds are referred to collectively as interferon alfa. None of these agents can be used orally, and hence administration is parenteral—almost always subQ. Mechanism of Action Interferon alfa has multiple effects on the viral replication cycle. Conventional Versus Long-Acting Interferons The alfa interferons can be divided into two groups—conventional and long acting—based on their time course of action. The conventional preparations have short half-lives, so they must be administered frequently—at least 3 times a week. In contrast, the long-acting preparations are administered less frequently— just once a week—making them more convenient. In addition, with the long- acting preparations, blood levels remain high between doses, and hence clinical responses are better. Therapeutic effects of the pegylated product are due solely to its interferon component. Because of their convenience and superior efficacy, these products are preferred to conventional interferons. However, note that several side effects—injection-site reactions, dose-related neutropenia, and thrombocytopenia—are more common with pegylated interferons than with the conventional formulations. Effects in Chronic Hepatitis C In patients with chronic hepatitis C, responses are equally modest with all forms of interferon alfa.
If these women present with heavy vaginal bleeding before the planned date of delivery order 0.5 mg decadron free shipping acne jensen boots, emergency caesarean section should be performed and this has to be under senior or consultant supervision buy generic decadron online skin care routine for dry skin. One should discourage this method of delivery if there is no valid clinical reason purchase decadron 1 mg online acne and diet. Careful discussion of the benefts and risks of both methods will allow making an informed choice. If the viral load is high as seen in the current case, caesarean section is indicated. Placenta praevia, placenta praevia accreta and vasa praevia: Diagnosis and management. Terefore, this method is not recommended for use in young women, especially if they want to preserve fertility. Terefore, one has to be careful and regularly assess fuid input and output during the procedure. If the negative balance is >1000 mL, the recommendation is to stop the procedure as this can be associated with electrolyte imbalance (hyponatremia). Such women would need a blood test to measure electrolytes and overnight observation in the hospital. The absolute risk of such birth-related perinatal loss is comparable to the risk for women having their frst birth. Tey should be informed that there is still 15–50% possibility of eventually needing surgical evacuation for clinical needs or because the woman prefers to have it. Question 3 As part of the infectious diseases in pregnancy screening programme, all pregnant women are routinely ofered screening for the following infections at their booking antenatal visit except which one? Rubella 75 Question 4 Which one of the following factors does not infuence the transmission of herpes to the fetus? Woman’s partner with herpes virus infection Question 5 A 28-year old woman had recurrent genital herpes at 28 and 33 weeks’ gestation and was started on suppressive antiviral therapy. She is currently 39 weeks’ gestation and presents in spontaneous labour with no active lesions. Both forceps and ventouse delivery Question 6 A 32-year-old para 2 woman presented at 28 weeks’ gestation with abdominal pain and uterine tightenings. Abdominal examination revealed no obvious uterine activity and on speculum examination the cervix was closed and long. She was given antibiotics for a suspected urinary tract infection and was discharged home. Her past history revealed history of premature labour at 32 and 34 weeks’ gestation. She subsequently presents with abdominal pain and urinary retention at 32 weeks’ gestation. Abdominal examination reveals uterine contractions of 3 in 10 minutes and speculum examination revealed 6 cm dilated cervical os. Her vulva also reveals multiple painful vesicles suggestive of primary herpes infection. Both forceps and ventouse delivery 76 Question 7 A 32-year-old woman presented with painful vulva at 36 weeks’ gestation. Clinical examination revealed multiple painful vesicles suggestive of genital herpes infection. However, she presents at 38 weeks’ in second stage and delivered vaginally within half an hour of admission to labour ward. Examination reveals that she has vesicular lesions on the abdomen and her arms and legs suspicious of chickenpox. A blood test for IgG antibody and IgM antibody for varicella infection is requested and a swab is taken from vesicular fuid for virology. The results come back 24 hours later and reveal positive for varicella IgG antibody but negative for IgM antibodies. She had developed this rash 10 hours previously and thought that she had developed a food allergy. On questioning she gives a history of coming in close contact, 3 days earlier, with her niece, who had developed chickenpox rash. She was prescribed oral acyclovir for 7 days but was warned to report back if unwell. Tree days later she presents to the emergency department with severe shortness of breath. She is planning to conceive in the next couple of months and would like to know the risks to her and the fetus if she gets pregnant. Cordocentesis Instructions For each clinical scenario below, choose the single most appropriate screening test from the above list of options. A 28-year-old south Asian woman with a history of irregular menstrual cycles attends for her dating scan at 12 weeks’ gestation and wishes to have the Down syndrome screening test. A 40-year-old woman, who teaches children with special needs, is 12 weeks into her frst pregnancy and is very anxious about the risk of Down syndrome. She wishes to have a diagnostic test, but is not ready to take the risk of miscarriage associated with invasive testing. A 38-year-old G2 para 1 at 13 weeks’ gestation attends fetal medicine unit for counselling afer the screen-positive combined screening results with a risk of 1:50 Down syndrome. No intervention needed Instructions For each clinical scenario below, choose the single most appropriate immediate plan of action from the above list of options. A 30-year-old para 1 woman at 32 weeks’ gestation seeks advice when her child is diagnosed with chickenpox and she is not sure whether she had chickenpox or not. A 23-year-old nulliparous woman at 36 weeks’ gestation attends the antenatal clinic afer a recent diagnosis of genital herpes in the department of sexual health. She is on oral acyclovir and is anxious about the fetal efects and the mode of delivery. She was recently treated for sepsis secondary to urinary tract infection as an inpatient and was discharged on oral antibiotics. Aspirin 75 mg + folic acid 5 mg Instructions For each clinical scenario below, choose the single most appropriate intervention from the above list of options. A 42-year-old G2 para 1 woman attends the antenatal clinic afer her dating scan at 12 weeks’ gestation. She had early onset pre-eclampsia and fetal growth restriction requiring preterm delivery at 32 weeks’ in her frst pregnancy. A 30-year-old nulliparous woman at 10 weeks’ gestation attends the antenatal clinic. She is taking multivitamins and concerned about the risks of diabetes in pregnancy. A 32-year-old nulliparous woman attends her booking antenatal visit at 10 weeks’ gestation. You have been asked to see this woman as she had a pulmonary embolism 2 years ago, while taking combined oral contraceptive pills.
Note that neostigmine and edrophonium are quaternary ammonium compounds purchase 0.5 mg decadron visa acne on nose, but physostigmine is not buy 0.5mg decadron visa skin care basics. What does this difference imply about the relative abilities of these drugs to cross membranes order 1 mg decadron otc acne zapper zeno, including the blood-brain barrier? Neostigmine and the other reversible cholinesterase inhibitors act as substrates for cholinesterase. As a result, one molecule of cholinesterase can break down a huge amount of acetylcholine in a very short time. The reaction between neostigmine and cholinesterase is much like the reaction between acetylcholine and cholinesterase. The only difference is that cholinesterase splits neostigmine more slowly than it splits acetylcholine. Hence, after neostigmine becomes bound to cholinesterase, the drug remains in place for a relatively long time. Because cholinesterase remains bound until it finally succeeds in degrading neostigmine, less cholinesterase is available to catalyze the breakdown of acetylcholine. By decreasing breakdown of acetylcholine, neostigmine and the other cholinesterase inhibitors make more acetylcholine available, and this can intensify transmission at virtually all junctions where acetylcholine is the transmitter. Muscarinic effects of the cholinesterase inhibitors are identical to those of the direct-acting muscarinic agonists. Because neostigmine carries a positive charge, the drug is poorly absorbed after oral administration; hence oral formulations have been discontinued in the United States, although they remain available in some other countries. Preparation and dosage of neostigmine and other cholinesterase inhibitors are provided in Table 12. Typical dosing is and swallowing 1-mL and 15–375 mg/day in divided doses 10-mL vials Generic: 0. Dose may be repeated every 10–30 Limit rate to 1 mg/min in minutes as needed adults or 0. If administered in toxic doses, cholinesterase inhibitors can cause accumulation of acetylcholine in amounts sufficient to produce depolarizing neuromuscular blockade. Most of the precautions and contraindications regarding the cholinesterase inhibitors are the same as those for the direct-acting muscarinic agonists. The effects of cholinesterase inhibitors at muscarinic receptors are opposite to those of atropine (and all other muscarinic antagonists). Consequently, cholinesterase inhibitors can be used to overcome excessive muscarinic blockade caused by atropine. Conversely, atropine can be used to reduce excessive muscarinic stimulation caused by cholinesterase inhibitors. In contrast to neostigmine, physostigmine is not a quaternary ammonium compound and hence does not carry a charge. Because physostigmine is uncharged, physostigmine readily crosses membranes, whereas neostigmine does not. Physostigmine is the drug of choice for treating poisoning by atropine and other drugs that cause muscarinic blockade, including antihistamines and phenothiazine antipsychotics—but not tricyclic antidepressants, owing to a risk for causing seizures and cardiotoxicity. Physostigmine counteracts antimuscarinic poisoning by causing acetylcholine to build up at muscarinic junctions. The accumulated acetylcholine competes with the muscarinic blocker for receptor binding and thereby reverses receptor blockade. Edrophonium [Enlon, Tensilon ] and pyridostigmine [Mestinon] have pharmacologic effects much like those of neostigmine. One of these drugs— edrophonium—is noteworthy for its very brief duration of action. In current practice, though, edrophonium is not commonly used for this purpose because better and more accurate testing is now available. Three cholinesterase inhibitors—donepezil [Aricept], galantamine [Razadyne], and rivastigmine [Exelon]—are approved for management of Alzheimer disease, and one of them—rivastigmine—is also approved for dementia of Parkinson disease. Irreversible Cholinesterase Inhibitors The irreversible cholinesterase inhibitors are highly toxic. Today, there is concern that these agents might be employed as weapons of terrorism. Because of this phosphorus atom, the irreversible inhibitors are known as organophosphate cholinesterase inhibitors. Easy absorption, coupled with high toxicity, is what makes these drugs good insecticides—and gives them potential as agents of chemical warfare. The irreversible cholinesterase inhibitors bind to the active center of cholinesterase, preventing the enzyme from hydrolyzing acetylcholine. Although these drugs can be split from cholinesterase, the splitting reaction takes place extremely slowly. Hence, under normal conditions, their binding to cholinesterase can be considered irreversible. Because binding is irreversible, effects persist until new molecules of cholinesterase can be synthesized. Although we normally consider the bond between irreversible inhibitors and cholinesterase permanent, this bond can, in fact, be broken. To break the bond and reverse the inhibition of cholinesterase, we must administer pralidoxime, a cholinesterase reactivator. The irreversible cholinesterase inhibitors produce essentially the same spectrum of effects as the reversible inhibitors. The principal difference is that responses to irreversible inhibitors last a long time, whereas responses to reversible inhibitors are brief. As mentioned previously, the irreversible cholinesterase inhibitors have only one indication: treatment of glaucoma. The limited indications for irreversible cholinesterase inhibitors should be no surprise given their potential for harm. Toxicology of Cholinesterase Inhibitors Sources of Poisoning Poisoning by organophosphate cholinesterase inhibitors is a common occurrence. Agricultural workers have been poisoned by accidental ingestion of organophosphate insecticides and by absorption of these lipid-soluble compounds through the skin. In addition, because organophosphate insecticides are readily available to the general public, poisoning may occur accidentally or from attempted homicide or suicide. Exposure could also occur if these drugs were used as instruments of warfare or terrorism. This condition, known as a cholinergic crisis, is characterized by excessive muscarinic stimulation and depolarizing neuromuscular blockade. Overstimulation of muscarinic receptors results in profuse secretions from salivary and bronchial glands, involuntary urination and defecation, laryngospasm, and bronchoconstriction. Prominent nicotinic effects reflect nicotinic activity at neuromuscular junctions resulting in muscle weakness, fasciculations, cramps, and twitching. Respiratory depression from cholinesterase inhibitors cannot be managed with drugs. Pralidoxime is a specific antidote to poisoning by the irreversible (organophosphate) cholinesterase inhibitors; the drug is not effective against poisoning by reversible cholinesterase inhibitors. In poisoning by irreversible inhibitors, benefits derive from causing the inhibitor to dissociate from the active center of cholinesterase.
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