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The frst symp- for hormone replacement in women who are post- toms are often vague purchase ketoconazole cream from india antibiotics for enterobacter uti, such as the malaise and menopausal generic ketoconazole cream 15gm antibiotics for staph acne, not to induce ovulation buy 15 gm ketoconazole cream with amex xkcd antibiotics. Although this is a serious complication, it appears to occur only in pa- 89 The answer is B: Diltiazem. Dihydropyridines are selective brush border enzymes to decrease the amount of for the calcium channels in vascular smooth muscle carbohydrate absorption after a meal and can cause and have the suffx -dipine such as amlodipine. Verapamil is selective for cardiac muscle cells, Sulfonylureas may cause hypoglycemia but are not whereas diltiazem affects the calcium channels in known to cause lactic acidosis. It affects principally those calcium is a 5a-reductase inhibitor used for the treatment of channels in vascular smooth muscle. Insulin release is stimu- used to treat hyperthyroidism and can be used in lated primarily by elevated levels of blood glucose. Insulin secretion is also stimulated by endogenous hor- Patients should be watched for the risk of increased mones called incretins. It is an inhibitor of growth needed for the fnal steps in carbohydrate breakdown hormone, which is overproduced in acromegaly. If necessary, drug therapy includes niacin, and/or (C) Propranolol could slow the heart but would fenofbrate, or a statin. The tatin would cause an increase in lovastatin’s concen- most common side effects of niacin therapy are an tration. Taking intense cutaneous fush (accompanied by an uncom- it together with lovastatin would cause an increase fortablefeelingofwarmth)andpruritus. Taking it daily at bedtime, reduces bothersome initial adverse together with lovastatin would cause an increase in effects. Although infertil- beneft from treatment with a sustained-release formu- ity can only be diagnosed following 1 year of unpro- lation of niacin. This couple appears to have a decreased fecundity (ability to conceive), but no abnormalities 101 The answer is B: Gallstone formation. However, fenof- is an aromatase inhibitor, which blocks the peripheral brate is more effective than gemfbrozil in lowering conversion of endogenous androgens to estrogens. Letrozole is a good choice for an early try to Cholestasis and increased biliary cholesterol excre- increase fertility because it is generally well tolerated tion are the most likely causes. It is often the substitute used when a It metabolizes dozens of drugs but can also be in- cough develops on angiotensin-converting enzyme duced or inhibited by others. Gemfbrozil interacts side effect with nitroglycerin and sildenafl, not oral with the statin class of cholesterol medications to contraceptive pills. Because of the increased risk and limited pills lead to a decreased risk of endometrial and benefts seen with the combination of gemfbrozil and ovarian cancer. A rash would be (D) This information can be determined from the more commonly seen as an allergic reaction to antibi- curves presented. The enzyme breaks down com- is a thyroid hormone that is overproduced in hyper- plex sugars into monosaccharides that are absorbed in thyroidism. Glyburide is a It usually only occurs when high doses of niacin second-generation sulfonylurea that increases the are used. Location 5 is the site of and creatine kinase levels to ensure proper liver and proteolytic release of hormones. However, we have no indica- tion of diabetes in this patient, and a hemoglobin A1c 118 The answer is B: Patient B. The child was born at term by 4 A 47-year-old immigrant from Japan with a long C-section because of failure of labor to progress. The history of untreated gastric ulcers develops stomach patient has been unable to void normally since the cancer. While receiving this drug, the patient develops (A) Bethanechol redness and numbness on the palms of his hands and (B) Carbachol soles of his feet. He has noticed the pain especially after eating 5 A 62-year-old man with congestive heart failure has spicy foods and oatmeal. The physician must warn the patient about which of the following possible adverse effects of this medication? Because of his renal insuffciency, he will likely have compensatory drug excretion via 11 A 12-year-old boy with obsessive-compulsive disorder (A) Breath and depression desires to be managed with a single (B) Liver pharmacologic agent. Rats (2 kg in weight) are being studied and 12 A 39-year-old man with schizophrenia presents to his then sacrifced according to institutional protocol. Which of the following state- the least amount of halothane carbon-labeled radio- ments regarding his recovery is true? Which of the following patients is at greatest pain caused by herniated L5 disk and depression is risk for the anesthetic agents entering the cerebral currently taking fuoxetine and tramadol. The com- (A) A 19-year-old man with blood pressure of bination of these two agents should raise the treating 120/80 mm Hg and pulse of 80 beats/minute physician’s concern for which of the following (B) A 41-year old man with sinusitis and hypertension reactions? Induction with intravenous propofol will frst be given prior to place- ment of a laryngeal mask airway. He is found to suffer from benign pros- brought to the emergency department because of tatic hyperplasia. Physical examination of the heart, 20 A 3-year-old girl is brought to the pediatrics clinic by lungs, and abdomen are within normal limits. They say that their daughter has had a of the following concomitant conditions is he most runny nose for a few days and recently began com- likely to suffer from? The parents also say that she has (A) Angina been treated for ear infections in the past but once (B) Asthma broke out in a rash while taking an antibiotic. The (C) Diabetes physician is worried about an allergic reaction but knows that some antibiotics can cause a nonallergic (D) Prior myocardial infarction rash and that she may not be allergic to this class of (E) Renal impairment antibiotics. He sees the anesthesiologist preopera- (C) Headache tively and is found to have a serum potassium of (D) Impotence 2. Physical exami- well and has been taking this medication for about nation reveals bilateral gynecomastia. Which of the following statements is true he has recently underwent an endoscopy, which about therapy with this agent? What is the most likely expla- (A) Dose adjustment is required in hepatic failure nation for these fndings? Diazoxide stimulates potassium channels 30 A 55-year-old woman with end-stage ovarian cancer leading to inhibition of insulin release. Which of the with extensive carcinomatosis has chronic nausea and following is most likely to occur in this patient as a vomiting. Should she elect to pursue this (B) Hypertension agent, she should be concerned about which of the (C) Hypoglycemia following effects? The physician suggests (C) Magnesium hydroxide an exercise regimen, dietary modifcations, and a bulk (D) Sodium bicarbonate laxative. He has been on (C) Nonabsorbable salt the medicine for 1 year and does complain of inter- (D) Osmotic laxative mittent chest pressure after meals. After hearing the risks of the surgery, (C) Gastric ulcers that appear unhealed the patient decides on a medical approach to treat- (D) Normal gastric epithelium ment. Which of (E) Normal lower esophageal epithelium the following is the most important for both the patient and the family to know about this medication? He sits in an offce all day (C) Infammatory response and recently began using an air conditioner as the (D) Neoplastic process weather has warmed.
Enfuvirtide order ketoconazole cream american express latest antibiotics for acne, which must be administered by subcutaneous injection effective 15 gm ketoconazole cream antibiotic resistance in america, is the only parenterally administered antiretroviral agent discount 15gm ketoconazole cream with amex virus malware removal. Resistance to enfuvirtide can result from mutations in gp41; the frequency and significance of this phenomenon are being investigated. However, enfuvirtide lacks cross-resistance with the other currently approved antiretroviral drug classes. The most common adverse effects associated with enfuvirtide therapy are local injection site reactions, consisting of painful erythematous nodules. No drug-drug interactions have been identified that would require the alteration of the dosage of concomitant antiretroviral or other drugs. The absorption of maraviroc is rapid but variable, with the time to maximum absorption generally being 1–4 hours after ingestion of the drug. Maraviroc has excellent penetration into the cervicovaginal fluid, with levels almost four times higher than the corresponding concentrations in blood plasma. There appears to be no cross-resistance with drugs from any other class, including the fusion inhibitor enfuvirtide. Potential adverse effects of maraviroc include cough, upper respiratory tract infections, muscle and joint pain, diarrhea, sleep disturbance, and elevations in serum aminotransferases. Hepatotoxicity has been reported, which may be preceded by a systemic allergic reaction (ie, pruritic rash, eosinophilia, or elevated IgE); discontinuation of maraviroc should be prompt if this constellation occurs. Myocardial ischemia and infarction have been observed in patients receiving maraviroc; therefore caution is advised in patients at increased cardiovascular risk. To date, however, there has been no evidence of an increased risk of either malignancy or infection in patients receiving maraviroc. As a class, these agents tend to be well tolerated, with headache and gastrointestinal effects being the most commonly reported adverse events. Other nervous system (including neuropsychiatric) effects are often reported but are milder and less frequent than with efavirenz. Dolutegravir should be taken 2 hours before or 6 hours after taking cation-containing antacids or laxatives, sucralfate, oral iron supplements, oral calcium supplements, or buffered medications. For this reason, co-administration with dofetilide is contraindicated and close monitoring, with potential for dose adjustment, is recommended for co-administration with metformin. Current evidence suggests that dolutegravir retains activity against some viruses resistant to both raltegravir and elvitegravir. Hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver injury, have been reported and may be life-threatening. Other reported side effects include elevations in serum aminotransferases and the fat redistribution syndrome. Elvitegravir is therefore available only as a component of a fixed-dose combination, with cobicistat, emtricitabine, and tenofovir. Cobicistat can inhibit renal tubular secretion of creatinine, causing increases in serum creatinine that may not be clinically significant; in the fixed-dose formulation it may be difficult to distinguish between cobicistat effect and tenofovir- induced nephrotoxicity. The recommendation is that the fixed-dose combination elvitegravir/cobicistat/tenofovir/emtricitabine should not be initiated in patients with calculated creatinine clearance < 70 mL/min and should be discontinued in those with creatinine clearance < 50 mL/min; discontinuation should be considered if the serum creatinine increases by 0. For example, since concurrent use of rifampin substantially decreases raltegravir concentrations, the dose of raltegravir should be increased. Since polyvalent cations (eg, magnesium, calcium, and iron) may bind integrase inhibitors and interfere with their activity, antacids should be used cautiously and ingestion separated by at least 4 hours from raltegravir. The chewable tablets may contain phenylalanine, which can be harmful to patients with phenylketonuria. Although virologic failure has been uncommon in clinical trials of raltegravir to date, in vitro resistance requires only a single point mutation (eg, at codons 148 or 155). The low genetic barrier to resistance emphasizes the importance of combination therapies and of adherence. Potential adverse effects of raltegravir include insomnia, headache, dizziness, diarrhea, nausea, fatigue, and muscle aches. Increases in pancreatic amylase, serum aminotransferases, and creatine kinase (with rhabdomyolysis) may occur. Severe, potentially life-threatening and fatal skin reactions have been reported, including Stevens-Johnson syndrome, hypersensitivity reaction, and toxic epidermal necrolysis. Interferon alfa appears to function by induction of intracellular signals following binding to specific cell membrane receptors, resulting in inhibition of viral penetration, translation, transcription, protein processing, maturation, and release, as well as increased host expression of major histocompatibility complex antigens, enhanced phagocytic activity of macrophages, and augmentation of the proliferation and survival of cytotoxic T cells. Interferon alfa-2a and interferon alfa-2b may be administered either subcutaneously or intramuscularly; half-life is 2–5 hours, depending on the route of administration. Alfa interferons are filtered at the glomerulus and undergo rapid proteolytic degradation during tubular reabsorption, such that detection in the systemic circulation is negligible. The use of pegylated (polyethylene glycol-complexed) interferon alfa-2a and pegylated interferon alfa-2b results in slower clearance, longer terminal half-lives, and steadier concentrations, thus allowing for less frequent dosing. Renal elimination accounts for about 30% of clearance, and clearance is approximately halved in subjects with impaired renal function; dosage must therefore be adjusted. The adverse effects of interferon alfa include a flu-like syndrome (ie, headache, fevers, chills, myalgias, and malaise) that typically occurs within 6 hours after dosing; this syndrome occurs in more than 30% of patients during the first week of therapy and tends to resolve upon continued administration. Transient hepatic enzyme elevations may occur in the first 8–12 weeks of therapy and appear to be more common in responders. Potential adverse effects during chronic therapy include neurotoxicities (mood disorders, depression, somnolence, confusion, seizures), myelosuppression, profound fatigue, weight loss, rash, cough, myalgia, alopecia, tinnitus, reversible hearing loss, retinopathy, pneumonitis, and possibly cardiotoxicity. Induction of autoantibodies may occur, causing exacerbation or unmasking of autoimmune disease (particularly thyroiditis). Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Co- administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. These end points are correlated with improvement in necroinflammatory disease, a decreased risk of hepatocellular carcinoma and cirrhosis, and a decreased need for liver transplantation. The use of interferon has been supplanted by long-acting pegylated interferon, allowing once-weekly rather than daily or thrice-weekly dosing. In general, nucleoside/nucleotide analog therapies have better tolerability and produce a higher response rate than the interferons and are now considered the first line of therapy. However, it is important to note that acute exacerbation of hepatitis may occur upon discontinuation or interruption of these agents; this may be severe or even fatal. Adefovir dipivoxil is the diester prodrug of adefovir, an acyclic phosphonated adenine nucleotide analog (eFigure 49–4. The intracellular half- life of the diphosphate is prolonged, ranging from 5 to 18 hours in various cells; this makes once-daily dosing feasible.
The best window for antithrombotics to be effective in cardiac choice antihypertensive agent for a 60-year-old black vessel recanalization is 2 to 6 h purchase ketoconazole cream 15 gm overnight delivery antibiotic 3 days uti. Alteplase is approved for hypertension associated with preeclampsia typically the treatment of myocardial infarction purchase 15gm ketoconazole cream antibiotics for acne inflammation, massive pul- does not warrant treatment generic 15gm ketoconazole cream mastercard virus martin garrix. Reteplase is similar pregnancy because of possible fetal cyanide poisoning to alteplase and can be used as an alternative. Prazosin produces frst- tered within 3 h of the onset of stroke for maximal dose hypotension, presumably by blocking a1- effectiveness. It decreases the anemia means a decrease in total hemoglobin but with secretion of potassium in the urine. The net loop diuretics are most effective in removing large result of the action potential to this point is a net gain fuid volumes from the body and are the treatment of of sodium and loss of potassium. Medication A is nitro- (E) Spironolactone is a potassium-sparing diuretic glycerin and is the agent of choice in acute chest pain. Acetazolamide is used prophylactically for several (C) Medication C is isosorbide mononitrate and only Cardiovascular Pharmacology 121 has an extended-release formulation and is not suit- decrease constriction of blood vessels but would not able in this patient. This agent has an onset of action of 5 to frst choice for pregnant women with hypertension 10 min and a duration of action of 6 to 8 h. It is not and results in a decreased sympathetic output reduc- useful in this patient who has a hypertensive emer- ing blood pressure. The medication of choice is medication A, threatening side effects and no teratogenic effects on which is sodium nitroprusside. It is an agent of node function rapidly and transiently (for only 15 to choice as a thrombolytic agent. It is still occasionally is urokinase, which has low antigenicity, high fbrin used to treat recalcitrant ventricular arrhythmias. This patient is presenting mation of arrhythmias in the infarcted tissue while with temporal arteritis or giant cell arteritis, which increasing blood supply as well. If left an epileptic drug and a treatment for a special drug- untreated, this patient may develop occlusion of the induced arrhythmia. The only medications shown to slow or stop the (E) Quinidine is a class Ia antiarrhythmic that is used granulomatous occlusion of these arteries are ste- as a long-term treatment for atrial and ventricular roids. This would not have a fast enough onset prazosin would decrease systemic blood pressure and for this patient. The patient asks about 4 A 58-year-old man with depression who takes a glucocorticoid injections, so his doctor begins to monoamine oxidase inhibitor has a love for aged explain the myriad effects of glucocorticoids in the cheese and wine. Among Which of the following would most likely beneft other immunosuppressant drugs, she has been taking from treatment with this medication yohimbine? With only a few doses of prednisone left, (A) A 19-year-old man with sexual arousal diffculties she gets snowed into her house and cannot refll her (B) A 29-year-old man with erectile and ejaculatory prescription (but she has enough of the other medica- dysfunction tions to last a few more weeks). If she runs out of (C) A 47-year-old man with erectile dysfunction and prednisone and cannot get it reflled, what is she most hypertension at risk for developing? Physical following drugs blocks de novo cholesterol synthesis examination reveals signifcant abdominal tenderness in hepatocytes? She is considering stopping her therapy, how- (E) Tolbutamide ever, because of a red, itchy rash on her face and neck that occurs following some doses. Her doctor (B) Fenofbrate prescribes an additional drug, which is an analog of (C) Gemfbrozil an endogenous peptide that inhibits glucagon secre- (D) Nicotinic acid tion. The most plausible mechanism of action for this medication is 13 A 57-year-old man with a 40 pack-year history of (A) Appetite stimulant smoking develops small cell lung cancer. His serum (B) Induction of chemotactic centers of the brain sodium is 121 mEq/L and his urine has a specifc (C) Stimulation of epidermal growth factor gravity of 1. They both agree that (D) Providing the starting material for bone they would like the wife to undergo fertility treat- mineralization ment. Which of the following drugs has the ability to either stimulate or inhibit ovulation depending only (E) Stimulating osteoblasts on the dosing schedule? Which of the following properties of this medication can limit (E) Propylthiouracil its effcacy for this patient? Endocrine Pharmacology 125 (A) Extensive hepatic frst-pass metabolism 20 A 52-year-old man is prescribed with furosemide by (B) Drug interaction with antacids his physician to help treat his hypertension. She shares a concern with her doctor about the elevation because 1 year ago, she went on a (E) Increase plasma volume ski trip to Colorado and developed altitude sickness. Her doctor prescribes a diuretic that can help her if 17 A 46-year-old man with hypertension presents to his she begins to have symptoms of altitude sickness. Her serum cholesterol and triglyceride 18 A 65-year-old man with long-standing hypertension levels are normal. What is the most appropriate initial on enalapril presents to his primary care physician treatment for this patient? This gene product normally inhib- most recent serum cholesterol level was in the normal its smooth muscle proliferation. His primary care physician adds pramlintide (C) Lovastatin in an effort to further reduce his blood sugar levels. This agent may be helpful in prevention of renal (E) Urinary retention stones through which of the following mechanisms? He walks approximately 30 min every other day throughout the year and eats 26 A 79-year-old woman with diabetes mellitus, hyper- three balanced meals per day. What is the most likely tension, and visual disturbances presents to her oph- explanation for these fndings? Prescription (B) Lack of proper diet for acetazolamide is given to produce which of the (C) Medication side effect following responses? Which of the following is the most likely (C) He can continue taking metformin and should sequelae of this action? She takes pio- glitazone daily and her blood sugar ranges approxi- 28 A 39-year-old man with insulin-dependent diabetes mately from 100 to 180 mg/dL. Which of the following mellitus is brought to the emergency department after indicators would likely have minimal or no change collapsing in a shopping mall. Which of the following preparations (A) Glucose would have the least minimal effect on his blood (B) Hemoglobin A1c sugar levels? His most recent after awakening without clothes on the following laboratory studies indicate normal serum glucose morning. An estimation of the risk of pregnancy in this (B) Inhibition of pancreatic amylase scenario is approximately (C) Pancreatitis (A) 0% (D) Pancreatic carcinoma (B) 1% to 3% (E) Subtherapeutic pharmacologic effect (C) 5% (D) 15% 34 A 58-year-old female with diabetes on sitagliptin pre- (E) 30% sents to her primary care physician because of recur- rent sinusitis and sore throat. What is the most likely explanation for 18 years thinks that this preparation may prove to be this fnding? Which of the (B) Gastroesophageal refux following cancers may show a decreased incidence (C) Treatment-related side effect because of her prolonged use of oral contraceptives? She has a family history of endometrial cancer and is concerned about her risk 40 A 32-year-old woman with endometriosis of the uterus, for this condition. Over the (A) Breast cancer is unlikely next few weeks, she experiences a 40% improvement in (B) Postmenopausal bleeding is unlikely her symptoms.
Syndromes
All of to the same anionic site on the receptor that agonists the antimuscarinic compounds are amino alcohol esters occupy order generic ketoconazole cream pills antibiotics for sinus infection side effects, these drugs do not fit into the narrow cleft and with a tertiary amine or quaternary ammonium group purchase ketoconazole cream with a visa antibiotics for uti missed period. Finally buy ketoconazole cream uk bacteria resistant to antibiotics, some Tissue or other classes of drugs can act in part as muscarinic an- system Effects tagonists. For example, the antipsychotics and antide- Skin Inhibition of sweating (hyperpyrexia may pressants produce antimuscarinic side effects (e. Therefore, the magnitude of pancreatic, intestinal, and biliary secre- tions the response produced by muscarinic antagonists de- Urinary Urinary retention (relaxation of the de- pends on the existing level of cholinergic activity or on trusor muscle); relaxation of ureter the presence of muscarinic agonists. At these locations, block of the activation of mus- Central nervous Decreased concentration and memory; carinic receptors can increase the tone provided by the system drowsiness; sedation; excitation; ataxia; adrenergic input. The tissues or systems affected will depend on the dose ad- ministered, the drug’s pharmacokinetic properties (e. Atropine can also facilitate atrioventricular Although muscarinic agonists typically do not exhibit (A-V) conduction and block parasympathetic effects on selectivity among muscarinic receptors (see Chapter the cardiac conduction system and on myocardial con- 12), some muscarinic antagonists are selective in their tractility. Blood Vessels Heart Atropine and other muscarinic antagonists produce Intravenous administration of low doses of atropine or minimal effects on the circulation in the absence of cir- scopolamine often produces slight bradycardia, whereas culating muscarinic agonists. This reflects the relatively higher doses produce tachycardia by directly blocking minor role of cholinergic innervation in determining the parasympathetic input to the sinoatrial node. Atropine can produce Although it has been suggested that the bradycardia re- flushing in the blush area owing to vasodilation. The inhibition of Antagonism of these presynaptic muscarinic receptors salivation by low doses of atropine results in a dry prevents feedback inhibition and increases the release mouth and difficulty in swallowing. Relatively large hibitors of secretions throughout the respiratory sys- doses of atropine are required to inhibit acid secretion, tem, from the nose to the bronchioles. Although the antimuscarinic drugs are normally selec- tive for muscarinic cholinergic receptors, high concen- trations of agents with a quaternary ammonium group Bladder (e. The active isomer, however, can doses of 10 mg or more are used, the patient may ex- undergo dealkylation, oxidation, and hydrolysis. Large doses of scopolamine amounts of these compounds are eliminated in the feces can produce all of the responses seen with atropine. The blood-brain barrier Other tertiary amine compounds with muscarinic re- prevents quaternary ammonium muscarinic blockers ceptor blocking activity have similar central effects. This results in dilation of the pupil (mydriasis) and paralysis of accommodation (cycloplegia), responses Atropine can be useful in patients with carotid sinus that cause photophobia and inability to focus on nearby syncope. Ocular effects are produced only after higher of afferent neurons whose stretch receptors are in the parenteral doses. By reflex mechanisms, this excessive affer- responses lasting several days when applied directly to ent input to the medulla oblongata causes pronounced the eyes. If sinus bradycardia is due to ex- Lung tracardiac causes, atropine can generally elicit a tachy- Muscarinic antagonists inhibit secretions and relax cardic response, whereas it cannot elicit tachycardia if smooth muscle in the respiratory system. Under cer- pathetic innervation of respiratory smooth muscle is tain conditions, atropine may be useful in the treatment most abundant in large airways, where it exerts a domi- of acute myocardial infarction. In agreement with this innerva- occurs after acute myocardial infarction, especially in tion pattern, muscarinic antagonists produce their the first few hours, and this probably results from ex- greatest bronchodilator effect at large-caliber airways. The increased tone and bradycardia 13 Muscarinic Blocking Drugs 137 facilitate the development of ventricular ectopy. Systemic absorption of Although atropine sulfate has proved beneficial in pa- these drugs from the conjunctival sac is minimal, but tients whose bradycardia is accompanied by hypoten- significant absorption and toxicity can occur if the an- sion or ventricular ectopy, it is generally not otherwise timuscarinic drugs come into contact with the nasal and recommended in this condition. To mini- without hazard, because cardiac work can be increased mize this possibility, pressure should be applied to the without improved perfusion, and ventricular arrhyth- lacrimal sac for a few minutes after topical application mias may occur. Shorter-acting drugs, such as cy- clopentolate and tropicamide, are now favored for this Uses in Anesthesiology application because complete recovery of accommoda- At one time, atropine or scopolamine was routinely ad- tion occurs within 6 to 24 hours and 2 to 6 hours, re- ministered before the induction of general anesthesia to spectively. With the newer, less irritating anesthetics, an- System timuscarinic premedication is not routinely required as an antisialagogue. Sedation can occur following scopolamine in the therapy of peptic ulcers (see Chapter 40) because administration, and preanesthetic or postoperative they can reduce gastric acid secretion; they also have agitation has been observed in some patients. High been used as adjunctive therapy in the treatment of ir- serum levels of drugs with antimuscarinic activity can ritable bowel syndrome. Glycopyrrolate bro- crease the pain associated with postprandial spasm of mide (Robinul) has also been given intramuscularly as intestinal smooth muscle by blocking contractile re- a preanesthetic medication with satisfactory results. Some of the agents used for this disor- This agent is a quaternary ammonium compound and der have only antimuscarinic activity (e. Dicyclomine (Bentyl) and oxybutynin (Ditropan) at therapeutic con- Use With Cholinesterase Inhibitors centrations primarily have a direct smooth muscle re- During reversal of competitive neuromuscular block- laxant effect with little antimuscarinic action. However, extra care must be hibited bladder syndrome, bladder spasm, enuresis, and exercised because the prevention of muscarinic recep- urge incontinence. Tolterodine (Detrol), a nonselective tor stimulation eliminates an important early sign of muscarinic antagonist, exhibits functional specificity for cholinergic crisis (see Chapter 12). However, total prevention of involuntary bladder contractions is difficult to Uses in Ophthalmology achieve. The participation of noncholinergic, nonadren- Antimuscarinic drugs are widely used in ophthalmology ergic nerves in bladder contraction may explain this ap- to produce mydriasis and cycloplegia. All of these agents are of antimuscarinic alkaloids in respiratory disorders are tertiary amines that reach the iris and ciliary body after low therapeutic index and impaired expectoration. Ipratropium bromide (Atrovent), in contrast, is a synthetic muscarinic blocking drug that has gained Uses as Antidotes for Cholinomimetic widespread use in recent years for the treatment of res- Poisoning piratory disorders. The drug is a quaternary ammonium compound, and it is applied topically to the airways Atropine is used as an antidote in poisoning by an over- through the use of a metered-dose inhaler. It portion of the dose is swallowed, but absorption from also is used in cases of poisoning from species of mush- the airways and gastrointestinal tract is negligible and room that contain high concentrations of muscarine and most of the drug is eliminated in the feces. Ipratropium does not affect mucociliary excessive doses of belladonna alkaloids, synthetic an- transport or the volume and viscosity of sputum. Maximum bronchodilator responses to speech disturbances, swallowing difficulties, cardioac- ipratropium develop in 1. Ipratropium is less effective than lessness, ataxia, and hallucinations) are more apparent the 2-receptor agonists in asthma, but it may be useful after large doses. Although therapy Poisoning of Parkinson’s disease is directed toward replacement of the dopaminergic deficiency rather than blocking Group Examples the cholinergic excess, antimuscarinics are sometimes Antihistamines Diphenhydramine employed for mild cases and in combination with (H1-receptor antagonists) Chlorpheniramine other agents (e. Propantheline Belladonna alkaloids and related drugs Atropine Scopolamine Uses in Motion Sickness Belladonna alkaloid-containing plants Deadly nightshade Angel’s trumpet Scopolamine is useful for prevention of motion sick- Jimsonweed ness when the motion is very stressful and of short du- Cyclic antidepressants Amitriptyline Doxepin ration. A transdermal preparation (Transderm-Scop) Fluoxetine with a 72-hour duration of action has been marketed Cycloplegics and mydriatics Cyclopentolate for this purpose. Blockade of cholinergic sites in the Tropicamide vestibular nuclei and reticular formation may account Muscle relaxants Orphenadrine for the effectiveness of this agent. When the motion is Cyclobenzaprine less stressful and lasts longer, the antihistamines (H1- Source: Modified from L. You most likely to be different in an elderly versus a proceed to ask questions that might provide a clue young patient?
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