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Labetalol (Normodyne and Trandate) discount methocarbamol 500 mg with mastercard, Carvedilol (Coreg) (1) Labetalol is a partial agonist that blocks b-receptors and a1-receptors (3:1 to 7:1 ratio) cheap methocarbamol 500mg amex. Carvedilol also has mixed activity but is equiactive at b-receptors and a1-receptors purchase 500 mg methocarbamol otc. Timolol (Blocadren), levobunolol (Betagan), nadolol (Corgard), and sotalol (Betapace) (1) These drugs are nonselective b-receptor antagonists. Pindolol (Visken), carteolol (Cartrol), and penbutolol (Levatol) are nonselective antagonists with partial b2-receptor agonist activity. Cardiovascular system (see also Chapter 4) (1) b-Adrenoreceptor antagonists are used to treat hypertension, often in combination with a diuretic or vasodilator. Long-term use of timolol, propranolol, and metoprolol may prolong survival after myocardial infarction. This effect is thought to be related to the slowing of ventricular ejection and decreased resistance to outflow. Eye (1) Topical application of timolol, betaxolol, levobunolol, and carteolol reduces intraocular pressure in glaucoma. Other uses (1) Propranolol is used to control clinical symptoms of sympathetic overactivity in hyper- thyroidism by an unknown mechanism, perhaps by inhibiting conversion of thyroxine to triiodothyronine. All agents (1) b-Adrenoreceptor antagonists should be administered with extreme caution in patients with preexisting compromised cardiac function because they can precipitate heart fail- ure or heart block. Nonselective adrenoceptor antagonists (1) These drugs may cause bronchoconstriction, and thus they are contraindicated for asth- matics. Propranolol, and other b-receptor blockers, cause sedation, sleep disturbances, and depression. What class of medications does bethanechol (A) Inhibiting choline acetyltransferase belong to? The (D) Norepinephrine patient is emergently intubated and given atro- (E) Serotonin pine and another medication that acts to reacti- vate acetylcholinesterase. Oxybutynin works by in nerve terminals (A) Inhibiting acetylcholinesterase at musca- (D) Potentiation of tyrosine hydroxylase, the rinic and nicotinic receptors rate-limiting enzyme in the synthesis of (B) Causing a neuromuscular blockade norepinephrine (C) Antagonizing a1-adrenoceptors (E) Promotion of release of norepinephrine (D) Binding to muscarinic receptors from adrenergic nerve endings (E) Activating b2-adrenoceptors 4. Since the disease is gated ion channel characterized by degeneration of dopaminergic (B) Activates G -protein, resulting in stimula- neurons, leading to the lack of inhibition of cho- s tion of adenylyl cyclase linergic neurons, the addition of which medica- (C) Activates G -protein, resulting in increase of tion is likely to help alleviate the patient’s q phosphatidylinositol and calcium symptoms? A 7-year-old boy is brought in by his parents heavy smoking presents to her doctor with com- for complaints of hyperactivity at school. He is plaints of shortness of breath and chronic also inattentive and impulsive at home. After a coughing that has been present for about 2 years detailed interview, the physician decides to give and has been worsening in frequency. The the boy amphetamine-containing medication doctor decides to prescribe a bronchodilator for presumed attention hyperactivity disorder. Which medication did the doctor likely (B) Indirectly acts on norepinephrine receptors prescribe? Which of the following medications is used (E) Pseudoephedrine to prevent premature labor? From the list below, choose the depolarizing (B) Cevimeline neuromuscular blocker most likely to be used in (C) Atracurium ‘‘rapid sequence intubation,’’ a procedure that (D) Tolterodine is done when the stomach contents have a high (E) Terbutaline risk of refluxing and causing aspiration. What significant side effect of terazosin (B) Succinylcholine should the doctor warn a 69-year-old patient (C) Neostigmine about? Ephedra (ephedrine) causes increased (D) Sedation blood pressure by (E) Drug abuse (A) Indirect action on cholinergic receptors (B) Blockade of adrenergic receptors 16. A floor nurse pages you about a patient who (C) Stimulation of release of epinephrine is having chest pain. You order an electrocar- (D) Inhibition of reuptake of catecholamines diogram and rush to see the patient. He (E) Direct action on dopamine receptors describes the pain as tight pressure and is demonstrably sweating and gasping for air. The local anes- another medication, which you have read may thetic used in the procedure did not contain prolong his survival in this dire situation. The reason for this is (A) b-Blocker (A) Epinephrine causes increased blood loss (B) a-Agonist during delicate surgery (C) Muscarinic agonist (B) Epinephrine causes swelling of the tissues, (D) Neuromuscular blocker making surgery more challenging (E) Dopamine agonist (C) Epinephrine is contraindicated in emer- gency surgery 17. A 35-year-old woman presents to your office (D) Epinephrine causes vasoconstriction, which for a regular check-up. Her only complaint is can lead to vascular ischemia in digits recurrent migraine headaches, which have (E) Epinephrine can cause hypotension when increased in frequency over the years. On exam- administered with sedative agents ination, her blood pressure is elevated at 54 Pharmacology 150/70. Dantrolene is the drug of choice to treat ma- sive therapy that is also used for prophylaxis of lignant hyperthermia caused by succinylcholine migraines.

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Under the squamous cells are round cells called situs inversus totalis See reversal of organs purchase 500 mg methocarbamol amex, basal cells methocarbamol 500mg with mastercard. Sweat and sebum reach the skin’s surface that classically combines dry eyes buy methocarbamol 500mg line, dry mouth, and through tiny openings called pores. Sjogren’s syndrome is an inflammatory disease of glands and other tissues of the body. Skin biopsy is (lacrimal glands) leads to decreased tears and dry most frequently done to diagnose skin growths, eyes. Inflammation of the glands that produce saliva such as moles, or skin conditions, such as rashes. A shave biopsy takes a thin slice and consequently be complicated by infections of the can be used to remove superficial lesions. About 90 per- biopsy takes a core and can be used to remove cent of Sjogren’s syndrome patients are female, usu- small lesions and to diagnose rashes and other con- ally middle aged or older. Excisional biopsies are generally larger and the presence of antibodies that are directed against deeper than shave and punch biopsies, and they are a variety of body tissues (autoantibodies). Diagnosis used to completely remove an abnormal area of can be made via biopsy of an affected gland. Treatment is directed toward the particular areas of the body involved and to complications, such as skin cancer See cancer, skin. The most effective skin grafts involve the body that collectively provide the frame for the moving the patient’s own skin from one part of the body. Beyond these skeletal dysplasia One of a large contingent two procedures, there is a strong chance that the of genetic diseases in which the bony skeleton body will reject the new skin, although the graft may forms abnormally during fetal development. It is the type of muscle that powers movement of the skeleton, as in walking and lifting. Also known as autogenic skin injected into the deep layer of the skin (dermis) and graft. One of the most common skin tests is the tuber- skin graft, composite A graft technique in culin test, which reveals whether a person has been which both the patient’s own skin and donor skin exposed to tuberculosis. For example, a full-thick- skull A collection of bones that encase the brain ness skin graft might be used to repair a severe burn and give form to the head and face. See tiple pieces of skin are carefully arranged to cover an also bones of the head. This technique is used most frequently when a large area needs to be protected, as after a severe slanted ear See ear, slanted. See lupus ery- skin graft, pedicle A graft technique in which a thematosis, systemic. Sleep is triggered by piece is reattached over the area that needs to be a complex group of hormones that respond to cues covered. Like grafts from human donors, 2 sleep features significant slowing of heartbeat and porcine grafts are usually just a short-term protec- breathing and makes up about 50 percent of all tive measure. Most adults need around 8 hours of sleep on a regular schedule to function well, although some skin tag A small tag of skin that may be squat require less and others more. Skin tags com- teenagers, often need 9 or 10 hours for optimal monly occur on the eyelids, neck, armpits, upper functioning. Treatment obstruction may require losing excessive weight, involves orthopedic surgery to bring the bone back avoiding alcohol and sedatives, sleeping on one into alignment. See also sleep period before the onset of a very gradual progres- apnea, central; sleep apnea, obstructive; sleep sive disease. See also sleep small for gestational age In a full-term infant, apnea, obstructive. Sleep apnea that is associated with small-cell lung cancer An aggressive type of air passage obstruction may require losing exces- lung cancer in which the cancerous cells appear sive weight, avoiding alcohol and sedatives, sleeping smaller under a microscope than those in the other on one side, medications to relieve nasal conges- tion, a breathing device, or surgical procedures. Treatment options for small cell cancer sleep disorder Any disorder that affects, dis- may be different than for other types of lung cancers rupts, or involves sleep. The most common sleep (non-small cell lung cancers) Small-cell lung can- disorder is snoring, although it is usually not med- cer cells have been described as resembling oats ically significant. Also known legs syndrome, and sleepwalking are also sleep dis- as oat-cell lung cancer. See also sleep apnea; smallpox A highly contagious and frequently fatal sleepwalking; snoring. Because of its high case-fatality rates and not always including walking, while in a deep stage transmissibility and because people haven’t been of sleep. Sleepwalking occurs most frequently in vaccinated against it in years, smallpox now repre- children, particularly boys. The incubation period is measures are preventive: Ensure that the sleep- about 12 days (range: 7–17 days) following expo- walker is in a safe room for walking and cannot sure. Initial symptoms include high fever, fatigue, accidentally fall through an open window or down headaches, and backaches. Some types of sleepwalking are related to most prominent on the face, arms, and legs, follows seizure disorders, bipolar disorders, and other neu- in 2 to 3 days.

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The metabolism of theophylline depends on age; the half-life of the drug in chil- dren is much shorter than in adults discount methocarbamol 500mg online. Theophylline may have several mechanisms of action order methocarbamol 500 mg on line, but its adenosine-recep- tor antagonist activity and the inhibition of phosphodiesterase are the best understood cheap methocarbamol 500mg visa. Opioids act centrally to decrease the sensitivity of the cough center; they also decrease propulsion in the bowel. It does not cross the blood–brain barrier and does not block mediator release or H1-receptors. By inhibiting 5-lipoxygenase, zileuton reduces leukotriene biosynthesis; it does not inhibit (and in fact it might increase) prostaglandin synthesis. Membrane-associated receptors transmit signals into the cell by a variety of ‘‘second messen- ger’’ mechanisms, including the following: a. Increased phosphoinositide turnover via increased phosphoinositide kinase activity 2+ 2+ c. Increased tyrosine phosphorylation on specific proteins by the action of tyrosine kinases B. Intracellular receptors bind hydrophobic hormones (which penetrate the plasma membrane easily) such as cortisol, retinol, and estrogen inside the cell—either in the cytoplasm or the nucleus. Intracellular receptors modulate the transcription rate of specific target genes to change the levels of cellular proteins. The endogenous ligand for this receptor is ghrelin, a peptide secreted by the stomach in response to fasting. Somatotropin release-inhibiting hormone has two forms, a 14-amino acid peptide and a 28- amino acid peptide that are produced by differential proteolysis from the same precursor. It also inhibits the secretion of vasodilator hormones, especially within the gut. Adverse effects of octreotide include nausea, cramps, and increased gallstone formation. This occurs by modu- lating the function of the hypophyseal–pituitary gonadal axis (Fig. Chemical castration, which is useful in the treatment of hormone-dependent cancers and hyperplasias such as prostate cancer, breast cancer, endometriosis, and fibroids b. Adverse effects include a transient worsening of symptoms, hot flashes, and induction of ovar- ian cysts in the first months of long-term treatment. The trophic hormones act on peripheral organs such as the ovary or testis to increase the production of gonadal steroids. Gonadal steroids in turn exert negative feedback on the hypothalamus and pituitary. Chapter 10 Drugs Acting on the Endocrine System 219 (3) Leuprolide acetate may be used to treat prostate cancer, prostatic hypertrophy, breast cancer, endometriosis, and fibroids. These include (1) Antipsychotics, including chlorpromazine and haloperidol (2) Antidepressants, including imipramine (3) Antianxiety agents, including diazepam c. Inhibition of prolactin secretion can be produced by a number of dopamine agonists. It is more effective in reducing hyperprolactinemia than bromocriptine and has a long half-life that permits twice-weekly dosing. Therapeutic uses of these agents include the inhibition of prolactin secretion in amenor- rhea, galactorrhea, and prolactin-secreting tumors; the correction of female infertility sec- ondary to hyperprolactinemia; and the treatment of Parkinson disease. Peak blood levels are obtained in 2–4 hours; activ- ity persists for 36 hours after administration, because of the relatively long half-life of soma- tomedins. Rather, the menopausal and chorionic gonadotropins described below are used as the source of biologically active peptides. Aqueous vasopressin (Pitressin), a short-acting preparation that acts on both V1 and V2 receptors, is administered parenterally and lasts 2–6 hours. Desmopressin is the most effective treatment for severe diabetes insipidus because its V2 ac- tivity is 3,000 times greater than its V1 activity; but it is not effective in the nephrogenic form of the disease. Oxytocin is a 9-amino acid peptide synthesized in the hypothalamus and secreted by the posterior pituitary. Is sometimes used to control postpartum uterine bleeding (more readily controlled with er- got alkaloids) 4. Oxytocin can cause uterine rupture and should not be used after uterine surgery or if signs of fetal distress are present. These events lead to a change in the synthesis of specific proteins within a target cell. Estrone sulfate, when combined with a-equilin or with other estrogenic sulfates, is effective orally, but natural estrogens are subject to a large first-pass effect. Synthetic estrogens may be administered orally, topically, transdermally, or by injection.

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Current resin materials are either autopolymerizing or photo-initiated purchase 500 mg methocarbamol mastercard, and most operators prefer the advantages of demand set offered by photo-initiation buy methocarbamol 500mg cheap. Although there are theoretical advantages to chemically cured materials in terms of retention generic methocarbamol 500 mg otc, as these materials have longer resin tags extending into the etched surface. Filled and unfilled resins are available, the filled materials being produced to provide greater wear resistance. However, this is not clinically relevant and clinical trials demonstrate superior efficacy for unfilled materials. Irrespective of the presence of fillers some materials are opaque or tinted to aid evaluation. This is an advantage but means the clinician is unable to view the enamel surface to assist with caries detection and to detect the presence of restorations such as sealant restorations. Key Points Fissure sealing technique • Prophylaxis before etching does not enhance retention but is advisable if abundant plaque is present. A dry brush should be used rather than paste as these are retained in the depths of the fissures preventing penetration of the resin. Operator and assistant must act as a team as it is impossible for single operators to apply sealant effectively. The vast majority of trials have demonstrated cotton wool and suction to be an effective means of isolation. Rubber dam is advocated by some because of the superior isolation offered by this material. This is probably true but its use is frequently not possible because of the stage of eruption of the tooth or level of co-operation of the patient. It would be inappropriate to delay sealant application to allow further eruption to permit the application of rubber dam. The application of sealant is a relatively non-invasive technique, frequently used to acclimatize a patient. It is difficult to justify the use of rubber dam with the associated use of local anaesthetic and clamps for the majority of patients, on both clinical and economic grounds. Glass ionomers have also been used as sealants, the application technique is less sensitive, than that for resins. It is suggested that the fluoride release from glass ionomers provides additional protection but the clinical relevance of this remains doubtful. The addition of fluoride to resin sealants has been demonstrated to provide no additional benefit. Glass ionomer sealants only have a place as temporary sealants during tooth eruption, when adequate isolation to permit the application of resin is not possible or in patients whose level of anxiety or co-operation similarly prevent placement of resin. Glass ionomers have been developed specifically for this role but clinical evidence of their effectiveness is not yet available. Key Points Application of glass ionomer sealants • Clean the surface • Isolate the tooth • Run the glass ionomer into the fissures • Protect the material during initial setting • Apply unfilled resin, petroleum jelly, or fluoride varnish to protect the material. For anxious patients application can be done with a gloved finger until the material is set. Resin fissure sealants are effective; a recent systematic review has demonstrated 57% caries reductions at 4 years, with retention of 71-85% at 2 years falling to 52% at 4 years (Ahovuo-Saloranta et al. To gain the full caries preventive benefit sealants should be maintained, that is, sealants with less than optimal coverage identified and additional resin applied. Since the development of sealants there has been a question regarding the effect of sealing over caries, the concern being that caries will progress unidentified under the sealant. Given the difficulty in diagnosing caries this must be a frequent occurrence in daily practice. A number of trials have examined this by actively sealing over caries, and all have shown that sealants arrest or slow the rate of caries progression. We are not at the point where sealing of active caries is recommended by most authorities but the maxim if in doubt seal is good advice. The surface should then be monitored clinically and radiographically at regular intervals until its status is confirmed. One instance where actively sealing over caries is to be recommended is in the pre- cooperative patient where the placement of sealant may help acclimatization of the patient, with the added benefit of controlling the caries, until a definitive restoration can be placed. Sealants are also effective at preventing pit and fissure caries in primary teeth. Primary teeth have more aprismatic enamel than permanent teeth, and doubt about the effectiveness of etching deciduous enamel lead to a belief that they required prolonged etching times. This has been demonstrated not to be the case and the technique for sealant application to primary teeth is identical to that employed with permanent teeth. Although the effectiveness of fissure sealants is beyond doubt, to be used cost effectively their use should be targeted. Guidelines for patient selection and tooth selection have been published by the British Society for Paediatric Dentistry, and these are summarized below. Fissure sealing of all occlusal surfaces of permanent teeth should be considered for those who are medically compromised, physically or mentally disabled, or have learning difficulties, or for those from a disadvantaged social background. Children with extensive caries in their primary teeth should have all permanent molars sealed soon after their eruption.