By N. Finley. The College of Saint Rose.
Thus generic trileptal 600 mg free shipping medicine used to treat chlamydia, because of their physicochemical character- In clinical practice cheap 300mg trileptal with mastercard medicine vending machine, drugs are more commonly ad- istics, different drugs can have quite different volumes ministered in multiple doses, with the second dose usu- of distribution in the same person. The ﬁnal concen- drug does not distribute widely into tissues (though it trations of drug reached depend on the elimination rate does reach tissues to some degree to exert its action). In contrast, the time to reach steady widely throughout the body; in fact, it does distribute to state is affected by neither the dose amount nor dosing various tissues, such as the liver, lungs, eyes, and adipose frequency. Since the total volume of the body does not equal fected by the elimination rate (which is reﬂected in the 4200 L, it can clearly be seen that this is not a “real” vol- t1/2). Giving a larger dose or giving the dose more often ume but one that relates the blood concentration to the will not change the time needed to reach steady state amount of drug in the body. Just as it takes approximately ﬁve half-lives for a Protein Binding drug to be essentially (97%) eliminated, it also requires ﬁve half-lives for a drug to reach steady state. This is ex- Most drugs bind to plasma proteins such as albumin and empliﬁed in the concentration–time proﬁles of Figure 1-acid glycoprotein (AGP) to some degree. The hypothetical drug in this example has a half-life comes clinically important as it is assumed that only un- of 8 hours and is dosed every 8 hours. The graph shows bound (free) drug is available for binding to receptors, that at about 40 hours (ﬁve half-lives), the maximum being metabolized by enzymes, and eliminated from the and minimum concentrations become consistent, indi- body. For example, phenytoin is approximately 90% bound to plasma proteins, leaving 10% of the concentration in the blood as free drug and available for pharmacologi- 1000 cal action and metabolism. If the presence of renal dis- ease or a drug interaction were to alter the degree of protein binding to only 80%, this change could have substantial clinical consequences. Even though the total t1/2 = 8hr percent bound changes relatively little, the net result is to double the amount of free drug. However, for most drugs, displacement from protein binding sites re- sults in only a transient increase in free drug concentra- tion, since the drug is rapidly redistributed into other body water compartments. Thus, interactions or changes 10 in protein binding in most cases have little clinical effect 0 despite these theoretical considerations. This nonlinearity often occurs be- cause the drug-metabolizing enzymes for the drug be- NONLINEAR PHARMACOKINETICS come saturated at typical blood concentrations, such that despite increases in dose, drug is still metabolized The underlying assumption in the discussion of these at the same rate and blood concentrations go up unex- concepts is that the drug of interest follows linear phar- pectedly. In this case, following Michaelis-Menten en- macokinetic principles; that is, the concentrations zyme kinetics, the maximum velocity (Vmax) has been achieved are proportional to the dose given. For exam- reached and the rate of drug metabolism remains con- ple, a doubling of the dose will produce a doubling of stant. For some drugs, however, this is not the case: an increase in dose may produce a con- centration much greater than expected. For example, in- creases in dosage of the antiepileptic agent phenytoin 60 above approximately 300 mg daily usually produce a 50 180 40 160 30 140 120 20 Phenytoin Therapeutic Range 100 10 80 60 0 40 Bolus dose + Continuous Infusion 20 Continuous Infusion Only 0 100 200 300 400 500 600 Phenytoin Dose (mg) 0 FIGURE 5. Within the either an intravenous bolus dose immediately followed by therapeutic range, a relatively small increase in dose results initiation of a continuous intravenous infusion or initiation of in a greater than proportional increase in concentration, a continuous intravenous infusion only. Frequently it is useful to consider the overall expo- (A) Theoretical dose sure of a person to a drug during the dosing inter- (B) Cmax val. Which of the following pharmacokinetic param- (C) Bioavailability eters deﬁnes the exposure of a person to a drug? The AUC (area under the curve) best describes (D) Half-life the overall exposure of a person to a given drug (E) Clearance over the course of the dosing interval. Organs such as the liver remove exogenous chemi- the concentration of drug integrated over the pe- cals, such as drugs, from the body. A (Cmax) is phenytoin, for which the difference between the not correct, as Cmax gives the maximum concentra- minimum effective concentration and the minimum tion achieved but does not reveal how long measur- toxic concentration is small, clinicians must calcu- able concentrations of the drug were present or late the rate at which a given individual removes how long until this concentration was achieved. The volume of ﬂuid from which (Tmax) only refers to the time until the maximum drug can be completely removed per unit of time concentration is achieved, again not giving a refer- (rate of drug removal) is termed: ence to overall exposure over time. D (half-life) (A) Distribution simply describes how much time is required for the (B) Clearance concentration to decrease by one-half. Finally, clear- (C) Metabolism ance (E) is the volume of ﬂuid (usually plasma) (D) Excretion from which drug can be removed per unit of time 3. Clearance is deﬁned as the volume of ﬂuid from hours), steady state will be reached shortly follow- which drug is completely removed per unit of time ing which DOSE (not which half-life)? Distribution is the theoreti- (C) 5th dose cal volume to which the drug distributes and me- (D) 8th dose tabolism and excretion are simply methods of (E) 12th dose clearing drug.
White cells are absent or normal in cholera and in Giardia and viral (rotavirus order trileptal 150 mg line medications listed alphabetically, Norwalk virus generic 600mg trileptal free shipping treatment 9mm kidney stones, etc) infections. Tzanck Smear This technique (named after Arnault Tzanck) is used in the diagnosis of herpesvirus infec- tions (ie, herpes zoster or simplex). Clean a vesicle (not a pustule or crusted lesion) with alcohol, allow it to air dry, and gently unroof it with a #15 scalpel blade. Giemsa stain can also be used, however, the sample must be fixed for 10 min with methyl alcohol before the Giemsa is applied. Then use high-power oil immersion to identify multinucleated giant cells (epithelial cells infected with herpes viruses). This strongly suggests viral infection; culture is necessary to identify the spe- cific virus. Vaginal Wet Preparation • See Chapter 13, page 291 Wayson Stain Wayson stain is a good quick scout stain that colors most bacteria. Pour freshly filtered Wayson stain onto the slide, and allow it to stand for 10–20 s (tim- ing is not critical). Anorectal stains may contain nonpathogenic Neisseria species; avoid fecal contact; apply swab to anal crypts. In males with a urethral discharge, insert a calcium alginate swab (Calgiswab) into the urethra to collect the specimen and then plate. The GC smear (see Chapter 13, page 291) has a low sensitivity (<50% in female endo- cervical smear, but is fairly reliable (>95%) in males with urethral discharge. A rapid en- zyme immunoassay (gonococcal antigen assay [Gonozyme]) is available to diagnose cervical or urethral GC (not throat or anus) infections in less than 1 h. NASOPHARYNGEAL CULTURES Ideally, the specimen for culture should be obtained from deep in the nasopharynx and not the anterior nares, and the swab should not touch the skin. Cultures of nasopharyngeal spec- imens are useful in identifying Staphylococcus aureus and N. BLOOD CULTURES Blood cultures are not usually indicated for the routine workup of fever. Fever of unknown origin, especially in adults with white blood counts of > 15,000/mm3 and no localizing signs or symptoms to suggest the source. Clinical situations in which the diagnosis is established by a positive blood culture (eg, acute and SBE). Chills and fever usually ensue from ¹ ₂–2 h after sudden entry of bacteria into the circu- lation (bacteremia). If bacteremia is suspected, several sets of cultures are usually needed to improve the chances of culturing the offending organism. Ideally, more than one set of cul- tures should be done at least 1 h apart; drawing more than three sets of specimens a day does not usually increase the yield. Each “set” of specimens for blood culture consists of both an aerobic and anaerobic culture bottle. If possible, culture the specimens before antibiotics are initi- ated; if the patient is already on antibiotics, use ARD culture bottles, which absorb the an- tibiotic that may otherwise destroy any bacteria. Legionella, Mycobacterium, Bordetella, and Histoplasma may require special blood collection devices. Remove the tourniquet, and compress the venipuncture site and apply an adhesive bandage. Discard the needle used in the puncture and replace it with a new, sterile 20–22- gauge needle. Place the blood in each of the bottles by allowing the vacuum to draw in the appropriate volume, usually specified on the collection device. Submit the samples to the lab promptly with the appropriate lab slips completed including current antibiotics being given. Interpretation Preliminary results are usually available in 12–48 h; cultures should not be formally re- ported as negative before 4 d. A single blood culture that is positive for one of the following organisms usually suggests contamination; however, on rare occasions these agents are the causative pathogen: Staphylococcus epidermidis, Bacillus sp. Negative results do not rule out bac- teremia, and false-positives can result for the contaminants noted. Gram-negative organ- isms, fungi, and anaerobes are considered to be pathogenic until proven otherwise.
Obstructive sleep apnea ing techniques such as a CT or MRI scan and can be is treated by surgically removing the tonsils and ade- treated with neurosurgery or shunting (draining) if it noids 300 mg trileptal for sale medications used for anxiety. Neurosurgery may be required to treat sleep apnea GALE ENCYCLOPEDIA OF GENETIC DISORDERS 19 Achondroplasia Autosomal Dominant 86y d order trileptal 150 mg free shipping medicine 230. Weight management The social adaptation of children with achondropla- may also play a role in the treatment of sleep apnea. Other potential problems in children with achon- Children with visible physical differences can have diffi- droplasia include overcrowding of the teeth (dental mal- culties in school and socially. Support groups such as occlusion), speech problems (articulation), and frequent Little People of America can be a source of guidance on ear infections (otitis media). All chil- with achondroplasia not be limited in activities that pose dren with achondroplasia should be evaluated by a speech no danger. In addition to monitoring their social adapta- therapist by two years of age because of possible prob- tion, every effort should be made to physically adapt their lems with the development of clear speech (articulation). Due to the abnormal shape of the eustachian accessibility and lowering of switches and counters. Approximately 80% final adult height of individuals with achondroplasia of infants with achondroplasia have an ear infection in the –limb-lengthening and growth hormone therapy. About 78% of these infants require ven- are risks and benefits to both treatments and as of 2001, tilation tubes to decrease the frequency of ear infections. Weight management is extremely important for an Limb-lengthening involves surgically attaching individual with achondroplasia. Over a period of 18-24 months, the tension on vature of the spine, and joint and lower back pain. Excess these rods is increased, which results in the lengthening weight can also contribute to sleep apnea. This procedure is long, costly, of good eating habits and appropriate exercise programs and has potential complications such as pain, infections, should be encouraged in individuals with achondroplasia. Limb-lengthening can increase These individuals should discuss their exercise programs overall height by 12-14 in (30. Because of the potential change the other physical manifestations of achondropla- for spinal cord compression, care should be used in sia such as the appearance of the hands and face. IACHOO syndrome Growth hormone therapy has been used to treat some Definition children with achondroplasia. Originally there was doubt about the effectiveness of this treatment because children ACHOO syndrome is a generally benign condition with achondroplasia are not growth hormone deficient. It is Description too early to say how effective this treatment is because The ACHOO syndrome, standing for autosomal the children involved in this study are still growing and dominant compelling heliopthalmic outburst syndrome, have not reached their final adult height. A person with Prognosis this condition will sneeze multiple times, and in rare The prognosis for most people with achondroplasia cases may sneeze 30-40 times. In general, they have minimal medical more intense if the person with the condition moves problems, normal IQ, and most achieve success and suddenly from darkness into an area with bright lights have a long life regardless of their stature. Obesity can increase the copy of the abnormal gene needs to be present for the risk for heart disease and some studies have revealed an syndrome to occur. If one parent has the condition, their increased risk of unexplained death in the fourth and children will have a 50% chance of also having the syn- fifth decade of life. Both the father in the ultimate success and happiness of an individual and brother would sneeze twice when going from an area with achondroplasia. Resources Because of the relatively benign nature of the condi- tion, there has been no reported scientific work trying to BOOKS locate the gene responsible for the syndrome. Occurrence of the ACHOO syndrome is widespread “Health Supervision for Children With Achondroplasia. The way in which sneezing is GALE ENCYCLOPEDIA OF GENETIC DISORDERS 21 When a person with the syndrome is exposed to a bright KEY TERMS light, the same mechanism in the body that triggers a sneeze due to an irritant such as pollen somehow con- Allergy—Condition in which immune system is fuses light with that irritant and causes a sneeze to occur. A third theory is that people of tissues and production of excess mucus in res- with the ACHOO syndrome are very sensitive to seeing piratory system. The sneeze reflex of the syndrome can then Antibody—A protein produced by the mature B be thought of as an involuntary defense reaction against cells of the immune system that attach to invading bright light; when the person sneezes, they automatically microorganisms and target them for destruction by close their eyes. Antigen—A substance or organism that is foreign Diagnosis to the body and stimulates a response from the The ACHOO syndrome is diagnosed simply by immune system. Immune system—A major system of the body that produces specialized cells and substances that interact with and destroy foreign antigens that Treatment and management invade the body.
However cheap 300mg trileptal visa treatment 2 prostate cancer, in the chromosome Genetic profile 3 and 10 families purchase trileptal 150 mg amex medicine 60, some individuals who appear to carry Most cases of Möebius syndrome are isolated and do a gene do not show signs of Möebius syndrome, suggest- not appear to be genetic, but occurrence in multiple indi- ing that factors other than genetics, such as uterine envi- viduals within some families indicates that there are mul- ronment, are involved even in these highly familial cases. One study in 1991 suggested that One family was reported in which two brothers and forms of Möebius syndrome which included abnormali- their male cousin who were the sons of sisters all had ties of the limbs and skeleton were less likely than other Möebius syndrome along with other physical abnormali- types to be genetic. Boys only have one X chro- such as to the drug misoprostol, appear to increase the mosome and can inherit an X-linked disease from their risk of Möebius syndrome. The GALE ENCYCLOPEDIA OF GENETIC DISORDERS 747 pattern of affected children in this family is therefore typ- expression. Since exact genes involved in Möebius syn- ical of X-linked inheritance, so it is suggested that there drome have not yet been identified as of 2001, molecular may be a gene involved in Möebius syndrome on the X genetic testing is not available at this time. If this is the case, the son of a woman with an altered Möebius gene on one X-chromo- Treatment and management some would have a 50% chance of inheriting the gene The ability to smile has been restored in some cases and having the condition. A man with this type of of Möebius syndrome by surgery which transfers nerve Möebius syndrome would be unlikely to have affected and muscle from the thigh to the face. Other surgeries can children since his daughters would likely have one nor- be used to treat eye, limb, and jaw problems. In children mal X chromosome from their mother and his sons would not receive his X chromosome but his Y chromo- with feeding problems, special bottles or feeding tubes some. Physical and speech therapy are used when nec- fected parents had Möebius syndrome, suggesting essary to improve control over coordination, speech, and autosomal recessive inheritance, in which two altered eating. In an autosomal recessive disorder, a couple in which each par- Prognosis ents carry one altered copy of the disease gene have a Möebius syndrome does not appear to affect life 25% chance of having a child with the condition with span, and individuals who are treated for their symptoms each pregnancy. Demographics Resources Möebius syndrome is extremely rare and does not PERIODICALS seem to affect any particular ethnic group more than oth- Kumar, Dhavendra. The first sign of Möebius syndrome in newborns is an inability to suck, sometimes accompanied by exces- Toni I. Also seen at birth in some patients are abnormalities of the limbs, tongue, and jaw. Mohr syndrome see Oral-facial-digital Children also often have low muscle tone, particularly in syndrome (OFD) the upper body. The lack of facial expression and inabil- ity to smile become apparent as children get older. Morquio syndrome (MPS IV) see When cranial nerve palsy is associated with limb Mucopolysaccharidosis (MPS) reduction abnormalities and the absence of the pectoralis muscles, the condition is known as Poland-Möebius or Möebius-Poland syndrome. It has been estimated in the past IMoyamoya to be between 10% and 50%, but these numbers are Definition thought to be overestimates resulting from the lack of facial expression and drooling seen in people with Moyamoya is a progressive syndrome characterized Möebius syndrome. It can be caused genetically, but can also KEY TERMS occur as a result of having other diseases. Moyamoya is seen in patients with a variety of diseases, including: Angiography—Injecting dye into blood vessels so neurofibromatosis, trisomy 21 (Down syndrome), they can be be seen on a radiograph or picture. The carotid arteries are two of the large arteries have 46 chromosomes arranged into 23 pairs. The external Changes in either the total number of chromo- carotid artery allows blood to reach areas within the neck, somes or their shape and size (structure) may lead while the internal carotid artery travels to the brain and to physical or mental abnormalities. In patients with moyamoya, there is a symmetric to a block of blood flow in part of the brain, which thinning of the width of the internal carotid arteries. The can lead to a variety of problems, including paral- brain responds to this thinning by making the smaller ysis, difficulty speaking, difficulty understanding blood vessels bigger, trying to get blood to the areas of others, or problems with balance. When dye is injected into the arteries of the brain (a cerebral angiogram), a characteristic pattern is seen. But, over a period of years, strokes and TIAs will Genetic profile leave patients with permanent weakness on both sides of the body, seizure disorders, and mental retardation. While The primary form of moyamoya is seen most often children will present with seizures or strokes, adults tend in Japan. Studies have found the familial form to account to present with intracerebral hemorrhage (bleeding for 7–10% of the cases. Depending on where the bleeding or families in order to find the genetic marker for the dis- strokes occur, there can be a variety of chronic symptoms ease. The gene locus was found to be present on the short including: speech disturbance, visual disturbance, arm of chromosome 3, specifically 3p26–p24. Other headaches, difficulties with sensation and involuntary studies have found possible involvement of genes on movements (moving parts of the body when you do not chromosomes 6 and 17 as well. Demographics Diagnosis Although the disease seems to occur most often in Cerebral angiography is the main method of diagno- Japanese people, patients have been found throughout the sis.
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