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Parenteral administration is used for drugs that are poorly absorbed from the Gl tract and for treatment of patients with serious infections who require maintenance of higher serum concentrations of antimicrobial agents womens health 022013 2.5 mg femara with visa. Utilizing these properties to optimize antibiotic dosing regimens can improve clinical outcomes and possibly decrease the development of resistance. Giving drugs that exhibit this concentration-dependent killing by a once-a-day bolus infusion achieves high peak levels, favoring rapid killing of the infecting pathogen. This effect is sometimes called time-dependent (or concentration-independent killing. The ninth section of the list is labeled "Other:· and it is used to represent any organism not included in one of the other eight categories. Narrow-spectrum antibiotics Chemotherapeutic agents acting only on a single or a limited group of microorganisms are said to have a narrow spectrum. Extended-spectrum antibiotics Extended spectrum is the term applied to antibiotics that are modified to be effective against gram-positive organisms and also against a significant number of gram-negative bacteria. Administration of broad-spectrum antibiotics can drastically alter the nature of the normal bacterial flora and precipitate a superinfection due to organisms such as Clostridium difficile, the growth of which is normally kept in check by the presence of other colonizing microorganisms. Because such synergism among antimicrobial agents is rare, synergistic combinations are only indicated in special situations (for example, in the treatment of enterococcal endocarditis). Combinations may also be used when an infection is of unknown origin or when there are organisms with variable sensitivity, such as when treating tuberculosis. Disadvantages of drug combinations A number of antibiotics act only when organisms are multiplying. Thus, coadministration of an agent that causes bacteriostasis plus a second agent that is bactericidal may result in the first drug interfering with the action of the second. Another concern is the risk of selection pressure and the development of antibiotic resistance by giving unnecessary combination therapy. Decreased accumulation: Decreased uptake or increased efflux of an antibiotic can confer resistance because the drug is unable to attain access to the site of its action in sufficient concentrations to injure or kill the organism. Prophylactic Use of Antibiotics 363 Drug resistance due to altered targets Drug resistance due to decreased accumulation ~ - Permeability - t Efflux - Drug resistance due to enzymatic inactivation Aminoglycosides - Aminoglycosides - - Chloramphenicol Clindamycin Chloramphenicol Fluoroquinolones P-Lactams Macrolldes Rifampin - Fluoroquinolones P-Lactams - - Fluoroquinolones P. However, resistant organisms may also have altered porin channels through which carbapenems do not pass. Tetracycline was effective against gynecologie infection due to Bacteroides, but now these organisms are resistant due to the presence of plasmidmediated protein that promotes efflux of the drug. Neisseria gonorrhoeae is now largely resistant to penicillin because of penicillinase activity. Also, the presence of an efflux pump can limit levels of a drug in an organism, as seen with tetracyclines. Enzymatic inactivation: the ability to destroy or inactivate the antimicrobial agent can also confer resistance on microorganisms. Examples of antibiotic-inactivating enzymes include 1) p-lactamases ("penicillinases") that hydrolytically inactivate the p-lactam ring of penicillins, cephalosporins, and related drugs; 2) acetyltransferases that transfer an acetyl group to the antibiotic, inactivating chloramphenicol or aminoglycosides; and 3) esterases that hydrolyze the lactone ring of macrolides. Because the indiscriminate use of antimicrobial agents can result in bacterial resistance and superinfection, prophylactic use is restricted to clinical situations in which the benefits 364 28. Pretreating of patients undergoing dental extractions who have implanted prosthetic devices, such as artificial heart valves, prevents seeding of the prosthesis. Hypersensitivity Hypersensitivity or immune reactions to antimicrobial drugs or their metabolic products frequently occur. For example, the penicillins, despite their almost absolute selective microbial toxicity, can cause serious hypersensitivity problems, ranging from urticaria (hives) to anaphylactic shock. Fluoroquinolones can have effects on cartilage and tendons, and tetracyclines have direct effects on bones. Effective prophylaxis is directed against the most likely organism, not eradication of every potential pathogen. Superinfections Drug therapy, particularly with broad-spectrum antimicrobials or combinations of agents, can lead to alterations of the normal microbial flora of the upper respiratory, oral, intestinal, and genitourinary tracts, permitting the overgrowth of opportunistic organisms, especially fungi or resistant bacteria. Doxycycline (a tetracycline) should be avoided due to the potential harm to the fetus. Nitrofurantoin, amoxicillin (a penicillin), and cephalexin (a cephalosporin) are generally considered safe. Modification of target site Decreased drug levels due to changes in permeability Decreased drug levels due to an efflux pump Enzymatic inactivation 28. Isoniazid is only active against Mycobacterium tuberculosis, while ceftriaxone, ciprofloxacin, and imipenem are considered broad spectr~m due to their activity against multiple types of bacteria and 1ncreased risk for contributing to the development of a superinfection. Aminoglycosides, including gentamicin, possess a long postantibiotic effect, especially when given as a high dose every 24 hours. Erythromycin is metabolized by the liver and should be used with caution in patients with hepatic impairment. Lipid solubility of the drug Minimum inhibitory concentration of the drug Protein binding of the drug Molecular weight of the drug Correct answer = B. Although the minimum inhibitory concentration impacts the effectiveness of the drug against a given bacteria, it does not affect the ability of a drug to penetrate Into the brain. Lipid solubility, protein binding, and molecular weight all determine the likelihood of a drug to penetrate the blood-brain barrier and concentrate in the brain. Stevens-Johnson syndrome is a severe idiosyncratic reaction that can be life threatening, and these patients should never be rechal enged with the offending agent. A patient may be rechallenged If the benefits outweigh the risk (for example, pregnant patient with syphilis) or the patient could be exposed through a desensitization procedure.
The associated inflammatory response pregnancy ultrasounds purchase femara cheap, which includes lymphocytes, plasma cells and occasionally eosinophils, may contribute to exudative losses from the colon. Rectal Prolapse Complete rectal prolapse occurs in 4% of patients with schistosomal colonic polyposis187 and in 32% of those with rectal polyps. The patient may be partially incontinent owing to lax anal sphincters which is a matter that must be considered when planning an operation. They found marked histological, immunological and ultrastructure changes of a myopathy in the pelvic floor muscles of over 70% of their patients having a rectal prolapsesecondary to schistosomal disease. They concluded that their findings were in keeping with the pathogenesis of rectal prolapse associated with bilharzia. Traditionally, surgery was advised for the treatment of schistosomal rectal prolapse. However, in cases of severe infection, particularly in children, chronic diarrhoea with passage of blood and mucus can occur, often associated with abdominal pain, tenesmus, anorexia and weight loss. Involvement of the appendix may produce symptoms of appendicitis, and rectal prolapse is not uncommon in infected children. Chronic infection can result in iron deficiency anaemia, hypoalbuminaemia and possibly impaired childhood growth and development. Endoscopic examination of the colon and rectum may reveal adult worms clinging to the mucosa. The male adult can be distinguished from the female, being slightly shorter, at 4 cm in length (compared with 5 cm), and having a coiled posterior end with prominent spicules. The prevalence varies from less than 1% to more than 90% in endemic areas such as the Philippines. Treatment Mebendazole is the treatment of choice in a dose of 100 mg twice daily for three days. Mebendazole, given in the second trimester of pregnancy, has been shown to be safe and effective. Larvae are released into the small intestine where they mature and develop into adult worms. The tail of the female is tapered and straight, whereas that of the male is curved and has a single hook-like spicule. Children are most commonly infected, but entire families and individuals living in overcrowded areas, particularly in residential institutions, are also at risk of infection. Treatment Mebendazole or albendazole are the drugs of choice, given as a single dose. Similarly, other members of the family who may be asymptomatic should also be treated at the same time. Pyrantel pamoate is equally effective when given as a single dose of 10 mg/kg, again followed by an intensive repeat treatment regimen for up to ten weeks. Alternatives include piperazine 5075 mg/kg daily for seven days and pyrvinium pamoate 5 mg/kg as a single dose. Transmission and Life-Cycle Human infection begins following ingestion of ova, usually by direct transmission from person to person or by ova in household dust and clothing. Autoinfection is common in children when embryonated eggs are transferred from the perianal area to the mouth. Following ingestion, ova hatch in the duodenum and the rhabditiform larvae proceed to the caecal region where they mature into adults. After mating, the male worm soon dies, but the female migrates to the anus where she deposits embryonated eggs in the perianal and perineal areas. The eggs become implanted within a few hours and remain visible for up to two weeks. The life-cycle is completed within six to eight weeks and humans are the only known host. Strongyloides Stercoralis Strongyloides stercoralis generally affects the small intestine often resulting in severe intestinal malabsorption. The importance of this disease has been emphasised by the often devastating effects of corticosteroids or other immunosuppressive therapy seen in infected but otherwise asymptomatic individuals. The worm most commonly resides in the duodenum and jejunum and invades the intestine, creating burrows within the mucosa. It is often found in association with hookworm and may reach prevalence rates in excess of 80%, particularly in socially deprived communities. Since the worm can survive through autoinfection for periods of up to 30 years without leaving its host, visitors to endemic areas may present with the disease many years later. A particular example was seen in prisoners of war from southeast Asia; approximately 25% of Australian prisoners had the infection identified only 30 years later. Secondary bacterial infection of these lesions may occasionally result in submucosal abscesses. Serious complications can occur when the adult worm migrates through the intestinal wall into extraintestinal locations. A marked inflammatory response occurs in these sites, which includes the urogenital tract, liver, spleen, kidney, omentum and lung. It is usually nocturnal and is due to the inoculation by the egg-laying adult females in the perianal region. Scratching results in dissemination of eggs into bed linen and clothing and to autoinfection by direct finger-oral transmission. Symptoms of appendicitis may be a presenting feature when worms are found within the lumen of the appendix. The larvae then migrate haematogenously to the lung where they develop into adolescent worms.
Propranolol is a non-selective beta blocker that is not indicated in overflow incontinence breast cancer vaccine trials order femara with mastercard. Epinephrine reverses hypotension by activating 1 receptors and relieves bronchoconstriction by activating 2 receptors in anaphylaxis. Since epinephrine was not effective in reversing hypotension or bronchoconstriction in this patient, it could be assumed that the patient was on a nonselective -blocker (propranolol). Doxazosin (1-blocker), metoprolol, or acebutolol (both 1-selective blockers) would not have completely prevented the effects of epinephrine. Which medication is he most likely taking that contributed to a reduced response to epinephrine Being antihypertensive agents, they are not useful in treating hypotension in anaphylaxis. They increase (not reduce) the frequency of urination by relaxing the internal sphincter of the urinary bladder, which is controlled by 1 receptors. If -blocker therapy is stopped abruptly, that could cause angina and rebound hypertension. Cardioselective -blockers antagonize only 1 receptors and do not worsen asthma, as they do not antagonize 2 receptors. Which of the following drugs is commonly used topically in the treatment of glaucoma Timolol is a nonselective -blocker that is commonly used topically to treat glaucoma. Esmolol is a short-acting -blocker that is used intravenously for hypertension or arrhythmias. Prazosin causes orthostatic hypotension due to its 1 blockade, which could be enhanced by adding labetalol. Which of the following drugs has the highest potential to worsen orthostatic hypotension when given together with prazosin In both systems, the recognition of the neurotransmitter by the membrane receptor of the postsynaptic neuron triggers intracellular changes. Open channels allow specific ions inside and outside the cell membrane to flow down their concentration gradients. Excitatory pathways Neurotransmitters can be classified as either excitatory or inhibitory, depending on the nature of the action they elicit. Stimulation of excitatory neurons causes a movement of ions that results in a depolarization of the postsynaptic membrane. A Receptor empty ((no agonists) g) Empty receptor is inactive, and the coupled sodium channel is closed. Inhibitory pathways Stimulation of inhibitory neurons causes movement of ions that results in a hyperpolarization of the postsynaptic membrane. This causes a transient increase in the permeability of specific ions, such as potassium (K+) and chloride (Cl-). Acetylcholine receptor Sodium channel (closed) B Receptor binding of excitatory neurotransmitter Binding of acetylcholine causes the sodium ion channel to open. Thus, several different types of neurotransmitters may act on the same neuron, but each binds to its own specific receptor. Many neuronal tracts, thus, seem to be chemically coded, and this may offer greater opportunity for selective pharmacological modulation of certain neuronal pathways. Acetylcholine receptor Na+ Na+ Entry of Na+ depolarizes the cell and increases neural excitability. The disease often manifests itself between the ages of 50 and 60 years, among whom the incidence is about 1 in 100 individuals. It was first described by James Parkinson in 1817; therefore, it is named after him. Drugs for Neurodegenerative Diseases substantia nigra with a consequent reduction of dopamine actions in the corpus striatum, parts of the basal ganglia system that are involved in motor control. Each dopaminergic neuron makes thousands of synaptic contacts within the neostriatum and therefore modulates the activity of a large number of cells. These dopaminergic projections from the substantia nigra fire tonically rather than in response to specific muscular movements or sensory input. This mutual inhibitory pathway normally maintains a degree of inhibition of both areas. This triggers a chain of abnormal signaling, resulting in loss of the control of muscle movements. Secondary parkinsonism: Antipsychotic drugs such as the phenothiazines and haloperidol, whose major pharmacologic action is blockade of dopamine receptors in the brain, may produce parkinsonian symptoms (also called pseudoparkinsonism or druginduced parkinsonism). Cl Entry of Cl hyperpolarizes the cell, making it more di cult to depolarize and, thereby, reducing neural excitability. Many of the symptoms of parkinsonism reflect an imbalance between the excitatory cholinergic neurons and the greatly diminished number of inhibitory dopaminergic neurons. Therapy is aimed at restoring dopamine in the basal ganglia and antagonizing the excitatory effect of cholinergic neurons, thus reestablishing the correct dopamine/acetylcholine balance. These agents offer temporary relief from the symptoms of the disorder, but they do not arrest or reverse the neuronal degeneration caused by the disease. Thus, in new patients, the therapeutic response to levodopa is consistent, and the patient rarely complains that the drug effects "wear off.