Persius/hicric huggingface dataset:
Cefuroxime clinical pharmacology
After intramuscular (IM) injection of a 750-mg dose of cefuroxime to normal volunteers, the mean peak serum concentration was 27 mcg/mL. The peak occurred at approximately 45 minutes (range, 15 to 60 minutes). Following IV doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following IV administration of 1.5-g doses every 8 hours to normal volunteers. The serum half-life after either IM or IV injections is approximately 80 minutes.
Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations.
Following the IM administration of a 750-mg single dose, urinary concentrations averaged 1,300 mcg/mL during the first 8 hours. Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8-hour period.
The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cefuroxime is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.
Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of cefuroxime achieved in cerebrospinal fluid during multiple dosing of patients with meningitis.
Cefuroxime is approximately 50% bound to serum protein.
Cephalexin indications and usage
Cephalexin is indicated for the treatment of the following infections when caused by susceptible strains of the designated microorganisms:
Respiratory tract infections caused by Streptococcus pneumoniae and Streptococcus pyogenes (Penicillin is the usual drug of choice in the treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever. Cephalexin is generally effective in the eradication of streptococci from the nasopharynx; however, substantial data establishing the efficacy of cephalexin in the subsequent prevention of rheumatic fever are not available at present.)
Otitis media due to Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Streptococcus pyogenes, and Moraxella catarrhalis
Skin and skin structure infections caused by Staphylococcus aureus and/or Streptococcus pyogenes
Bone infections caused by Staphylococcus aureus and/or Proteus mirabilis
Genitourinary tract infections, including acute prostatitis, caused by Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae
NoteCulture and susceptibility tests should be initiated prior to and during therapy. Renal function studies should be performed when indicated.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin capsules, cephalexin for oral suspension, cephalexin tablets, and other antibacterial drugs, cephalexin capsules, cephalexin for oral suspension, and cephalexin tablets should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Congenital insensitivity to pain
Congenital insensitivity to pain (or congenital analgia) is a rare condition where a person cannot feel (and has never felt) physical pain.

# Presentation
Cognition and sensation is otherwise normal; for instance they can still feel discriminative touch (though not always temperature), and there is no detectable physical abnormality.
Children with this condition often suffer oral cavity damage both in and around the oral cavity (such as having bitten off the tip of their tongue) or fractures to bones. Unnoticed infections and corneal damage due to foreign objects in the eye are also seen. Because the child can not feel pain, they may not respond to problems, thus being at a higher risk of more severe diseases or otherwise.
In some people with this disorder, there may be slight mental retardation, as well as an impaired corneal reflex.

# Causes
There are some cases where the condition is caused by increased production of endorphins in the brain, in which case naloxone may be used as treatment. This treatment does not always work.
In some cases, this disorder can be caused by mutations in the voltage-gated sodium channel SCN9A (NaV1.7). Patients with such mutations are congenitally insensitive to pain and lack other neuropathies. There are three mutations in SCN9A: W897X, located in the P-loop of domain 2; I767X, located in the S2 segment of domain 2; and S459X, located in the linker region between domains 1 and 2. This results in a truncated non-functional protein. NaV1.7 channels are expressed at high levels in nociceptive neurons of the dorsal root ganglia. As these channels are likely involved in the formation and propagation of action potentials in such neurons, it is expected that a loss of function mutation in SCN9A will lead to abolished nociceptive pain propagation.
One of the side effects of Hansen's Disease is the progressive destruction of the nerves; this can be passed on to offspring, remaining dormant except for nerve insensitivity.

# Types of congenital pain indifference
There are generally two types of non-response exhibited.
- Insensitivity to pain means that the painful stimulus is not even perceived: a patient cannot describe the intensity or type of pain.
- Indifference to pain means that the patient can perceive the stimulus, but lacks an appropriate response: they will not flinch or withdraw when exposed to pain.
Chloroquine phosphate overdosage

# Overdosage

## Symptoms
Chloroquine is very rapidly and completely absorbed after ingestion. Toxic doses of chloroquine can be fatal. As little as 1 g may be fatal in children. Toxic symptoms can occur within minutes. These consist of headache, drowsiness, visual disturbances, nausea and vomiting, cardiovascular collapse, shock and convulsions followed by sudden and early respiratory and cardiac arrest. Hypokalemia has been observed with arrythmias in cases of intoxication. The electrocardiogram may reveal atrial standstill, nodal rhythm, prolonged intraventricular conduction time, and progressive bradycardia leading to ventricular fibrillation and/or arrest.

## Treatment
Treatment is symptomatic and must be prompt with immediate evacuation of the stomach by emesis (at home, before transportation to the hospital) or gastric lavage until the stomach is completely emptied. If finely powdered, activated charcoal is introduced by stomach tube, after lavage, and within 30 minutes after ingestion of the antimalarial, it may inhibit further intestinal absorption of the drug. To be effective, the dose of activated charcoal should be at least five times the estimated dose of chloroquine ingested.
Convulsions, if present, should be controlled before attempting gastric lavage. If due to cerebral stimulation, cautious administration of an ultra short-acting barbiturate may be tried but, if due to anoxia, it should be corrected by oxygen administration and artificial respiration. Monitor ECG. In shock with hypotension, a potent vasopressor should be administered. Replace fluids and electrolytes as needed. Cardiac compressing or pacing may be indicated to sustain the circulation. Because of the importance of supporting respiration, tracheal intubation or tracheostomy, followed by gastric lavage, may also be necessary. Peritoneal dialysis and exchange transfusions have also been suggested to reduce the level of the drug in the blood.
Intervention options can involve: diazepam for life-threatening symptoms, seizures and sedation, epinephrine for treatment of vasodilation and myocardial depression, potassium replacement with close monitoring of serum potassium levels.
A patient who survives the acute phase and is asymptomatic should be closely observed for at least six hours. Fluids may be forced, and sufficient ammonium chloride (8 g daily in divided doses for adults) may be administered for a few days to acidify the urine to help promote urinary excretion in cases of both overdosage or sensitivity.
Cholesterol absorption inhibitor
Cholesterol absorption inhibitors are a class of compounds that prevents the uptake of cholesterol from the small intestine into the circulatory system.

# How They Work
There are two sources of cholesterol in the upper intestine: dietary (from food) and biliary (from bile).  Dietary cholesterol, in the form of lipid emulsions, combines with bile salts, to form bile salt micelles from which cholesterol can then be absorbed by the intestinal enterocyte.
Once absorbed by the enterocyte, cholesterol is reassembled into large intestinal lipoproteins called chylomicrons.  These chylomicrons are then secreted into the lymphatics and circulated to the liver.  These cholesterol particles are then secreted by the liver into the blood as VLDL particles, precursors to LDL.
As a class, cholesterol absorption inhibitors block the uptake of micellar cholesterol, thereby reducing the incorporation of cholesteryl esters into chylomicron particles. By reducing the cholesterol content in chylomicrons and chylomicron remnants, cholesterol absorption inhibitors effectively reduce the amount of cholesterol that is delivered back to the liver.
The reduced delivery of cholesterol to the liver increases hepatic LDL receptor activity and thereby increases clearance of circulating LDL.  The net result is a reduction in circulating LDL particles.

# Importance
Managing cholesterol at the site of absorption is an increasingly popular strategy in the war on hypercholesterolemia.  Cholesterol absorption inhibitors are known to have a powerful synergistic effect when combined a class of anti-hyperlipidemics called statins.
Even small reductions in cholesterol absorption have been found to dramatically reduce the statin dosage that is required to achieve an overall serum cholesterol target. For statin-resistant or statin-sensitive populations that are characterized by low one-year compliance rates, such a combination therapy is proving to be especially effective.
Partially due to the challenges of statin dose toxicity, cholesterol absorption inhibitors have emerged as a new class of anti-hyperlipidemics that are very effective strategy for the treatment of hypercholesterolemia.
Ciclopirox clinical pharmacology

# Clinical Pharmacology
Ciclopirox is a broad-spectrum, antifungal agent that inhibits the growth of pathogenic dermatophytes, yeasts, and Malassezia furfur. Ciclopirox exhibits fungicidal activity in vitro against isolates of Trichophyton rubrum, Trichophyton mentagrophytes, Epidermophyton floccosum, Microsporumcanis, and Candida albicans.
Pharmacokinetic studies in men with tagged ciclopirox solution in polyethylene glycol 400 showed an average of 1.3% absorption of the dose when it was applied topically to 750 cm2 on the back followed by occlusion for 6 hours. The biological half-life was 1.7 hours and excretion occurred via the kidney. Two days after application only 0.01% of the dose applied could be found in the urine. Fecal excretion was negligible.
Penetration studies in human cadaverous skin from the back, with ciclopirox olamine cream with tagged ciclopirox showed the presence of 0.8 to 1.6% of the dose in the stratum corneum 1.5 to 6 hours after application. The levels in the dermis were still 10 to 15 times above the minimum inhibitory concentrations.
Autoradiographic studies with human cadaverous skin showed that ciclopirox penetrates into the hair and through the epidermis and hair follicles into the sebaceous glands and dermis, while a portion of the drug remains in the stratum corneum.
Draize Human Sensitization Assay, 21-Day Cumulative Irritancy study, Phototoxicity study, and Photo-Draize study conducted in a total of 142 healthy male subjects showed no contact sensitization of the delayed hypersensitivity type, no irritation, no phototoxicity, and no photo-contact sensitization due to ciclopirox olamine cream.
Clarithromycin contraindications

# Contraindications
Clarithromycin is contraindicated in patients with a known hypersensitivity to clarithromycin or any of its excipients, erythromycin, or any of the macrolide antibiotics.
Clarithromycin is contraindicated in patients with a history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin.
Concomitant administration of clarithromycin and any of the following drugs is contraindicated: cisapride, pimozide, astemizole, terfenadine, and ergotamine or dihydroergotamine (see Drug Interactions). There have been post-marketing reports of drug interactions when clarithromycin and/or erythromycin are coadministered with cisapride, pimozide, astemizole, or terfenadine resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation, and torsades de pointes) most likely due to inhibition of metabolism of these drugs by erythromycin and clarithromycin. Fatalities have been reported.
Concomitant administration of clarithromycin and colchicine is contraindicated in patients with renal or hepatic impairment.
Clarithromycin should not be given to patients with history of QT prolongation or ventricular cardiac arrhythmia, including torsades de pointes.
Clarithromycin should not be used concomitantly with HMG-CoA reductase inhibitors (statins) that are extensively metabolized by CYP3A4 (lovastatin or simvastatin), due to the increased risk of myopathy, including rhabdomyolysis (see WARNINGS).
For information about contraindications of other drugs indicated in combination with BIAXIN, refer to the CONTRAINDICATIONS section of their package inserts.
Colistimethate sodium overdosage

# OVERDOSAGE
Overdosage with colistimethate sodium can cause neuromuscular blockade characterized by paresthesia, lethargy, confusion, dizziness, ataxia, nystagmus, disorders of speech and apnea. Respiratory muscle paralysis may lead to apnea, respiratory arrest and death. Overdosage with the drug can also cause acute renal failure, manifested as decreased urine output and increases in serum concentrations of BUN and creatinine.
As in any case of overdose, colistimethate sodium therapy should be discontinued and general supportive measures should be utilized.
It is unknown whether colistimethate sodium can be removed by hemodialysis or peritoneal dialysis in overdose cases.
Daptomycin indications and usage
CUBICIN is indicated for the treatment of the infections listed below.
1- Complicated Skin and Skin Structure Infections
Complicated skin and skin structure infections (cSSSI) caused by susceptible isolates of the following Gram-positive bacteria: Staphylococcus aureus(including methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae subsp. equisimilis, and Enterococcus faecalis (vancomycin-susceptible isolates only).
2- Staphylococcus aureus Bloodstream Infections (Bacteremia), Including Those with Right-Sided Infective Endocarditis, Caused by Methicillin-Susceptible and Methicillin-Resistant Isolates
Staphylococcus aureus bloodstream infections (bacteremia), including those with right-sided infective endocarditis, caused by methicillin-susceptible and methicillin-resistant isolates.

## Limitations of Use
CUBICIN is not indicated for the treatment of pneumonia.
CUBICIN is not indicated for the treatment of left-sided infective endocarditis due to S. aureus.  The clinical trial of CUBICIN in patients with S. aureus bloodstream infections included limited data from patients with left-sided infective endocarditis; outcomes in these patients were poor .  CUBICIN has not been studied in patients with prosthetic valve endocarditis.

# Usage
Appropriate specimens for microbiological examination should be obtained in order to isolate and identify the causative pathogens and to determine their susceptibility to daptomycin.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of CUBICIN and other antibacterial drugs, CUBICIN should be used only to treat infections that are proven or strongly suspected to be caused by susceptible bacteria.
When culture and susceptibility information is available, it should be considered in selecting or modifying antibacterial therapy.  In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.  Empiric therapy may be initiated while awaiting test results.
Descending limb of loop of Henle
The descending limb of loop of Henle is the portion of the renal tubule constituting the first part of the loop of Henle.

# Physiology
The permeability is as follows:
Also, the medullary interstitium is highly concentrated (because of the activity of the ascending limb), leading to a strong osmotic gradient from the descending limb to the medulla.
Because of these factors, the concentration of the urine increases dramatically in the descending limb. Osmolality can reach up to 1400 mOsmol/kg by the end of the descending limb.

# Histology
The epithelium is low simple cuboidal.
They can be distinguished from the vasa recta by the absence of blood, and they can be distinguished from the thick ascending limb by the thickness of the epithelium.

# Nomenclature
Like the ascending limb, the descending limb has thick and thin portions. However, this distinction is not as important physiologically as in the ascending limb, so often the two are treated as one structure. The thick descending limb is less important than the thin descending limb, so often the terms "descending limb" and "thin descending limb" are used interchangeably.
Some sources simply refer to a "thin limb". In this context, the thin ascending limb of loop of Henle would be included.

# Additional images
- Longitudinal section of descending limb of Henles loop. a. Membrana propria. b. Epithelium.
Direct methods (crystallography)
In crystallography, direct methods are a family of methods for estimating the phases of the Fourier transform of the scattering density from the corresponding magnitudes.  The methods generally exploit constraints or statistical correlations between the phases of different Fourier components that result from the fact that the scattering density must be a positive real number.
In two dimensions, it is relatively easy to solve the phase problem directly, but not so in three dimensions.  The key step was taken by Hauptman and Karle, for which they were awarded the 1985 Nobel prize in Chemistry.
At present, direct methods are the preferred method for phasing crystals of small molecules having up to 1000 atoms in the asymmetric unit.  However, they are generally not feasible by themselves for larger molecules such as proteins.
Several software packages implement direct methods.
Doxycycline calcium how supplied

# How Supplied
Vibramycin Hyclate (doxycycline hyclate) is available in capsules containing doxycycline hyclate equivalent to:
100 mg doxycycline
bottles of 50 (NDC 0069-0950-50)
The capsules are light blue and are imprinted with "VIBRA" on one half and "PFIZER 095" on the other half.
Vibra-Tabs (doxycycline hyclate) is available in salmon colored film-coated tablets containing doxycycline hyclate equivalent to:
100 mg doxycycline
bottles of 50 (NDC 0069-0990-50)
The tablets are imprinted on one side with "VIBRA-TABS" and "PFIZER 099" on the other side.
Vibramycin Calcium Syrup (doxycycline calcium) oral suspension is available as a raspberry-apple flavored oral suspension. Each teaspoonful (5 mL) contains doxycycline calcium equivalent to 50 mg of doxycycline: 1 pint (473 mL) bottles (NDC 0069-0971-93).
Vibramycin Monohydrate (doxycycline monohydrate) for Oral Suspension is available as a raspberry-flavored, dry powder for oral suspension. When reconstituted, each teaspoonful (5 mL) contains doxycycline monohydrate equivalent to 25 mg of doxycycline: 2 oz (60 mL) bottles (NDC 0069-0970-65).
All products are to be stored below 86F (30C) and dispensed in tight, light-resistant containers (USP).
Somnolence (patient information)
For the WikiDoc page for this topic, click here

# Overview
Drowsiness refers to feeling abnormally sleepy during the day. People who are drowsy may fall asleep in inappropriate situations or at inappropriate times.

# What are the symptoms of Somnolence?
- Excessive daytime sleepiness (without a known cause) suggests that you have a significant sleep disorder. It is different from fatigue.
- Depression, anxiety, stress, and boredom can all contribute to excessive sleepiness, but these conditions more typically cause fatigue and apathy.

# What causes Somnolence?
- Having to work long hours or different shifts (nights, weekends)
- Medications (tranquilizers, sleeping pills, antihistamines)
- Medical conditions (such as hypothyroidism, hypercalcemia, and hyponatremia/hypernatremia)
- Not sleeping for long enough
- Sleep disorders (such as sleep apnea syndrome and narcolepsy)

# When to seek urgent medical care?
Contact your health care provider if you think the cause of your drowsiness is from any of the above conditions.

# Diagnosis
- The doctor will examine you to determine the cause of your drowsiness. The doctor will investigate your sleep patterns, and you'll have a psychological profile taken.
- You may be asked the following medical history questions about your drowsiness:
- Sleep pattern:
- How well do you sleep?
- How much do you sleep?
- Do you snore?
- Do you have episodes in which you do not breathe during sleep (sleep apnea)?
- Do you fall asleep during the day when you are not intending to nap (such as when watching TV or reading)?
- If so, do you awake feeling refreshed?
- How often does this happen?
- Emotional state:
- Are you depressed?
- Are you anxious or feeling stressed?
- Are you bored?
- Other:
- What medications do you take?
- What have you done to try to relieve the drowsiness?
- How well did it work?
- What other symptoms do you have?
- Diagnostic tests that may be performed include:
- Blood tests (such as a CBC and blood differential, electrolytes, and thyroid hormone levels)
- CT scan of the head
- EEG
- Sleep studies
- Urine tests (such as a urinalysis)
- If your health care provider makes a diagnosis related to drowsiness, you may want to note that diagnosis in your personal medical record.

# Treatment options
- You can relieve drowsiness by treating the cause of the problem. First, determine whether your fatigue is due to depression, anxiety, boredom, or stress. If you are not sure, talk with your health care provider.
- For drowsiness due to medications, talk to your health care provider about switching or stopping your medications. DO NOT CHANGE MEDICATIONS WITHOUT FIRST TALKING TO YOUR HEALTH CARE PROVIDER.
- Your health care provider can treat hypothyroidism, hypercalcemia, and hypo/hypernatremia.
- For drowsiness due to narcolepsy, your doctor may prescribe stimulants (such as Ritalin).

# Where to find medical care for Somnolence?
Directions to Hospitals Treating Somnolence

# Source