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Biomedical subjects

M R Holdiness

Publications and source records attributed to M R Holdiness.

At least 19 recordsLinked to original sources
PubMed1991

Clinical pharmacokinetics of N-acetylcysteine.

N-Acetylcysteine is useful as a mucolytic agent for treatment of chronic bronchitis and other pulmonary diseases complicated by the production of viscous mucus. It is also used as an antidote to paracetamol (acetaminophen) poisoning and found to be effective for the prevention of cardiotoxicity by doxorubicin and haemorrhagic cystitis from oxazaphosphorines. After an oral dose of N-acetylcysteine 200 to 400 mg the peak plasma concentration of 0.35 to 4 mg/L is achieved within 1 to 2 hours. Although the data are conflicting, it appears that the administration of charcoal may interfere with drug absorption, with up to 96% of the drug adsorbed on to the charcoal. Information on absorption in the presence of food or other drugs is not available. The volume of distribution ranges from 0.33 to 0.47 L/kg and protein binding is significant, reaching approximately 50% 4 hours after the dose. Pharmacokinetic information is not available as to whether or not N-acetylcysteine crosses the blood-brain barrier or placenta, or into breast milk. Renal clearance has been reported as 0.190 to 0.211 L/h/kg and approximately 70% of the total body clearance is nonrenal. Following oral administration, reduced N-acetylcysteine has a terminal half-life of 6.25h. Little is known of the metabolism of this agent, although it is believed to be rapidly metabolised and incorporated on to proteins. The major excretory product is inorganic sulphate. Frequently reported side effects are nausea, vomiting and diarrhoea. Biochemical and haematological adverse effects are observed but are not clinically relevant. Drug interactions of clinical significance have been observed with paracetamol, glutathione and anticancer agents.

Acetylcysteine↗
PubMed1990

Management of tuberculosis meningitis.

This article examines the detection, assessment, and therapeutic modalities available for tuberculosis meningitis. Without appropriate treatment this disease is fatal within 2 months of development, and mortality is closely associated with the stage of disease upon initiation of chemotherapy. Initial lumbar puncture reveals smear-positive acid-fast bacilli in up to 40% in most series; however, repeat examinations increase the yield, via direct smear, to as high as 87%. Analysis of cerebrospinal fluid is described, along with advanced techniques for early detection of this infection. Eight antituberculosis agents have known penetration into the cerebrospinal fluid. The most important prognostic factor is the neurological stage at which the individual presents at the initiation of therapy. Various chemotherapeutic approaches are available but it appears the use of rifampicin (rifampin) with isoniazid-containing regimens gives the best results. Regardless of the therapy undertaken, a significant number of individuals are left with some degree of neurological deficit. The roles of bacillus of Calmette and Guérin (BCG) vaccine, steroids, and neurosurgery in the treatment of this disease are also discussed.

Antitubercular Agents↗
PubMed1990

Atypical mycobacterial infections.

Atypical mycobacterial infections play an important role in human pathogenicity. Mycobacterium avium complex has been reported to occur in 17% to 50% of individuals infected with human immunodeficiency virus. In the southwestern United States, Mycobacterium kansasii is reported to be a predominate mycobacterial infection in middle-aged men. The epidemiology of the pathological species is discussed along with current recommendations for chemotherapeutic regimens.

Humans↗
PubMed1989

A review of contact dermatitis associated with transdermal therapeutic systems.

The literature is reviewed for contact dermatitis associated with transdermal therapeutic systems. Clonidine, nitroglycerin, scopolamine, estradiol and testosterone are utilized in such applications, and fentanyl is under investigation. Most cutaneous reactions are limited to localized dermatitis; however, generalized systemic effects may occur. Investigators are reporting skin-related side-effects in up to 50% of patients using transdermal clonidine; however, with the other agents, this is demonstrated much less frequently. Reactivation of the dermatitis via oral medication, following sensitization to the patch, is noted in rare instances.

Administration, Cutaneous↗
PubMed1989

Clinical pharmacokinetics of clofazimine. A review.

Clofazimine is useful in the treatment of Hansen's disease (leprosy) and some dermatological disorders, and is currently being used in drug regimens for patients with human immunodeficiency viral infections who are also infected with Mycobacterium avium complex. After an oral dose, absorption is variable, but when given in an oil-wax suspension is approximately 70%. Administration with food appears to increase the peak plasma drug concentration and reduce the time to peak level. Data on the volume of distribution and percentage or type of protein binding are not available; however, the drug undergoes extensive tissue distribution. Clofazimine does not cross the blood-brain barrier, but does cross the placenta, and is found in human breast milk. To date 3 urinary metabolites have been identified in man, but their biological activity is unknown. A substantial portion of the unchanged drug is excreted in faeces. The elimination half-life is variable, with values as long as 70 days being quoted in the literature. Frequently reported side effects of clofazimine are hyperpigmentation of the skin and conjunctiva, and abdominal pain. These resolve upon cessation of therapy. Biochemical and haematological adverse effects have been reported, but are generally not clinically relevant. Pharmacokinetic drug interactions of potential clinical significance have been observed with dapsone, oestrogen, rifampicin and vitamin A.

Clofazimine↗
PubMed1989

Tuberculosis.

The yield for detection of tuberculosis is increased when selected groups of individuals are evaluated. Various modalities are available for treatment; however, recent studies reveal 6-month chemotherapeutic regimens are effective in treating disease. Also, the use of preventive therapy is discussed herein.

Humans↗
PubMed1987

Teratology of the antituberculosis drugs.

The teratogenic effects of twelve antituberculosis drugs in animal models and man are reviewed. A number of congenital malformations have been associated with the use of these agents; however, for the most part, the birth defect rate is not above that expected for the normal population. Isoniazid and ethambutol are considered the safest for maternal use. Although rifampicin appears to be more problematic, if the disease is severe or extensive, it may be added, preferably after the first trimester. Streptomycin and kanamycin are associated with eighth cranial nerve damage and should be avoided if possible during cyesis. At least five of these compounds have documented evidence of transplacental passage. In consideration of the number of drugs that are available for treatment, routine therapeutic abortions in pregnant females with tuberculosis is not medically indicated.

Abnormalities, Drug-Induced↗
PubMed1986

High-performance liquid chromatographic determination of N-acetylcysteine in human serum following acetaminophen overdosage.

An analytical method has been developed for the determination of N-acetylcysteine in human serum following acetaminophen overdosage in humans. Serum samples were treated with dithiothreitol and the protein-freed product was derivatized with 2,4-dinitrofluorobenzene. N-Acetylhomocysteine thiolactone was used as an internal standard. Following diethyl ether extraction, the components were separated on a reversed-phase column with retention times of 7.4 and 9.9 min for N-acetylcysteine and internal standard, respectively. Ultraviolet detection at 365 nm was employed and little interference was noted from other serum components. The method has been applied to quantitation of N-acetylcysteine given as treatment for acetaminophen intoxication.

Acetaminophen↗