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These in- the most common means of parenteral drug administra- clude (1) capillary permeability purchase imodium 2mg with amex, (2) blood flow–tissue tion. Drug absorption (6) the permeability characteristics of specific tissue from intramuscular and subcutaneous sites depends on membranes. The rate of Advantages of the intramuscular and subcutaneous passage of drugs across capillary walls can be influenced routes include an increased reliability and precision in by agents that affect capillary permeability (e. Pain, tender- ness, local tissue necrosis (primarily with highly alkaline injections), microbial contamination, and nerve damage AVAILABLE DISTRIBUTION VOLUME may be associated with these forms of parenteral ad- The total volume of the fluid compartments of the body ministration. These compartments include plasma Intravenous Administration water (approximately 10 L), interstitial fluid (10 L), and the intracellular fluid (20 L). Total extracellular water is Intravenous drug administration ensures immediate the sum of the plasma and the interstitial water. Factors pharmacological response; problems of absorption are such as sex, age, edema, pregnancy, and body fat can in- circumvented because the entire quantity of drug enters fluence the volume of these various compartments. The pharmacokinetic concept of vol- A serious disadvantage of intravenous drug admin- ume of distribution (a derived parameter that relates istration becomes clearly apparent when an overdose the amount of drug in the body to the plasma concen- is inadvertently given: Neither can the drug be re- tration) is discussed more fully in Chapter 5. Other disadvan- tages include the possibilities of embolism (particu- larly if an insoluble drug is given), introduction of BINDING OF DRUGS TO PLASMA bacteria, and when this route is used for prolonged pe- PROTEINS riods, subcutaneous tissue infiltration. The possible in- troduction of the human immunodeficiency virus Most drugs found in the vascular compartment are (HIV) is a well-known consequence of intravenous bound reversibly with one or more of the macromole- drug administration in addicts who use contaminated cules in plasma. Many highly al- ion and in dynamic equilibrium, according to the law of bumin-bound drugs are poorly soluble in water, and for mass action. Since only the unbound (or free) drug dif- such drugs, binding to hydrophobic sites on albumin is fuses through the capillary walls, extensive binding may often important. The magnitude of of an acidic drug are bound per albumin molecule, this decrease is directly proportional to the fraction of whereas basic, positively charged drugs are more drug bound to plasma protein.

Cyclophos- does cyclophosphamide; however purchase imodium 2mg with amex, its bone marrow sup- phamide reduces the number of circulating lympho- pression tends to be more prolonged and affects both cytes and impairs the function of both humoral and white cells and platelets. Rarely, fibro- Chlorambucil (Leukeran) is an aromatic nitrogen mus- sis and a permanently decreased bladder capacity may tard that is intermediate in chemical reactivity between ensue. Chlorambucil shares the immuno- suppressive, teratogenic, and carcinogenic properties of Ifosfamide the nitrogen mustards. Ifosfamide (Ifex) is an analogue of cyclophosphamide that requires metabolic activation to form 4-hydroxy- Nitrosoureas ifosfamide. In general, the metabolism, serum half-life, Carmustine, Lomustine, and Semustine and excretion of ifosfamide are similar to those of cy- clophosphamide. The nitrosoureas are alkylating agents that are highly Ifosfamide is active against a broad spectrum of tu- lipid soluble and share similar pharmacological and mors, including germ cell cancers of the testis, lym- clinical properties. Carmustine (BCNU), lomustine phomas, sarcomas, and carcinomas of the lung, breast, (CCNU), and semustine (methyl-CCNU) are chemi- and ovary. It is thought to be more active than cy- cally unstable, forming highly reactive decomposition clophosphamide in germ cell cancers and sarcomas. The chemical half-life of these drugs in plasma Ifosfamide is less myelosuppressive than cyclophos- is only 5 to 15 minutes. It also may cilitates distribution into the brain and cerebrospinal produce alopecia, nausea, vomiting, infertility, and sec- fluid (CSF). Neurological The chloroethyl moiety of these nitrosoureas is capa- symptoms including confusion, somnolence, and hallu- ble of alkylating nucleic acids and proteins and produc- cinations have also been reported. It is recommended ing single-strand breaks and interstrand cross-linkage 642 VI CHEMOTHERAPY of DNA. Both alkylation and carbamoylation contribute Alkyl Sulfonates to the therapeutic and toxic effects of the nitrosoureas. Busulfan These agents can kill cells in all phases of the cell Busulfan (Myleran) is a bifunctional methanesulfonic cycle.

L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind imodium 2mg mastercard, randomized, placebocontrolled study. MRI and neuropsychological improvement in Huntington disease following ethyl-EPA treatment. Melatonin in medically ill patients with insomnia: a double-blind, placebo-controlled study. Improvement of sleep quality in elderly people by controlled-release melatonin Lancet 1995; 346:541–1 59. The role of melatonin and circadian phase in age-related sleep- maintenance insomnia: assessment in a clinical trial of melatonin replacement. Melatonin effects on sleep, mood, and cognition in elderly with mild cognitive impairment. A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome. Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency. Melatonin for chronic sleep onset insomnia in children: a randomized placebocontrolled trial. Cytokine secretion and eicosanoid production in the peripheral blood mononuclear cells of MS patients undergoing dietary supplementation with n-3 polyunsaturated fatty acids. A double-blind controlled trial of long chain n-3 polyunsaturated fatty acids in the treatment of multiple sclerosis. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. The effect of gamma-linolenic acid on human diabetic peripheral neuropathy: a double-blind placebocontrolled trial.

During meiosis I buy imodium 2mg free shipping, a cell with 46 replicated chromosomes divides to form two cells that each contain 23 replicated chromosomes. Normally, the meiosis I division separates the 23 pairs of chromo- somes evenly, so that each daughter cell contains one chromosome from each chromosome pair. During meiosis II, the two daughter cells containing 23 replicated chro- mosomes divide to form four daughter cells, each con- taining 23 non-replicated chromosomes. Chromosome pairs may fail to separate during meiosis I, or a replicated chromosome may fail to separate during meiosis II. Meiosis produces four daughter cells, each with half the normal number of chromosomes. Non-sex cells in humans are called diploid (meaning “double the number”) since they contain the full number of normal chromosomes. Human diploid cells normally each have 46 chromosomes, and haploid cells normally each have 23 chromosomes. Alterations in chromosome number Two kinds of chromosome number alterations can occur in humans: aneuploidy, an abnormal number of chromosomes, and polyploidy, more than two complete sets of chromosomes. During normal meiosis, chromosomes are distributed evenly among the four daughter cells. Sometimes, however, an uneven number of chromosomes are distributed to the daughter cells. As noted in the pre- vious section, chromosome pairs may not move apart in meiosis I, or the chromosomes may not separate in meio- Figure 1. The result of both kinds of mistakes (called nondis- junction of the chromosomes) is that one daughter cell receives an extra chromosome, and another daughter cell zygote is missing a chromosome, the condition is called does not receive any chromosome.