Vincristine Vinblastine and Vinorelbine

Vincristine (Oncovin) and vinblastine (Velban) are both produced by the leaves of the periwinkle plant. Despite their structural similarity, there are significant differences between them in regard to clinical usefulness and toxicity. The vinca alkaloids bind avidly to tubulin, a class of proteins that form the mitotic spindle during cell division. The drugs cause cellular arrest in metaphase during mitosis, and cell division cannot be completed. Although the vinca alkaloids usually have been...

Adverse Effects and Contraindications

The opioids generally have a high level of safety when used in therapeutic dosages. However, there are several notable exceptions. Morphine and other opioids are contraindicated in patients with hypersensitivity reactions to the opioids. In addition, morphine should not be used in patients with acute bronchial asthma and should not be given as the drug of first choice in patients with pulmonary disease, because it has antitussive effects that prevent the patient from clearing any buildup of...

Tumor Growth And Growth Fraction

The rate of growth of human and experimental cancers is initially quite rapid (exponential) and then slows until a plateau is reached. The decrease in growth rate with increasing tumor size is related both to a decrease in the proportion of cancer cells actively proliferating (termed the growth fraction) and to an increase in the rate of cell loss due to hypoxic necrosis, poor nutrient supply, im-munological defense mechanisms, and other processes. The rate of spontaneous cell death for some...

Physiology Of Penile Erection

The physiology of penile erection involves an interplay of anatomical, hemodynamic, neurophysiological, and sex hormone interaction. Penile erection is the result of a complex interaction between the central nervous system and other local factors. This physical event also can be influenced by psychological factors. The penis is mainly supplied by the internal puden-dal artery, and three major sets of veins, superficial, intermediate, and deep veins, drain it. Drug-induced changes in...

Hormone Replacement Therapy

The beginning of menopause is marked by the last menstrual cycle. This is the result of declining ovarian func tion and reduced synthesis of estrogens and progesterone. Estrogen production in postmenopausal women is usually only about 10 of that in premenopausal women. Almost no progesterone is synthesized in postmenopausal women. Hormone replacement therapy (HRT) generally refers to the administration of estrogen-progestin combinations. Estrogen replacement therapy (ERT) consists of the use of...

Physiological Barriers To Drug Distribution

The capillary membrane between the plasma and brain cells is much less permeable to water-soluble drugs than is the membrane between plasma and other tissues. Thus, the transfer of drugs into the brain is regulated by the blood-brain barrier. To gain access to the brain from the capillary circulation, drugs must pass through cells rather than between them. Only drugs that have a high lipid-water partition coefficient can penetrate the tightly apposed capillary endothelial cells. Drugs that are...

Absorption Of Drugs From The Alimentary Tract

Oral Cavity and Sublingual Absorption In contrast to absorption from the stomach and intestine, drugs absorbed from the oral cavity enter the general circulation directly. Although the surface area of the oral cavity is small, absorption can be rapid if the drug has a high lipid-water partition coefficient and therefore can readily diffuse through lipid membranes. Since the diffusion process is very rapid for un-ionized drugs, pKa will be a major determinant of the lipid-water partition...

Codeine and Other Phenanthrene Derivatives

Like morphine, codeine is a naturally occurring opioid found in the poppy plant. Codeine is indicated for the treatment of mild to moderate pain and for its antitus-sive effects. It is widely used as an opioid antitussive because at antitussive doses it has few side effects and has excellent oral bioavailability. Codeine is metabolized in part to morphine, which is believed to account for its analgesic effect. It is one of the most commonly used opioids in combination with nonopioids for the...

Carmustine Lomustine and Semustine

The nitrosoureas are alkylating agents that are highly lipid soluble and share similar pharmacological and clinical properties. Carmustine (BCNU), lomustine (CCNU), and semustine (methyl-CCNu) are chemically unstable, forming highly reactive decomposition products. The chemical half-life of these drugs in plasma is only 5 to 15 minutes. Their marked lipid solubility facilitates distribution into the brain and cerebrospinal fluid (CSF). The chloroethyl moiety of these nitrosoureas is capable of...

The Log Cell Kill Hypothesis

Cytotoxic drugs act by first-order kinetics that is, at a given dose, they kill a constant fraction of the tumor cells rather than a fixed number of cells. For example, a drug dose that would result in a three-log cell kill (i.e., 99.9 cytotoxicity) would reduce the tumor burden of an animal that has 108 leukemic cells to 105 cells. This killing of a fraction of cells rather than an absolute number per dose is called the log cell kill hypothesis. The earliest detectable human cancers usually...

Clinical Manifestations of Hypothyroidism

During the perinatal period, there is an absolute requirement for thyroid hormone for the development and maturation of the nervous and musculoskeletal systems. In the perinatal nervous system, thyroid hormone plays a critical role in normal growth of the cerebral and cerebellar cortices, the proliferation of axons, the branching of dendrites, synaptogenesis, myelination, cell migration, and so on. Thyroid hormone also plays a major role in the maturation of bone. A deficiency of thyroid...

Drugs Affecting The Endocrine System

Hypothalamic and Pituitary Gland Hormones 677 60. Adrenocortical Hormones and Drugs Affecting the Adrenal Cortex 686 Ronald P Rubin 61. Estrogens, Progestins, and SERMs 704 Jeannine S. Strobl 62. Uterine Stimulants and Relaxants 716 Leo R. Brancazio and Robert E. Stitzel 63. Androgens, Antiandrogens, and Anabolic Steroids 724 Frank L. Schwartz and Roman J. Miller 64. Drugs Used in the Treatment of Erectile Dysfunction 735 John A. Thomas and Michael J. Thomas 65. Thyroid and Antithyroid...

Treatment of Anticholinesterase Poisoning

The first step in treatment of anticholinesterase poisoning should be injection of increasing doses of atropine sulfate to block all adverse effects resulting from stimulation of muscarinic receptors. Since atropine will not alleviate skeletal and respiratory muscle paralysis, mechanical respiratory support may be required. If the poisoning is due to an organophosphate, prompt administration of pralidoxime chloride will result in dephosphorylation of cholinesterases in the periphery and a...

Mechanism of Ganglionic Blockade

Large doses of nicotine produce a prolonged blockade of ganglionic nicotinic receptors. Unlike the blockade of ganglionic transmission produced by most ganglionic blocking agents, that is, a nondepolarizing competitive antagonism, the blockade produced by nicotine consists of two phases. Phase 1 can be described as persistent depolarization of the ganglion cell. The initial application of nicotine to the ganglion cells depolarizes the cell, which initiates an action potential. After a few...

Clinical Uses Of Catecholamines

The clinical uses of catecholamines are based on their actions on bronchial smooth muscle, blood vessels, and the heart. Epinephrine is also useful for the treatment of allergic reactions that are due to liberation of hista-mine in the body, because it produces certain physiological effects opposite to those produced by histamine. It is the primary treatment for anaphylactic shock and is useful in the therapy of urticaria, angioneurotic edema, and serum sickness. Epinephrine also has been used...

Ganglionic Blocking Agents

The basis for the antihypertensive activity of the ganglionic blockers lies in their ability to block transmission through autonomic ganglia (Fig. 20.2C). This action, which results in a decrease in the number of impulses passing down the postganglionic sympathetic (and parasympathetic) nerves, decreases vascular tone, cardiac output, and blood pressure. These drugs prevent the interaction of acetylcholine (the transmitter of the preganglionic autonomic nerves) with the nicotinic receptors on...

Ganglionic Stimulants

A variety of agents, including nicotine, lobeline, and di-methylphenyl piperazinium (DMPP), can stimulate gan-glionic nicotinic receptors. Although these drugs have little or no therapeutic use, they offer considerable interest for several reasons. First, drugs such as nicotine that both stimulate and block ganglionic receptors have proved valuable as an aid in identifying and localizing postgan-glionic fibers. Second, nicotine's use as a potent insecticide and rodenticide and its presence in...

Psoralen and Ultraviolet A Therapy

Psoralens form covalent linkages with pyrimidine bases in DNA when exposed to light of the appropriate wavelength, and if oxygen is present, reactive oxygen species also are generated. Although inhibition of DNA replication may account for some of the beneficial effects of PUVA therapy in certain hyperproliferative disorders such as psoriasis, PUVA has other important biological effects. It suppresses contact hypersensitivity and may evoke other immunological changes by affecting T lymphocytes...

75 Year Old Man Has Inoperable Coronary Artery Disease

Case Study Therapy for Inoperable Coronary Artery Disease A 75-year-old man has inoperable coronary artery disease with an EF of 31 . He is receiving digoxin, furosemide, and an ACE inhibitor. He is unable to walk more than 50 feet on flat ground before getting short of breath (dyspnea on exertion at 50 feet). His heart rate at rest is 85 beats per minute and his blood pressure while seated is 130 85. His neck veins are flat carotid upstrokes are normal lungs are clear and heart examination...

Digitalis Glycosides and Vagomimetic Drugs

Digitalis glycosides, especially digoxin Lanoxin , because of their positive inotropic effects, are widely used for treating patients with congestive heart failure. They also continue to be used for the management of patients with supraventricular arrhythmias. Since the digitalis glycosides are discussed elsewhere see Chapter 15 , a full discussion of their mechanism of action is not provided here. Digitalis glycosides enhance the inotropic state by increasing the intracellular calcium...

Treatment For Infections Caused By Trematodes

Trematodes (flukes) are nonsegmented flattened helminths that are often leaflike in shape. Most have two suckers, one found around the mouth (oral sucker) and the other on the ventral surface. Most are hermaphroditic. The eggs, which are passed out of the host in sputum, urine, or feces, undergo several stages of maturation in other hosts before the larvae enter humans. The larvae are acquired either through ingestion of food (aquatic vegetation, fish, crayfish) or by direct penetration of the...

Miscellaneous Topical Antifungal Agents

Ciclopirox olamine (Loprox) is a pyridone derivative available for the treatment of cutaneous dermatophyte infections, cutaneous C. albicans infections, and tinea versicolor caused by Malassezia furfur. It interferes with fungal growth by inhibiting macromolecule synthesis. Tolnaftate (Tinactin, others) is a nonprescription an-tifungal agent effective in the topical treatment of der-matophyte infections and tinea. The mechanism of action is unknown. Other older, less effective topical...

Steps In Neurochemical Transmission

Regardless of the type of neuron under consideration, the fundamental steps in chemical transmission are the same. Each of these steps is a potential site for pharmacological intervention in the normal transmission process 1. Synthesis of the transmitter 3. Release of the transmitter by a nerve action potential 4. Interaction of the released transmitter with receptors on the effector cell membrane and the associated change in the effector cell 5. Rapid removal of the transmitter from the...