Phase I Reactions

Biotransformation Chlorpromazine

Monooxygenations of xenobiotics are the major type of Phase I reaction. They are also called mixed-function oxidations. One atom of a molecule of oxygen is accepted by the substrate while the other oxygen atom is reduced to water. A summary of this process is shown here RH + O2 + NADPH + H + NADP + + ROH + H2O There are two different classes of enzymes which belong to the category of monooxy-genases (or mixed function oxidases, also called microsomal oxygenases) and, therefore, carry out the...

Acetylcholine

Acetylcholine (AC) is the most abundant neurotransmitter. It is found in many synapses in the autonomic nervous system (related to involuntary muscle movement), in neurons that control voluntary muscle movement, and in many parts of the central nervous system. AC is stored in the neuron in subcellular vesicles and released from the axon into the synapse when a rapid influx of calcium occurs from an action-potential-induced change in membrane potential. Botulinum toxin has the unenviable...

Metals

Metals, particularly heavy ones, are capable of causing kidney damage. The specific site of damage is usually the proximal tubules and cell death or impairment results. At a biochemical level metals bind to sulfhydryl groups on proteins found in membranes or in enzymes, and thereby interfere with normal function leading to various degrees of reduced function or death. At least one metal, mercury, is believed to have one additional deleterious action, namely, constriction of blood vessels with a...

Relative Substance Toxicity

Amount which causes death in 50 of a of the outcome that is measured, death. This is because LD50 must be determined in animals. When the data are collected, they are extrapolated to humans. Is it reasonable to assume that a substance which is especially toxic to rats will also be very toxic to humans Usually this assumption is correct but only in a very approximate manner. If there is reason to believe that a particular test organism has a large biochemical difference from humans in regard to...

Toxins That Attack the Nerve Cell Body

Many agents are found within this category. Some of them are metals such as mercury, lead, manganese, and aluminum. Common agents that have this activity include cyanide. More exotic compounds that are able to attack the neuron cell body include domoic acid and MPTP (methyl-phenyl-tetrahydropyridine). Cyanide is deleterious for the simple reason that neurons have very high metabolic rates. In the presence of cyanide the electron transport system is inhibited and adenosine tri-phosphate energy...

Dialysis and Hemoperfusion

Dialysis is the process in which the blood is circulated through a bath in which a semipermeable membrane separates the components of the blood from the constituents of the dialysis fluid (Figure 3.1). In dialysis the various substances in blood will diffuse across into the dialysis bath provided that they are small enough (low molecular weight) to transit the membrane and their concentration is lower in the bath than in blood. Many factors relate to the potential effectiveness of dialysis....

Hexachlorophene

Similar in effect to damage to electrical conduction. There is a delay or reduction in action potentials. Numbness, weakness, and paralysis may result. One compound that damages myelin is triethyl tin (Figure 10.8). It is very lipid-soluble and binds to sites on myelin. The result is splitting of the myelin and the appearance of fluid-filled spaces, vacuoles, in the myelin. In rats, triethyl tin causes a decrease in conduction velocity in peripheral nerves and brain damage with reduction in...

Toxins That Attack Axons

Toxins are known that attack either the part of the axon near the neuron body, the proximal axon, or the remote part, the distal axon (Figure 10.9). The axon is less susceptible to toxins than the cell body in one sense it has very limited metabolic functions. The axon derives needed molecules by transport down the length of the axon from the neuron body. This may involve a transfer of several feet as, for example, for some motor neurons of the spinal cord. Axonal proteins such as enzymes or...

Anticholinergic Toxidrome

Tachycardia Dry skin Dilated pupils Raised body temperature Myoclonus Urinary retention Decreased bowel sounds Agitation Hot as a hare, Blind as a bat, Dry as a bone, Red as a beet, Mad as a hatter Anticholinergic Toxidrome (Continued) Toxins that Cause Anticholinergic Syndrome Antihistamines Antipsychotic drugs Plants Antiparkinson Delusions Hyperpyrexia Hyperreflexia Note Distinction from anticholinergic diaphoresis and no urinary retention are characteristic of sympathomimetic dry skin and...

Case Study 6 The Satanic Cult

A 17-year-old male was under house arrest in the home of his parents for drug-related offenses. When he created a serious domestic dispute with his parents, they felt a need to call the police. When the police arrived, the young man stated, You should not have called them. I told you they would never take me alive He then rapidly swallowed a brown liquid from a test tube. Parents learned later that a fellow member of a Satanic cult to which this boy belonged had given him the liquid as a means...

Case Study 7 The Dead Farmer

A 32-year-old man who worked as a farmer awakened his wife at 5 a.m. one morning and announced that their barn was on fire. The two of them rushed to the barn to remove valuable equipment before it was destroyed by the fire. As they fought the fire and waited for assistance from the local fire fighters, the farmer vomited and experienced several convulsions. His wife tried in vain to help him and reported later that when she touched her husband he only went into additional convulsions. He...