Central nervous system respiratory centers

Air-poUutant effects on neural and sensory functions in humans vary widely. Odorous pollutants cause only minor annoyance yet, if persistent, they can lead to irritation, emotional upset, anorexia, and mental depression. Carbon monoxide can cause death secondary to the depression of the respiratory centers of the central nervous system. Short of death, repeated and prolonged exposure to carbon monoxide can alter sensory protection, temporal perception, and higher mental functions. Lipid-soluble aerosols can enter the body and be absorbed in the lipids of the central nervous system. Once there, their effects may persist long after the initial contact has been removed. Examples of agents of long-term chronic effects are organic phosphate pesticides and aerosols carrying the metals lead, mercury, and cadmium. 

The clinical picture of carbaryl intoxication results from inactivation of cholinesterase, resulting in the accumulation of acetylcholine at synapses in the nervous system, skeletal and smooth muscle, and secretory glands. Signs and symptoms of overexposure may include (1) muscarinic manifestations such as miosis, blurred vision, lacrimation, excessive nasal discharge or salivation, sweating, abdominal cramps, nausea, vomiting, and diarrhea (2) nicotinic manifestations including fasiculation of fine muscles and tachycardia and (3) central nervous system manifestations characterized by headache, dizziness, mental confusion, convulsions, coma, and depression of the respiratory center. 

Exposure to disulfoton can result in inhibition of cholinesterase activity in blood and at nerve synapses of muscles, secretory organs, and nervous tissue in the brain and spinal cord. Central nervous system signs and symptoms include anxiety, restlessness, depression of respiratory and circulatory centers, ataxia, convulsions, and coma. 

Caffeine and theophylline are more active on the central nervous system, while theobromine is much less active. Caffeine and theophylline also appear to stimulate the respiratory centers, making them useful in the treatment of infants who stop breathing for extended periods of time (sleep apnea), which can lead to sudden infant death. 

Hydromorphone affects the respiratory center in the brain, and this is why it suppresses the cough reflex. Hydromorphone is partially broken down, or metabolized, by the liver and is absorbed by a variety of tissues and organs, including the gastrointestinal tract, smooth muscle, skeletal muscle, pancreas, lungs, cardiovascular system, and central nervous system. Once metabolized by the liver, hydromorphone moves out of the body by way of the kidneys and into the urine. The precise mechanisms by which hydromorphone and the other narcotic analgesics work are not entirely known. 

Chlorobenzene affects the central nervous system. Humans occupationally exposed to chlorobenzene intermittently for up to 2 years at levels above current federal limits displayed signs of neurotoxicity including numbness, cyanosis (from depression of respiratory center), hyperesthesia, and muscle spasms (Rozenbaum et al. 1947). Specific exposure levels and histopathologic data have not been provided. 

In spite of the smaller ratio of nicotinic to muscarinic receptors in the brain, nicotine and lobeline (Figure 7-3) have important effects on the brainstem and cortex. The mild alerting action of nicotine absorbed from inhaled tobacco smoke is the best-known of these effects. In larger concentrations, nicotine induces tremor, emesis, and stimulation of the respiratory center. At still higher levels, nicotine causes convulsions, which may terminate in fatal coma. The lethal effects on the central nervous system and the fact that nicotine is readily absorbed form the basis for the use of nicotine as an insecticide. Dimethylphenylpiperazinium (DMPP), a synthetic nicotinic stimulant used in research is relatively free of these central effects because it does not cross the blood-brain barrier. 

Since volatile solvents depress the central nervous system, including the respiratory center of the brain, prolonged use can be hazardous. Respiratory depression can progress to respiratory arrest, in which the user stops breathing and dies. Death by choking is another possibility. Some users of inhalants have choked to death on their own vomit. 

Poisoning with samandarine first causes convulsions followed by irregular palpitation and finally paralysis. Samandarine affects the central nervous system. The vasomotor center is stimulated, causing an increase in blood pressure. Death occurs within a few hours because of primary respiratory paralysis without damaging the heart. 

Ethyl benzene is extremely irritating in animal studies. Repeated skin application has caused blisters. Inhalation or ingestion of high concentrations has led to central nervous system (CNS) depression with death attributed to depression of the respiratory center. Pathological observations include pulmonary edema and generalized visceral hyperemia. The oral LD50 for ethyl benzene is 3500 mg kg The dermal... 

Fentanyl stimulates mu-opioid receptors in the central nervous system (CNS), altering the body s response to pain. Fentanyl may alter the release of different neurotransmitters, such as jS-endorphin, sensitive to pain. Fentanyl can produce profound CNS and respiratory depression through mechanisms common to other opioids. Respiratory depression is mediated through action on the medullary respiratory center. Fentanyl is 50-100 times more potent... 

The binding of nerve agent to the enzymes is considered irreversible unless removed by therapy. The accumulation of acetylcholine in the peripheral and central nervous systems leads to depression of the respiratory center in the brain, followed by peripheral neuromuscular blockade causing respiratory depression and death. 

Exposure to high concentration (severe exposure) of mercaptans may produce central nervous system effects such as headache, staggering gait, muscular weakness, tremors, lung edema, convulsions, and paralysis of the respiratory center. Long-term health effects are not well documented. 

Classic signs of acute toxicity include pinpoint pupils, muscular fasciculations, slow pulse, excessive salivation and lacrimation, and gastrointestinal symptoms (nausea, abdominal cramps, diarrhea, and loss of sphincter control). In severe cases, convulsions, coma, and heart block are common. Death is generally attributed to respiratory insufficiency caused by the combination of respiratory center depression, paralysis, and increased bronchial secretions. In children, the classic signs described previously may be infrequent, with the major symptoms being central nervous system depression, stupor, flaccidity, dyspnea, seizures, and coma. 

The binding of the nerve agent to the enzyme is considered irreversible unless removed by therapy. The accumulation of acetylcholine in the peripheral nervous system and central nervous system (CNS) leads to depression of the respiratory center in the brain, followed by peripheral neuromuscular blockade causing respiratory depression and death. The pharmacologic and toxicologic effects of the nerve agents are dependent on their stability, rates of absorption by the various routes of exposure, distribution, ability to cross the blood-brain barrier, rate of reaction and selectivity with the enzyme at specific foci, and their behavior at the active site on the enzyme. 

Narcotic analgesics (narcotic agonists) such as opioids act on the central nervous system to treat moderate and severe pain, suppress respiration and coughing by acting on the respiratory and cough centers in the medulla of the brain stem. All narcotic analgesics relieve pain. All except meperidine (Demerol) are also antitussive (cough suppression) and antidiarrheal. 

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