Weakness intravenous

The importance of the carboxylic acid moiety for activity is clearly illustrated by the next group of compounds. Removal of the carbethoxy substituent provided 7,8-dimethoxypyrimido[4,5-b]quinolin-4(3H)-one (LIN) which is inactive at 3 mg/kg i.v. in the PCA procedure. Interestingly, the 2-methyl analog (LIV) exhibits excellent oral activity while displaying only weak intravenous activity. This may be rationalized on the basis of metabolic oxidation of this compound to the carboxylic acid (LX, Figure 10). The fact that the 2-ethyl (LV), 2-trifluoromethyl (LVI), and 2-acetyI (LVIl) analogs are considerably less active, and the 2-phenyl (LVI II) and 2-hydroxy (LIX) analogs are inactive, supports this explanation. 

The most important type of mixed solution is a buffer, a solution in which the pH resists change when small amounts of strong acids or bases are added. Buffers are used to calibrate pH meters, to culture bacteria, and to control the pH of solutions in which chemical reactions are taking place. They are also administered intravenously to hospital patients. Human blood plasma is buffered to pH = 7.4 the ocean is buffered to about pH = 8.4 by a complex buffering process that depends on the presence of hydrogen carbonates and silicates. A buffer consists of an aqueous solution of a weak acid and its conjugate base supplied as a salt, or a weak base and its conjugate acid supplied as a salt. Examples are a solution of acetic acid and sodium acetate and a solution of ammonia and ammonium chloride. 

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

The pretreatment of MH-susceptible patients with oral or intravenous dantrolene prior to surgery in order to avoid a crisis is controversial. Most physicians do not recommend prophylactic pretreatment except in patients who have had a previously documented episode. However, if pretreatment is desired, it is recommended that therapy be begun with intravenous dantrolene in a dose of 2 mg/Kg just prior to induction of anesthesia. This prevents the uncertainty of predictive blood values associated with the use of the oral route. The adverse effects of intravenous dantrolene prophylaxis include phlebitis and tissue necrosis. Patients who receive prophylactic treatment with oral dantrolene often complain of incapacitation, gastrointestinal irritation, prolonged drowsiness, and clinically significant respiratory muscle weakness. 

A 27- year-old male with a three-year history of AIDS complains of progressive blurring of vision for two days. Eye examination reveals evidence of retinitis consistent with cytomegalic virus inclusion disease. Intravenous treatment is started, and within five days the patient complains of muscular weakness and cramping. Blood chemistries show a creatinine of. 5.2 mEq/L and a Ca of 6.9 mEq/L. 

Hydrogen cyanide (HCN) is a colorless, highly poisonous gas or liquid (below 26.7 °C) having an odor of bitter almonds (Hartung 1994 Pesce 1994). It is a weak acid. Exposures may occur in industrial situations as well as from cigarette smoke and combustion products and from naturally occurring cyanide compounds in foods. There is a potential for exposure when any acid is mixed with a cyanide salt. Intravenously administered sodium nitroprusside (Na2[Fe(CN)5N0]-2H20) has been used clinically to lower blood pressure (Schulz et al. 1982). Chemical and physical properties are listed in Table 5-2. 

Atropine does not counter muscle weakness and respiratory failure. To overcome this, pralidoxime (P2AM), a cholinesterase reactivator, is used in many countries, in an initial dose of 30 mg/kg intravenously followed by 8 mg/kg/h until clinical recovery. Oximes have to be given before the irreversible aging of the enzyme-organophosphorus... 

Benzodiazepines are usually given orally and are well absorbed by this route. Since the benzodiazepines are weak bases, they are less ionized in the relatively alkaline environment of the small intestine, and therefore, most of their absorption takes place at this site. For emergency treatment of seizures or when used in anesthesia, the benzodiazepines also can be given parenter-ally. Diazepam and lorazepam are available for intravenous administration. 

Flulike symptoms, including fever, chills, weakness, fatigue, myalgia, and arthralgia, are the most common side effects of interferon therapy. These symptoms occur in more than 50% of patients given injections of interferons either intravenously, intramuscularly, or subcutaneously. Intralesional injection may produce milder flulike symptoms with somewhat less frequency. Tolerance to these symptoms generally develops with repeated dosing. 

Diuretic activity. Decoction of the dried fruit, administered nasogastrically to rats at a dose 1 g/kg, was active " . Fruit juice, administered intravenously by infusion to dogs at a dose of 3 mL/minute for 100 minutes, produced weak activity """. Ethanol... 

Insecticide activity. Acetone extracts of the dried leaf, dried root, and dried stem, at a low concentration, were inactive on Culex quinquefasciatus - Water extract of the dried leaf, administered intravenously, produced weak activity on Periplaneta ameri caruL . 

Procaine forms poorly soluble salts or conjugates with some drugs [12], and was reported to be a strong prostaglandin antagonist and a weak agonist [13]. It is used in the treatment of malignant hyperpyrexia [14-17]. Procaine hydrochloride was also used by intravenous injection for the relief of pain in acute pancreatitis [18-21],... 

Butorphanol tartrate is a weak partial p-receptor agonist, 3.5-5 times as potent as morphine. The incidence of psychotomimetic effects is relatively low. The recommended doses are 1-4 mg intramuscularly every 3-4 h or 0.5-2 mg intravenously. Respiratory depression produced by butorphanol 2 mg IV is similar to that of 10 mg morphine. However, there is a ceiling effect for respiratory depression, and near-maximum depression occurs after 4 mg in normal adults. In healthy volunteers, butorphanol 0.03-0.06 mg-kg-1 produces no significant cardiovascular changes. However, in patients with cardiac disease, progressive increases in cardiac index and pulmonary artery pressure occur, and butorphanol should be avoided in patients with recent myocardial infarction. Butorphanol is metabolised mainly in the liver to inactive metabolites. The terminal half-life is 2.5-3.5 h. 

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