Inhibition peripheral

B. D., Sironi, M., Benigni, F., and Ghezzi, P Chlorpromazine specifically inhibits peripheral and brain TNF production, and up-regulates EL-10 production, in mice. Immunology, 82, 207-210(1994). 

Thyroid abnormalities Am o6arone inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3), prompting increased T4levels, increased levels of inactive reverse T3 and decreased levels of T3. It is also a potential source of large amounts... 

PTU possesses special benefit it inhibits peripheral deiodination, thereby blocking the conversion of thyroxine to the active hormone tri-iodothyronine. PTU is rapidly absorbed from the gut, reaching peak blood levels within one hour, and is excreted in urine as the inactive glucuronide within 24 hours. In contrast methimazole which is absorbed at variable rates, is excreted slower (only 65-70% within 48 hours in urine). The short plasma half-life of... 

Geriatric Considerations - Summary Entacapone inhibits peripheral COMT and increases levodopa s effects. Itsprimary role is as adjunctive therapy to prolong the beneficial effects of levodopa and to decrease end-of-dose fluctuations in response to treatment. Concurrent use of levodopa is necessary for entacapone to be effective and unlike tolcapone, hepatic monitoring is not required. 

Levodopa + carbidopa (Sinemet) Carbidopa inhibits peripheral metabolism of levodopa to dopamine and reduces required dosage and toxicity. Carbidopa does not enter CNS. 

Propylthiouracil (PTU) Inhibit thyroid peroxidase reactions block iodine organification inhibit peripheral deiodination of T4 and T Hyperthyroidism Oral duration of action 6-8 h delayed onset of action Toxicity Nausea, gastrointestinal distress, rash, agranulocytosis, hepatitis,hypothyroidism... 

In rats equilibrated with radioiodine-labelled T4 or T3 roughly half of the radioactivity appears as I- in the urine and the other half as free iodothyronines in the feces [12]. Treatment of the rats with 6-propyl-2-thiouracil (PTU) results in a marked decrease in urinary radioactivity and a reciprocal increase in fecal clearance [12]. Also, in humans, PTU has been shown to inhibit peripheral iodothyronine deiodination besides its well-known effect on thyroid hormone biosynthesis [13]. Compared with the rat, deiodination is an even more important pathway for the clearance of thyroid hormone in man as evidenced by the greater proportion undergoing urinary clearance [2]. Furthermore, estimation of iodothyronine turnover kinetics in humans has demonstrated that a major fraction of T4 disposal is accounted for by plasma production rates of T3 and rT3 [2,3],... 

Inhibitor of catecholamine O- methyltrans-ferase (COMT). The CNS-impermeant enta-capone inhibits peripheral degradation of L-dopa and thus enhances availability of L-dopa for the brain. Accordingly, it is suitably only for combination therapy with L-dopa. 

Q8 The drug treatment of thyrotoxicosis involves using antithyroid drugs car-bimazole (which is converted to the active compound methimazole) and propylthiouracil inhibit the synthesis of thyroid hormone. Propylthiouracil also inhibits peripheral conversion of T4 to T3. Many of the symptoms of hyperthyroidism can also be alleviated by fl-adrenoceptor antagonists. Iodine... 

Theoretically, butyrylcholinesterase inhibition peripherally could enhance side effects... 

SAFETY PROFILE Poison by ingestion, inhalation, skin contact, intraperitoneal, intravenous, subcutaneous, and ocular routes. Human systemic effects by ingestion a cholinesterase inhibitor. Has been found to inhibit peripheral cholinesterase without pronounced effects on the central nervous system. An insecticide. When heated to decomposition it emits toxic fumes of NO and POx. See also PARATHION and ANHYDRIDES. 

Propylthiouracil differs from other members of the group in that it also inhibits peripheral conversion of T to Tj, but only at the high doses used in treatment of thyroid storm (p. 705). 

While aspirin significantly inhibits peripheral prostaglandin and thromboxane synthesis, paracetamol is less potent as a synthetase inhibitor than the NSAIDs, except in the brain, and paracetamol has only a weak anti-inflammatory action. It is simple to ascribe the analgesic activity of aspirin to its capacity to inhibit prostaglandin synthesis, with a consequent reduction in inflammatory edema and vasodilatation, since aspirin is most effective in the pain associated with inflammation or injury. However, such a peripheral effect cannot account for the analgesic activity of paracetamol, which is less well understood. 

Treatment of biopterin and biopterin reductase deficiency consists not only of regulating the blood levels of phenylalanine but of supplying the missing form of coenzyme and the precursors of neurotransmitters, namely, dihydroxyphenylalanine and 5-hydroxytryptophan, along with a compound that inhibits peripheral aromatic decarboxylation. This compound is necessary because the amine products do not cross the blood-brain barrier. 

Inhibit peripheral metabolism by dopa decarboxylase Carbidopa Benserazide... 

Precursor, converted to DA by aromatic amino acid decarboxylase (AAAD, dopa-decarboxy-lase)—usually given with carbidopa, which inhibits peripheral AAAD and increases CNS availability of L-dopa (carbidopa does not cross the blood-brain barrier [BBB]). 

When AAAD is inhibited, more L-dopa is converted hy COMT to 3-0-methyldopa, a partial agonist at DA receptors that can also compete with L-dopa for uptake into the CNS. These drugs inhibit peripheral COMT, enhancing the CNS uptake of L-dopa and possibly reducing its on-off effects. Tolcapone is hepatotoxic. 

B. Carbidopa increases levodopa entry into the CNS by inhibiting peripheral COMT. 

Muscarinic receptor blockers may improve muscle rigidity and tremor in Parkinsons disease but result in very little improvement in bradykinesia thus, they are mainly considered as adjunctive to the use of drugs that improve dopaminergic function. Selegiline is the inhibitor of MAO type B, and pramipexole is a non-ergot DA receptor agonist. Carbidopa inhibits peripheral AAAD (dopa decarboxylase) tolcapone is an inhibitor of COMT. Levodopa causes a high incidence of dose-dependent dyskinesias that are not slow in onset, like tardive dyskinesia that results from chronic administration of DA receptor blockers. 

Carbidopa inhibits peripheral decarboxylation of levodopa, making more levodopa available for transport to the brain. Levodopa is a precursor of dopamine, which is deficient in parkinsonism patients. Entacapone inhibits the enzyme that metabohzes levodopa (catechol-O-methyltransferase [COMT]), which increases and prolongs levodopa plasma levels. The combination is indicated in the treatment of idiopathic Parkinson disease (1) to substitute (with equivalent strength of each of the 3 immediate-release components) for the previously administered individual products, (2) to replace immediate-release carbidopa/levodopa therapy (without entacapone) when patients experience signs and symptoms of end-of-dose wearing-off (only for patients taking a total daily dose of levodopa of 600 mg or less and not experiencing dyskinesias). 

Carbidopa. This drug inhibits peripheral dopa decarboxylase activity. 

Respiratory System Spontaneous respiration is rapid and shallow during halothane anesthesia. The decreased alveolar ventilation results in an elevation in arterial CO tension from 40 mm Hg to >50 mm Hg at 1 MAC. The elevated CO does not provoke a compensatory increase in ventilation, because halothane causes a concentration-dependent inhibition of the ventilatory response to COj. Halothane also inhibits peripheral chemoceptor responses to arterial hypoxemia. Thus, neither hemodynamic (tachycardia and hypertension) nor ventilatory responses to hypoxemia are observed during halothane anesthesia, making it prudent to monitor arterial oxygenation directly. 

SELECTIVE MAO-B INHIBITORS Two isozymes of MAO (MAO-A and MAO-B) oxidize monoamines and both are present in the periphery and GI tract MAO-B is the predominant form in the striatum and is responsible for most of the oxidative metabolism of dopamine in the brain. At low-to-moderate doses (10 mg/day or less), selegiline (eldepryl) selectively and irreversibly inhibits MAO-B. Unlike nonspecific inhibitors of MAO (e.g., phenelzine, tranylcypromine, isocarboxazid), selegiline does not inhibit peripheral metabolism of catecholamines and can be taken safely with levodopa. Selegihne does not cause the lethal potentiation of indirectly acting sympathomimetic amines such as dietary tyramine. Doses of selegiline higher than 10 mg daily can produce inhibition of MAO-A and should be avoided. 

Propylthiouracid (PTU) and methylthiouracil (Tapazole) are effective thioamide antithyroid dmgs used for treating thyrotoxic crisis and in preparation for subtotal thyroidectomy. Methimazole does not inhibit peripheral conversion of T4 to T3 as does PTU, but it is 10 times more potent and has a longer half-life than PTU. Prolonged use of thioamides may cause a goiter because of the... 

It inhibits peripheral dopamine D receptors resulting in increased Gl motility and tone. Its antagonism of the central D receptors raises the threshold of aaivity in the CTZ and decreases the sensitivity of visceral nerves supplying afferents to the vomiting center. It also antagonizes 5- FIT3 receptors at high dose... 

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