Pharmacological effect

The effects of thyroid hormone may persist for up to a week because of its long half-life in the circulation, its long-acting effect on the genome of the target cell, and the slow rate of recovery of some target tissues (e.g., brain). 

Thyroid disorders. Disturbances in thyroid metabolism can occur at any level of the hypothalams-pituitary-thyroid-peripheral tissue axis. Several of these disorders have been discussed previously. Hyperthyroidism is more prevalent in women than men. The three most common causes of hyperthyroidism are Graves hyperthyroidism, toxic multinodular goiter, and toxic adenoma. The clinical features of hyperthyroidism include hyperkinesis, weight loss, cardiac anomalies (e.g., atrial fibrillation), fatigue, weakness, sweating, palpitations, and nervousness. The typical biochemical laboratory parameters are increased serum free T4 and decreased serum TSH. 

The most common cause of hypothyroidism is failure of the thyroid gland this is known as primary hypothyroidism. In adults, the cause of primary hypothyroidism is often spontaneous autoimmune disease (e.g., Hashimoto s thyroiditis) or destructive therapy for hyperthyroid states 

Bodenner and R. W. Lash Thyroid disease mediated by molecular defects in cell surface and nuclear receptors. American Journal of Medicine 105, 524(1998). 

Boyages Clinical review 49 Iodine deficiency disorders. Journal of Clinical Endocrinology and Metabolism 77, 587 (1993). 

Wilson s disease. Penicillamine is a chelating agent that removes excess copper in patients with Wilson s disease. From in vitro studies that indicate that one atom of copper combines with two molecules of penicillamine, it would appear that 1 g of 

Precipitant drug Object drug Effect Description 

Penicillamine Digoxin 1 Digoxin serum may be reduced, possibly decreasing its pharmacological effects. The digoxin dose may need to be increased. 

Penicillamine Gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone A Do not use these drugs in patients who are concurrently receiving penicillamine. These drugs are associated with similar serious hematologic and renal reactions. 

Penicillamine Gold salts A Patients who have had gold salt therapy discontinued due to a major toxic reaction may be at greater risk of serious adverse reactions with penicillamine, but not necessarily of the same type. However, this is controversial. 

---

Isoproterenol is given sublingually or by iv. It is metabolized by monoamine oxidase and catechol-0-methyltransferase in brain, Hver, and other adrenergically innervated organs. The pharmacological effects of isoproterenol are transient because of rapid inactivation and elimination. About 60% is excreted unchanged. Adverse effects using isoproterenol therapy include nervousness, hypotension, weakness, dizziness, headache, and tachycardia (86). 

Zipeprol [34758-83-3] (58) is another European antitussive with a wide range of pharmacological effects, including antispasmodic, antihistaminic, and local anesthetic activities (85,86). It has been reported that zipeprol has been abused in Italy because high doses cause hallucinations (87). Spontaneous withdrawal symptoms similar to those of opiates have been observed withdrawal symptoms can also be precipitated by naloxone. Zipeprol can be... 

Research for an antidepressant among non-tricyclic compounds with pharmacological effects qualitatively different from those of the conventional tricyclic compounds led to the preparation and testing of a series of indazole derivatives for reserpine-like activity in mice. l-[3-(Dimethylamino)propyl]-5-methyl-3-phenyl-l//-indazole (FS-32 692) antagonizes reserpine-induced effects and potentiates amphetamine-induced self-stimulation and l-Dopa-induced increase in motor activity. FS-32 produces an anticholinergic action mainly on the central nervous System, while the action of imipramine occurs centrally as well as peripherally (79AF511). 

Cotarnine resembles hydrastinine (p. 167) in its pharmacological effects, but Its action on the uterus is less marked. It does not constrict the arterioles and appears to have a depressant action on the heart. Magidson and Gorbovizki have shown 1 that the Schiff s bases formed by the condensation of aldehydes with 1-aminomethylanhydrocotarnine have a marked local anaesthetic action but are irritant. 

This work on the modification of the morphine molecule and its pharmacological effects has attracted a good deal of attention and several interesting interim summaries and commentaries upon it have been published. ... 

Leptactina senegambica (Rubiaceas). The root-bark contains about 1 per cent, of alkaloids, including leptactinine, m.p. 264f-6°, which forms a picrate, m.p. 258° (dec.), picrolonate, m.p. 196°, and styphnate, m.p. 240-2°. The colour reactions with numerous alkaloidal reagents are recorded, some of which indicate that an indole nucleus is present. Pharmacological effects of an extract of the root bark are described (Paris and Bouquet, Ann. pharm. franc., 1946, 4, 233). 

Replacement of the terminal nitrogen of the piperazine by carbon is said to enhance the antiemetic activity of the phenothiazines at the expense of the other pharmacologic effects. The simplest compound in this series, pipamazine (88), is prepared by alkylation of nipecotamide (87) with the chloropropyl phenothiazine (58). Preparation of the analogous sulfoxide begins with acetylation of the thiomethyl compound, 89 [prepared by a route... 

Qualitative difference in pharmacological effect Opposite enantiomer may cause unwanted effects... 

The applicant should provide justification for using the racemate. Where the interconversion of the enantiomers in vivo is more rapid than the distribution and elimination rates, then use of the racemate is justified. In cases where there is no such interconversion or it is slow, then differential pharmacological effects and fate of the enantiomers may be apparent. Use of the racemate may also be justified if any toxicity is associated with the pharmacological action and the therapeutic index is the same for both isomers. For preclinical assessment, pharmacodynamic, pharmacokinetic (using enantiospecific analytical methods) and appropriate toxicological studies of the individual enantiomers and the racemate will be needed. Clinical studies on human pharmacodynamics and tolerance, human pharmacokinetics and pharma-cotherapeutics will be required for the racemate and for the enantiomers as appropriate. 

Concentration-response curve, a more specific (and technically correct) term for a dose-response curve done in vitro. This curve defines the relationship between the concentrations of a given molecule and the observed pharmacological effect. 

Null method, physiological or pharmacological effects are translations of biochemical events by the cell. The null method assumes that equal responses emanate from equal initial stimulation of the receptor therefore, when comparing equal responses, the complex translation is cancelled and statements about the receptor activity of agonists can be made. Relative potencies of agonists producing equal responses thus are interpreted to be measures of the relative receptor stimuli produced by the agonists at the receptor see Chapter 5.6.2. 

Diltiazem is the only benzothiazepine in clinical use. Its molecular mechanism of action as well as its pharmacological effects closely resemble those of phenylalkylamines. 

Following concurrent administration of two drugs, especially when they are metabolized by the same enzyme in the liver or small intestine, the metabolism of one or both drugs can be inhibited, which may lead to elevated plasma concentrations of the dtug(s), and increased pharmacological effects. The types of enzyme inhibition include reversible inhibition, such as competitive or non-competitive inhibition, and irreversible inhibition, such as mechanism-based inhibition. The clinically important examples of drug interactions involving the inhibition of metabolic enzymes are listed in Table 1 [1,4]. 

DISPLAY 19-1 Secondary Pharmacological Effects of the Narcotic Analgesics... 

The adrenergic dragp produce pharmacologic effects similar to the effects that occur in die body when die adrenergic nerves and the medulla are stimulated. The primary effects of these drugp occur on the heart, the blood vessels, and die smooth muscles, such as die bronchi. A basic knowledge of the nervous system is necessary to understand tiiese drugp and how they work in the body. 

Levodopa is a chemical formulation found in plants and animals that is converted into dopamine by nerve cells in the brain. Levodopa does cross die blood-brain barrier, and a small amount is dien converted to dopamine. This allows the drug to have a pharmacologic effect in patients witii Parkinson s disease (Pig. 29-1). Combining levodopa witii another drug (carbidopa) causes more levodopa to reach die brain. When more levodopa is available, the dosage of levodopa may be reduced. Carbidopa has no effect when given alone. Sinemet is a combination of carbidopa and levodopa and is available in several combinations (eg, Sinemet 10/100 has 10 mg of carbidopa and 100 mg of levodopa Sinemet CR is a time-released version of die combined drugs). 

The following drugp have a decreased pharmacologic effect when administered with an antacid corticosteroids, digoxin, chlorpromazine, oral iron products, isoniazid, phenothiazines, ranitidine, phenytoin, valproic acid, and the tetracyclines. 

---