Analgesics history

Scopolamine (42), an optically active, viscous Hquid, also isolated from Solanaceae, eg. Datura metell. decomposes on standing and is thus usually both used and stored as its hydrobromide salt. The salt is employed as a sedative or, less commonly, as a prophylactic for motion sickness. It also has some history of use ia conjunction with narcotics as it appears to enhance their analgesic effects. BiogeneticaHy, scopolamine is clearly an oxidation product of atropiae, or, more precisely, because it is optically active, of (—)-hyoscyamiae. 

The miscellaneous anticonvulsants are used cautiously in patients with glaucoma or increased intraocular pressure a history of cardiac, renal or liver dysfunction and psychiatric disorders. When the miscellaneous anticonvulsants are used with other CNS depressants (eg, alcohol, narcotic analgesics, and antidepressants), an additive CNS depressant effect may occur. 

GC, a 28-year-old woman, complains of a "terrible headache that won t go away." She describes the pain as "on one side and throbbing." The pain began yesterday morning and caused her to leave work. She reports a history of similar headaches since the age of 16, but none that lasted this long. In the past, her headaches were relieved with the use of over-the-counter non-steroidal anti-inflammatory drugs (NSAIDs). She often has to take analgesics multiple times per week. 

The analgesic effects of NSAIDs are attributed to inhibition of the COX-2 enzyme, whereas the negative GI effects are due to inhibition of COX-1.28 Patients taking oral anticoagulants, those with a history of peptic ulcer disease, or others at high risk for GI complications may be considered candidates for a COX-2 inhibitor or a combination of a nonselective NSAID with a gastroprotective agent such as a proton pump inhibitor (PPI). Because most PPIs are available by prescription only, such patients should be referred to a physician. 

Choice of initial analgesic should be based on previous pain crisis pattern, history of response, current status, and other medical conditions... 

Transition to oral analgesics as the patient improves choose an oral agent based on previous history, anticipated duration, and ability to swallow tablets if sustained-release products are used, a fast-release product is also needed for breakthrough pain... 

Yet another (see lenperone) butyrophenone related to haloperidol is pipamperone (64). N-benzyl-4-piperidone (60) has a venerable history as starting material for both central analgesics and CNS drugs. This synthon has been used by the Janssen group as a building block for numerous such drugs. Reaction of... 

The development of the first effective analgesic drug, opium, was almost certainly adventitious, and occurred in prehistoric times. The use of the dried exudate from slitting the immature capsule of the opium poppy, Papaver somniferum, as an analgesic, sedative and euphoriant, has a long folkloric history. Isolation of the principal active component morphine (1) as a pure crystalline compound represented one of the early landmarks in organic chemistry. 

The history of this class of analgesics might have stopped there were it not for the manifold ancillary activities shown by that molecule. Although still one of the most widely used agents for treatment of severe pain, morphine is a drug that must be used with caution. Side effects include respiratory depression, induction of constipation, and sometimes marked sedation. The one property that most severely limits use of this drug is its propensity to induce physical dependence in patients subjected to more than casual exposure. 

Other measures include the clinician s global assessment based on the patient s history of activities and limitations caused by OA, the Western Ontario and McMaster Universities Arthrosis Index, Stanford Health Assessment Questionnaire, and documentation of analgesic or NSAID use. 

Analgesic Plants Opium Poppy History and Botany... 

Patients receiving opioid analgesics opioid-dependent patients patients in acute opioid withdrawal failed naloxone challenge positive urine screen for opioids history of sensitivity to naltrexone acute hepatitis or liver failure. 

Hematologic effects Aspirin interferes with hemostasis. Avoid use if patients have severe anemia, history of blood coagulation defects, or take anticoagulants. Long-term therapy To avoid potentially toxic concentrations, warn patients on long-term therapy not to take other salicylates (nonprescription analgesics, etc). Salicylism Salicylism may require dosage adjustment. 

Acetaminophen is similar to salicylates in that it is a useful analgesic for mild to moderate pain, with equal efficacy to aspirin, and like aspirin, it is antipyretic. However, acetaminophen exerts little if any effects on platelet aggregation and is not antiinflammatory. Thus, it is not useful for patients with arthritis or other inflammatory diseases. It is also not useful as an antithrombotic agent in the prevention of myocardial infarction or transient ischemic attacks. Acetaminophen does not produce the gastric ulceration that can occur with aspirin and is useful in patients who are salicylate sensitive or who have a history of ulcers or other gastric ulcerations. 

Propoxyphene (dextropropoxyphene Darvon) is structurally related to methadone but is much less potent as an analgesic. Compared with codeine, propoxyphene is approximately half as potent and is indicated for the treatment of mild pain. It is not antipyretic or antiinflammatory like aspirin and is less useful than aspirin in most cases of mild pain. Toxicity from propoxyphene, especially in combination with other sedatives, such as alcohol, has led to a decrease in its use. Death following ingestion of alcohol in combination with propoxyphene can occur rapidly (within 20 minutes to 1 hour). The drug is not indicated for those with histories of suicide or depressive illnesses. 

Aspirin is the most widely used medication. Over 10,000 tons of aspirin are used in this country annually, and worldwide the annual consumption is 35,000 tons. The history of acetylsalicylic acid actually goes back thousands of years. Hippocrates (460-377 B.c.) and the ancient Greeks used powdered willow bark and leaves to reduce fever (antipyretic) and as a pain reliever (analgesic). Native American populations also used willow and oil of wintergreen for medication. The chemicals responsible for the medicinal properties in willow and oil of wintergreen are forms of salicylates. Willows (genus Salix) contain salicin and oil of wintergreen contains methyl salicylate. 

Tabernaemontana spp. This genus is from a tribe within the family Apocynaceae that is called the Tabernaemontaneae. As an official sub-family it would be called Tabernaemontanoideae. It is because of the casual use of names such as these that botanical binomialists are rarely invited to social functions. It (this Genus, that is) contains several dozen species, some with ibogaine, many with analgesic or sedative action in experimental animals, and some with a quite a history of native usage either in Africa or Southeast Asia. 

Despite its long clinical history after its discovery in 1893 (von Mering, 1893), the mechanism of action of paracetamol is not fully understood. It shows some weak inhibition of the COX isoenzymes and there is speculation on a third COX isoenzyme, COX-3, induced during the resolution phase of an inflammatory response, that might be specifically targeted by paracetamol (Willoughby et al., 2000). Furthermore, there is evidence for a possible central analgesic effect mediated indirectly by 5-HT (Courade et al., 2001). 

It is interesting to compare two compounds introduced by Bayer laboratories in Germany at this time in history. We ve already encountered one of them diacetylmorphine, or heroin. The other was acetylsalicylic acid, or aspirin, which is now the most widely used analgesic. Both drugs are rapidly transformed to their original form after absorption—that is, they are converted to their active forms by removal of the acetyl groups. Bayer had discovered two very important pain-relieving medications that would have a dramatic impact on the lives of millions of people around the world. 

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