Chemistry and Therapeutic Effects of Analgesics
Chapter One
SPECIFIC FORMS AND USES OF ANALGESICS
Analgesics are frequently used in combination, such as the acetaminophen and codeine preparations found in many non-prescription pain relievers. Propoxyphene and acetaminophen are used together (Darvocet N), as are oxydodone and acetaminophen (Percocet, Roxicet), and hydrocodone and acetaminophen (Lortab, Anexsia) (Ross-Flanigan 2002). Analgesics also can be found in combination with vasoconstrictor drugs such as pseudoephedrine for sinus-related preparations, or with antihistamine drugs for allergy sufferers.
The use of acetaminophen (paracetamol), as well as aspirin, ibuprofen, naproxen, and other NSAIDs concurrently with weak to mid-range opiates (up to about the hydrocodone level) has been shown to have beneficial synergistic effects by combating pain at multiple sites of action—NSAIDs reduce inflammation that in some cases, is the cause of the pain itself while opiates dull the perception of pain. Thus, in cases of mild to moderate pain caused in part by inflammation, it is generally recommended that the two be prescribed together (Mehlisch 2002).
CHAPTER TWO
CHEMISTRY OF ANALGESICS, OPIOID PEPTIDES: THEIR SKELETAL MOLECULAR IMAGES
AND CHEMICAL SYNTHESIS OF SELECTED ANALGESICS
THE CHEMISTRY OF ANALGESICS
The chemistry of analgesic studies the signal-response of the CNS or PNS of a receptor or target area and the effect of analgesic on site of action by interfering with the normal brain response to the signal.
This study seeks to appreciate analgesics and to give a comprehensive view of the chemistry approach to pain management using analgesics. The understanding of the transmission and process of pain and how chemists around the World have contributed to design of analgesic drugs for management and treatment of pain would be appreciated more.
Physiology of Pain: Pathways and Effects on Pain Perception
Pain is a complex process mediated by multiple pathways and mechanisms in both the peripheral and central nervous systems (PNS and CNS [spinal cord and brain])
Fundamental characterization of pain is of two types Nociceptive; from activation of pain-sensitive afferent neural pathways in response to mechanical, thermal or chemical stimuli (injury) and Neuropathic; from abnormal pain processing due to lesions in the PNS, CNS or both.
CHEMICAL SYNTHESIS OF NONOPIOID ANALGESICS: ASPIRIN & ACETAMINOPHEN
EXPERIMENTAL TECHNIQUES REQUIRED
Recrystallisation (T 2), filtration (T 3), melting point determination (T 4), yield calculation (T 14) Chemical synthesis and purification of two common analgesics (painkillers) aspirin and acetaminophen: Aspirin is prepared by the O-acylation (i.e. addition of an acyl group to an oxygen) of salicylic acid. Similarly, acetaminophen is prepared by the N-acylation (i.e. addition of an acyl group to a nitrogen) of p-aminophenol.
It is important to note the similarity between the two reactions should one decide to adapt this work and to carry out this experiment .The crude samples will be purified by recrystallisation and the melting points of the products measured as a means of checking their identity and purity.
The purpose of the addition of this experiment is to encourage the practice of the art of chemical synthesis; to practice the fundamentally important skill of purification by efficient recrystallisation, and application of the previously learned technique of melting point determination. It’s fun to try to have the two crude products prepared by the end of the first week.
CHAPTER THREE
THERAPY GUIDELINES, THERAPEUTIC EFFECTS, CONTRAINDICATIONS, ABUSES, GOVERNMENT AND ORGANIZATIONAL SUPPORT IN OPIOID REGULATION AND THE COMPARISON OF SELECTED ANALGESICS
General Therapy Guidelines (Principles of Analgesic Therapy)
Some principles of analgesic therapy are drug-pain-type specific. However, some general principles guide all pharmacologic treatment of pain:
Identify and treat the source of the pain.
Whenever possible, identify and treat the Pain: Current Understanding of Assessment, Management, and Treatments underlying cause of the pain. However, pain management can begin before the source of the pain is determined.
Select the simplest approach to pain management.
Although invasive methods are sometimes required, most pain can be relieved via simple methods. Cost of treatment is also a consideration in some cases.
Select an appropriate drug.
Individualization of a pain management regimen begins with selection of an appropriate drug. Factors that guide this process include:
- Characteristics of the pain (e.g., duration, intensity, quality),
- Characteristics of the agent (e.g., analgesic ceiling, expected time of onset and duration of analgesia, available routes of administration, dosing interval, side effects, potential for accumulation of toxic metabolites, potential for addiction) Patient factors (e.g., age, coexisting diseases, other medications, preferences, response to previous treatments).
Establish a management plan.
The next step is to establish a management plan, which may include the later addition of other drugs. Use of several analgesics in combination offers several advantages. It may:
- allow use of lower doses of some agents, thus reducing the risk of side effects
- Inhibit nociceptive processing at multiple (i.e., peripheral and central) levels, thus enhancing analgesia
- facilitate treatment of pain in patients who do not respond to a single agent. Common acceptable combination regimens include: 1) a nonopioid plus an opioid or 2) a nonopioid plus an opioid plus an adjuvant analgesic.
CONCLUSION
In the process of putting together various works done on drugs with analgesic properties, studying there therapeutic effects on man and little on animals, I would say tremendous job has been done. There remain, on the inroad to understanding pain management, gaps which I believe with the right equipment and environment or condition for a good chemist, they can be filled.
Opioid analgesic drugs through studies, has revealed great potency on their therapeutic effect in human medicine, but I have come to support the various organizations {not mentioned intentionally in this work} that are kicking against their recreational use because of prevalent damage it causes our society and the world at large.
NSAIDs are effective medications that afford many veterinary patients a significant amount of relief from pain associated with both chronic disease states and acute inflammatory events. However, before initiating NSAID therapy, it is prudent for veterinarians to educate clients on signs of toxicity and to exercise sound clinical judgment in animal selection based on physical examination findings, concurrent drug therapy and preexisting diseases. Billions of doses of NSAIDs are consumed annually making them responsible for more toxic deaths than any other pharmaceutical agent. The vast majority of these deaths are from the GI toxicity from non-selective NSAIDs. COX-2 inhibitors are costly and may be less toxic than other NSAIDs. Patient education and understanding of appropriate dosing/ risk factors can prevent needless deaths and morbidity. Adjunctive methods such as weight loss and chondroprotective agents may help reduce untoward side effects of NSAIDs.
During therapy, early recognition of signs of toxicity, both through routine clinicopathological monitoring and keen client based observations, are essential for safe NSAID therapy for veterinary patients
It is clear that the COX-2 inhibitors are safer, better tolerated, and equally efficacious, but many clinical issues need to be fully resolved. Numbered compounds such as SC58125 have been now synthesised and being tested clinically. Early results show that these do not have significant gastrotoxicity or nephrotoxicity even in doses greater than those required for anti-inflammatory effects. Similarly, compounds such as 1.475.337 and flusolide (CGP28258) are COX-2 inhibitors that are being developed and have more than 1,000 times selectivity for COX-2. It is, however, evident that such high degree of selectivity will not offer any advantage over the conventional NSAIDs, unless full information about their side effects is known. Nimesulide is one such example, which, inspite of being a selective COX-2 inhibitor, has recently been shown to have the same spectrum of adverse events as compared to the conventional NSAIDs in a large study from Italy.
Presently, adverse reactions because of selective COX-2 inhibition are being studied, and whether these agents are real advancement or not, only time will tell; but early results show promise. Proper clarification of these issues is important because these drugs are now being used increasingly instead of the conventional NSAIDs in spite of being many times expensive.
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