Analgesics Lecture Notes PDF

There are two major groups of analgesics: anti-inflammatory analgesics and opioids.  1-Anti-inflammatory drugs work by reducing inflammation (swelling) at the site of the pain. Examples include:  Acetaminophen.  Aspirin.  COX-2 inhibitors.  Nonsteroidal anti-inflammatory drugs (NSA...

There are two major groups of analgesics: anti-inflammatory analgesics and opioids.  1-Anti-inflammatory drugs work by reducing inflammation (swelling) at the site of the pain. Examples include:  Acetaminophen.  Aspirin.  COX-2 inhibitors.  Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen.  2- Analgesic opioids (also called narcotics) work by changing the brain’s perception of pain. Examples include:  morphine  Codeine.  Fentanyl.  Hydrocodone.  Meperidine.  Methadone.  Naloxone or naltrexone.  Nonsteroidal anti-inflammatory drugs (NSAIDs) Mechanism of action  Nonsteroidal anti-inflammatory agents (usually abbreviated to NSAIDs) are a group of medicines that relieve pain and fever and reduce inflammation.  NSAIDs work by blocking cyclo-oxygenase enzymes, (COX enzymes).  These enzymes are responsible for the production of prostaglandins.  Prostaglandins control many different processes such as inflammation, blood flow, and the formation of blood clots. NSAID Mechanism of action and side effects  Side effects NSAIDs may be grouped according to their preference for COX-1 and COX-2 enzymes.  Those that favor COX-1 are more likely to cause gastrointestinal side effects.  Those that favor COX-2 have a higher risk of cardiovascular effects but less gastrointestinal effects.  Higher dosages of NSAIDs tend to result in more COX-2 enzyme inhibition (and more cardiovascular side effects), even in those NSAIDs traditionally seen as low risk (such as ibuprofen).  NSAIDs with higher activity against COX-2 enzymes should be used with caution in people with cardiovascular disease.  What are analgesics used for? Analgesics are used to relieve pain and inflammation. For example:  After surgery.  Due to injury, such as a fractured bone.  For acute (sudden, short-term) pain, such as a twisted ankle or headache, migraines.  For aches and pains like menstrual cramps or, sprains, toothache.  For chronic painful conditions such as arthritis, cancer or back pain.  Nonsteroidal anti-inflammatory drugs (NSAIDs) Therapeutic Uses:  Aspirin is a NSAID that is used in small doses to lower the risks of having a heart attack or a stroke caused by a blood clot.  It may also be given as a single dose at the time of a heart attack to improve outcomes.  This is because it irreversibly inhibits the COX-1 enzyme. Acetaminophen  Inhibits brain much more that peripheral COX  Produces analgesia and antipyrexia  Poor anti-inflammatory  Good analgesic for acute mild to moderate pain, generally well tolerated  Analgesic, antipyretic and anti-inflammatory  Relative COX 1-2 blockade per drug  Lose cardioprotective effects of aspirin and COX-2 inhibition may increase risks of MI  Use GI cytoprotectives concurrently for long-term NSAID use  Opioids, also known as "narcotics"  Opioid analgesics act on three major classes of receptors: μ, δ, and κ receptors.  Each of these classes of receptors has its representative endogenous ligand (eg, endorphin for the μ receptor and dynorphin for the κ receptor).  These classes of opioid receptors are widely distributed throughout the central and peripheral nervous system as well as other systems such as the gastrointestinal tract.  Three major classes of opioid receptors have been defined: mu, kappa, and delta.  The mu receptors have been further subclassified into two distinct subtypes (mu 1 and mu 2), as have the delta receptors (delta 1 and delta 2).  Kappa receptors have been subdivided into kappa 1, kappa 2, or kappa 3 subtypes.  All of these subtypes modulate pain perception.  Activation of opioid receptors modulate nociceptive transmission by: 1- inhibiting Ca++ influx into the presynaptic terminal. Ca++ is necessary for the release of neurotransmitters from the presynaptic terminal into the synapse. 2- opening K+ channels causing an efflux of K+ which hyperpolarizes the neuron making it more difficult to depolarize.  Activation of opioid receptors produces profound analgesia through a combined presynaptic and postsynaptic effect.  Presynaptically, opioid analgesics act on primary nociceptive afferents (inhibition of calcium channels), resulting in the reduced release of neurotransmitters such as substance P and glutamate implicated in nociceptive transmission.  Postsynaptically, opioid analgesics directly inhibit postsynaptic neuronal activity by hyperpolarizing cell membranes via opening potassium channels.  Other effects of opioids: (eg, antitussive, reducing gastrointestinal tract motility) also have practical therapeutic use  Because of a widespread distribution of opioid receptors both within and outside the nervous system, opioid analgesics also produce a broad spectrum of adverse effects including euphoria, dysphoria, sedation, respiratory depression, constipation, suppression of endocrine systems, cardiovascular disorders (eg, bradycardia), convulsion, nausea, vomiting, pruritus, and miosis.  Opioid tolerance Opioid tolerance is a pharmacological phenomenon caused by repeated opioid exposure that results in decreased analgesic effects and patient needs to increase dose to have the same analgesic effect.