ANALGESICA drug that selectively relieves pain by acting on CNS or on peripheral pain mechanisms without significantly altering consciousness
ALGESIA or PAINIt is an illdefined, unpleasent sensation, usually evoked by an external or internal noxious stimulus
PAIN RECEPTOR Pain receptor in our bodies are nerves that transmit pain. These are free nerve endings located in various body tissues that respond to thermal, mechanical, & chemical stimuli. When tissue becomes injured, they release chemicals called prostaglandins and leukotrienes that make the pain receptor more sensitive and these causing pain.
Types of Pain Visceral According to source Somatic NeuropathicPAIN Acute According to chronicity Chronic
Peripheral AnalgesicCausal: Non-causal: -Treat the cause -Not treat the cause eg:- atropine Examples: 1- Local anesthetics (for superficial tumor) 2- Counter-irritant (apply pain that counteract or mask the original one e.g. acupuncture)
OPIOID ANALGESIC“Opium” is a Greek word meaning “juice,” or the exudates from the poppy.Opium is extracted from poppy seeds (Paper somniforum)“Opioid” is a natural or synthetic drug that binds to opioid receptors producing agonist effects.
Fresh capsule of opium poppy Cut capsule showing latex exuding from cut
Classification Based on According toChemically receptor source occupation Phenanthrene Agonists Natural opium group alkaloids Eg: Morphine Eg: Morphine Eg: Morphine Benzolisoquino Antagonists Semisynthetic line group derivatives Eg: Papaverine Eg: Naloxone Eg: Heroine Mixed agonist- Synthetic antagonist opioids Eg: Nalorphine Eg: Pethidine
MORPHINE• Morphine is the most important alkalloid of opium.• Many new opioids have been synthesized but none of them are superior to morphine as an analgesic.• It is the protype of this group.
Mechanism of Action Opioids exert their major effects by interacting with opioid receptors in the CNS Opioids activate 7- transmembrane GPCRs located pre-symaptically and post-symaptically along pain transmission pathways. High densities of opioid receptors known as mu, delta and kappa are found in the dorsal horn of the spinal cord and higher CNS centers. Most currently used opioid analgesics act mainly at mu- opioid receptors Morphine acts at kappa receptors in lamina 1 and 11 of the substantia Granulose of the spinal cord and decreases the release of substance p, which is modulates pain perception in the spinal cord. Opioids have an onset of action that depends on the route of administration . Opioids causes hyper polarization of nerve cells , inhibition of nerve firing and presynaptic inhibition of transmitter relea Cellular effects of these drugs involve enhancement of neuronal potassium efflux ( hyperpolarizes neurons and makes them less likely to respond to a pain stimulus ) and inhibition of calcium influx ( decreases neuro- transmitter release from neurons located along the pain transmission pathway ) Opioids relieve pain both by raising the pain threshold at the spinal cord level and more importantly by altering the brains perception of pain
Adverse effects• Morphine can produce a wide range of adverse effects like nausea, vomiting, dizziness, mental clouding, respiratory depression, constipation, dysphoria, urinary retention, & hypotension, allergic reactions.• Tolerance- Repeated administration of morphine results in the development of tolerance to some of its effects including respiratory depression, analgesia, sedation, etc .• Dependence- Opium has been a drug of addiction for many centuries. Its ability to produce euphoria makes it a drug of addiction. Opioids produce both physiological & pshycological dependence. Manifestations are lacrimination, sweating, yawning, anxiety, restlessness..etc.
NSAIDsNon steroidal anti-inflamatory drugs are aspirine-type or non-opioid analgesics.In addition they have anti- inflamatory, anti pyretic & uricosuric properties without addiction liability.
Adverse effects Analgesics doses are usually well tolerated but anti-inflamatory doses are usually associated with adverse effects whed used for a long period.A. G.I tract:- Epigastric distress, nausea, vomiting, erosive gastritis, peptic ulcer, increase occult blood loss in stools are commonB. Allergic reactions are not common and may be manifested as rashes, photo sensitivity..etcC. HaemolysisD. NephrotoxicityE. Reye’s syndromeF. SalicylismG. Acute salicylate intoxication
Analgesics used in deintistry• Non opiod analgesics are mostly used for mild to moderate pain.• NSAIDs COX1 & COX2: Ibuprofen, aspirin, ketrolac, diclofenac COX-2: celecoxib, rofecoxib, nimesulide.
Acetaminophen• Dose: -Adult: 0.5 – 1g every 4-6 hrs. -6-12 years: 250-500mg every 4-6hrs. -1-5 years: 150-250mg every 4-6hrs.• Contraindication: Renal failure, asthma, liver failure.
OPIOIDSAlthough opiod as a class areeffective analgesics, somecommonly formulation shows pooranalgesic efficacy for dental pain,and is not used for their adverseeffects.
Tramadol• Tramadol is a synthetic centraly acting analgesic indicated to moderate to moderately severe pain.• Dose:- 50-100mg every 4-6 hours. (400mg/day- maximum)
Combination!!• Analgesic monotherapy has shown equivocal success in treating dental pain.• The goal of combining analgesics with different mechanisms of action is to use lower doses of the component drugs.
Acetaminophen combination• Acetaminophen is an effective analgesic for mild pain, but to manage more severe pain it typically is combined with codeine or one of its derivatives.• Acetaminophen 1000mg combined with codeine 60mg.• Acetaminophen 1000mg combined with oxycodone 10mg.• Acetaminophen 650mg combined with tramadol 75mg.• Acetaminophen 500mg combined with hydrocodone 7.5mg.
NSAIDs Combination• Ibuprofen 400mg combined with codeine 60mg.• Ibuprofen 400mg combined with oxycodone 10mg.• Ibuprofen 400mg combined with hydrocodone 15mg.