Non-Opioid Analgesics Pharmacology PDF
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This document provides details on acetaminophen, including its pharmacokinetics, mechanism of action, therapeutic uses, and adverse effects. Acetaminophen is a non-opioid analgesic used for pain relief and fever reduction.
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█ NON N-OPIOID ANALGES SICS 1. Ace etaminophen (Para acetamoll) Pharm macokinetics Abssorption is complete and rapid from GIT with w peak levels afteer 30 min. Mettabolism: liver by conjugation...
█ NON N-OPIOID ANALGES SICS 1. Ace etaminophen (Para acetamoll) Pharm macokinetics Abssorption is complete and rapid from GIT with w peak levels afteer 30 min. Mettabolism: liver by conjugation c n. At highh doses, it is convverted into o toxic mettabolite (N N-acetyl-be ne) that is responsible for hepaatotoxicity.. enzoquinon Exc cretion: maainly renal. Mecha anism & Ph harmacolo ogical effe ects It iss a selectivve Cox III inhibitor sso it inhibitts PGs syn nthesis in tthe brain only o and hass analgesic & antip pyretic acttions witho out effects on the eenzymes that t are respponsible fo or synthesis of perip pheral PGss and so it has no a nti-inflammatory action. It ha as little orr No effects on the C CVS, GIT, re espiratory or platelett functions s. Therap peutic use es As anaalgesic andd antipyretic when aspirin is s contraindicated (ee.g. patien nts with peptic ulcer, hemmophilia, etc). e Aceta aminophen n can be administer a red in preggnancy with greater safetty than asp pirin. Advers se effects At therapeuttic doses: acetami nophen iss well-tolerated but may cause: c – Skin rash h& drug fever (a as allergic c reactions).. – Long term m use may lead l to ren nal failure. In ttoxic dose es: dose-d dependen nt hepato-- toxiicity (centtrilobular necrosis): It occurs s with h large dosses (about 15 gm in a adults and d m in childrren) 4 gm Mec chanism of o hepatottoxicity A Acetamino ophen is converted d to toxic c metabolite e (N-acety yl-benzoquuinone) inn tthe liver that need ds detoxifiication by y reduced glutathione e. 337 When glutathione store is depleted, the toxic metabolite binds covalently to cellular proteins producing hepatocellular damage. Clinical symptoms of toxicity (e.g. vomiting) occur within 24 hrs but signs of hepatic damage (e.g. jaundice) occur after 2-6 days. Treatment of toxicity The 20 hour IV protocol of Gastric lavage with activated charcoal. acetylcysteine Sulfhydryl donors (acetylcysteine) to – First, administer an initial restore hepatic glutathione. It must be loading dose of 150 mg/kg IV started within 8 hours of toxicity. over 60 minutes. Hemodialysis: better within the first 12 – Next, administer 12.5 mg hrs after ingestion. /kg per hour IV for 4 hours. – Finally, administer 6.25 mg Nefopam (Acupan) /kg per hour IV for 16 hours. Mechanism and effects It is a central analgesic without antipyretic or anti-inflammatory activity. It is more potent than NSAIDs. The analgesic mechanism is unclear but may be related to inhibition of many transmitters reuptake or blocking central voltage-gated Na+ channels. Nefopam is also used to combat severe hiccups. Adverse effects – Precipitation of epileptic convulsions in patients with epilepsy. – Weak atropine-like actions: dry mouth, urine retention, etc. Contraindications: history of epilepsy Dipyrone (Novalgin) Mechanism and effects Analgesic antipyretic that is more potent than aspirin. It has no anti- inflammatory action. Its use was restricted in many countries because of risk of agranulocytosis which is not dose-dependent. Adverse effects – Agranulocytosis: reversible in 10 days after stoppage of the drug but lethal in 10% of cases. – Allergic reactions and anaphylaxis. – It can trigger bronchoconstriction in patients with Asthma. 338