Pharmacology Past Paper PDF

█ 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