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بحث بشير أمين حيدر Cimetidine.pptx

  1. PHARMACOKINETICS OF CIMETIDINE PREPARED BY ‫حيدر‬ ‫عبدهللا‬ ‫امين‬ ‫بشبر‬ ‫إشراف‬ ‫تحت‬ ‫الفاضل‬ ‫الدكتور‬ : ‫محمود‬ ‫البريهي‬
  2. CIMETIDINE Table Of Content Background Structure Indication Contraindications & Blackbox Warnings Pharmacodynamics Mechanism of action Pharmacokinetics Drug Interactions Calculations for the parameters
  3. Background SUMMARY Cimetidine is a histamine H2 receptor antagonist used to manage GERD, peptic ulcer disease, and indigestion. BRAND NAMES Good Sense Heartburn Relief, Tagamet GENERIC NAMES Cimetidine BACKGROUND: important hydrogen histamine receptor. It is widely employed in medicine due to its protective action in stomach ulcerations. Cimetidine is highly stable, thus in 24 h about 50 to 80% of the delivered dose is excreted unaltered. A recent study investigated changes in pH and levels of histamine over the oxyntic glands of guinea pig stomach. Researchers observed decrease in pH, which was due to acid secretion. Simultaneous measurements were carried out during the cimetidine pharmacological treatment. A sharp increase in histamine and a decrease in acid secretion were observed. Cimetidine accumulation is associated to the risk of prostate cancer, due to the reduction in zinc levels, which are essential to the regulation of cell cycles and apoptosis induction
  4. Structure DRUG NAME INFO Drug Name Info US Trade Names Tagamet Tagamet HB Class Gastric Acid Secretion Inhibitor Histamine H2 Antagonis Regulatory Status RX/OTC Generic Availability Yes Structure INN name: Cimetidine, Chemical name: N00cyano-N-methyl-N0 -[2([(5-methyl-1H-imidazol- 4yl)methyl]thio)ethyl] guanidine. WEIGHT Average: 252.339 Monoisotopic: 252.115715232
  5. CHEMICAL PROPERTIES OF CIMETIDINE Chemical formula C10H16N6S Molecular weight 252.339 g/mole PH : basic drug Solubility: Hydrophobic 8.0-9.5 Solubility: Soluble (1.14%) in water at 37°C;soluble in ethanol; very slightly soluble in chloroform; insoluble in diethyl ether
  6. Clinical use of Cimetidine FDA-Labeled Indications Erosive esophagitis Gastric ulcer,Active, Systemic mast cell disease Erosive esophagitis Gastric ulcer,Active Zollinger-Ellison syndrome Ulcer of duodenum Active Ulcer of duodenum Maintenance Zollinger-Ellison syndrome Systemic mast cell disease
  7. Clinical use of Cimetidine Non-FDA Labeled Indications Aspiration pneumonitis; Prophylaxis Contrast media adverse reaction Gastric ulcer, Maintenance Gastric ulcer, Maintenance Measurement of renal clearance Verruca vulgaris Measurement of renal clearance Stress ulcer Verruca vulgaris Aspiration pneumonitis;
  8. Dosage of Cimetidine Injectable solution 150mg/mL Oral solution 300mg/5mL Tablet 200mg , 300mg , 400mg (Rx)600mg (Rx) 800mg (Rx)
  9. Contraindication of Cimetidine Hypersensitivity to cimetidine or other H2 receptor antagonists
  10. Protein binding, 13% to 26% Vd: 1 L/kg Pharmacokinetics of Cimetidine 30 L/hr to 48 L/hr ABSORPTION Tmax, Oral: 45 to 90 minutes Bioavailability, Oral: 70% to 76% DISTRIBUTION METABOLISM Hepatic, approximately 50% Cimetidine sulfoxide (major): inactive EXCRETION Renal excretion: 48% Renal clearance: 13.8 L/hr to 30 L/hr Dialyzable: yes (hemodialysis) , 20.4 mL/min to 37.4 mL/min; Eliminatio n Half Life 2 hours ELIMINATION HALF LIFE yes (peritoneal dialysis), 4.2 mL/min to 5 mL/min Total body clearance:
  11. Cimetidine is a histamine H -receptor antagonist. It reduces basal and nocturnal gastric acid secretion and a reduction in gastric volume, acidity, and amount of gastric acid released in response to stimuli including food, caffeine, insulin, betazole, or pentagastrin. It is used to treat gastrointestinal disorders such as gastric or duodenal ulcer, gastroesophageal reflux disease, and pathological hypersecretory conditions. Cimetidine inhibits many of the isoenzymes of the hepatic CYP450 enzyme system. Other actions of Cimetidine include an increase in gastric bacterial flora such as nitrate-reducing organisms. Pharmacodynamics
  12. M echanism of action Cimetidine receptor binds to located an H - on the basolateral membrane of the gastric parietal cell, blocking histamine effects. This competitive inhibition results in reduced gastric acid secretion and a reduction in gastric volume and acidity. Cimetidine is a H2 blocker that acts by inhibiting histamine action at the histamine H2 receptors of the parietal cells. Cimetidine inhibits both daytime and nocturnal basal gastric acid secretion, as well as gastric acid secretion stimulated by food, histamine, pentagastrin, caffeine, and insulin.
  13. Pharmacokinetics parameter of Cimetidi Therapeutic Plasma concentration range (0.64–1.64 μg/ml). Bioavailability (65%). Volume Distribution VD (1 L/kg) ×70 =70 L for ideal body weight 70kg. T1/2 (2hur). 1)Cp target =0.6 ng/ml +1.64 ng/ml =0.98/2= 0.5 ng/ml ×0.00l mg/L =0.0005 mg/L 2) K = 0.693 /t1 /2 =0.693 /2 =0.34 3) Cl =k ×vd =0.34 ×70 =24.2 L/hrs 7) AUC =dose/CL =400 /24.2 L/hr = 1 6.5 mg.h/L 4) LD =Cp ×vd /F =0.0005 mg/L ×70L /0.65 =0.05 mg 6) T1 /2 =0.693 ×Vd /Cl =0.693 ×70/24.2 L/hr =2 hr 8) TW=C max/C min = 1 .64 ng/ml /0.6 ng/ml =2.7 9) DI max= 1.44× t1/2 ×ln ( TW) =1.44 ×2 ×ln(2.7) =2.86 hr
  14. DRUG Abacavir Abemaciclib Abrocitinib Acalabrutinib Acamprosate Acebutolol Aceclofenac Acemetacin Acenocoumarol Acetaminophen INTERACTION INTEGRATE DRUG-DRUG INTERACTIONS IN YOUR SOFTWARE Cimetidine may decrease the excretion rate of Abacavir which could result in a higher serum level. The metabolism of Abemaciclib can be decreased when combined with Cimetidine. The metabolism of Abrocitinib can be decreased when combined with Cimetidine. The metabolism of Acalabrutinib can be decreased when combined with Cimetidine. The excretion of Acamprosate can be decreased when combined with Cimetidine. The metabolism of Acebutolol can be decreased when combined with Cimetidine. Aceclofenac may decrease the excretion rate of Cimetidine which could result in a higher serum lev Acemetacin may decrease the excretion rate of Cimetidine which could result in a higher serum leve The serum concentration of Acenocoumarol can be increased when it is combined with Cimetidine. The metabolism of Acetaminophen can be decreased when combined with Cimetidine. Drug - Drug Interactions
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