Drug Elimination - Biotransformation | Non-adrenergic Non-cholinergic Transmission | Coagulation Disorder Drugs Flashcards
Biotransformation
Liver is the major source of biotransformation reactions that converts metabolites or drugs into inactive [or active if prodrug] from lipid soluble to water soluble compounds to make exretion easier via Kidneys and Urine. However bile excretion is also a way where somewhat-water soluble metabolites are excreted
Consists of 2 phases which are not done in succession for all drugs:
- Phase 1:
Oxidation, Reduction, Hydrolysis reactions occuring in ER [Hydroxylation; Hydrolysis in Inner Mitochondrial Membrane] of hepatocytes and other cells [but majorly liver]
Enzymes are the CYP450 enzyme family which uses NADPH and O2
Rate of CYP450 can be changed via Inducers [Smoking and Drinking in Barbs Car Rifs her Phen] and Inhibitors [COKE + Grapefruit with your PI]
- Phase 2:
Conjugation reactions consisting of Glucuronidation [UDP-Glucuronosyltransferase], Acetylation [M-acetyltransferase], Methylation [methyltransferase] and Glutathione GSH [glutathione-S-tansferase] all of which produces a highly hydrophilic inactive metabolite that is easily excreted
Enalapril to Enalaprilate [Inactive Prodrug to Active drug]
Codeine to Morphine [Active drug to Active metabolite]
COKE - Cimetidine, Omeprazole, Ketoconazole, Erythromycin
PI - Protease Inhibitors
NANC transmission
Neurotransmitters that are not Catecholaimes [not dopamine] or Acetylcholine
These neurotransmitters are often present in Gut, Airways, Bladder and Brain. These are often cotransmitters
These agents are:
- ATP [fast depol, contraction]
- GABA [Pro peristalsis]
- 5-HT [Pro peristalsis]
- Dopamine [Vasodilation]
- NO [Gastric emptying, Vasodilation, Erectile functions]
- NPY [Enhance vasoconstriction of NE, NE release inhibitor]
- VIP [Vasodilation, bronchodilation]
- SubstanceP [Slow depol, cotransmitter Ach]
- Somatostatin [Vasodilation, bronchodilation]
- CCK [triggers gallbladder and pancrease contraction to release Bile and Pancreatic juices]
- CGRP [Vasodilation, increase vascular permiability]
Drugs used in Coagulation Disorders
Traditional drugs: Heparin [water soluble, large polysaccharide] and Warfarin [lipid soluble, small molecule]
- Heparin stimulate AT3 binding to Factors 2, 9, 10, 11, 12 for a rapid inactivation and anticoagulant effect | Protamine sulphate is antidote | 2h HL, given IV, SC and does not cross the placenta
- Warfarin blocks VitK dependent epoxide reductase which leads to Factors 2, 7, 9, 10 synthesis inhibition [does not effect already present factors], slow acting and longterm therapy | Given PO, 30h + HL and crosses the placenta
Direct Thrombin Inhibitors:
- Dabigatran, Argatroban, Bivalirudin
Direct Factor Xa Inhibitor:
- Rivaroxaban
The newish drug do not need PT or INR monitoring as these have a safe window
For bleeding disorders:
- Platelet transfusions [Thrombocytopenias or platelet dysfunctions]
- Blood product transfusions [Factors VIII, IX, XI, vWF, Desmopressin for hemophilias or active bleeding]
- Phytonadione [VitK deficiency]
