Detoxification Bruno Sopko Content Introduction Ethanol Nicotine THC

Detoxification Bruno Sopko

Content � Introduction � Ethanol � Nicotine � THC � Amphetamines � Cocaine � Opiates

Introduction – descripton of the effect

Introduction – Targets

Ethanol � Description of the effect � Metabolic pathway ◦ ADH - ALDH ◦ Microsomal Ethanol Oxidizing System � Ethanol ◦ ◦ toxicity NADH/NAD+ Acetaldehyde Free radicals Decrease of the liver functionality (cirrhosis)

Ethanol - Description of the effect

Ethanol – metabolic pathway: ADH-ALDH

Ethanol – metabolic pathway: MEOS

Ethanol toxicity - NADH/NAD+

Ethanol toxicity - acetaldehyde

Ethanol – breath analysis � Reaction of K 2 Cr 2 O 7 in H 2 SO 4 with Ethanolem � Conductivity sensor ◦ Active layer changes its conductivity via reaction with gaseous reducing compounds ◦ This change can be measured as the change of resistance.

Ethanol – breath analysis � Theoretical estimation of ethanol concentration in blood: � Compare with experimental results: Time (min) Theoretical value (g/l) Measured value (g/l) 0 30 60

Nicotine

Nicotine – the effect � Interaction with acetylcholine receptors � Stimulation of cholinergic neurons stimulates the dopamine production (hippocampus), similar effect to cocaine. � Glutamate release (neurotransmitter) – strengthens glutamatergic connection in hippocampus. � MAO inhibition. � There is no direct prove of Nicotine cancerogenity. Other compounds in tobacco smoke are cancerogenic.

THC � THC is metabolized by P 450 (3 A 4) to 11 hydroxy –THC, and then to THC-COOH � 55 % excreted bye feces as adduct of THCCOOH and glukuronic acid � 20 % excreted by urine in form of THC-COOH

THC � Cannabinoid receptors CB 1 and CB 2 (natural cannabinoid - anandamid) � Decrease of adenylylcyclase activity

Ampetamines

Amphetamines � „Replacement“ of dopamine in vesicles and then its release. � MAO-A inhibition

Cocain � Effect similar to amphetamines, mechanism different – binding to the dopamine transporters in presynaptic membrane � Metabolic pathway: hydrolisis of the ester bond with benzoylecgonin as a metabolite

Opiates

Opiates � Interaction with endorphin receptors (μ, κ a δ) decreases the release of GABA, and, therefore, increases indirectly the concentration of dopamine � Long/term inhibition of c. AMP production

Literature: � � � Allan D. Marks, MD: Basic Medical Biochemistry a Clinical Approach, Lippincott Williams & Wilkins, 2009 Ellen M Mc. Donagh, Michelle Whirl-Carrillo, Yael Garten, Russ B Altman & Teri E Klein: From pharmacogenomic knowledge acquisition to clinical applications: the Pharm. GKB as a clinical pharmacogenomic biomarker resource, Biomarkers Med. (2011) 5(6), 795– 806 Robert Melamede: Cannabis and tobacco smoke are not equally carcinogenic, Harm Reduction Journal 2005, 2: 21 TAMIHIDE MATSUNAGA, NOBUYUKI KISHI, SHINSUKE HIGUCHI, KAZUHITO WATANABE, TOHRU OHSHIMA, AND IKUO YAMAMOTO: CYP 3 A 4 IS A MAJOR ISOFORM RESPONSIBLE FOR OXIDATION OF 7 -HYDROXY-D 8 -TETRAHYDROCANNABINOL TO 7 -OXO-D 8 -TETRAHYDROCANNABINOL IN HUMAN LIVER MICROSOMES, DRUG METABOLISM AND DISPOSITION (2000), 28(11), 1291 -1296 C. L. FAINGOLD, P. N'GOUEMO and A. RIAZ: ETHANOL AND NEUROTRANSMITTER INTERACTIONS - FROM MOLECULAR TO INTEGRATIVE