DRUG METABOLISM IN

THE LIVER ByMelissaHong12549907

Metabolism is just one of the processes humans and living organisms go through in order to maintain a happy and healthy life. Xenobiotics is one of the substances in which we try to remove so that their damaging effects are never experienced by us. Examples of xenobiotics include food additives, environment pollutants and drugs. Here, we will be focusing on drugs and its metabolism in the liver.

WHAT IS DRUG METABOLISM Drug metabolism is the process of the removal of foreign substances from the body, through the use of enzymes which are catalysts. They allow substances to be broken down or to grow within the body. The main site of drug metabolism is in the liver, which occurs in two stages: Phase 1 and Phase 2. These are explained below.

PHASE 1 Phase 1 pathways in the liver is where the drug is processed. They are induced by a group of enzymes known as the Cytochrome P450 system which has a crucial role in drug metabolism. The reactions are grouped into three different categories consisting of oxidation, reduction and hydrolysis. It has been found that drugs metabolised in phase 1 have longer half- lives, hence drug metabolism converts hydrophobic compounds into more water soluble compounds – this is so that easy excretion occurs.

PHASE 2 Phase 2 metabolism is directly involved with conjugation which is the coupling of an ionised group to the drug and occurs in the hepatocyte cytoplasm. This allows the metabolite to be more water soluble and encourages easy renal excretion as well as decreasing pharmacological activity. Phase 2 metabolism also involves glucuronidation, acetylation and sulfation reactions. In comparison with Phase 1 metabolism, phase 2 attracts less attention due to the rarity of the enzymes involved.

Source:Dreamstime

Source:Dreamstime

Sourceofpillimages:Clker

PHASE 1 EXAMPLE: PROCAINE Procaine is a local anaesthetic used for oral surgeries and has a fairly short duration of action. Procaine is quickly hydrolysed into para-aminobenzoic acid (PABA) by the enzyme – pseudochloinesterase – in the plasma and liver. However, when there is the presence of sodium, an action potential cannot be created, hence interrupting the signals. The kidney then can easily remove the hydrophilic metabolites through renal excretion.

PHASE 2 EXAMPLE PARACETAMOL Paracetamol is a drug used to treat numerous conditions including mild plain, fever, strong pain and colds and fly. It can be conjugated into paracetamol glucuronide which is generated in the liver by an enzyme called UDP gluconyltransferase. Glucuronidation is used to help the removal of toxic substances and drugs. The attachment of a glycosidic bond to glucuronic acid results in a glucuronide which has a much higher water solubility than the original substance and is removed by the kidneys.

Hydrolysationofprocainetopara-aminobenzoicacid(PABA)

Conjugationofparacetamoltoparacetamolglucuronide

Source:Dreamstime

Source:Colourbox

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