liver metabolism

What is the elimination of a substance

The removal of a substance or termination of its biological action

It occurs in two ways:

Metabolism- anabolism and catabolism

Excretion-kidneys, urine,feacal matter

What is the role of the liver in metabolism of drugs

The ingested molecules enter the liver through the hepatic portal vein or artery

Most lipophilic molecules are metabolised by liver enzymes to form polar products which can then be excreted

There’s two stages to metabolism

Explain phase 1 of metabolism

• The phase is catabolic and occurs in the hepatocytes

• The molecule is either oxidised ,reduced or hydrolysed to add an additional functional group onto it like a hydroxyl group

• Doing this provides a point of conjugation for phase 2

• This is done by hepatic microsomes enzymes- cytochrome p450 specifically

• These enzymes are found in the hepatocytes smooth ER

• The products of phase 1 may still be reactive or be even more reactive

Explain phase 2 metabolism

• This is anabolic and occurs in the liver

• Involves the conjugation of a subsitient group like a methyl group onto the point of conjugation created by phase 1

• Most of the product is inactive

• Most of the drug is then secreted into the bile where it enters the small intestines and due to enterohepatic recirculation, it re-enters the liver before going back into systemic circulation

• During phase 2 most of the active form of the drug has been lost

Explain how stereoisomers effect metabolism

some molecules or drugs exists as racemic mixtures and Different stereoisomers interact differently with the same enzymes so they may be metabolised differently

This could effect the duration of action of a drug

Explain why IV given drugs have a higher bioavailability in terms of metabolism

As when drugs are given orally first they need to be absorbed by the small intestines then they are passed through the hepatic portal vein into the liver where it begins to metabolise so the amount of active drug decreases before its entered systemic circulation in the blood

But drugs given by IV bypass the first pass metabolism and go straight into the circulation

What is the impact of patients with decreased liver/GI function on drug metabolism/drug effect?

As their liver isn’t able to metabolise drug as effectively it will result in increased drug effect

More of the active drug will be available

And if GI isn’t effective then less is reabsorbed by the liver

So it’s really important to monitor the liver function patients

Explain the effect of polymorphic variation on CYP450 enzymes

• Single nucleotide polymorphism is commonly found in them

• This gives rise to different polymorphic forms of the same enzyme

• This causes them to metabolise at different rate s

• A faster metaboliser will deactivate an active drug quicker but produce the active prodrug faster

• Vice versa for slow metaboliser

What are examples of things that induce the effect of CYP450

Dietary- Brussels sprouts

Lifestyle-smoking

Medicinal-st johns wort

The drug might not reach its intended activity

What is a inhibitors of CYP450

Grapefruit

The drug will be active for longer in the body