Drug Metabolism Flashcards
Drugs journey- 4 stages
Absorption
Distribution
Metabolism
Excretion
Absorption
Drugs are absorbed from administration site to the body’s circulations
Common ways to administer
- Oral
- Intramuscular (flu jab in an arm muscle)
- Subcutaneous (injecting insulin under the skin)
- Intravenous (chemotherapy through a vein)
- Transdermal (wearing a skin patch)
Distribution
Main vehicle- the blood stream
- Desired effect
- Undesired effect- side effect or toxicity
5 ways to administer drugs
Oral
- Intramuscular (flu jab in an arm muscle)
- Subcutaneous (injecting insulin under the skin)
- Intravenous (chemotherapy through a vein)
- Transdermal (wearing a skin patch)
metabolism
the process to break down the medicine is called metabolism
purpose of metabolism
deactivate the medicine (sometimes activate the drug, prodrug such as aspirin)
- via enzymatic process
- the main site of this action- liver
- the products are called metabolites
excretion
removal of the compounds
via urine or faeces
why do we study the metabolism
provides information such as
- what drug has been used
- how effective the person to process the drug
- how long the drug stays in the body
- what happens to the drug
Drug metabolism (biotransformation) is divided in to what 2 phases
phase 1 (functionalisation phase) and phase 2 (conjugation phase)
- Common know drugs metabolism routes (reactions)
Phase 1: oxidation, reduction, hydrolysis
Phase 2: conjugation and condensation
common known drug metabolism routes
Phase 1: oxidation, reduction, hydrolysis
Phase 2: conjugation and condensation
Purpose of metabolic phases
Phase 1 is called functionalisation phase- main purpose is to expose or add polar functional group to the original molecule
Phase 2 is call conjugation phase- main purpose is to add a very polar molecule to the metabolite or the original molecule to make the molecule water soluble and ready for excretion.
oxidation
Adding OH group (replacing H in the molecule)
Adding O such as alcohol to turn into carboxylic acid e.g
Losing hydrogen, carbon carbon single bond to double bond
reduction
Losing or reducing some form of O carboxylic acid turns in to alcohol
hydrolysis
Breaking up a molecule by water e.g ester to alcohol and carboxylic acid
Phase I metabolism
- Oxidation involving cytochrome p450- mixed function oxidases enzymes
1) Aromatic hydroxylation (Using OH group to replace aromatic ring hydrogens) (This is a oxidation reaction)
2) De alkylation (remove alkyl groups such as methyl, ethyl) depending on the type of atom of the alkyl group is attached to it is often referred to as N- or O- dealkylations - Oxidations not catalysed by cytochrome P450
- ALCOHOL DEHYDROGENASE
- ALDEHYDE DEHYDROGENASE
Hydrolysis (use water to split the molecules up)
- Hydrolysis of esters
- Hydrolysis of amides
Phase I metabolism summary
- Virtually every possible chemical reaction a compound can under go in the lab can also be catalysed by enzyme systems
- The products normally end up containing chemically reactive functional groups such as OH, NH2 COOH (polar groups, ready for next steps)
- Many drugs can undergo more then one of the phase I reactions
Phase II metabolism
- Generally leading to a water soluble product which can be excreted in faeces or urine
- The most commonly used sugar for this purpose is glucuronic acide which can conjugate with alcohol, phenol, amine and COOH
summary of phase II metabolism
- Phase II metabolites are more water soluble
- Preparing the drug or the metabolite for excretion by one pathway or another
Factors that affect drug metabolism
• Genetics
- Body weight
- Race
- Sex
• Physiologic
- Age
- Diet
- Diseases/conditions
- Kidney function
- Liver function
example.. morphine as an opiod analgesics
- μ-Opioid receptor (MOR) in the central nervous system
- Morphine is an agonist of this receptor
- μ-Opioid receptor activation causes analgesia and sedation
- Opioid addiction also related to μ-opioid receptor
- Class A
example.. codeine
- Codeine does crossed BBB but can’t bind effectively to the opioid receptor
- Only 15% of codeine is O-demethylated to morphine
- The principal pathways for metabolism of codeine occur in the liver
- Less strong biological effect
- Class B
example heroine
- Heroin is totally metabolized into morphine when take orally.
- If injected it will rapid crossing BBB into the brain (a lipophilic molecule)
- Then rapidly metabolized into morphine
- So you have a high concentration of morphine in the brain to bind to the opioid receptor
- Class A
