MindMap Gallery Drug Biotransformation And Drug Metabolism Mind Map
Drug biotransformation, or drug metabolism, is the process by which drugs are converted by living organisms into intermediates and ultimately into their active metabolites. The mind map of drug biotransformation illustrates the various pathways involved in this process and highlights the main biochemical and physiological processes involved. It also provides an overview of the different enzymes that catalyze drug metabolism as well as chemical and enzymatic transformations that occur during the process. As illustrated in the drug biotransformation mind map, drug biotransformation/metabolism can be broken down into two major categories: Phase I metabolism and Phase II metabolism. The former involves oxidations, reductions, hydrolysis, and other reactions that are catalyzed by microsomal cytochrome P450 enzymes. The latter involves the conjugation of drugs with glucuronic acid, sulfate, and amino acids that are mediated by transferases. Understanding drug transformation and metabolism is important in predicting the pharmacological outcome of a medication in a patient since it can affect bioavailability as well as toxicity. Use EdrawMind to create a similar mind map for your academic research paperwork.
Edited at 2023-01-30 17:57:22Healing and repair are essential processes that occur in various aspects of life, including physical, emotional, and societal realms. This mind map aims to explore the concept of healing and repair. Whether it is recovering from physical injuries, emotional trauma, or restoring broken relationships, healing and repair play a crucial role in promoting well-being and growth. By following this mind map, individuals can gain insights into the different dimensions of healing and repair and discover effective methods to facilitate their own personal growth and contribute to the healing of others and the world around them. Let's embark on this journey and explore the transformative power of healing and repair.
Healing and repair are essential processes that occur in various aspects of life, including physical, emotional, and societal realms. This mind map aims to explore the concept of healing and repair. Whether it is recovering from physical injuries, emotional trauma, or restoring broken relationships, healing and repair play a crucial role in promoting well-being and growth. By following this mind map, individuals can gain insights into the different dimensions of healing and repair and discover effective methods to facilitate their own personal growth and contribute to the healing of others and the world around them. Let's embark on this journey and explore the transformative power of healing and repair.
Healing and repair are essential processes that occur in various aspects of life, including physical, emotional, and societal realms. This mind map aims to explore the concept of healing and repair. Whether it is recovering from physical injuries, emotional trauma, or restoring broken relationships, healing and repair play a crucial role in promoting well-being and growth. By following this mind map, individuals can gain insights into the different dimensions of healing and repair and discover effective methods to facilitate their own personal growth and contribute to the healing of others and the world around them. Let's embark on this journey and explore the transformative power of healing and repair.
Healing and repair are essential processes that occur in various aspects of life, including physical, emotional, and societal realms. This mind map aims to explore the concept of healing and repair. Whether it is recovering from physical injuries, emotional trauma, or restoring broken relationships, healing and repair play a crucial role in promoting well-being and growth. By following this mind map, individuals can gain insights into the different dimensions of healing and repair and discover effective methods to facilitate their own personal growth and contribute to the healing of others and the world around them. Let's embark on this journey and explore the transformative power of healing and repair.
Healing and repair are essential processes that occur in various aspects of life, including physical, emotional, and societal realms. This mind map aims to explore the concept of healing and repair. Whether it is recovering from physical injuries, emotional trauma, or restoring broken relationships, healing and repair play a crucial role in promoting well-being and growth. By following this mind map, individuals can gain insights into the different dimensions of healing and repair and discover effective methods to facilitate their own personal growth and contribute to the healing of others and the world around them. Let's embark on this journey and explore the transformative power of healing and repair.
Healing and repair are essential processes that occur in various aspects of life, including physical, emotional, and societal realms. This mind map aims to explore the concept of healing and repair. Whether it is recovering from physical injuries, emotional trauma, or restoring broken relationships, healing and repair play a crucial role in promoting well-being and growth. By following this mind map, individuals can gain insights into the different dimensions of healing and repair and discover effective methods to facilitate their own personal growth and contribute to the healing of others and the world around them. Let's embark on this journey and explore the transformative power of healing and repair.
Drug Biotransformation(Drug Metabolism)
What is it
Most drugs are treated by the body as foreign substances (Xenobiotics)
order to get rid of these chemical intruders they become subject to various mechanisms
Biotransformation is a general term for chemical transformations that occur inside the body to affect the drug
major ways for Drug Biotransformation(Drug Metabolism)
Reducing lipid solubility
Drugs that are already water soluble are generally excreted unchanged by the kidney.
- Lipid soluble drugs are not easily excreted by the kidney because following glomerular filtration they are reabsorbed from the proximal tubule.
Biotransformation converts these lipid soluble drugs to more polar and water-soluble compounds that are more readily excreted by the kidney.
Alteration of biological activity
The end result of biotransformation is the abolition of biological activity.Various steps in between may have the following consequences
Conversion of a pharmacologically active to an inactive compound; this is the case with most drugs
Conversion of a pharmacologically active to another active compound
e.g., codeine can be changed to morphine and diazepam to oxazepam
Both the drug and its metabolite are active
Conversion of a pharmacologically inactive to an active compound
When the metabolite itself is the active drug, the parent compound is said to be a "Prodrug"
Prodrugs
Prodrugs are pharmacologically inactive compounds that are converted to their active forms by metabolism.
This approach can maximize the amount of the active species that reaches its site of action
Inactive prodrugs are converted rapidly to biologically active metabolites, often by the hydrolysis of an ester or amide linkage.
e.g., Enalapril (inactive) is converted to enalaprilat (active).
Examples of common Prodrugs
Acyclovir
5-Flurouracil
L-Dopa
Zidovudine
Carbamazepine
Enalapril
Heroin
Phenacetin
Importance of Biotransformation
Inactivation or termination of drug action (most drugs).
Detoxification
Biotransformation is required for protection of body from toxic metabolites
Activation of prodrug
(convert inactive form of drug to active form). E.g. Levodopa – Carbidopa – Prednisone- Prednisolone
Alteration of biological activity
conversion of a pharmacologically active to an inactive compound
conversion of a pharmacologically active to another active compound
conversion of a pharmacologically inactive to an active compound; the parent compound is said to be a "Prodrug"
Reducing lipid solubility
Lipid soluble drugs are not easily excreted by the kidney.
Biotransformation converts these lipid soluble drugs to more polar and water soluble
compounds that are more readily excreted by the kidney.
Sites of Biotransformation
plasma, kidney, lungs, brain, but the main site is the Liver
Liver
The majority of drugs are metabolized by the hepatic microsomal enzymes. By group of isozymes called cytochromes P450 isozymes
microsomal enzymes mosly in the liver
Lipid solubility is an important requirement for a drug to be metabolized by hepatic microsomes ,it aides penetration of the drug into the endoplasmic reticulum and the binding with the cytochrome P450.
group of isozymes called cytochromes P450 isozymes
it present on the smooth surface of the rough endoplasmic reticulum of liver cells
It represent a group of oxidoreductases responsible of drug oxidation and reduction reactions
Microsomes
Microsomal enzyme system is cytochrome P-450 and the most important famlies in humans are CYP1 ,CYP2,AND CYP3
CYP3A4/5 carry out biotransformation of the largest number of drugs (3--50%) of drugs exepresed in the mostly in the liver and intestine ( first pass metabolism)
non-microsomal enzymes
Some drugs are metabolized by enzymes present outside the microsomes (non microsomal enzymes) located
Intracellularly (e.g., in cytosol, mitochondria, lysosomes, microsomes).
Mirochondria
N-acetyl transferase
Introduction of acetyl group (CH3COO-)
Monoamino oxidase enzyme (MAO)
Oxidation of catecholamines as adrenaline
Cytoplasm
Oxidation of alcohol
(Alcohol -> Aldehyde-> Acid ) OR (Ethanol->Acetaldehyde->Acetic acid)
(CH3CH2OH->CH3CHO->CH3COOH)
Extracellularly (e.g., in plasma).
Examples
Ethanol is inactivated by alcohol dehydrogenase,
Succinylcholine by plasma pseudocholinestrase,
6-mercaptopurine by xanthine oxidase and
Epinephrine by monoamine oxidase.
Factors influencing drug Biotransformation
the are two important factors
Genetic Polymorphism
some individuals drug metabolism may occur so rapidly (Fast metabolizers), so the therapeutically effective blood and tissue levels are not achieved
Isoniazid
(antiTB drug) may cause peripheral neuropathy in slow acetylators
hepatocellular necrosis is more common in rapid acetylators
others may be so slow (Slow metabolizers) , so toxic effects result with usual doses
e.g Phenytoin
Such individual variations might be explained by genetically determined differences in the amount of key enzyme cytochrome P450 available in the liver. Acetylation polymorphism is considered the best known example of genetic defect in drug biotransformation.
Pharmacogenomics
what is it
is an important example of the field of precision medicine, which aims to tailor medical treatment to each person
Pharmacogenomics looks at how your DNA affects the way you respond to drugs
Age
Newborn infants metabolize drugs at a much slower rate than that observed in adults
Pathological Conditions
Liver disease
cardiac insufficiency
obstructive lung disease
hypoxemia
malnutrition
reduce metabolic activities of the hepatic microsomal enzyme systems
L.M (Cyt-P450) Enzymes Inducers
Hepatic extraction, the first-pass effect, and clearance for CYP3A4 substrates will be increased by inducers
The activities of hepatic microsomal drug metabolizing enzymes are influenced by
dietary and nutritional factors
hormonal changes
ingestion of various chemical agents
environmental factors
Examples of enzyme inducers
Phenobarbital,
Phenytoin,
Carbamazepine
Tolbutamide,
Rifampicin..etc.
polycyclic hydrocarbons (cigarette smoke), DDT
Enzyme induction may result in
Increases the metabolism and excretion of the inducer drug it self and co-administered drug
decrease the action of inducer drug itself and co-administered
Tolerance may occure
decreases in the pharmacological action of the drug by continuous or repeated administration
Drug interactions may occur
decrease in action of one drugby administration of another drug
e.g ORAL CONTRACEPTIVE AND PHENYTOIN (INDUCER)
May leads to pregnancy because pf the failure of the oral contraceptive due to the combination with phenytoin
L.M (Cyt-P450) Enzyme inhibitor
Some drugs can also produce reduction in the activities of drug metabolizing enzymes i.e. metabolic inhibition
Examples of enzyme inhibitors are
Starvation or malnutrition (poor protein intake in diet)
Cimetidine,
Ethanol (chronic ingestion),
Aspirin,
Paracetamol,
Valproic acid, ...etc.
Enzymes inhibitors may result in
decreased delay the metabolism and excretion of the inhibitor drug and co-administered drugs
increased prolong the action of the inhibitor drug and co-administered drugs
e.g warfarin inhibitor and erythromycin (inhibitor)
Inhibition of warfairn metabolism my lead to increase it anticoagulant effect ( risk of bleeding
First pass metabolism
Pathways of drug biotransformation
Phase I or "Non-Synthetic" Reactions
Metabolites may be active or inactive, And phase I is the first stage of biotransformation
Oxidation Reactions
Microsomal Oxidation
Occures in microsomes
e.g cytochrome P450 and NADPH and oxygen
non-Microsomal Oxidation
Occures in cytosole or mitocondria and these enzymes include
Dehydrogenase
Required for oxidation of alcohol
Alcohole dehydrogenase
converts alcohole to aldeyde
Aldehyde dehydrogenase
converts aldehyde to acid
Oxidase
Monoamine oxidase (MAO)
Is responsible for metabolism of catecholmines as adrenaline and serotonin
e.g moclobemide
Is a monoamine oxidase inhibitor
It increses serotonin in the brain
used as antidepressant drug
Xanthine oxidase
Is required for the oxidation of xanthine
Hypoxanthine --> oxidation --> xanthine --> oxidation --> uric acid . AND uric acid accumulation causes GOUT
Allopurinol is and xanthine oxidase inhibitor used for treatment of GOUT
Summary
Reduction reactions
Removal of oxygen or addition of hyrogen
Maybe microsomal or non-microsomal
Example
Levodopa(Dopa) --> Dopamine
Hydrolysis
non-Microsomal
Occures by addition of water molecules in presence of enzymes
Esterases: Hydrolyze drugs that are esters
Ester as acetylcholine (neurotransmitter)
acetylcholine -->ESTERASE--> acetate+choline
Amidases: hydrolyze drugs that are amides
Amides as lidocaine
lidocaine is used as a local anesthetic
Amide + H2O ---> acid + amine
Drug activation/inactivation
Phase II or "Synthetic" Reactions (Conjugation)
metabolites usually inactive
The active drugs or intermediates formed by phase I reactions undergo coupling with a polar endogenous substrate such as
Glucuronic acid,
Glycine,
inorganic sulfate,
Methyl groups or
Acetyl groups to yield conjugation products
Characteristics of Phase-II metabolites
It is generally the conjugation reactions lead to inactive conjugates.
Usually a conjugate is more polar and more readily water soluble that is rapidly excreted in urine and bile.
Types of conjugation reactions
Glucouronide conjugation
required enzyme is Glucouronyl transferase
Acetylation(CH3COO-)
required enzyme N-acetyl transferase
sulphation (SO4--)
required enzyme sulfo transferase
methylation (CH3)
required enzyme Methyl tramsferase
amino acids conjugation
Glycine comjugation
Drug becomes conjugation product