Metronidazole as Therapeutic Agent for Amoebiasis: An Overview

Amoebiasis is a parasitic infection caused by the protozoan parasite Entamoeba histolytica. It is one of the most common parasitic infections worldwide, affecting millions of people each year. Amoebiasis can cause a range of symptoms, from mild diarrhea to life-threatening colitis and liver abscesses. One of the most commonly used drugs for the treatment of amoebiasis is metronidazole.

Metronidazole is a synthetic nitroimidazole derivative with broad-spectrum antibacterial and antiprotozoal activity. It is effective against a range of anaerobic bacteria, as well as certain protozoan parasites, including Entamoeba histolytica. Metronidazole works by disrupting the DNA of the parasites and bacteria, leading to their death.

Metronidazole is the drug of choice for the treatment of amoebiasis, as it is highly effective, well-tolerated, and relatively inexpensive. It is available in both oral and intravenous formulations, making it easy to administer.

The recommended dose of metronidazole for the treatment of amoebiasis is 500mg to 750mg orally three times daily for 5-10 days. For severe cases of amoebic colitis or liver abscesses, intravenous metronidazole may be used initially, followed by oral treatment.

The use of metronidazole in the treatment of amoebiasis is generally safe and well-tolerated, although some patients may experience mild side effects, such as nausea, vomiting, and diarrhea. In rare cases, metronidazole can cause more serious side effects, such as seizures and peripheral neuropathy.

To ensure the effectiveness of metronidazole in the treatment of amoebiasis, it is important to adhere to the prescribed dosage and duration of treatment. Patients should also be advised to avoid alcohol while taking metronidazole, as this can cause a disulfiram-like reaction.

In conclusion, metronidazole is a highly effective and safe therapeutic agent for the treatment of amoebiasis. It is widely available, relatively inexpensive, and well-tolerated by most patients. However, as with any medication, it is important to follow the prescribed dosage and duration of treatment and to monitor for any potential side effects.

Amoebiasis: Pharmacotherapy - Pharmacology

Amoebiasis: Pharmacotherapy & Classification of amebicidal agents - Pharmacology The video discusses the pharmacotherapy of amebiasis and classifies the therapeutic agents into three categories: luminal amebicides, systemic amebicides, and mixed amebicides. The video begins by highlighting the importance of luminal amebicides in eradicating asymptomatic colonization of trophozoites in the intestinal lumen, which is necessary to prevent the recurrence of the disease. The luminal amebicides discussed in the video are iodoquinol, diloxanide furoate, and paromomycin, with paromomycin being the most effective agent in this class. The video then moves on to systemic amebicides, which are effective against the amoebas in the intestinal wall and liver. Chloroquine and Dehydroemetine are discussed in this category, with Chloroquine being the most widely used agent and effective against a hepatic abscess but not useful for luminal amoebiasis. Dehydroemetine has some toxicities that limit its use, and the intramuscular form is preferred over the oral form. Finally, the video discusses mixed amebicides, which are effective against both systemic and luminal amoebas. Metronidazole, widely known as Flagyl, is the mixed amebicide of choice for treating amebic infections and is also used to treat other diseases caused by other protozoans and anaerobic bacteria. Tinidazole is another agent in this class, similar to metronidazole in the spectrum of activity and adverse effects. Overall, the video provides a detailed overview of the pharmacotherapy of amebiasis, including the classification of different agents and their modes of action. Thanks for watching & do support us. COVERED TOPICS 0:00 Intro 0:10 Diagram from previous video (amoebiasis) 0:25 Classification of amoebicidal agents 0:40 Luminal amoebicides 2:10 Systemic amoebicides 3:20 Mixed amoebicides 4:10 End LINKS: Also, watch Amoebiasis: Life cycle, Types & Pharmacotherapy - Pharmacology https://youtu.be/-n80uxtD8KA Parasympathomimetics: Clinical Uses & Classification of Direct Acting Cholinergic Drugs https://youtu.be/Uhp_GivuSQg Cholinergic Drugs: Pharmacological actions of Parasympathomimetics, Direct acting drugs https://youtu.be/XxeitbKE68w Cholinergic drugs | Parasympathomimetics classification and mechanism of action - Pharmacology https://youtu.be/0ylQGye76xc Cholinergic transmission | acetylcholine synthesis & metabolism | cholinergic drugs | pharmacology https://youtu.be/PBsCl95X3DI Support us on: Facebook https://web.facebook.com/MK-MediGuide-Lectures-103055758022942/?view_public_for=103055758022942 #MKMediguide #mediguide #amoebiasis #amebiasis #entameba #amebicdysentry #ameba #amoeba

Cholinergic drugs | Parasympathomimetics classification and mechanism of...

Cholinergic drugs - 01 | Parasympathomimetics classification and mechanism of action - Pharmacology This video is all about Cholinomimetics also known as Cholinergic agonists, Parasympathomimetics, parasympathetic agonists, cholinergic receptor agonists. these are the agents which mimic or produce action like that of parasympathetic nervous system stimulation and that's why called parasympathomimetics. they are named cholinomimetics, as these agents show action like that of acetylcholine. acetylcholine is an acetylated choline molecule that normally functions as a neurotransmitter in our body. cholinergic drugs are classified as direct-acting drugs and indirect-acting drugs. direct-acting drugs or agonists bind directly to cholinergic receptors such as muscarinic receptors and nicotinic receptors, show their actions. while the indirect-acting agonists bind to and inhibit the action of the acetylcholinesterase enzyme. acetylcholinesterase is an enzyme present in the synaptic cleft that metabolizes acetylcholine and terminates its action. by inhibiting this enzyme the acetylcholine concentration rises in the synaptic cleft and thus activates all cholinoceptors that is muscarinic receptors and nicotinic cholinoceptors.

the direct-acting agonists are further classified as muscarinic agonists, nicotinic agonists, and mixed agonists. the muscarinic agonists specifically bind to muscarinic receptors and show their actions, while the nicotinic agonists bind to nicotinic receptors only and show their action, in contrast, the mixed agonists bind to both cholinoceptors and show their effects. the indirect-acting agonists are further classified on the basis of the interaction between the enzyme and the cholinergic agonists. and these are classified as reversible indirect-acting agonists and irreversible indirect-acting agonists. the reversible agents bind to the enzyme for a short period of time and leave the enzyme functional again, while the irreversible acting agents form a strong covalent bond with the enzyme which is not reversible. COVERED TOPICS PARASYMPATHOMIMETICS also known as cholinomimetics, cholinergic agonists, cholinergic receptors agonists, acetylcholine receptors agonists, parasympathetic drugs, parasympathetic agonists. 1. parasympathomimetics classification 1.1. direct-acting agonists 1.1.1. muscarinic agonists 1.1.2. nicotinic agonists 1.1.3. Mixed agonists 1.2. Indirect acting agonists 1.2.1. Reversible acting agonists 1.2.2. Irreversible acting agonists 2. Mechanism of action of parasympathomimetics or cholinergic drugs 2.1. Mechanism of action of muscarinic agonists 2.2. Mechanism of action of nicotinic agonists 2.3. Mechanism of action of mixed agonists 2.4. Mechanism of action of reversible agonists 2.5. Mechanism of action of irreversible agonists LINKS: Also, watch Cholinergic transmission | acetylcholine synthesis & metabolism | cholinergic drugs | pharmacology https://youtu.be/PBsCl95X3DI Cholinergic receptors | Muscarinic and Nicotinic receptors - Pharmacology https://youtu.be/uQ4ILypFKog sympathetic vs parasympathetic nervous system | Autonomic nervous system - Pharmacology https://youtu.be/U7qbF42G6kA Sympathetic nervous system | Autonomic nervous system | Nervous system - pharmacology https://youtu.be/aI4yub5GMF0 Autonomic nervous system | nervous system pharmacology | ANS- sympathetic & parasympathetic https://youtu.be/8zkEknWiEj0 Support us on: Facebook https://web.facebook.com/MK-MediGuide... ==================================================================== #MKMediguide #mediguide #cholinomimetics #CholinergicAgonists #CholinerReceptorsAgonists #acetylcholineReceptorsAgonists #pharmacology #Parasympathomimetics #MucarinicAgonists #NicotinicAgonists

Cholinergic receptors | Muscarinic and Nicotinic receptors - Pharmacology

Cholinergic receptors | Muscarinic and Nicotinic receptors - Pharmacology This video is all about the Cholinergic receptors ( Cholinoceptors ) and their subtypes. cholinergic receptors are those receptors to which neurotransmitter acetylcholine binds and show its pharmacological action. these cholinergic receptors are found mainly in the Nervous system but also present throughout the body and they are concerned with different functions in our body, which is all discussed in this video. cholinergic receptor ( cholinoceptors ) are mainly divided into two classes is the muscarinic receptors and nicotinic receptors, based on their affinity for different agonists to which these receptors respond. for example, the muscarinic receptors have a high affinity for muscarine beside acetylcholine while the nicotinic receptors have a high affinity for nicotine beside acetylcholine. nicotine is an alkaloid of tobacco. muscarine also binds to nicotinic but have a low affinity and same is the case with nicotine which can also bind to muscarinic receptors but have a low affinity for it. The muscarinic receptors are further divided into the M1 ( neuronal muscarinic receptors ), M2 ( cardiac muscarinic receptors ), M3 ( smooth and glandular muscarinic receptors ), M4 and M5 receptors. The nicotinic receptors are also divided into neuronal nicotinic or Nn receptors and Neuromuscular nicotinic or Nm receptors. COVERED TOPICS: 1. Cholinergic receptor or Cholinoceptors 1.1 Classification of cholinergic receptors or acetylcholine receptors 1.2 Signal transduction pathway of cholinergic receptors 1.3 Locations of cholinergic receptors ( acetylcholine receptors or cholinoceptors ) in the human body 1.3 Musacarinic receptors location and related effects when stimulated 1.3.1 M1 receptors or neuronal muscarinic receptors location and resultant effects 1.3.4 M2 receptors or cardiac muscarinic receptors location and effects 1.3.5 M3 muscarinic receptors or smooth and glandular muscarinic receptors location and effect 1.3.6 M4 and M5 muscarinic receptors 1.4 Nicotinic receptors 1.4.1 Neuronal nicotinic or Nn receptors 1.4.2 Neuromuscular nicotinic or Nm receptors LINKS: Also, watch sympathetic vs parasympathetic nervous system | Autonomic nervous system - Pharmacology https://youtu.be/U7qbF42G6kA Sympathetic nervous system | Autonomic nervous system | Nervous system - pharmacology https://youtu.be/aI4yub5GMF0 Autonomic nervous system | nervous system pharmacology | ANS- sympathetic & parasympathetic https://youtu.be/8zkEknWiEj0 Nervous system | Divisions of the nervous system | CNS & PNS divisions https://youtu.be/3h5vEFTZ6Vc cerebrum | Lobes and physiologic regions of the cerebrum https://youtu.be/63ibcfOZtpw Support us on: Facebook https://web.facebook.com/MK-MediGuide-Lectures-103055758022942/?view_public_for=103055758022942 ==================================================================== #MKMediguide #mediguide #paraympatheticNervousSystem #CholinergicReceptors #Cholinoceptors #acetylcholineReceptors #pharmacology #anatomy #MucarinicReceptors #NicotinicReceptors

sympathetic vs parasympathetic nervous system | Autonomic nervous system...

Sympathetic nervous system vs parasympathetic nervous system | Autonomic nervous system - Pharmacology In this video lecture we have discussed the main differences between the sympathetic nervous system and the parasympathetic nervous system. the sympathetic nervous system and the parasympathetic nervous system are two main divisions of the autonomic nervous system. the sympathetic system is also known as the fight or flight response and prepare us for stressful and emergency situations, as well as for exercise. in contrast, the parasympathetic nervous system is known as the rest and digest response. parasympathetic response predominate the sympathetic nervous system in situation like when we are eating or lying down. For more knowledge about the sympathetic, parasympathetic and autonomic nervous system watch our previous videos on these nervous system divisions. LINKS: Also watch parasympathetic nervous system https://youtu.be/g0TPyMoPP0g Sympathetic nervous system | Autonomic nervous system | Nervous system - pharmacology https://youtu.be/aI4yub5GMF0 Autonomic nervous system | nervous system pharmacology | ANS- sympathetic & parasympathetic https://youtu.be/8zkEknWiEj0 Nervous system | Divisions of the nervous system | CNS & PNS divisions https://youtu.be/3h5vEFTZ6Vc cerebrum | Lobes and physiologic regions of the cerebrum https://youtu.be/63ibcfOZtpw Support us on: Facebook https://web.facebook.com/MK-MediGuide-Lectures-103055758022942/?view_public_for=103055758022942 Twitter https://www.twitter.com/Maazkha55086767 ==================================================================== #MKMediguide #mediguide #paraympatheticNervousSystem #AutonomicNervousSystem #parasympatheticNerves #NervousSystem #pharmacology #anatomy #ySmpatheticVsParasympatheticNervousSystem

Parasympathetic nervous system | Autonomic nervous system - Pharmacology

parasympathetic nervous system pharmacology

Sympathetic nervous system | Autonomic nervous system | Nervous system -...

Sympathetic nervous system | Autonomic nervous system | Nervous system - pharmacology This video is all about the sympathetic nervous system. the sympathetic nervous system along with the parasympathetic nervous system is divisions of the autonomic nervous system. the autonomic nervous system and somatic nervous system mutually are called the peripheral nervous system. and this peripheral nervous system is the division of our nervous system along with the central nervous system. the sympathetic nervous system prepares us for energy expending, stressful and emergency situations as well as prepares us for doing exercise. the sympathetic division is also known as "the fight or flight response" and "thoracolumbar division" the sympathetic nervous system innervates many organs of our body like eyes, salivary glands, heart, lungs, spleen, stomach, small and large intestines, kidneys, adrenal gland, urinary bladder, and reproductive organs. the sympathetic may activate or inhibit the functions of the organs depending upon the organ and the receptors on that organ. COVERED TOPICS 1. Autonomic nervous system 1.1 Sympathetic nervous system aka thoracolumbar division & fight or flight response 1.2.1 Organs innervated by the sympathetic nervous system discussed in this video are 1.2.1 eye 1.2.2 salivary glands 1.2.3 heart 1.2.4 lungs 1.2.5 spleen 1.2.6 stomach 1.2.7 small and large intestines 1.2.8 kidneys 1.2.9 adrenal gland 1.2.10 urinary bladder 1.2.12 reproductive organs 1.3 how these above organs respond when are get sympathetic impulses 1.4 general discussion on the preganglionic and postganglionic fibres of sympathetic division.

Autonomic nervous system | nervous system pharmacology | ANS- sympatheti...

Our nervous system is mainly divided into two divisions: the Centeral nervous system and peripheral nervous system. The central nervous system or CNS include Brain and spinal cord, while the peripheral nervous system or PNS is further divided into the somatic and autonomic nervous system or ANS. Autonomic nervous system or ANS controls all the involuntary functions of our body and concerned with the functions of visceral body parts and innervate smooth muscles, cardiac muscles and glands. This system act autonomously and continuously without the conscious control. For example this division controls Heart activities, GIT motility and secretions, Glands secretions, pupil size, energy metabolism, lungs airways diameter, etc. Covered Topics In this video we have generally discussed the autonomic nervous system, their pathway, autonomic Centers, divisions of ANS that is sympathetic nervous system and parasympathetic nervous system, neurons of ANS that is preganglionic neurons and postganglionic neurons and lastly the organs that are innervated by the autonomic nervous system for example Heart, stomach, GIT, liver, eyes, smooth muscles, pancreas, blood vessels, sweat gland, hair follicles, urinary bladder, spleen, etc

Classification of neurons | Nervous system

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Classification of neurons | Nervous system This video is all about the classification of neurons. The neuron is the structural and functional unit of the nervous system. Neurons greatly vary structurally but all have some structures in common, that is the soma or cell body, dendrites and axon. neurons can be divided based on structure, function, and myelin sheath. based on structure, we have multipolar, unipolar, and bipolar neurons. while functionally neurons are divided as sensory neurons. association or interneurons, and motor neurons. while another classification is based on myelin sheath and we have myelinated and unmyelinated neurons under this heading. besides, most of the neurons supplying specific organs or tissues are named differently. for example, motor neurons to the skeletal muscles are called somatic while neurons innervating the internal visceral organs are called visceral motor neurons and form the autonomic division. COVERED TOPICS Neuron classification structural classification of neurons multipolar neurons bipolar neurons unipolar neurons functional classification of neurons sensory or afferent neurons association or interneurons motor or efferent neurons myelin sheath based classification of neurons myelinated neurons unmyelinated neurons Links: Also watch: Nervous system | Divisions of the nervous system | CNS & PNS divisions https://youtu.be/3h5vEFTZ6Vc cerebrum | Lobes and physiologic regions of the cerebrum https://youtu.be/63ibcfOZtpw How drugs act https://www.youtube.com/watch?v=iZLAMgHIH2k How drug-receptor interact https://youtu.be/UIukuAKy66c Support us on: Facebook https://web.facebook.com/MK-MediGuide-Lectures-103055758022942/?view_public_for=103055758022942 Twitter https://www.twitter.com/Maazkha55086767 #mediguide #mkMediguide #NerousSystem #Neuron #NeuronStructure #dendrites #soma #cellbody #axon

Nervous system | Neuron Structure

Nervous system | Neuron Structure This video is all about the neuron. The neuron is the structural and functional unit of the nervous system. Neurons greatly vary structurally but all have some structures in common, that is the soma or cell body, dendrites and axon. Soma is the biosynthetic centre and contains the neuroplasm and other important organelles require for normal functioning of the neuron, while the dendrites and axon also contain some organelles like the soma and these structures are involved in the transmission of the impulses. Sometimes the axon has a protective cover called the Myelin sheath, produced by the Schwann cells. COVERED TOPICS Neuron Structure of neuron Cell body or soma Dendrites Axon Myelin sheath Neurilemma Schwann cells Neurofibrils Links: Also watch: Nervous system | Divisions of the nervous system | CNS & PNS divisions https://youtu.be/3h5vEFTZ6Vc cerebrum | Lobes and physiologic regions of the cerebrum https://youtu.be/63ibcfOZtpw How drugs act https://www.youtube.com/watch?v=iZLAMgHIH2k How drug-receptor interact https://youtu.be/UIukuAKy66c Support us on: Facebook https://web.facebook.com/MK-MediGuide-Lectures-103055758022942/?view_public_for=103055758022942 Twitter https://www.twitter.com/Maazkha55086767 #mediguide #mkMediguide #NerousSystem #Neuron #NeuronStructure #dendrites #soma #cellbody #axon

Nervous system | cerebrum | Lobes and physiologic regions of the cerebrum

Nervous system | cerebrum | lobes and physiologic regions of the cerebrum - pharmacology

keywords: nervous system, cerebrum, lobes, hemispheres, functional regions, motor area, sulcus, gyrus, The nervous system is the control centre of all the functions either voluntary or involuntary, of our body. it has two main divisions the central nervous system and the peripheral nervous system. the central nervous system is composed of the brain and spinal cord, while the peripheral nervous system consists of neurons located outside the central nervous system. the cerebrum is the largest part of the brain and controls most of the voluntary movements with addition to the sensor and association functions. This video is all about the anatomical and physiological divisions of the cerebrum, hemispheres of the cerebrum, lobes of the cerebrum like frontal, parietal, temporal and occipital lobes. the cerebrum also consists of grey matter and white matter which is all discussed in the video. the cerebrum is also divided on the basis of its functional divisions as sensory areas, association areas, and motor areas. and these areas are scattered throughout the cerebral cortex. Covered topics: cerebrum cerebral hemispheres lobes of the cerebrum functional regions Links: Also watch: drug biotransformation part 01 https://youtu.be/06c4lNQPMDk How drugs act https://www.youtube.com/watch?v=iZLAM... How drug-receptor interact https://youtu.be/UIukuAKy66c Support us on: Facebook https://web.facebook.com/MK-MediGuide... Twitter https://www.twitter.com/Maazkha55086767

Nervous system | Divisions of nervous system | CNS & PNS divisions

Nervous system | Divisions of the nervous system | CNS & PNS divisions

 

This video is all about the nervous system’s divisions. The nervous system is the control centre of our body and it controls the function either voluntary or involuntary. The nervous system can be divided and subdivided into many divisions on the basis of anatomy or physiology. The nervous system is divided into two main divisions: the central nervous system and peripheral nervous system. The central nervous system is further divided into the brain and the spinal cord.

The main part of the nervous system is the brain which is the control centre of the nervous system. The brain has many divisions for example the forebrain, the midbrain, and the hindbrain while further each of them is subdivided into different parts and division. At the lower level, we have different parts of the brain for example cerebrum (which is further divided into various lobes like frontal lobe, parietal lobe, temporal lobe, and occipital lobe), cerebellum, midbrain, pons, and medulla oblongata. While the midbrain, pons, and medulla oblongata is collectively called the brain stem. The spinal cord is also a part of the central nervous system and helps in the communication between the brain and the peripheral nervous system.

The peripheral nervous system comprised of neurons that are outside of the central nervous system and transfer the signals from the central nervous system to the periphery or vice versa. The peripheral nervous system is further divided into two main divisions that are somatic nervous system and autonomic nervous system.

 

COVERED TOPICS

Nervous system

Divisions of the nervous system

Central and peripheral nervous system

Brain and spinal cord

Forebrain, midbrain, and hindbrain

Cerebrum, cerebellum, pons and medulla oblongata

Diencephalon and telencephalon

Lobs of the cerebrum

Somatic nervous system and autonomic nervous system

Sympathetic nervous system and parasympathetic nervous system

Biotransformation of drugs -part 4 | cytochrome P450 isozymes | CYP450 i...

Isozymes

CYP450 Enzymes are divided into
subgroups, Depending upon the sequence of amino acid in each isozyme.  These enzymes have the capacity to modify a large
number of structurally diverse substrates. In human beings, isozymes that fall
into families CYP1, CYP2, and CYP3 are primarily involved in the metabolism of
most drugs, in which the most active CYPs for drug metabolisms are those in the
CYP2C, CYP2D, and CYP3A subfamilies. In addition, an individual drug may be a
substrate for more than one isozyme. such as tolbutamide, paracetamol,
barbiturates, and nifedipine are substrates for more than one isoform. Which
will be discussed later in this session.

IMPORTANT ISOZYMES include

CYP3A4 which is thought to be the
most predominant CYP isoform involved in human drug metabolism, both in terms
of the amount of enzyme in the liver and the variety of drugs that are
substrates for this enzyme isoform. In addition to liver, these isoforms are expressed
in intestine, responsible for first pass metabolism at this site, and kidney as
well. This isoform may account for more than 50% of all CYP-mediated drug
oxidation reactions, and CYP3A4 is likely to be involved in the greatest number
of drug–drug interactions. However, the fact that two drugs are metabolized
predominantly by CYP3A4 does not mean that coadministration will result in a
drug–drug interaction, since drugs can bind in different regions of the CYP3A4
active site, and these regions may be different. In fact, it is believed that two
drugs can occupy the active site simultaneously, with both available for
metabolism by the enzyme. This finding helps account for several absent interactions
that would have been predicted to occur based on strict substrate specificity
rules.

CYP3A5, whose amino acid sequence is
like that of CYP3A4, appears to have approximately the same substrate
specificity characteristics as CYP3A4. However, it differs in that it is not present
in all individuals. Thus, individual expressing both CYP3A4 and CYP3A5 have the
potential to show increased metabolism of CYP3A drug substrates as compared to
individuals expressing only the CYP3A4 isoform. Drugs metabolized by these
isozymes include cyclosporine, simvastatin, HIV protease inhibitors, Ca channel
blockers, hydrocortisone, carbamazepine, midazolam, Losartan, and nifedipine.

The other identified human CYP3A
isoform is CYP3A7, which appears to be expressed in fetus and rapidly
disappears following birth, to be replaced by CYP3A4 and CYP3A5.

CYP2D6 This is the next most
important CYP isoform which metabolizes 25% of the CYP-mediated oxidation
reactions of drugs including tricyclic antidepressants, selective serotonin
reuptake inhibitors, antipsychotic agents, antiarrhythmics, β-blockers and opioid analgesics.

CYP2C8/9 this isoform handles about 16% of the CYP-mediated drug
oxidation reactions. This isoform metabolizes several clinically important
drugs with narrow therapeutic margins, two of these drugs is phenytoin and
warfarin, and other drugs like ibuprofen, tolbutamide, repaglinide, celecoxib
and losartan. CYP2C9 appears to prefer weakly acidic drugs as substrates, which
limits the number of drugs metabolized by this isoform since most drugs are
weak bases.

CYP2C19 isoform Metabolizes > 12
frequently used drugs including omeprazole, lansoprazole, naproxen, diazepam,
and propranolol.

CYP1A1/2 subfamilies take part in
the metabolism of only few drugs like theophylline, caffeine, tacrine,
phenacetin, paracetamol, and carbamazepine.

CYP2E1 isoform catalyzes metabolism
of only few drugs. like ethanol, halothane, enflurane, and paracetamol.

Large number of drugs are oxidized
through these pathways. Few drugs like cimetidine, ranitidine, clozapine are oxidized
by a group of flavin-monooxygenases that are also located at hepatic
endoplasmic reticulum, but are distinct from CYP enzymes. Some other drugs,
e.g. adrenaline, alcohol, mercaptopurine are oxidized by mitochondrial or
cytoplasmic enzymes.

When two coadministered drugs are
both metabolized by a single CYP, they compete for binding to the enzyme’s
active site. This can result in the inhibition of metabolism of one or both drugs,
leading to elevated plasma levels. If there is a narrow therapeutic index for
the drugs, the elevated serum levels may elicit unwanted toxicities. e.g., a
statin and a macrolide antibiotic or antifungal

Cytochrome P450 enzyme system - Pharmacology

Cytochrome P450 enzyme system drug metabolism Pharmacology:

Definition and general overview

Cytochrome P450 enzyme system Also known as microsomal mixed-function oxidases (MFOs) and cyp450 monooxygenases and simply abbreviated as CYP, p450 or CYP450 enzymes system.

The CYPs are a superfamily of isozymes made of haem proteins that catalyzes most of the phase 1 oxidation-reduction processes of drugs metabolic reactions.

The name cytochrome P450 is derived from the spectral properties of this hemoprotein; In its reduced mean ferrous form, it bind with carbon monoxide to form a pink compound, which shows maximum absorption at 450 nm, that’s why they are named as p450,

In humans, over 50 individual P-450s have been identified but only about 12 are involved in the metabolism of most drugs. each member of which catalyzes the biotransformation of a unique spectrum of drugs, with some overlap in the substrate specificities and may act on the same substrates but at different rates. The only common feature of the many drugs metabolized by this pathway is lipid solubility.

The CYPs carry out drug metabolism and metabolize many structurally diverse chemicals. This is due to the multiple forms of CYPs and the capacity of a single CYP to metabolize many structurally distinct drugs. In addition, CYPs can metabolize a single compound at different positions on the molecule. the CYPs are considered unselective to bind and metabolize multiple substrates.

These enzymes are also responsible for all or part of the anabolism and catabolism of a number of endogenous compounds, such as steroid hormones, bile acids and prostaglandins.

Structure

Heme protein of the cytochrome p450 contains one atom of iron in a hydrocarbon cage that functions to bind oxygen during the reaction. Many other enzymes that use O2 as a substrate for their reactions contain heme.  E.g. hemoglobin. These enzymes catalyze an oxidation-reduction processes that requires CYP450, CYP450 reductase, NADPH (reducing agent), and O2.

 location

Many drug-metabolizing enzymes are located in the lipophilic endoplasmic reticulum membranes of the hepatic cells which has the greatest specific enzymatic activity, and other sites like GIT and Kidneys.

Nomenclature

CYPs are named with the root CYP followed by a number appointing the family, a letter denoting the subfamily, and another number naming the CYP form. Thus, CYP3A4 is family 3, subfamily A, and gene number 4.

Mechanism of drugs metabolism

These enzymes catalyze reactions that requires CYP450, CYP450 reductase, NADPH, and oxygen. First of all, in step 1, P450 containing ferric iron (Fe3+) combines with a molecule of drug (RH). And form a complex. Subsequently, in second step, NADPH donates an electron to the flavoprotein P450 reductase, and the flavoprotein is reduced from oxidized form which in turn reduces the iron to ferrous form (Fe2+), In third step, it combines with molecular oxygen and subsequently, combines with a proton and a second electron from flavoprotein P450 reductase to form an activated oxygen-P450-substrate (Fe2+OOH–RH) complex. This combines with another proton to yield water with the liberation of oxidized drug from the complex in the next step and regeneration of P450 enzyme.

In this oxidation-reduction process, two microsomal enzymes play a key role which are NADPH cytochrome P450 oxidoreductase and cytochrome P450.

In the overall reaction, the drug is oxidized, and oxygen is reduced to water. The mechanism involves a complex cycle but the overall net effect of the reaction is quite simple, the addition of one atom of oxygen to the drug to form a hydroxyl group, the other atom of oxygen being converted to water.

Cytochrome P-450 catalyzes several reactions, including aromatic and aliphatic hydroxylation reactions, dealkylation at nitrogen, sulfur, and oxygen atoms; heteroatom oxidations at nitrogen and sulfur atoms; reductions at nitrogen atoms; and ester and amide hydrolysis