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

Please I need your support. I am a hardworking university student. and very hardly manage this stup. please support

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

cytokine storm and aging | cytokine storm | COVID-19 lecture

Welcome to my channel MK
MediGuide Lectures, learning with artworks like drawing and calligraphy. In
this lecture, we will discuss the interrelationship between the cytokine storm
and aging. Strangely, plenty of evidence has been shown that the severity of COVID-19
infections vary widely from children usually asymptomatic, adults with a mild infection,
as well as elderly adults appear
to be more severe typically deadly critical. It has proven that COVID-19 infection
in some elderly critical adults leads to a cytokine storm, which is characterized by severe
systemic elevation of several pro-inflammatory cytokines. Then, a
cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ
failure in aged patients. It is far from clear till now that why cytokine storm
induced in only COVID-19 elderly patients, and not in young patients. Answer to
this question is it seems that cytokine storm phenomena is associated with age
because Aging is related to
increased levels of systemic pro-inflammatory cytokines and decreased levels of
anti-inflammatory cytokines. Ample studies have indicated elevated levels of
interleukin (IL)-6, IL-1, tumor necrosis factor-α (TNF α), as well as C-reactive protein (CRP) in aged subjects. among
other cytokines, these cytokines are reported to be high in patients with severe
cases of COVID-19. In which IL-6 plays a key role in contributing to cytokine
storm. Accordingly, it seems that increased generation of
pro-inflammatory markers due to SARS-CoV 2 and aging have a critical role in
the process of cytokine storm in severe COVID-19 patients.  Although,
the exact underlying mechanism of cytokine storm in elderly adults with severe COVID-19
infection is far from clear. However, It seems that “cytokine storm” the phenomenon in elderly patients with severe COVID-19 infection is associated
with many age-related pathophysiologic processes, including alteration of
angiotensin-converting enzyme 2 (ACE2) receptor expression, excess ROS
production, alteration of autophagy, senescent adipocytes activity mean the
inflammatory phenotype of senescent cell activity, particularly adipose tissue,
and immune-senescence, as well as lack of vitamin D content. Here, we are going
to review and discuss all above mentioned age-related pathophysiological pathways
that appear to contribute to the dysregulation of cytokine networks and
possibly a cytokine storm in elderly patients with severe COVID-19 infection.

First of these we
will discuss relation between aging and angiotensin‑converting
enzyme 2 receptor (ACE2)

The renin-angiotensin system (RAS) is an important
regulator of several physiologic events, including cardiovascular

and blood volume, diabetes, and chronic renal disease.
This system is composed of two different pathways, which have opposing
effects to stimuli which
are angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin
receptor type 1 (AT1) (ACE/Ang II/AT1) pathway; this pathway is related
to tissue injury, inflammation and fibrosis,

 the other pathway
is angiotensin-converting enzyme 2 (ACE2)/Ang 1–7/Mas receptor (ACE2/Ang
1–7/Mas) pathway that exerts anti-inflammatory and anti-fibrosis
effects. Recently, it is well accepted that ACE2 on lung epithelial cells are
the entry-point receptors for COVID-19 particles and making it unattainable to
catalyze the reactions. Unfortunately,
several studies identified that ACE2 expression significantly reduces with
aging. These evidences may partially suggest that the increase concentration of
ACE2 receptors in lung epithelial cells in children and young adults may have a
protective effect on severe clinical manifestations due to COVID-19 infection.
Therefore, it is highly likely that low ACE2 expression with aging can lead to
cytokine storm.

  

After this
the next topic of our lecture is the relation between

Aging and excess production of ROS

It is well accepted that ROS considered as a signaling Molecule at
low concentrations, and also as a mediator of inflammation at high concentrations.
The main sources of ROS are mitochondrial respiratory chain and NADPH oxidase. It
is suggested that ROS production augment with age and the excess ROS production
in aging can initiate many proinflammatory cytokines generation through activation
of multiple transcription factors, including nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), specificity protein 1 (Sp1), and
peroxisome proliferator-activated receptors (PPARs) and subsequently increased release of pro-inflammatory cytokines,
including; TNF-α, IL-1β, IL-2, and IL-6, as well as adhesion
molecules. Interestingly,
as the excess ROS production can increase pro-inflammatory cytokines, the
pro-inflammatory cytokines can also increase ROS production.

Hence, excess ROS
production and inflammation are closely related, which are taking part in the
pathogenesis of chronic inflammation and cytokine storm in elderly adults.

Aging and autophagy

Autophagy is a conserved catabolic turnover pathway in eukaryotic
cells by which cellular material delivered into the

lysosomes for degradation. Autophagy process is related to the
maintenance of cellular
homeostasis, and its dysregulation could lead to the development of several
aging-related pathophysiological diseases. It has been shown that the autophagy
process, decrease during aging and leads to the accumulation of damaged
macromolecules and organelles. importantly mitochondria, which is the major
source of ROS result in increased ROS production. In this context, two major processes are for
protection from harmful effects of ROS, including mitophagy and antioxidant capacity.
at one side, mitophagy, which is characterized by autophagic degradation of
mitochondria, decreased with aging. On the other hand, decreased mitophagy, together
with decreased antioxidant capacity during aging can increased ROS levels in
the body. The excess production of ROS leads to increase pro-inflammatory

cytokine secretion. Although, the exact underlying mechanism of
how the decline in autophagy and a rise in ROS levels during aging can elevate
pro-inflammatory cytokine release is far from clear. However, it is well accepted
that low activity of autophagy process and high level of ROS production during
aging, can activate and upregulate

Nod-like receptors (NLRs). It is observed that activation of
cytosolic NLRs increased during aging. And can increase the production of
pro-inflammatory cytokines, including IL-1β and IL-18. So, it seems that crosstalk
between

the decline of mitophagy pathways and elevated ROS level during
aging can imbalance, immune system activity of

elderly adults.

Aging and senescent adipocytes

Senescent cells accumulate with aging in many human tissues,
leading to chronic inflammation and organ dysfunction. Senescent cells have
lower cell viability, as well as insufficient protection against oxidative
stress. Adipose tissue is a dynamic structure that plays an important
contribution in modulating of metabolism and inflammation. It is highly likely
that adipose tissue dysfunction in aged obese subjects leads to more serious
complications of COVID-19 as compared to younger individuals. In obese
COVID-19 patients, the adipose tissue interacts with the immune system and
increased the lethality of the infection by fat tissue-associated cytokines or adipokines
which are released. like amyloid-A which acts directly on macrophages and
increases the generation of pro-inflammatory cytokines. Therefore, the elevated
release of pro-inflammatory cytokines by senescence adipocytes possibly leads
to the elevated risk of the cytokine storm in COVID-19 patients.

And with this thanks for watching and The remaining part of this
lecture will be covered in the next video. Make sure you have subscribed our
channel so don’t miss it

Cytokine storm | Cytokine release syndrome | pathophysiology mechanism of CS

In this lecture, we’ll talk over what is known so far about cytokine storm syndrome linked with SARS-CoV-2 infection, including cytokines that are chiefly involved. This lecture mainly enlightens about the immunological mechanism of immune system hyperactivation, which releases a lot of cytokines, that act as cell signaling molecules in the immune system, particularly during COVID-19 proinflammatory cytokines are released in high proportion leading to CYTOKINE STORM. This is a very serious complication that is emerging in a subset of patients which is the leading cause of death in mostly COVID-19 ill patients. Once the cytokine storm occurs, it can cause pneumonia, ARDS and multi-organ failure, MOF occur due to the blood vessel wall become thin and cause the release of blood plasma leads to the blood clot in the blood vessel and that leads to the prevented blood supply to the vital organs of our body like lungs, kidney, and liver.

The following TOPICS are COVERED in this lecture
cytokine storm or cytokine release syndrome or hypercytokinemia in COVID-19
Mechanism of the pathophysiology of cytokine storm
in normal mean asymptomatic and mild patients
in severe patients
cytokines majorly involved in cytokine storm
Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-a), Interleukin-1B, TGF-B, G-CSF, GM-CSF, Interleukin-17 (IL-17), and other important cytokines
Diagnostic features of cytokine storm

Links:
Also watch:

SARS-CoV-2 || pathophysiology and symptoms of COVID-19
https://youtu.be/B2pRcQ3xUa4
Dexamethasone for COVID-19 | Mechanism of action
https://youtu.be/PIr23fNCOE8
How drugs act
https://www.youtube.com/watch?v=iZLAMgHIH2k
Receptor and its types
https://www.youtube.com/watch?v=-xS5rBJwAKM

Support us on:
Facebook https://web.facebook.com/MK-MediGuide-Lectures-103055758022942/?view_public_for=103055758022942
Twitter
https://www.twitter.com/Maazkha55086767