The document discusses the autonomic nervous system and how drugs can affect it. It begins by explaining that the autonomic nervous system maintains homeostasis in the body by linking to target organs like the cardiovascular system and smooth muscles. It then describes how drugs can mimic or block neurotransmitters in the autonomic nervous system to decrease or increase the activity of organs. Specifically, it provides the examples of atropine blocking muscarinic receptors to decrease intestinal motility and propranolol blocking beta-adrenergic receptors to decrease blood pressure. In summary, the document outlines how the autonomic nervous system works to regulate the internal environment and how drugs are used to interact with its neurotransmitters to affect various organ systems.
Introduction to An Overview of Antipsychotic Drugs
Definition of psychosis, Causes of psychosis, Symptoms of psychosis, Classification of anti psychotic drugs, Mechanism of action, Pharmacokinetics, Adverse effects, Therapeutic uses, Contraindications, New inventions
Presented by
T. Niranjan Reddy
Department of Pharmacology
Introduction to An Overview of Antipsychotic Drugs
Definition of psychosis, Causes of psychosis, Symptoms of psychosis, Classification of anti psychotic drugs, Mechanism of action, Pharmacokinetics, Adverse effects, Therapeutic uses, Contraindications, New inventions
Presented by
T. Niranjan Reddy
Department of Pharmacology
Serotonin is major neurotransmitter and affects the physiology of our body. Serotonin antagonists are used in various pathological conditions of body. This is a small presentation showing feature of serotonin.
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Serotonin is major neurotransmitter and affects the physiology of our body. Serotonin antagonists are used in various pathological conditions of body. This is a small presentation showing feature of serotonin.
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Autonomic nervous system: divisions
General organization of ANS Neurons of ANS
Physiological anatomy of sympathetic nervous system& parasympathetic nervous System
Autonomic neurotransmitters and receptors
Functions of ANS: effects of autonomic nerve impulses on effector organs
Differences between sympathetic and parasympathetic systems
APPLIED ASPECTS- Autonomic drugs, Autonomic failure, Autonomic function tests
introduction to Autonomic Nervous System consisting of Cholinergic, adrenergic and enteric Nervous system with focus on location of neurotransmitters and broad functions of parasympathetic and sympathetic nervous system.
vn nbsxjhx 59595959His temperature is 38.2°C (100.8°F), pulse is 110/min, respirations are 20/min, and blood pressure
is 80/60 mm Hg. The upper and lower extremities are cold and clammy. Pulmonary artery catheterization shows a
pulmonary capillary wedge pressure of 23 mm Hg (N=5-16). Which of the following is the most likely explanation for
these findings?
0 A) Inadequate volume replacement
0 B) Intra-abdominal hemorrhage
0 C) Myocardial infarction
0 D) Pulmonary embolism
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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1. Autonomic Nervous System -
“Autonomic Pharmacology”
Department of Pharmacology
NEIGRIHMS, Shillong
2. Goal
To Learn about the drugs affecting the
autonomic nervous system
Be prepared to link mechanism of drug action
with knowledge mainly of cardiovascular anatomy,
physiology and neurobiology
to predict effects of drugs –
3. The autonomic nervous system
maintains the internal environment
of the body – called HOMEOSTASIS
Role of ANS in homeostasis
links to target organs -
(Cardivascular System, smooth
muscle of GI and glands)
4. +
Drug A decreases
activity of
organ O
Autonomic Pharmacology is Practical
Nerves to organ O
release neurotransmitter N,
and N increases
the activity of organ O
Mimic or Block
transmitters
Drug A blocks
receptors for
neurotransmitter N
5. +
Atropine blocks muscarinic
receptors
and decreases intestinal
motility
Atropine blocks
muscarinic
cholinergic
receptors
that respond to
ACh
Understanding actions of drugs that
influence the autonomic nervous
system allows prediction of their
effects!
Parasympathetic
nerves
release ACh
and increase
intestinal motility
6. For a definite clinical outcome!
Sympathetic
nerves
release
Noradrenaline
and increase
Blood Pressure
Propranolol
blocks
β-adrenergic
receptors
that respond to
NA
Propranolol blocks β-adrenergic
receptors
and decreases Blood Pressure
10. Autonomic drugs are used for th
treatment of High Blood
Pressure
• Autonomic drugs also used for
treatment of
- Anaphylactic shock
- Septic shock
- Benign prostatic hypertrophy
- Alzheimer’s disease
- Asthma
11. Objectives
• Review the anatomy of the autonomic nervous system
• Know the neurotransmitters at autonomic synapses
• Understand the mechanism of neurotransmission in the
autonomic nervous system
• Be able to describe the distribution of adrenergic and
cholinergic receptors
• Describe general mechanisms by which drugs interact with
the autonomic nervous system
13. Organization of
Nervous System - Recall
Central Nervous System
“Brain and spinal cord”
Peripheral Nervous System
Autonomic Nervous System Somatic Nervous System
Afferent Division Efferent Division
Sympathetic
“thoracolumbar”
Parasympathetic
“craniosacral”
16. ANS - Organization
• Autonomic afferents:
– Mixed and nonmyelinated Nerves
– Cell bodies are located in the dorsal root ganglion
of Spinal Nerves and the sensory ganglia of
Cranial Nerves
– Mainly mediate visceral pain
– Also reflexes from CVS, visceral and respiratory
17. Organization of ANS –
Central Connections
• No Exclusive autonomic area in CNS
• Intermixing and integration of somatic and ANS occurs
• Hypothalamus is the organ to regulate
• Sympathetic – Lateral and Posterior sympathetic
• Parasympathetic – Anterior and Medial
• Many autonomic centres are located in mid brain
medulla
18. Organization of ANS – Efferent fibres
• Motor limb – Sympathetic
and Parasympathetic
• Most organs receive both
innervations
• Functionally antagonistic of
each other
• Overall – depends on the tone
at particular moment
• EXCEPTIONS:
– Most Blood vessels, sweat
glands and hair follicles –
Sympathetic
– Gastric and pancreatic glands,
cilliary muscles -
Parasympathetic
19. AUTONOMIC NERVOUS SYSTEM
• SYMPATHETIC
– Fight or Flight
• PARASYMPATHETIC
– Rest and Digest
Next slide –
Distriibution:
20. Parasympathetic Nervous System (Craniosacral Outflow)
Genitalia
Bladder
Large Intestines
Kidney
Bile Ducts
Gallbladder
Small Intestines
Stomach
Bronchi/Bronchial
Glands
SA & AV Node
Sphincter Muscle of Iris
Ciliary Muscle
Lacrimal Gland
Submaxillary &
Sublingual
Glands
Parotid Gland
21. Radial Muscle of Iris
Ciliary Muscle
SA & AV Nodes
His-Purkinje System
Myocardium
Bronchi/Bronchial
Glands
Stomach
Kidneys
Intestines
Bladder//Genitalia
Sublingual/Submaxillary
& Parotid Gland
Pilomotor Muscles
Sweat Glands
Blood Vessels
Sympathetic Nervous System
(Thoracolumbar Outflow)
Paravertebral Ganglia
Prevertebral Ganglia
24. Sympathetic Parasympathetic
Origin Dorso-lumber (T1 to L2 or 3) Craniosacral (S2-4)
Distribution Wide Head, neck and trunk
Ganglia Away from Organ supplied On or close to the organ
Postganglionic fibers Long Short
Pre and post fiber
ratio
1:20 to 1:100 1:1 or 1: 2
Transmitter Noradrenalin Acetylcholine
Duration Long and wider action Ach – rapid destroy
Function Tackling stress and emergency Assimilation of food and
conservation of energy
25. Enteric Nervous System
• Considered 3rd
Division of ANS
– Auerbach`s plexus or myenteric plexus
– Meissner`s plexus or submucous plexus
• Stimulation of these neurones causes release of – Ach, NE,
VIP, ATP, Substance P, 5-HT etc.
• May be excitatory or inhibitory in Nature
27. Neurohumoral
Transmission
• Neurohumoral transmission
means the transmission of
message across synapse and
neuroeffector junctions by
release of humoral (chemical)
messages
• Initially junctional
transmission was thought to
be Electrical
• But, Dale (1914) and Otto
Loewi (1921) provided direct
proof of humoral transmission
– vagusstoff and
acceleranstoff
• Many Neurohumoral
transmitters identified:
Acetylcholine, noradrenalin,
28. Neurohumoral
Transmission - Steps
1. Impulse Conduction
– Tetrodotoxin and
saxitoxin
1. Transmitter Release
2. Transmitter release on
postjunctional membrane
EPSP and IPSP
1. Postjunctional activity
2. Termination of transmitter
action
– NET, SERT, DT
31. Cholinergic and Adrenergic System
• Accordingly:
– Cholinergic Drugs, i.e., they act by releasing
acetylcholine
• But also utilize nitric oxide (NO) or peptides for
transmission
– Noradrenergic (commonly called "adrenergic")
Drugs - act by releasing norepinephrine (NA)
32. Cotransmission
• Peripheral and central Neurons release more than one active
substance when stimulated
• In ANS, besides Ach and NA – neurones elaborate Purines
(ATP, adenosines), Peptides (VIP) or NPY, substance P, NO,
enkephalins etc.
• ACH and VIP, ATP with both Ach and NA
• Stored in same neurones, but distinct vesicles – ATP and NA in
same vesicle
• NANC – gut, vas deferens, urinary tract, salivary glands and
certain blood vessels.
33.
34.
35. Sites of Cholinergic Transmission
Acetylcholine (Ach) is major neurohumoral transmitter at
autonomic, somatic and central nervous system:
1. All preganglionic sites (Both Parasympathetic and
sympathetic)
2. All Postganglionic Parasympathetic sites and sympathetic to
sweat gland and some blood vessels
3. Skeletal Muscles
4. CNS: Cortex Basal ganglia, spinal chord and others
Parasympathetic Stimulation – Acetylcholine (Ach) release at neuroeffector
junction - biological effects
Sympathetic stimulation – Noradrenaline (NA) at neuroeffector junction -
biological effects
36. Cholinergic
Transmission:
• Cholinergic neurons contain large
numbers of small membrane-bound
vesicles (containing ACh) concentrated
near the synaptic portion of the cell
membrane
• ACh is synthesized in the cytoplasm
from acetyl-CoA and choline by the
catalytic action of Choline
acetyltransferase (ChAT)
• Acetyl-CoA is synthesized in
mitochondria, which are present in large
numbers in the nerve ending
• Choline is transported from the
extracellular fluid into the neuron terminal
by a sodium-dependent membrane carrier
(carrier A). This carrier can be blocked by
a group of drugs called hemicholiniums
The action of the choline
transporter is the rate-limiting
step in ACh synthesis
37. Cholinergic Transmission:
• Synthesized, ACh is transported from the
cytoplasm into the vesicles by an antiporter
that removes protons (carrier B). This
transporter can be blocked by vesamicol
• Release is dependent on extracellular Ca2+
and occurs when an action potential reaches
the terminal and triggers sufficient influx of
Ca2+ ions
• The increased Ca2+ concentration
"destabilizes" the storage vesicles by
interacting with special proteins associated
with the vesicular membrane (VAMPs)
Fusion of the vesicular membranes with the
terminal membrane results in exocytotic
expulsion of ACh into the synaptic cleft
• The ACh vesicle release process is blocked
by botulinum toxin through the enzymatic
removal of two amino acids from one or more
of the fusion proteins. Black widow spider??
38. Cholinergic Transmission:
• After release - ACh molecules may bind to
and activate an ACh receptor
(cholinoceptor)
• Eventually (and usually very rapidly), all of
the ACh released will diffuse within range
of an acetylcholinesterase (AChE)
molecule
• AChE very efficiently splits ACh into
choline and acetate, neither of which has
significant transmitter effect, and thereby
terminates the action of the transmitter.
• Most cholinergic synapses are richly
supplied with AChE; the half-life of ACh in
the synapse is therefore very short. AChE
is also found in other tissues, eg, red blood
cells.
• Another cholinesterase with a lower
specificity for ACh, butyrylcholinesterase
[pseudo cholinesterase], is found in blood
plasma, liver, glial, and many other tissues
39. Differences between 2 AChEs
True AChE Pseudo AChE
Distribution All cholinergic
sites, RBCs,
gray matter
Plasma, liver,
Intestine and
white matter
Action on:
Acetycholine
Methacholine
Very Fast
Slower
Slow
Not hydrolyzed
Inhibition More sensitive
to
Physostigmine
More sensitive to
Organophosphates
Function Termination of
Ach action
Hydrolysis of
Ingested Esters
41. Acetylcholine (cholinergic receptors)
– Muscarinic Receptors
1. Selectively stimulated by Muscarine and blocked by Atropine – all are G-
protein coupled receptors
2. Primarily located in heart, eye, smooth muscles and glands of GIT
3. Subsidiary M receptors are also present in ganglia for modulation
4. Autoreceptors (M type) are present in prejunctional cholinergic Nerve
endings – also in adrenergic nerve terminals leading to vasodilatation
when Ach is injected
5. Blood vessels: All blood vessels have muscarninc receptors although no
cholinergic innervations
Amanita
muscaria
42. Muscarinic Receptors - Subtypes
• Pharmacologically - M1, M2, M3, M4 and M5
• M4 and M5 are present in certain areas of Brain and regulate
other neurotransmitters
• M1, M3 and M5 fall in one class, while M2 and M4 in another
class
• However till today, M1, M2 and M3 are major ones and
present in effector cell and prejunctional nerve endings in
CNS
• All subtypes have little agonist selectivity but selective
antagonist selectivity
• Most organs usually have more than one subtype but one
subtype predominates in a tissue
43. Muscarinic Receptors - Location
• M1: Ganglion Cells and Central Neurons (cortex,
hippocampus, corpus striatum)
– Physiological Role: Mediation of Gastric acid secretion and
relaxation of LES
• Learning, memory and motor functions
• M2: Cardiac Muscarinic receptors
– Mediate vagal bradycardia
– Also auto receptors in cholinergic nerve endings
• M3: Visceral smooth muscles, glands and vascular
endothelium. Also Iris and Ciliary muscles
44. M1 M2 M3
Location Autonomic ganglia,
Gastric glands and CNS
Heart and CNS SMs of Viscera,
Eye, exocrine
glands and
endothelium
Functions EPSP & Histamine
release & acid
secretion with CNS
learning and motor
functions
Less impulse
generation, less
velocity of
conduction,
decreased
contractility,
less Ach
release
Visceral SM
contraction,
Constriction of
pupil,
contraction of
Cilliary muscle
and
vasodilatationAgonists Oxotremorine and MCN
and MCN-343A
Methacholine Bethanechol
Antagonis
ts
Pirenzepine Methoctramine
& Triptramine
Darifenacin
Muscarinic Receptor
Subtypes
45. Acetylcholine (cholinergic receptors)
– Muscarinic Receptors
• Selectively stimulated by Muscarine and
blocked by Atropine
M1 M2 M3
Ganglia Heart Glands and
Smooth
Muscles
46. Nicotinic (N) Receptors
Nicotinic receptors: nicotinic actions of ACh are
those that can be reproduced by the injection of
Nicotine (Nicotiana tabacum)
Can be blocked by tubocurarine and
hexamethonium
• ligand-gated ion channels
– activation results in a rapid increase in cellular
permeability to Na+ and Ca++ resulting -
depolarization and initiation of action potential
47. Nicotinic (NM and NN) Receptor -
comparison
NM (Muscle type)
1. Location: Skeletal Muscle
end plates
2. Function: Stimulate skeletal
muscle (contraction)
3. MOA: Postsynaptic and
Excitatory (increases Na+ and
K+ permeability)
4. Agonists: ACh, carbachol
(CCh), suxamethonium
– Selective stimulation by phenyl
trimethyl ammonium (PTMA)
1. Antagonists: tubocurarine,
hexamethonium
NN (Ganglion type)
1. Location: In autonomic ganglia of
all type (ganglion type) –
Sympathetic, Parasympathetic and
also Adrenal Medulla
2. Function: Depolarization and
postganglionic impulse – stimulate
all autonomic ganglia
3. MOA: Excitatory – Na+, K+ and
Ca+ channel opening
4. Agonists: ACh, CCh, nicotine
– Selectively stimulated by
phenyl piperazinium (DMPP)
1. Antagonists: mecamylamine,
trimetaphan
48. Sites of Cholinergic transmission
and types of Receptors
Site Types Selective
agonist
Selective
antagonist
All Postganglionic
Parasympathetic
Postganglionic sympathetic to
sweat gland & BV
Muscarini
c
Muscarine Atropine
Ganglia (Both Para and
sympathetic and also
Adrenal Medulla
NN DMPP Hexamethoniu
m
Skeletal Muscle NM PTMA Curare
CNS Muscarini
c
Muscarine
Oxotremorin
e
Atropine
50. Cholinergic Drugs or Cholinomimetic
or Parasympathomimetics
Drugs producing actions similar to Ach – by
interacting with Cholinergic receptors or
by increasing availability of Ach at these
sites.
53. Question…
• What side effects might you expect to
see in a patient taking a cholinergic
drug?
• Hint… Cholinergic = “Colon-Urgent”
54. Ach actions - Muscarinic
1. Heart: M2
– Hyperpolarization of SA node, reduction in impulse generation and
Bradycardia
– RP in SAN and PF increased but atrial muscles fibers abbreviated
– Slowing of AV conduction and His-purkinje fibres – partial or
complete block
– Atrial fibrillation and flutter – nonuniform vagal innervations
– Decrease in ventricular contractility
1. Blood Vessels: M3
– Cholinergic innervations is limited – skin of face and neck
– But, M3 present in all type blood vessel – Vasodilatation by Nitric
oxide (NO) release
– Penile erection
55. Muscarinic action – contd.
3. Smooth Muscles: M3
– Abdominal cramps, diarrhoea – due to increased peristalsis and
relaxed sphincters
– Voiding of Bladder
– Bronchial SM contraction – dyspnoea, attack of asthma etc.
4. Glands: M3
– Increased secretions: sweating, salivation, lacrimation,
tracheobronchial tree and gastric glands
5. Eye: M3
– Contraction of circular fibres of Iris – miosis
– Contraction of Ciliary muscles – spasm of accommodation,
increased outflow and reduction in IOP
56. Ach actions - Nicotinic
1. Autonomic ganglia:
– Both Sympathetic and parasympathetic ganglia are stimulated
– After atropine injection Ach causes tachycardia and rise in BP
1. Skeletal muscle
– IV injection – no effect
– Application causes contraction of skeletal muscle
3. CNS:
– Does not penetrate BBB
– Local injection in CNS – complex actions
(Acetylcholine is not used therapeutically)
Bethanecol Uses: Postoperative and postpartum urinary
obstruction, neurogenic bladder and GERD (10-40 mg oral)
57. Pilocarpine
• Alkaloid from leaves of Pilocarpus
microphyllus
• Prominent muscarinic actions
• Profuse salivation, lacrimation,
sweating
• Dilates blood vessels, causes
hypotension
• On Eyes:
– it produces miosis by contraction
of circular muscles of iris
– Contraction of cilliary muscles
• spasm of accommodation -
fixed for near vision
• Increased outflow of AH
• Lowers intraocular pressure (IOP) in
Glaucoma when applied as eye
drops
• Too toxic for systemic use
58. Pilocarpine –
contd.
• Used as eye drops in treatment of narrow angle and wide
angle glaucoma to reduce IOP
• Used to reverse mydriatic effect of atropine
• To break adhesion between iris and cornea/lens alternated
with mydriatic
• Pilocarpine nitrate eye drops ( 1 to 4% )
• CNS toxicity after systemic use
• Atropine used as antidote in acute pilocarpine poisoning ( 1-2
mg IV 8hrly )
59. Muscarine
• Alkaloid from mushroom Amanita muscaria
• Only muscarinic actions
• No clinical use
• Mushroom poisoning due to ingestion of poisonous
mushroom
= Early onset mushroom poisoning (Muscarine type)
= Late onset mushroom poisoning (neurogenic)
60. Early Onset Mushroom Poisoning
• Occurs ½ to 1 hour
• Symptoms are characteristic of Muscarinic actions
• Inocybe or Clitocybe – severe cholinergic symptoms like
vomiting, salivation, lacrimation, headache, bronchospasm,
diarrhoea bradycardia, dyspnoea, hypotension, weakness,
cardiovascular collapse, convulsions and coma
• Antidote is Atropine sulphate ( 2-3 mg IM every hrly till
improvement)
Hallucinogenic type: due to Muscimol or ibotenic acid present
in A. muscria. Blocks muscarinic receptors in brain and
activate mio acid receptors. No specific treatment – Atropine
is contraindicated.
Volvariella volvacea
61. Late Onset Mushroom
Poisoning
• Occurs within 6-15 hours
• Amanita phylloides – due to peptide toxins – Inhibit RNA and
protein synthesis
• Irritability, restlessness, nausea, vomiting, bloody diarrhoea
ataxia, hallucination, delirium, sedation, drowsiness and sleep
– Kidney, liver and GIT mucosal damage
• Maintain blood pressure, respiration
• Inj. Diazepam 5 mg IM
• Atropine contraindicated as it may cause convulsions and
death
• Gastric lavage and activated charcoal
64. Overall …
• Most reversible Anti-ChEs are Carbamic acid compounds –
Physostigmine, Neostigmine, pyridostigmine and
Edrophonium
Physostigmine is tertiary amine (has tertiary amino N radical) – lipid
soluble
Neostigmine – Quarternary amine (has tertiary amino N radical) - lipid
insoluble
Exception: Tacrine – Acridine derivative
• Most Irreversible Anti-ChEs contain Phosphoric acid –
ORGANOPHOSPHATES – highly lipid soluble
• A few Irreversible Anti-ChEs are lipid soluble Carbamates - Carbaryl
and Propoxur
65. AChEs - MOA
• Acetylcholinesterase is the primary target
• Normally Acetylcholine - binds to the enzyme's active site and is
hydrolyzed, yielding free choline and the acetylated enzyme
• The active site has two subsites – anionic and esteratic
• The anionic site serves to bind a molecule of ACh to the enzyme
• Once the ACh is bound at anioic site, the hydrolytic reaction occurs at
a second region of the active site - esteratic subsite
• AChE itself gets acetylated by acetylation of serine site
• Acetylated enzyme reacts with water to form Acetic acid and choline
(Bond splits)
66. Anti-ChEs (MOA) – contd.
• Anticholinesterases also react with the enzyme ChEs in similar
fashion like Acetylcholine
– Carbamates – carbamylates the active site of the enzyme
– Phosphates – Phosphorylates the enzyme
• Carbamylated (reversible inhibitors) reacts with water slowly
and the esteratic site is freed and ready for action – 30
minutes (less than synthesis of fresh enzyme)
• But, Phosphorylated (irreversible) reacts extremely slowly or
not at all – takes more time than synthesis of fresh enzyme
– Sometimes phosphorylated enzyme losses one alkyl group
and become resistant to hydrolysis – aging
• Edrophonium and tacrine reacts only at anionic site while
Organophosphates reacts only at esteratic site
76. Anti-ChEs – Pharmacological
Actions
• Qualitatively similar to directly acting cholinergics, but quantitatively
different – two important clinically used drugs:
– Lipid soluble agents (physostigmine) – more muscarinic and CNS effects
(stimulate ganglia) – less skeletal muscle effect
– Lipid insoluble ones like Neostigimine – more skeletal muscle effect, stimulate
ganglia but less muscarinic effect
• Ganglia: Stimulates ganglia through muscarinic receptors, but high doses
may cause persistent depolarization of Nicotinic receptors and block
transmission
• CVS: Complex action – muscarinic-bradycardia, ganglionic-tachycardia etc.
• Skeletal Muscle: Repetitive firing – twitching and fasciculation
– High doses – persistent depolarization and NM blockade
77. Physostigmine
• Alkaloid from dried ripe seed (Calabar bean) of African plant Physostigma
venenosum
• Tertiary amine, lipid soluble, well absorbed orally and crosses BBB
• Hydrolyzed in liver and plasma by esterases.
• Long lasting action (4-8 hours)
• Reversible anticholinesterase drug
• It indirectly prevents destruction of acetylcholine released from
cholinergic nerve endings and causes ACh accumulation
• Muscarinic action on eye causing miosis and spasm of accommodation on
local application
• Antagonises mydriasis and cycloplegia produced by atropine and
anticholinergic drugs
• Salivation, lacrimation, sweating and increased tracheobronchial
secretions.
• Increased heart rate & causes hypotension
78. Physostigmine - uses
1. Used as miotic drops to decrease IOP in Glaucoma
2. To antagonise mydriatic effect of atropine
3. To break adhesions between iris and cornea alternating with
mydriatic drops
4. Belladonna poisoning, TCAs & Phenothiazine poisoning
5. Alzheimer’s disease- pre-senile or senile dementia
Atropine is antidote in physostigmine poisoning
ADRs – CNS stimulation followed by depression
79. Neostigmine
• Synthetic reversible anticholinesterase drug
• Quaternary ammonium compound and lipid soluble
• Cannot cross BBB
• Hydrolysed by esterases in liver & plasma
• Short duration of action (3-5 hours)
• Direct action on nicotinic (NM) receptors present in
neuromuscular junction (motor end plate) of skeletal muscle
• Antagonises (reverses) skeletal muscle relaxation (paralysis)
caused by tubocurarine and other competitive neuromuscular
blockers
• Stimulates autonomic ganglia in small doses
• Large doses block ganglionic transmission
• No CNS effects
80. Neostigmine – Uses and ADRs
• Used in the treatment of Myasthenia Gravis to increase
muscle strength
• Post-operative reversal of neuromuscular blockade
• Post-operative complications – gastric atony paralytic ileus,
urinary bladder atony
• Cobra snake bite
• Produces twitchings & fasciculations of muscles leading to
weakness
• Atropine is the antidote in acute neostigmine poisoning
82. Therapeutic Uses – cholinergic drugs
1. Myasthenia gravis:
• Edrophonium to diagnose
• Neostigmine, Pyridostigmine & Distigmine to treat
1. To stimulate bladder & bowel after surgery:
– Bethanechol, Carbachol, Distigmine
1. To lower IOP in chronic simple glaucoma:
– Pilocarpine, Physostigmine
1. To improve cognitive function in Alzheimer’s disease:
Rivastigmine, Gallantamine, Donepezil
2. Physostigmine in Belladonna poisoning
83. Myasthenia gravis
• Autoimmune disorder affecting 1 in 10,000 population
• Causes: Development of antibodies directed to Nicotinic
receptors in muscle end plate – reduction in number by 1/3rd
of NM receptors
– Structural damage to NM junction
• Symptoms: Weakness and easy fatigability
• Treatment:
– Neostigmine – 15 to 30 mg orally every 6 hrly
– Adjusted according to the response
– Dose requirement may fluctuate time to time – adjustment required
– Pyridostigmine – less frequency of dosing
– Other drugs: Corticosteroids (prednisolone 30-60 mg /day)
• Azathioprin and cyclosporin also Plasmapheresis
– Plasmapheresis
85. Myasthenic crisis
• Acute weakness and respiratory paralysis
– Tracheobronchial intubation and mechanical ventilation
– Methylprednisolone IV with withdrawal of AChE
– Gradual reintroduction of AChE
– Thymectomy
• Edrophonium is used for diagnosis of Myasthenic crisis
(disease itself) and cholinergic crisis (overdose of Anti-ChE)
– Improvement of symptoms – myasthenic crisis
– Worsening – Cholinergic crisis
86. Snake venom Poisoning
• Asian Cobra Bite
• Symptoms are similar to Myasthenia gravis
• Atropine sulfate 0.6 mg IV slowly – to
counteract Muscarinic action
• Edrophonium chloride (Tensilon) - 10 mg IV
over 2 minutes – reversal of occulomotor and
respiratory paralysis
87. AChE Poisoning (Organophopsphorous
Poisoning)
• Poisoning may be – Occupational, accidental,
Suicidal
• Symptoms:
– Fall in BP, bradycardia or tachycardia, cardiac arrhythmia
and vascular collapse
– Irrittion of Eye, lacrimation, salivation, colic, involuntary
defection, breathlessness, blurring of vision
– Muscular fasciculations and weakness
– Death due to respiratory paralysis – peripheral and central
88. Principles of Treatment
• Remove soiled clothes
• Wash soiled skin and eyes
• Prone Positioning and clear mouth and throat
• Intubation of airway
• Gastric lavage
• Atropine: All cases of AChE poisoning, 2mg IV every
`10 minutes – continue till atropinization occurs
• Cholinesterase reactivators: Oximes
89. Cholinesterase Reactivators - Oximes
• Pralidoxime (2-PAM), Obidoxime Diacetyl monoxime (DAM)
• Oximes have generic formula R-CH=N-OH
• Provides reactive group OH to the enzymes to reactivate the
phosphorylated enzymes
• PAM:
– Quaternary Nitrogen of PAM has a quaternary Nitrogen – gets
attached to Anionic site of the enzyme - unoccupied in
Organophosphorous poisoning
– and reacts with Phosphorous atom at esteratic site
– Forms Oxime-phosphonate complex making esteratic site free
– Not effective in Carbamate poisoning
– Available as 500 mg/20 ml infusion or 1 gm/vial for infusion
– Injected slow IV - 1-2gm
Endocrine and ANS have similarity – high level of integration in CNS, transmitter release (different in different types of nerves) – nerve to nerve (ganglia) then nerve to effector organ etc.
Angina is a Pain Syndrome due to induction of adverse oxygen supply or demand situation in a portion of myocardium. Types – classical and variant/prinzmetal`s angina. Classical – attack provoked by exercise, emotion etc. Variant – At rest or during sleep
Congestive heart failure
As of 2008, the cholinesterase inhibitors approved for the management of AD symptoms are donepezil (brand name Aricept),[144] galantamine (Razadyne),
Most Visceral afferents are mixed nerves and non-myelinted in nature. Cell bodies of these nerves lie in spinal nerves and sensory ganglia of cranial nerves. The carry the sensory stimulations from visceral organs.
Paravetrtebral – lateral chain – 22 pairs
A highly simplified diagram of the intestinal wall and some of the circuitry of the enteric nervous
system (ENS). The ENS receives input from both the sympathetic and the parasympathetic
systems and sends afferent impulses to sympathetic ganglia and to the central nervous system.
Many transmitter or neuromodulator substances have been identified in the ENS; see Table 6–1.
(LM, longitudinal muscle layer; MP, myenteric plexus; CM, circular muscle layer; SMP,
submucosal plexus; ACh, acetylcholine; NE, norepinephrine; NO, nitric oxide; NP, neuropeptides;
SP, substance P; 5-HT, serotonin.)
Latrodectism – black widow spider, vesicle-associated membrane protein (VAMP) family, SNAP - Soluble NSF Attachment Protein (N-ethylmaleimide-sensitive factor)
A site on a neuron that binds the neurotransmitter released by that neuron, which then regulates the neuron's activity.