The parasympathetic division typically acts in opposition to the sympathetic autonomic nervous system through negative feedback control.
This action is a complementary response, causing a balance of sympathetic and parasympathetic responses.
Overall, the parasympathetic outflow results in the conservation and restoration of energy, reduction in heart rate and blood pressure, facilitation of digestion and absorption of nutrients, and excretion of waste products.
These are drugs that produce actions similar to that of Acetylcholine hence known as parasympathomimetics.
They act either by directly interacting with cholinergic receptors or by increasing the availability of Acetylcholine at these sites.
introduction ,classification of cholinergic receptor ,and its function ,anti cholinergic agents -atropine and its pharmacology ,semi synthetic and synthetic atropine substitutes
The parasympathetic division typically acts in opposition to the sympathetic autonomic nervous system through negative feedback control.
This action is a complementary response, causing a balance of sympathetic and parasympathetic responses.
Overall, the parasympathetic outflow results in the conservation and restoration of energy, reduction in heart rate and blood pressure, facilitation of digestion and absorption of nutrients, and excretion of waste products.
These are drugs that produce actions similar to that of Acetylcholine hence known as parasympathomimetics.
They act either by directly interacting with cholinergic receptors or by increasing the availability of Acetylcholine at these sites.
introduction ,classification of cholinergic receptor ,and its function ,anti cholinergic agents -atropine and its pharmacology ,semi synthetic and synthetic atropine substitutes
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Announcement about my previous presentations - Thank youAreej Abu Hanieh
ANNOUNCEMENT Thank you for all of you, my followers who sent me messages with a lot of love and appreciations, I finally graduated after 6 years of studying in Birzeit University , In doctor of Pharmacy department I hope all of you benefited from all the presentations posted before Thank you a new PharmD GraduatedAreej ^^
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Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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2. ANS along with the endocrine system coordinate
the regulation and integration of bodily functions
Autonomic drugs: Drugs that produce their
therapeutic effects by mimicking or altering the
functions of the ANS
3. Visceral, vegetative, involuntary nervous
system
ANS regulates everyday requirements of
vital bodily functions without the
conscious participation of the mind
ANS is composed of efferent neurons
innervating smooth muscles of viscera,
cardiac muscle, vasculature and exocrine
glands
ANS controls digestion, cardiac output,
blood flow and glandular secretions
4. Efferent neurons: carry nerve
impulses from the CNS to effector
organs
◦ Sympathetic neurons
◦ Parasympathetic neurons
◦ Enteric neurons: fibers that innervate
GIT, pancreas and gall bladder
5. Sympathetic nervous system: adjusts response to
stressful situations like fear, trauma,
hypoglycemia, cold and exercise
◦ Fight or Flight response
(changes in the body during emergencies)
Sympathetic activation of effector organs
Stimulation of adrenal medulla to release Epinephrine and
norepinephrine
◦ Heart rate, blood pressure, mobilize energy stores
6. Parasympathetic nervous system:
◦ Maintaining homeostasis in the body
◦ Maintain essential body functions like digestion,
elimination of waste
◦ Oppose and balance the actions of sympathetic
nervous system
◦ Rest or digest situations
7.
8. CNS control over autonomic
functions involves reflex
responses without
consciousness
Stimuli causing strong
feelings like rage, fear can
modify ANS activities
Most organs receive dual
innervation by both systems
9. Acetylcholine (ACh) Cholinergic neurons
◦ Transmission of nerve impulse across ganglia in sympathetic
and parasympathetic systems
◦ From postganglionic nerves to the effector organs in the
parasympathetic system
Norepinephrine (NE) and epinephrine Adrenergic
neurons
◦ Transmission of nerve impulse from postganglionic nerves to
the effector organs in the sympathetic system
10.
11. ACh’s effects are mediated through two subtypes of
receptors: muscarinic (M) and nicotinic (N) receptors.
M receptors are present in the neuro-effector junction
of the parasympathetic division
N receptors are present in the autonomic ganglia of
both sympathetic and parasympathetic divisions of the
ANS and in the neuro-muscular junction
12. NE and epinephrine’s effects are mediated by two
receptor subtypes: and
receptors are either 1 or 2
1 receptors are present in the arteriolar smooth
muscles, Activation leads to vasoconstriction.
2 receptors are found pre-ganglionically and in the
CNS. Activation leads to decrease in the sympathetic
flow from CNS
13. receptors are either 1 or 2.
1 receptors are found in the heart and kidney.
Activation leads to increase H.R., force of
contraction, and release of renin from kidney.
2 receptors are found in smooth muscles of blood
vessels and bronchi. Activation leads to
vasodilation and bronchodilation.
16. Autonomic drugs: Drugs that produce their
therapeutic effects by mimicking or altering
the function of the autonomic nervous system
(ANS)
◦ Stimulating portions of the ANS
◦ Blocking the action of the autonomic nerves
Divided based on the type of neuron involved
in their mechanism of action
◦ Cholinergic drugs act on receptors activated by
acetylcholine (ACh)
◦ Adrenergic drugs act on receptors stimulated by
norepinephrine or epinephrine
17. 1. Synthesis of ACh
2. Storage of ACh
in vesicles
3. Release of ACh
4. Binding of ACh
to the receptor
5. Degradation of
ACh
6. Recycling of
choline and
acetate
18.
19. 1. Muscarinic receptors
◦ G-protein coupled receptors
◦ 5 subclasses
M1, M2, M3, M4, M5
◦ Location, all 5 subtypes were found on neurons
M1 on gastric parietal cells
M2 on cardiac cells and smooth muscle
M3 on bladder, exocrine glands and smooth muscle
21. Bind directly to cholinergic receptors and mimic
the effects of ACh
◦ Acetylcholine
Rapidly inactivated by cholinesterase
Heart rate and cardiac output
Blood pressure
Salivary secretion and intestinal motility
Urinary expulsion
Miosis
No therapeutic use
Due to multiplicity of its action leading to diffuse effects
Rapid inactivation by cholinesterase
22. 1. Decrease heart rate and cardiac output
◦ Mimic the effect of vagal stimulation
◦ Negative chronotropic effect (decrease in heart rate)
◦ Decreases stroke volume by reducing the rate of firing
at the sinoatrial (SA) node
2. Decrease blood pressure
◦ By causing vasodilation
◦ ACh activates M3 receptors on the endothelial lining of
the smooth muscles in blood vessels
◦ This causes the release of nitric oxide (NO) which
relaxes smooth muscles in the blood vessels by
inhibition of phosphodiesterase-3
23. Bethanechol
◦ Muscarinic agonist
◦ Poor substrate for choliesterase
◦ Increase intestinal motility
◦ Stimulates the detruser muscle of the bladder while
relaxing the trigone and sphinctor muscles causing
urine expulsion
◦ Uses
To stimulate atonic bladder postpartum or postoperative
◦ Adverse effects
Sweating, salivation, decreased blood pressure, nausea,
abdominal pain, diarrhea and bronchospasm.
24. Carbachol
◦ Muscarinic and nicotinic agonist
◦ Poor substrate for cholinesterase
◦ Profound effects on cardiovascular and GI systems
first stimulating and then depressing (ganglion stimulation)
◦ Can cause release of epinephrine from adrenal medulla
due to its nicotinic action
◦ Use: rarely used except in the eye as a miotic agent to
treat glaucoma causing pupillary contraction and
decreased intraocular pressure (IOP)
◦ Opthalmic preperation has no or little systemic effects
25. Pilocarpine
◦ Muscarinic agonist
◦ Stable to hydrolysis by cholinesterase
◦ Opthalmic preparation is used to treat Glaucoma
causing contraction of ciliary muscles and miosis
◦ Used for emergency lowering of intraocular pressure
◦ Oral pilocarpine is used for Sjören’s syndrome (dry
mouth and lack of tears)
Adverse effects
◦ Can cross the BBB and cause CNS disturbance
◦ Salivation and sweating (diaphoresis)
27. AChE is the enzyme that cleaves
ACh to acetate and choline,
terminating its action
AChE inhibitors provide a
cholinergic action by prolonging
the time ACh is available at the
cholinergic nerve endings
Act on muscarinic, nicotinic
receptors and NMJ
28. Edrophonium
◦ Prototype short acting AChE inhibitor
◦ Binds reversibly to the active site of AChE preventing ACh
hydrolysis
◦ Used in diagnosis of myasthenia gravis (autoimmune
disease caused by antibodies causing degradation of
nicotinic receptors on NMJs)
◦ IV injection rapidly increases muscle strength in
myasthenia gravis
◦ Use is limited due to the risk of cholinergic crisis
29. Physostigmine
◦ Reversibly inactivates AChE potentiating
cholinergic activity in the body
◦ Stimulates muscarinic and nicotinic sites
of ANS and NMJ
◦ Increases intestinal and bladder motility,
used in the case of atony in either organs
◦ Topically in the eye, produces miosis and
lowering of intraocular pressure
◦ Used to treat glaucoma
◦ Used for treatment of overdose of
anticholinergic drugs
30. Physostigmine
◦ Adverse effects (rarely seen at therapeutic doses)
Can cross BBB and lead to convulsions at high doses
Bradycardia and reduced cardiac output
Paralysis of skeletal muscle due to overaccumulation of
ACh at NMJ
31. Neostigmine
◦ Reversibly inhibits AChE
◦ Does not enter the CNS
◦ Used to stimulate the bladder and GI
◦ Used to treat myasthenia gravis
◦ Antidote for neuromuscular blocking agents
◦ Adverse effects
(Generalized cholinergic stimulation)
Salivation, flushing, decreased blood pressure, nausea,
abdominal pain, diarrhea and bronchospasm.
32. Myasthenia gravis: chronic autoimmune
neuromuscular disease characterized by
weakness of the skeletal muscles
◦ Treatment (AChE inhibitors)
Neostigmine
Pyridostigmine
Ambenonium
◦ Adverse effects: similar to neostigmine
33. Alzheimer’s disease: Progressive memory loss
with a decline in cholinergic neurons in the
central nervous system
◦ Treatment: AChE inhibitors
Tacrine (less used because of hepatotoxicity)
Donepezil
Rivastigmine
Galantamine
Adverse effects: mainly GI disturbances
Only delay the progression of the disease, can not stop
the disease.
34. Organophosphate compounds
◦ Irreversible inhibitors of AChE
◦ Long-lasting increase in ACh
◦ Many are extremely toxic and were developed by military
as nerve agents (e.g. sarin)
◦ Some are insecticide (e.g. parathion, malathion)
◦ Cause paralysis of skeletal muscles including breathing
difficulties and convulsions
◦ Echothiophate
Ophthalmic solution for chronic treatment of glaucoma
35. Treatment of toxicity caused by organophosphate
insecticides (AChE inhibitors)
◦ Pralidoxime reactivates inhibited AChE, but it can not cross
the BBB, can not reverse CNS toxicity
(Pralidoxime is a weak AChE inhibitor)
◦ Atropine (antimuscarinic) to reverse muscarinic side effects
◦ Diazepam for persistent convulsions
◦ Artificial respiration
36. Parasympatholytics, cholinergic blockers,
cholinergic antagonists, anticholinergic drugs
Drugs that bind to cholinergic receptors but they
do not trigger the usual response
Divided into 3 groups
◦ Antimuscarinic agents
◦ Ganglionic blockers
◦ Neuromuscular blockers
39. Belladonna alkaloid
Mechanism: Binds to muscarinic receptors
competitively and prevents ACh from binding
Effects: (peripheral and central)
◦ Eye: Mydriatic
◦ GI: Antispasmodic, reduces activity of GI, reduces
saliva secretion
◦ Urinary retention
40. Uses
◦ Mydriatic agent (opthalmic preparation) for eye examination,
causes cycloplegia (inability to focus on near vision).
◦ Antispasmodic
◦ Antidote for cholinergic agonists like in AChE inhibitors toxicity
such as some insecticides
◦ Antisecretory to block secretions prior to surgery
Side effects (dose dependent)
◦ Dry mouth
◦ Blurred vision
◦ Tachycardia
◦ Urinary retention
◦ Constipation
◦ CNS effects (restlessness, confusion, hallucinations, delirium)
◦ Collapse of respiratory and circulatory systems
◦ Death
Low dose AChE inhibitors like physostigmine can be used
for atropine toxicity
41. Scopolamine
◦ Used for motion sickness
◦ Causes sedation
◦ Adjunct drug in anesthetic procedures
◦ Side effects: similar to atropine
Ipratropium and tiotropium: Inhaled bronchodilators
◦ Used for maintenance of bronchospasm associated with
chronic obstructive pulmonary disease (COPD), chronic
bronchitis, and emphysema
42. Tropicamide and cyclopentolate
◦ Opthalmic solutions for mydriasis and cycloplegia
◦ Have largely replaced atropine due to the prolonged mydriasis observed
with atropine
Benztropine and tryhexyphenidyl
◦ Centrally acting antimuscarinic agents
◦ Used for Parkinson’s disease which is characterized by imbalance between
ACh and dopamine in the brain
Oxybutynin and tolterodine
◦ Block muscarinic receptors in the bladder, increasing bladder capacity and
reduces frequency of bladder contraction
◦ Used for overactive urinary bladder disease
◦ Side effects: dry mouth, constipation and blurred vision
◦ Oxybutynin transdermal patch shows reduced mouth dryness than with
oral preparations
43.
44. Act on the nicotinic receptors of both sympathetic
and parasympathetic ganglia
No therapeutic application, they do not show
specificity for sympathetic or parasympathetic
ganglia
Nicotine
45. A poison with many undesired actions
No therapeutic benefit
Affects both sympathetic and
parasympathetic ganglia resulting in
complex effects
Increases release of neurotransmitters
Overall effects, increased heart rate and
blood pressure
Nicotine patches
46. Block cholinergic transmission between motor nerve
endings and the nicotinic receptors on skeletal muscles
Structural analogs of acetylcholine
Used during surgery for complete muscle relaxation , so
that less anesthetic is required to produce muscle
relaxation and patients and recover quickly after surgery
(high doses of anesthesia can produce respiratory
paralysis and cardiac depression)
Also used in facilitating tracheal intubation
47. Curare and tubocurare
◦ No longer used for anesthesia
Newer agents: Atracurium, cisatracurium,
pancuronium, rocuronium, vecuronium
Mechanism:
◦ Bind to nicotinic receptors at the neuromuscular junction
and prevent Ach binding
◦ Prevent the depolarization of the muscle cell membrane
and inhibit muscular contraction
Antidote: Neostigmine, pyridostigmine
(Cholinergic agonists, cholinesterase inhibitors)
48. Actions
◦ Small rapidly contracting muscles of the face and eye are
paralyzed first followed by fingers
◦ Limbs, neck and trunk muscles are paralyzed afterwards
◦ Lastly the diaphragm muscles are paralyzed
◦ Recovery occurs in a reverse manner with the diaphragm
first
Therapeutic uses: adjuvant in anesthesia to relax
skeletal muscles, to facilitate intubation
49. Depolarize the plasma membrane of the muscle
fiber, similar to ACh
More resistant to degradation by AChE
Remain attached to the receptor for a longer
time causing constant stimulation of the
receptor
Continuous binding makes the receptor unable
to transmit further impulses causing flaccid
paralysis
50. Succinyl choline
◦ Attaches to nicotinic receptors and act like ACh to
depolarize the junction
◦ Remains attached to the receptor providing constant
stimulation of the receptor, hence causing flaccid paralysis
◦ Respiratory muscles paralyze last
◦ Used for endotracheal intubation or electroconvulsive shock
treatment
◦ Adverse effects:
Hyperthermia when administered with halothane as anesthetic
Apnea