1. Narcotic analgesics are drugs that can relieve pain without causing loss of consciousness by agonizing opioid receptors μ, κ, and δ.
2. Opioid analgesics work by inhibiting neuronal pain transmission through multiple mechanisms like blocking voltage-gated calcium channels and increasing potassium conductance.
3. Morphine is a naturally occurring opioid extracted from poppy plants that is a potent analgesic. It works by agonizing μ receptors and inhibiting pain signal transmission.
Narcotic and Nonnarcotic analgesic(Medicinal Chemistry)Yogesh Tiwari
Analgesics are agents that relieve pain by acting centrally to elevate pain threshold without disturbing consciousness or altering other sensory modalities.
This ppt covers the classification, structures and IUPAC names, Mechanism of action and uses of individual drugs...under anticonvulsants topic..Side effects/metabolism are also given for few
Narcotic and Nonnarcotic analgesic(Medicinal Chemistry)Yogesh Tiwari
Analgesics are agents that relieve pain by acting centrally to elevate pain threshold without disturbing consciousness or altering other sensory modalities.
This ppt covers the classification, structures and IUPAC names, Mechanism of action and uses of individual drugs...under anticonvulsants topic..Side effects/metabolism are also given for few
This ppt covers the classification of anti psychotics with structures and IUPAC names, MOA, uses, metabolism and side effects. Dopaminergic pathways also given
Phenytoin is an anticonvulsant drug or anti-epileptic drug . It can be prepared from the organic compound Benzil, which is formed by the oxidation of Benzoin.
Neurohumoral transmission in CNS-
The term neurohumoral transmission designates the transfer of a nerve impulse from a presynaptic to a postsynaptic neuron by means of a humoral agent e.g. a biogenic amine, an amino acid or a peptide.
This ppt covers the classification of anti psychotics with structures and IUPAC names, MOA, uses, metabolism and side effects. Dopaminergic pathways also given
Phenytoin is an anticonvulsant drug or anti-epileptic drug . It can be prepared from the organic compound Benzil, which is formed by the oxidation of Benzoin.
Neurohumoral transmission in CNS-
The term neurohumoral transmission designates the transfer of a nerve impulse from a presynaptic to a postsynaptic neuron by means of a humoral agent e.g. a biogenic amine, an amino acid or a peptide.
Mechanism of drug action, Relationship between drug conc & effect, Receptors, Structural & families of receptors, Quantitation of drug receptor interaction & elicited effects
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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
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.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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
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
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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.
2. • Analgesics- substance that relieves
pain
• Narcotic analgesics are drugs that
can relief pain without causing
narcosis (loss of consciousness)
Salahuddin Rakib,Dept of Pharmacy,IIUC. 2
3. Uses
• Choice of drugs for managing chronic pain as
with cancer or RA
• Used as inducing agent (fentanyl) or analgesic
supplement with General anesthetics
• They have clinical use as anti-diarrheal and
antitussive eg Loperamide and Dextromorphan
• Some opioids such as methadone and
buprenorphine are used to counter addiction of
more potent opioids such as heroin
Salahuddin Rakib,Dept of Pharmacy,IIUC. 3
4. Mechanism of action
• Opiod analgesic agonize opiod receptors µ,κ and δ
which are G-protein couples receptors. This
leads to a series of event which ultimately block
neuronal pain transmission by:
1. Inhibition of activation of voltage gated Ca+2 channels
• which depresses NT release
2. Increases K+ conductance outside the cell tocause
• hyper polarization of cell thus reducing it’s excitability
3. Inhibtion of adenyl cyclase
• (adenyl cyclase--> cAMP --> PKA --> phosphorylation of
• ion channels --> increase chances of channel opening)
Salahuddin Rakib,Dept of Pharmacy,IIUC. 4
5. Morphine
• It is a naturally occurring analgesic alkaloid extracted from
opium of poppy plant
• Modification to it’s structure has resulted more potent
compound
• Used in chronic pain management
• It is potent enough that it’s 60mg oral dose has analgesic effect
equal to parental administration
• MOA: agonizes µ receptor which depresses pain signals by
• inhibiting VGCC and prevent release of Neurotransmitters
• Opening VGPC and causing hyperporalization of nerves cells
• Inhibiting adenyl acylase
Salahuddin Rakib,Dept of Pharmacy,IIUC. 5
7. 1. Morphine has 5 Chiral centers. Only the
Levo(-) rotatory isomer is active
Salahuddin Rakib,Dept of Pharmacy,IIUC. 7
8. 2. The OH group in the phenolic ring and basic Nitrogen is needed for
activity and seen in all potent µ agonist.
Activity can be preserved or enhanced by removing other rings.
Changing -OH to just –H or -OCH3 lowers activity as seen with
codeine
R= C3
substituent
Activity effect
-H 10X Decrease
-OH morphine
-OCH3
(codeine)
Decrease
Salahuddin Rakib,Dept of Pharmacy,IIUC. 8
10. 3. The Nitrogen is mostly tertiary with a methyl substitution in
morphine. The size of substituent on Nitrogen dictates
potency and agonist or antagonist activity.
4. Reduction of 7,8 double bond increases activity
5. Inclusion of Hydroxyl group at 14 increases activity
6. Removal of Hydroxyl at 6 increases activity
7. Oxidation of Hydroxyl to keto group at 6 increases activity, if
there is also reduction of 7,8 double bond e.g.. hydrocodone
8. Acetylation of Hydroxyl at 6 increases activity
9. Removal of the ether linkage produces compounds called
morphinans that has increases activity.
Salahuddin Rakib,Dept of Pharmacy,IIUC. 10
11. The Beckett-Casy Hypothesis
• Positively charged nitrogen group of opioid
will form an ionic bond with anionic group
of receptor.
• In order to accomplish this “there must be
a basic nitrogen group which is then
ionized at physiological pH for form a
positively charged group (3),’ because the
positively charged group could not cross
the blood brain barrier.
• This would result in the opioids having a
pKa of around 7.8 to 8.9, which is
consistent with all opioid analgesics
Salahuddin Rakib,Dept of Pharmacy,IIUC. 11
12. The Beckett-Casy Hypothesis
• The hypothesis also proposes van der Waals
interaction between the aromatic ring and a
hydrophobic region of the binding site
• This suggests a close spatial relationship between
the aromatic ring of the opioid and the surface of
the binding site
• The hypothesis also suggests hydrogen bonding with
the phenol group of the opioid and the receptor binding
site
• It also proposes that the receptor possesses a unique
structural feature that allows the ethylene bridge of the
opioid to snugly fit into the binding site and in doing so
properly aligning the rest of the molecule with the
associated binding regions.
Salahuddin Rakib,Dept of Pharmacy,IIUC. 12
13. Drawbacks with the Beckett-Casy hypothesis
* Ethylene bridge is not important in some analgesics (fentanyl)
* No account for extra binding regions found by extension
* Does not explain different SAR results (e.g. meperidine vs morphine)
* Does not explain mixed antagonist/agonist properties
Salahuddin Rakib,Dept of Pharmacy,IIUC. 13
14. Multiple Analgesic Receptors
* Three different analgesic receptors (mu, kappa and delta)
* Binding sites for all three receptors contain ionic, hydrogen bonding and hydrophobic
regions as proposed by Beckett-Casy
* Activation of all three produce analgesia, but differ in other effects
* All three interact with morphine
* Potential to target drugs selectively
Salahuddin Rakib,Dept of Pharmacy,IIUC. 14
15. Mu Receptor (m)
* Morphine binds strongly
* Activation produces analgesia plus side effects
(respiratory depression, euphoria, addiction)
* G-Protein coupled receptor
* m-Receptor subtypes identified which may allow separation of analgesia from
side effects
* m-Receptors related to all sources of pain stimuli
Salahuddin Rakib,Dept of Pharmacy,IIUC. 15
16. Kappa Receptor (k)
* Morphine binds less strongly
* Activation produces analgesia plus sedation
* Insignificant side effects
* Potential target for safe analgesics (compounds acting as agonists at k, antagonists at m
and no activity at the d receptor).
* G-Protein-coupled receptor
* k Receptors related to non-thermal pain induced stimuli
Salahuddin Rakib,Dept of Pharmacy,IIUC. 16
17. Delta Receptor (d)
* Morphine binds strongly
* Receptor for enkephalins
* Activation produces analgesia plus some side effects
* G-Protein-linked receptor
* d receptors related to pain induced stimuli from all sources
Sigma Receptor (s)
* Activated by some opoid analgesics (e.g. nalorphine)
* Non-analgesic, non-opoid receptor
* Activation produces hallucinogenic effects
* Thought to be responsible for effects of phencyclidine (PCP) (Angel Dust)
Salahuddin Rakib,Dept of Pharmacy,IIUC. 17
18. Receptor mechanisms
All receptors in the body are situated on the surface of cells and act as
communication centres for the various messages being sent from one part of the
body to another. The message may be sent through nerves or via hormones, but
ultimately the message has to be delivered from one cell to another by a chemical
messenger.
This chemical messenger has to 'dock' with the receptor which is waiting for it.
When it does so, it forces the receptor to change shape. This change in shape of
the receptor molecule may force a change in the shape of some neighbouring
protein or perhaps an ion channel, resulting in an alteration of ion flows in and
out of the cell. Such effects will ultimately have a biological effect, dependent on
the cells affected.
Salahuddin Rakib,Dept of Pharmacy,IIUC. 18
19. The mu receptor (µ)
Morphine binds to the (µ) receptor and induces a change in shape. This change
in conformation opens up an ion channel in the cell membrane and as a result,
potassium ions can flow out of the cell. This flow hyperpolarizes the membrane
potential and makes it more difficult for an active potential to be reached.
Therefore, the frequency of action potential firing is decreased, which results in
a decrease in neurone excitability. This increase in potassium permeability has
an indirect effect, since it also decreasesthe influx of calcium ions into the
nerve terminal and this in turn reduces neurotransmitter release. Both effects,
therefore, 'shut down' the nerve and block the pain messages. Unfortunately,
this receptor is also associated with the hazardous side-effects of narcotic
analgesics Salahuddin Rakib,Dept of Pharmacy,IIUC. 19
20. The kappa receptor (K)
The K receptor is directly associated with a calcium channel (Fig. 12.42).
When an agonist binds to the K receptor, the receptor changes
conformation and the calcium channel (normally open when the nerve is
firing and passing on pain messages) is closed. Calcium is required for the
production of the nerves neurotransmitters and therefore the nerve is shut
down and cannot pass on pain messages.
The nerves affected by the K mechanism are those related to pain induced by
nonthermal stimuli. This is not the case with the JJL receptor where all pain
messages are inhibited. This suggests a different distribution of K receptors
from JJL receptors Salahuddin Rakib,Dept of Pharmacy,IIUC. 20
21. The delta receptor (d)
There are no ion channels involved (Fig. 12.43). The substrate molecule binds to the A
receptor and, in some way, the message is transmitted through the cell membrane to
a second membrane-bound protein. This protein then acts as an enzyme for the
formation of cyclic AMP (Fig. 12.44). Normally, theactive site is open when the nerve
is receiving pain
messages, such that cyclic AMP acts as a secondary messenger and passes on the pain
messages. However, when the A receptor is activated it probably changes shape and
as a result leads to a change in shape of the cyclase enzyme to close down the
phosphate (cAMP).
active site by which it can make cyclic AMP.
Salahuddin Rakib,Dept of Pharmacy,IIUC. 21
22. Sigma Receptor (s)
This receptor is not an analgesic receptor, but we have seen that it can be
activated by certain opiate molecules such as nalorphine. When activated, it
produces hallucinogenic effects. The a receptor may be the one associated with
the hallucinogenic and psychotomimetic effects of phencyclidine (PCP), otherwise
known as 'angel dust
Salahuddin Rakib,Dept of Pharmacy,IIUC. 22
