COX inhibitors like NSAIDs work as nonopioid analgesics and anti-inflammatory drugs. They function by inhibiting the COX enzymes and thereby decreasing the production of prostaglandins and other inflammatory mediators derived from arachidonic acid. This leads to their analgesic, antipyretic, and anti-inflammatory effects but also side effects involving the gastrointestinal tract and kidney function. Aspirin is a prototypical NSAID that was first isolated from willow bark and introduced in 1899, demonstrating the clinical usefulness of this class of drugs.
COX inhibitors have been known to cause platelet inhibition by inhibiting thromboxane A2 production. Aspirin causes irreversible inhibition of COX, and therefore, the duration of platelet inhibition lasts until 7 to 10 days after drug discontinuation.
A type of drug that is used to treat inflammation and pain, and is being studied in the prevention and treatment of cancer. COX inhibitors belong to the family of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Also called cyclooxygenase inhibitor.
COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.Coxibs are NSAIDs that are highly selective for the COX2 enzyme. Because the COX2 enzyme mediates prostaglandin production responsible for inflammation and pain, coxibs are analgesic and antiinflammatory, but they lack the side effects related to inhibiting the COX1 enzyme (e.g., bleeding and gastrointestinal irritation).
COX inhibitors have been known to cause platelet inhibition by inhibiting thromboxane A2 production. Aspirin causes irreversible inhibition of COX, and therefore, the duration of platelet inhibition lasts until 7 to 10 days after drug discontinuation.
A type of drug that is used to treat inflammation and pain, and is being studied in the prevention and treatment of cancer. COX inhibitors belong to the family of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Also called cyclooxygenase inhibitor.
COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly targets cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.Coxibs are NSAIDs that are highly selective for the COX2 enzyme. Because the COX2 enzyme mediates prostaglandin production responsible for inflammation and pain, coxibs are analgesic and antiinflammatory, but they lack the side effects related to inhibiting the COX1 enzyme (e.g., bleeding and gastrointestinal irritation).
A PowerPoint presentation on "NSAIDS" suitable for reading by UG and PG Medical/Paramedical students of Pharmacology and Pharmacy sciences. This Ppt. is prepared for academic purpose only and already presented to my students in one of the theory classes of mine.
Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs /ˈɛnsɛd/ en-sed), also called nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal anti-inflammatory medicines (NSAIMs), are a drug class that groups together drugs that provide analgesic (pain-killing) and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects.
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
NSAIDs are the chemically diverse class of drugs that have anti-inflammatory, analgesic & antipyretic properties.
They are also called as Non Narcotic, Non Opioid, Aspirin like analgesics.
They are among the widely used therapeutic agents world wide and often taken without prescription for minor aches and pain.
They are used to suppress the symptoms of inflammation associated with rheumatic disease.
Presentation for Medical undergraduates for teaching pharmacology. It deals with Physiology of steroid hormones and their action along with agents which are used therapeutically with their action, adverse effects and therapeutic uses.
A PowerPoint presentation on "NSAIDS" suitable for reading by UG and PG Medical/Paramedical students of Pharmacology and Pharmacy sciences. This Ppt. is prepared for academic purpose only and already presented to my students in one of the theory classes of mine.
Nonsteroidal anti-inflammatory drugs (usually abbreviated to NSAIDs /ˈɛnsɛd/ en-sed), also called nonsteroidal anti-inflammatory agents/analgesics (NSAIAs) or nonsteroidal anti-inflammatory medicines (NSAIMs), are a drug class that groups together drugs that provide analgesic (pain-killing) and antipyretic (fever-reducing) effects, and, in higher doses, anti-inflammatory effects.
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
NSAIDs are the chemically diverse class of drugs that have anti-inflammatory, analgesic & antipyretic properties.
They are also called as Non Narcotic, Non Opioid, Aspirin like analgesics.
They are among the widely used therapeutic agents world wide and often taken without prescription for minor aches and pain.
They are used to suppress the symptoms of inflammation associated with rheumatic disease.
Presentation for Medical undergraduates for teaching pharmacology. It deals with Physiology of steroid hormones and their action along with agents which are used therapeutically with their action, adverse effects and therapeutic uses.
the topic contain nonsteroidal antiinflammatory drugs which include, mediatorsof inflammation, cox-1 and cox-2, classification of drugs, its pharmacological effect and adverse reaction of drug.
NSAIDs have an extremely safe profile when used for acute dental pain.
Within a group they tend to have similar characteristics & tolerability. There is little difference in clinical efficacy among the NSAIDs when used at equivalent doses.
Rather, differences among compounds usually relate to dosing regimens (related to compound’s elimination half –life), route of administration, & tolerability profile.
So, clinician should have a thorough knowledge of mechanism of action, pharmacokinetics, pharmacodynamics, dosage & adverse effects of each drug before prescribing the same.
Overview of Discussion
Introduction
Which are the features of inflammation…?
Functional importance of eicosanoids and other chemical mediators
Pharmacological/physiological effects of inflammatory mediators
How PGs produce PAIN?
How PGs produces FEVER?
How PGs produces INFLAMMATION?
About NSAIDs...
Classification of NSAIDs
Mechanism of Action: NSAIDs
Pharmacology of Individual Class of NSAIDs
Choice of NSAIDs
Analgesic combinations
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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.
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
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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!
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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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
2. The clinical features of inflammation have been
recognized since ancient times as swelling, redness,
pain, and heat. The underlying mechanisms which
produce these symptoms are complex, involving
many different cells and cell products. A normal
inflammatory response is essential to fight infections
and is part of the repair mechanism and removal
of debris following tissue damage. Inflammation
can also cause disease, due to damage of healthy
tissue. This may occur if the response is over-
vigorous, or persists longer than is necessary.
Additionally, some conditions have a previously
unrecognized inflammatory component, e.g.
atherosclerosis.
3. The inflammatory response occurs
in vascularised tissues in response
to injury. It is part of the innate
nonspecific immune response.
Inflammatory responses require activation of
leukocytes: neutrophils, eosinophils, basophils,
mast cells, monocytes, and lymphocytes,
although not all cell types need be
involved in an inflammatory episode. The cells
migrate to the area of tissue damage from the
systemic circulation and become activated.
6. Inflammatory mediators
Activated leukocytes at a site of inflammation release
compounds which enhance the inflammatory response
mainly cytokines and eicosanoids (arachidonic acid
metabolites). But the complexity of the response
is indicated by the range of many mediators:
complement products, kinins (bradykinin)
and the contact system (coagulation factors XI and
XII, pre-kallikrein, high molecular weight kininogen);
nitric oxide and vasoactive amines (histamine,
serotonin and adenosine); activated forms of oxygen;
platelet activating factor (PAF); metalloproteinases
(collagenases, gelatinases, and proteoglycanase), etc.
7. Cytokines (ILs, TNFs, IFNs, CSFs, etc.)
are peptides regulating cell growth,
differentiation, and activation, and some have
therapeutic value:
• IL-1 plays a part in the sepsis syndrome
and rheumatoid arthritis, and successful
blockade of its receptor offers a
therapeutic approach for these conditions.
• TNFα is similar to IL-1. Agents that block him,
e.g. etanercept, infliximab are finding their place
among Disease modifying antirheumatic drugs.
9. Eicosanoids (prostaglandins, thromboxanes,
leukotrienes, lipoxins) is the name given to a
group of 20-carbon unsaturated fatty acids,
derived principally from arachidonic acid in cell
walls. They are short-lived, extremely potent,
and formed in almost every tissue in the body.
Eicosanoids are involved in most types of
inflammation and it is on manipulation of their
biosynthesis that most current antiinflammatory
therapy is based. Their biosynthetic paths
appear in the next slides.
11. PGI2 (prostacyclin) is located
predominantly in vascular
endothelium. Main effects:
•vasodilatation
•inhibition of platelet aggregation
TxA2 is found in the platelets.
Main effects:
•platelet aggregation
•vasoconstriction
PROSTANOIDS (PGs & Txs)PROSTANOIDS (PGs & Txs)
12. PGE2 causes:
• inhibition of gastric acid secretion
•contraction of pregnant uterus
•contraction of GI smooth muscles
PGF2α – main effects:
•contraction of bronchi
•contraction of miometrium
13. Cyclooxygenase (COX) is found
bound to the endoplasmatic
reticulum. It exists in 3 isoforms:
• COX-1 (constitutive) acts
in physiological conditions.
• COX-2 (inducible) is
induced in inflammatory cells
by pathological stimulus.
• COX-3 (in brain).
14. Essential of Medical Pharmacology – 5st
Ed. (2003)Essential of Medical Pharmacology – 5st
Ed. (2003)
19. Beneficial actions of NSAIDs due
to prostanoid synthesis inhibition
1. Analgesia
prevention of pain nerve ending sensitization
2. Antipyresis
connected with influence of thermoregulatory
centre in the hypothalamus
3. Antiinflammatory action
mainly antiexudative effect
4. Antithrombotic action
in very low daily doses
5. Closure of ductus arteriosus
20. Shared toxicities of NSAIDs due
to prostanoid synthesis inhibition
1. Gastric mucosal damage
connected with PGE inhibition
2. Bleeding: inhibition of platelet
function (TxA2 synthesis)
3. Limitation of renal blood flow
Na+
and water retention
4. Delay / prolongation of labour
connected with PGF2α inhibition
5. Asthma and anaphylactoid reactions
connected with PGF2α inhibition
21. Mechanisms by which NSAIDs may induce mucosal injury
Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
22. Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
23. Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
26. Effects of NSAIDs
1. Analgesic and antipyretic action
Aspirin is a weaker analgesic than morphine-type drugs
Aspirin 600 mg < Codeine 60 mg < 6 mg Morphine
Aspirin relieves inflammatory, tissue injury related,
onnective tissue and integumental pain but is rela-
vely ineffective in severe visceral and ischemic pain.
The analgesic action is mainly due to obtunding perip-
heral pain receptors and prevention of PG mediated
ensitization of nerve endings. A central subcortical
action, raising threshold to pain perception also contri-
butes. No sedation, tolerance, and dependence are produced.
27. Aspirin resets the hypothalamic thermostat and
rapidly reduces fever by promoting heat loss (swea-
ting, cutaneous vasodilation), but does not decrease
heat production.
2. Antiinflammatory action is exerted at high daily
doses of Aspirin (3 to 6 g). Clinical symptoms of inflam-
mation are suppressed, but prolongation of the under-
lying disease in rheumatoid arthritis, rheumatic fever,
and osteoarthritis is not affect.
3. Inhibition of platelet aggregation in low doses
(75–100 mg/24 h Aspirin).
4. Metabolic effects of Aspirin and other NSAIDs are
significant only at antiinflammatory doses. Cellular
metabolism is increased, especially in skeletal muscles,
due to uncoupling of oxidative phosphorylation as a
28. result of increased heat production. There is increased
utilization of glucose and blood sugar may
decrease (specially in diabetics) and liver glycogen
is depleted. However, hyperglycemia is often seen
at toxic doses: this is due to central sympathetic
stimulation and release of adrenaline and GCS. Chronic
use of large doses cause negative nitrogen balance by
increased conversion of protein to carbohydrate.
Plasma free fatty and cholesterol are reduced.
5. Respirations. At antiinflammatory doses respiration
is stimulated by peripheral (increased CO2 production)
and central (increased sensitivity of respiratory centre
to CO2) action. Hyperventilation is prominent in salicy-
late poisoning. Further raise in the salicylate level
causes respiratory depression and failure, and death.
29. 6. Acid-base and electrolyte balance. Antiinflammatory
doses produce significant changes. Initially respiratory
stimulation predominates and tends to wash out CO2
despite increased production and the result is respiratory
alkalosis, which is compensated by increased renal
excretion of HCO3
-
(with accompanying Na+
, K+
, and
water). Most adults treated with 4–6 g/daily of Aspirin
stay in a state of compensated respiratory alkalosis.
Still higher doses cause respiratory depression with
CO2 retention, while excess CO2 production continues
to develop respiratory acidosis. To this are added dis-
sociated salicylic acid as well as metabolic acid
(because there is rebound depression). It develops
uncompensated metabolic acidosis. Dehydration
occurs in poisoning due to increased water loss in urine.
30. 7. CVS. Larger doses of Aspirin increase cardiac output
to meet increased peripheral oxygen demand and
cause direct vasodilatation. Toxic doses depress vaso-
motor centre: BP falls. Because of increased
cardiac work as well as sodium and water retention,
CHF my develop if the heart reserves are low.
8. GIT. Aspirin and its metabolite salicylic acid irritate
gastric mucosa and cause epigastralgia, nausea, and
vomiting. In higher doses it also stimulates CTZ.
Aspirin (pKa 3.5) remains unionized and diffusible in
the acid gastric juice, but on entering the mucosal cell
(pH 7.1) it ionizes and becomes indiffusible. This
“ion trapping” in the gastric mucosal cell enhances
gastric toxicity.
31. Further, Aspirin partial contact with gastric mucosa
promotes local back diffusion of acid, respectively
focal necrosis of mucosal cells and capillaries,
acute ulcers, erosive gastritis, congestio, and
microscopic haemorrhages. The occult blood loss in
stools is increased with any dose of Aspirin, averaging
5 ml/24 h at antinflammatory doses.
Soluble Aspirin tablets containing calcium carbonat +
citric acid and other buffered preparations have less
gastric toxicity.
32. Alcohol increasis
GI toxicity of NSAIDs.
9. Urate excretion. Aspirin in high dose reduces renal
tubular excretion of urate (both substances are trans-
ported by the same mechanism).
33. Uses of Aspirin®
(Bayer, 1899)
As analgesic (300 to 600 mg during 6 to 8 h) for head-
ache, backache, pulled muscle, toothache, neuralgias.
As antipyretic in fever of any origin in the same
doses as for analglesia. However, paracetamol and
metamizole are safer, and generally preferred.
Acute rheumatic fever. Aspirin is the first drug of
choice. Other drugs substitute Aspirin only when it
fails or in severe cases. Antirheumatic doses are 75 to
100 mg/kg/24 h (resp. 4–6 g daily) in the first weeks.
Rheumatoid arthritis. Aspirin a dose of 3 to 5 g/24 h
after meal is effective in most cases. Since large
doses of Aspirin are poorly tolerated for a long time, the
new NSAIDs (diclofenac, ibuprofen, etc.) in depot
form are preferred.
34. Aspirin therapy in children with rheumatoid arthritis
has been found to raise serum concentration trans-
aminases, indicating liver damage. Most cases are
asymptomatic but it is potentially dangerous.
An association between salicylate therapy and
“Reye’s syndrome”, a rare form of hepatic
encephalopathy seen in children, having viral infection
(varicella, influenza), has been noted.
Aspirin should not be given to children under 15
years unless specifically indicated, e.g. for juvenile
arthritis (paracetamol is preferred).
Postmyocardial infarction and poststroke patients.
By inhibiting platelet aggregation in low doses (100 mg
daily) Aspirin decreases the incidence of reinfarction.
37. Drugs Result
Diuretics Decrease diuresis
Beta-blockers Decrease antihypertensive effect
ACE inhibitors Decrease antihypertensive effect
Anticoagulants Increase of GI bleeding
Sulfonylurea Increase hypoglycemic risk
Cyclosporine Increase nephrotoxicity
GCS Increase of GI bleeding
Alcohol Increase of GI bleeding
Drug interactions with NSAIDs
38. Ibuprofen is a derivative of phenylpropionic acid.
In doses of 2.4 g daily it is is equivalent to 4 g
of Aspirin in anti-inflammatory effect. Oral ibuprofen is
often prescribed in lower doses (< 2.4 g/d), at which
it has analgesic but not antiinflammatory efficacy.
It is available in low dose forms under several trade
names (e. g. Nurofen®
– film-tabl. 400 mg). A topical
cream preparation is absorbed into fascia and muscle.
A liquid gel preparation of ibuprofen provides
prompt relief in postsurgical dental pain. In comparison
with indometacin, ibuprofen decreases urine
output less and also causes less fluid retention. It is
effective in closing ductus arteriosus in preterm infants,
with much the same efficacy as indometacin.
40. Flurbiprofen is a propionic acid derivative with a
possibly more complex mechanism of action than
other NSAIDs. Its (S)(-) enantiomer inhibits COX
nonselectively, but it has been shown in rat tissue to
also affect TNF-α and NO synthesis. Hepatic
metabolism is extensive. It does demonstrate
enterohepatic circulation. The efficacy of
flurbiprofen at dosages of 200–400 mg/d is compa-
rable to that of Aspirin and other NSAIDs for patients
with rheumatoid arthritis, ankylosing spondylitis,
gout, and osteoarthritis. Flurbiprofen i.v. is effective
for perioperative analgesia in minor ear, neck, and
nose surgery and in lozenge form for sore throat.
Its adverse effect profile is similar to other NSAIDs.
41. Ketoprofen is a propionic acid derivative that
inhibits both COX (nonselectively) and lipoxygenase.
Concurrent administration of probenecid elevates
ketoprofen levels and prolongs its plasma half-life.
The effectiveness of ketoprofen at dosages of
100–300 mg/d is equivalent to that of other NSAIDs
in the treatment of rheumatoid arthritis, osteoarthritis,
gout, dysmenorrhea, and other painful conditions.
In spite of its dual effect on prostaglandins and
leukotrienes, ketoprofen is not superior to other
NSAIDs. Its major adverse effects are on the GIT
and the CNS.
Phenylbutazone is a derivative of pyrazolidinedione
with a high GI toxicity. It is rarely used now.
42. Indometacin is a potent nonselective COX inhibitor
and may also inhibit phospholipase A and C, reduce
neutrophil migration, and decrease T cell and B cell
proliferation. Probenecid prolongs indometacin's
half-life by inhibiting both renal and biliary clearance.
Indometacin is indicated for use in juvenile rheumatoid
arthritis, gout and ankylosing spondylitis, postepisio-
tomy pain, etc. It has been used to treat patent ductus
arteriosus. An ophthalmic preparation seems to be
efficacious for conjunctival inflammation and to reduce
pain after traumatic corneal abrasion. Gingival
inflammation is reduced after administration of
indometacin oral rinse. A high incidence (up to 50%)
of GI and CNS side effects is produced: GI bleeding,
diarrhoea, frontal headache, mental confusion, etc.
43. Diclofenac is a phenylacetic acid derivative.
A 0.1% ophthalmic preparation is recommended for
prevention of postoperative ophthalmic inflammation
and can be used after intraocular lens implantation
and strabismus surgery. A topical gel containing
3% diclofenac is effective for solar keratoses.
Diclofenac in rectal suppository form can be
considered a drug of choice for
analgesia and postoperative nausea. It is also
available for intramuscular and oral administration
(Voltaren®
and Feloran®
– SR tablet: 100 mg/24 h).
Side effects occur in approximately 20%: GI distress
and occult bleeding, gastric ulceration. A preparation
combining diclofenac and misoprostol (PGE1) decrea-
ses upper GI ulceration but may result in diarrhoea.
44. Piroxicam, an oxicam (enolate derivative), is a
nonselective COX-1/COX-2 inhibitor that at high
concentrations also inhibits polymorphonuclear
leukocyte migration, decreases oxygen radical
production, and inhibits lymphocyte function.
Its long half-life permits once-daily dosing.
Piroxicam can be used for the usual rheumatic
indications. Toxicity includes GI symptoms (20%
of patients), dizziness, tinnitus, headache, rash.
When piroxicam is used in dosages higher than
20 mg/d, an increased incidence of peptic ulcer
and bleeding is encountered. This risk is as much as
10 times higher with piroxicam than with other NSAIDs.
47. Coxibs are selective COX-2 inhibitors. They exert
antiinflammatory, analgesic, and antipyretic action
with low ulcerogenic potential. Coxibs can cause
infertility. They have prothrombotic cardiovascular
risk. The ulcerogenic potential of preferential
COX-2 inhibitors Meloxicam, Nabumetone, and
Nimesulide (Aulin®
) is significant.
Etoricoxib Parecoxib
48. Celecoxib is as effective as other NSAIDs in the
treatment of rheumatoid arthritis and osteoarthritis,
and in trials it has caused fewer endoscopic ulcers
than most other NSAIDs. Probably because it is
a sulfonamide, celecoxib may cause rashes.
It does not affect platelet aggregation at usual
doses. It interacts occasionally with warfarin –
would be expected of a drug metabolized
via CYP 2C9.
49. Etoricoxib is a second-generation COX-2-selective
inhibitor with the highest selectivity ratio of any coxibs.
It is extensively metabolized by hepatic CYP450 enzy-
mes followed by renal excretion and has an elimination
t1/2 of 22 h. Etoricoxib is approved in the UK for
the treatment of the symptoms of osteoarthritis (60 mg
once daily) and rheumatoid arthritis (90 mg once daily),
acute gouty arthritis (120 mg once daily), and for the
relief of acute musculoskeletal pain (60 mg once daily).
Ninety mg daily of etoricoxib has superior efficacy com-
pared with 500 mg of naproxen twice daily in the treat-
ment of rheumatoid arthritis over 12 weeks. Etoricoxib
has similar efficacy to traditional NSAIDs for osteo-
arthritis, acute gouty arthritis, and primary dysmenor-
rhea and has a GI safety profile similar to other coxibs.
50. Meloxicam is an enolcarboxamide related to
piroxicam that has been shown to preferentially
inhibit COX-2 over COX-1, particularly at its lowest
therapeutic dose of 7.5 mg/d. It is not as selective
as the other coxibs and may be considered “
preferentially" selective rather than
“highly” selective.
The drug has been approved for the treatment
of osteoarthritis and rheumatoid arthritis.
It is associated with fewer clinical GI
symptoms and complications than piroxicam,
diclofenac, and naproxen. Other toxicities are
similar to those of other NSAIDs.
55. Acetaminophen (USAN)
(Paracetamol – INN)
•Efferalgan®
•Panadol®
•ParacetaMAX®
Propacetamol is a prodrug.
It converts into paracetamol.
Acetylsalicylic acid
•Aspirin®
•Aspegic®
lisinate
Dipyrione (BAN)
(Metamizole – INN)
•Analgin®
•Proalgin®
Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
Lüllmann, Color Atlas of Pharmacology – 2nd
Ed. (2000)
56. Paracetamol Although equivalent to
Aspirin as an effective analgesic and antipyretic
agent, paracetamol differs in that it lacks antiinflam-
matory properties. It does not affect uric acid levels
and lacks platelet-inhibiting properties. The drug is
useful in mild to moderate pain: headache, myalgia,
postpartum pain. Paracetamol alone is inadequate
therapy for inflammatory conditions such as rheuma-
toid arthritis, although it may be used as an analgesic
adjunct to antiinflammatory therapy. For mild analge-
sia, paracetamol is the preferred drug in patients aller-
gic to Aspirin or when salicylates are poorly tolerated.
It is preferable to Aspirin in patients with hemophilia
or a history of peptic ulcer and bronchospasm. It
is preferred to Aspirin in children with viral infections.
57. Acute paracetamol poisoning occurs especially in
small children who have low hepatic glucuronide conjugating
ability. If a large dose (> 150 mg/kg or > 10 g in adult)
is taken, serious toxicity can occur. The letal dose is 250 mg/kg.
N-acetyl-p-benzoquinoneimine (NABQI) is a highly
reactive arylating metabolite of paracetamol which detoxicated
by conjugation with glutathione. When a very large doses
of paracetamol are taken, the glucuroconjugation capacity is
saturated, more NABQI is formed, hepatic glutathione is
depleted and NABQI binds covalently to proteins in liver
cells (and renal tubules) causing necrosis. In chronic alcoholics
even 5-6 g/d taken for a few days can result in hepatotoxicity
because ethanol induces CYP 2E2, that metabolizes
paracetamol, to NABQI. Treatment needs activated
charcoal, given orally or through the tube to prevent GI
absorption, and acetylcysteine (150 mg/g by i.v. infusion).
59. Rang et al. Pharmacology – 6th Ed. (2007)Rang et al. Pharmacology – 6th Ed. (2007)
60. Metamizole (Analgin®
– tabl. 500 mg, Dipyron)
s a derivative of pyrazolone. It is a potent and
promptly acting analgesic, antipyretic, and
spasmolytic but has poor antiinflammatory
and not uricosuric activity. Analgin can be given
orally, i.m. as well as i.v. (very slowly).
Pain at the i.m. injection site and rarely
abscess can occur. Occasionally an i.v. injection
produces fall in BP. Few cases of agranulocytosis
were reported and metamizole was banned in the
USA and some European country. However, it has
been extensively used in Bulgaria and many other
European country, as well as in India and Russia.
Adverse reaction data collected over four decades
shows that the risk of serious toxicity with metamizole is
very low than with Aspirin or many other NSAIDs.
61. Pathophysiologic events in a gouty joint
Synoviocytes phagocytose urate crystals and then secrete
inflammatory mediators, which attract and activate polymor-
phonuclear leukocytes (PMN) and mononuclear phagocytes
(MNP) (macrophages). Drugs active in gout inhibit crystal
phagocytosis and polymorphonuclear leukocyte and macro-
phage release of inflammatory mediators.
(PG – prostaglandin; IL-1 – interleukin-1; LTB4 – leukotriene B4)
GOUT
Basic & Clinical Pharmacology – 10th
Ed. (2007)