NSAIDs work by inhibiting the biosynthesis of prostanoids like prostaglandins and thromboxane by blocking the cyclooxygenase (COX) enzyme. Aspirin is a non-selective NSAID that irreversibly inhibits both COX-1 and COX-2 isoforms, reducing inflammation and pain. It is used for conditions like arthritis but can cause gastrointestinal adverse effects. Newer selective COX-2 inhibitors have fewer gastrointestinal side effects.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
This ppt discusses pharmacological actions, toxic effects and clinical applications of corticosteroids. It also mentions precations to be taken while using steroids
Introduction to CNS Pharmacology, with Anatomy and physiology of CNS, mode of neuro-transmission via action potential and role of major neurotransmitter in the brain with drug design pharmacology of CNS drugs.
Carbon 14 and archeological ages, Christian and Intelligent Design discussion of source, measurement, results, interpretation, and errors in Carbon-14 dating.
5-Hydroxytryptamine & it’s Antagonist is a Topic in Pharmacology which will defiantly Help You in pharmacy field All information is related to pharmacology drug acting and it's effect on body. it is collage project given by our department i would like to share with you.
This ppt discusses pharmacological actions, toxic effects and clinical applications of corticosteroids. It also mentions precations to be taken while using steroids
Introduction to CNS Pharmacology, with Anatomy and physiology of CNS, mode of neuro-transmission via action potential and role of major neurotransmitter in the brain with drug design pharmacology of CNS drugs.
Carbon 14 and archeological ages, Christian and Intelligent Design discussion of source, measurement, results, interpretation, and errors in Carbon-14 dating.
Tetracyclines slide contains full information about uses, adverse effect, marketed preparation, precaution, route of drug administration, antimicrobial spectrum, mechanism of action, pharmacokineticks and pharmacodynamics of tetracyclines. This slide is very helpful for pharmacy and pharmacology student for the study about tetracyclines.
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
Anti-inflammatory drugs
Inflammation is a normal, protective response to tissue injury caused by physical trauma, noxious chemicals, or microbiologic agents. Inflammation is the body's effort to inactivate or destroy invading organisms, remove irritants, and set the stage for tissue repair. When healing is complete, the inflammatory process usually subsides.
However, inflammation is sometimes inappropriately triggered by an innocuous agent, such as pollen, or by an autoimmune response, as in asthma or rheumatoid arthritis. Inflammation is triggered by the release of chemical mediators from injured tissues and migrating cells and include amines, such as histamine and 5-hydroxytryptamine; lipids, such as the prostaglandins; small peptides, such as bradykinin; and larger peptides, such as interleukin-l.
Complete pharmacology of Non steroidal Anti inflammatory Drugs, classification, Mechanism of action, Pharmacological actions, Indications, Contraindications, Adverse effects
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.
9. NSAIDS.pptxNSAIDS inhibit the enzyme cyclooxygenase (COX) types 1 and 2, w...samiyamohammed284
Renal
Renally produced prostaglandins (PGE2 and PGI2) are essential
in maintaining adequate renal perfusion when the level of circulating vasoconstrictors Platelets
Impaired platelet function (reduced aggregation).
as a result of decreased thromboxane A2 (TXA2) production.
TXA2 is present in large amounts in activated platelets and acts locally as a chemo-attractant for other platelets, leads to the formation of a platelet plug and induces localized vasoconstric
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
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.
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.
3. Inflammation
It is a non-specific manifestation of many diseases.
Acute
Chronic
Anti-inflammatory drugs are extensively used.
3
4. Non steroidal Anti- inflammatory drugs
(NSAIDs) mainly produce their effects by
inhibiting the biosynthesis of
Prostanoids
Prostaglandins , Thromboxane A2
& Prostacyclin.
4
9. Arachidonic acid is the primary precursor of prostanoids
Prostanoids are also called ‘Eicosanoids’
Arachidonic acid is a component of the phospholipids of
cell membrane.
Free Arachidonic acid is released by cell damage mainly
by the action of Phospholipase A2 enzyme.
Arachidonic acid undergoes 2 pathways, by the enzymes
Cyclooxygenase & Lipooxygenase,
Biosynthesis of Prostanoids: 9
11. Inhibition of cyclooxygenase enzyme & reduced
biosynthesis of Prostanoids
(Prostaglandins Prostacyclin ,Thromboxane A2)
Aspirin & older non-selective NSAIDs reduce
biosynthesis of Prostanoids by inhibiting both
isoforms of the Cyclooxygenase (COX) enzyme
(COX-1& COX-2)
MOA of ASPIRIN / NSAIDs
11
12. COX-1
It is responsible for the Physiologic production of
prostanoids.
It is “House keeping “enzyme that regulates the
normal cellular processes (via production of PGs)
such as
Gastric cytoprotection
Vascular homeostasis
Platelet aggregation
Kidney function.
12
13. COX-2
It is constitutively expressed only in brain, kidney & bone
Its expression at other sites is increased in inflammation.
It is responsible for the elevated production of prostanoids
in inflammation & disease.
The selective COX-2 inhibitors have been synthesized.
Its expression is inhibited by Glucocorticoids
COX-3 more effects in CNS
13
14. Aspirin is unique, it acetylates , & irreversibly inhibits the
enzymes, all other drugs produce reversible inhibition
There is ↓ PGs & Thromboxane synthesis throughout the body.
Release of PGs for inflammation as well as for homeostatic
function is disrupted (specially cytoprotection in gastric mucosa
& auto regulation of renal function)
Newer drugs, coxibs are COX2 selective inhibitors .
14
20. ASPIRIN
Chemistry: Aspirin is Acetyl salicylic Acid.
Pharmacokinetics of Aspirin:
Absorption: Well from stomach & upper small intestine
Distribution: wide , crosses placental barrier
PPL: In 1-2hrs. t1/2: 15 min.
Metabolism: Rapid hydrolysis by Esterases in blood & tissues in to
Salicylate & Acetic Acid.
Salicylate is 80-90-% PPB
20
21. Salicylate is metabolized in liver into:
1.Salicyluric acid (glycine conjugate)
2.Glucuronide conjugate
3. Gentisic acid
21
23. MOA of ASPIRIN / NSAIDs
As Anti-inflammatory:
Aspirin irreversibly acetylates both isoforms of cyclooxygenase
enzyme , COX-1 & COX-2 & inactivates them. So it inhibits
biosynthesis of PGs which, primarily modulates those aspects of
inflammation in which PGs act as mediators.
Aspirin inhibits inflammation in Rheumatoid Arthritis but it neither
arrests the progress of disease nor it induces remission.
Other NSAIDs reversibly inhibit cyclooxygenase enzyme .
23
24. As Analgesic:
1. Aspirin & Other NSAIDs inhibit cyclo-oxygenase enzyme ,
reduce production of PGs in injured tissue.
PGE2 is thought to sensitize the nerve ending
(pain receptors)to action of bradykinin , Histamine & other
mediators released by the inflammatory process.
So due to reduced production of PGE2 , they repress the sensation of pain.
2. Inhibit pain stimuli at subcortical sites --Thalamus & Hypothalamus.
24
25. As Antipyretic:
Aspirin lowers raised body temperature , no effect on normal
temperature
Fever occurs when the set point of the thermoregulatory
center in anterior hypothalamus is elevated.
This may be due to PGE2 synthesis , stimulated by pyrogen such as
cytokine.
Cytokine is released from WBCs, activated by infection, malignancy
or inflammation.
Because of inhibition of PGE2 synthesis , the thermostat is reset
towards normal. & rapidly lowers body temperature by increasing
heat dissipation due to peripheral vasodilation & sweating.
25
26. AS Antiplatelet:
TXA2 normally promotes platelet aggregation. prostacyclin –PGI 2
normally inhibit platelet aggregation.
In low doses Inhibit Platelet Aggregation due to irreversible
acetylation of COX-1 enzyme in platelets.
Low doses 81-100mg/ d inhibit TXA2 synthesis in platelets , higher
doses inhibit prostacyclin –PGI2 also.
Platelet aggregations is the first step in coagulation so it prevents
coagulation & prolongs bleeding time .
The action lasts for 3-8 days -- life span of platelets, because they
lack nuclei & can’t synthesize new enzyme.
Aspirin should be stopped 7-10 prior to operations, to avoid risk of
bleeding.
26
27. Therapeutics Uses of Aspirin/ NSAIDS
1. Analgesic :
a. used alone in pain like.
: Headache, Myalgia, Arthralgia, Neuralgia
osteomyelitis, osteoarthritis. Toothache, Dysmenorhoea
b. With opioids – synergistic action
In pain of cancer metastases in bone
Post operative pain- requirement of opioids.
27
28. 2. Anti pyretic :↓ body temp in fever
Not effective in raised body temp. due to heat stroke or malignancy.
Does not lower normal body temp .
3. Acute rheumatic fever :Both for antipyretic & anti-inflammatory
effects.
4. Rheumatoid Arthritis, Osteoarthritis:
To control symptoms.
No effect on progression of disease.
Does not induce remission.
28
29. 5. Anti Platelet :
Aspirin is used prophylactically :
For primary & secondary prevention (In Post myocardial
infarction & post stroke patients) of :
Transient ischemic attacks & stroke.
Unstable angina
Coronary artery thrombosis & Myocardial infarction.
To prevent Thrombosis after coronary artery bypass grafting.
29
30. 6. In Bartter’s syndrome:
There is defect in tubular transport of K---Hypokalemia----PG
synthesis stimulated---Increased Renin---
Hyperaldosteronism.
Aspirin prevents this secondary Hyperaldosteronism due to
inhibition of PG synthesis .
30
31. 7.Chemoprophylaxis of cancer of colon .50% decrease with
frequent use of aspirin
8.Closure of PDA . As PGs keep patency of Ductus arteriosus.
9. Diarrhea after Radiation & Cholera in which PGs are implicated.
10.Prophylaxis of Cataract: some studies indicate decrease in
incidence of cataract with frequent use of aspirin.
11. With Niacin to improve compliance because Aspirin ↓ flushing,
which is an A/E of Niacin due to PGs.
31
32. Dosage of Aspirin:
3 therapeutic dose ranges:
1. Low range<300mg/d(81, 100mg) as single dose --to↓ Platelet
Aggregation
2. Intermediate dose :300-2400mg/d as 3 divided doses) Analgesic,
Antipyretic.
3. High dose : 2400- 4000mg/d– as 3 divided doses --for Anti-
Inflammatory effect.
32
33. Adverse Effects of Aspirin
At therapeutic doses
1. Gastric Intolerance:
The most common & serious is gastritis, Gastric
ulceration or Exacerbation of Peptic ulcer
symptoms.
Dyspepsia & Heart burn , Abdominal Pain .
Nausea & Vomiting, Hematemesis
Fecal blood loss
Iron deficiency Anemia
33
34. To decrease gastric intolerance:
Aspirin may be given with Misoprostol.
Addition of Proton pump inhibitors with Aspirin.
H2 Blockers, if aspirin has been stopped
Use of Special Prep. Of Aspirin: only marginally
effective
Aloxiprin (Enteric coated aspirin)
Buffered Aspirin
34
36. 5. Decreased renal function:
Normally PGE2 & PGI2are responsible for maintaining
renal flow specially in presence of circulating
vasoconstrictors.
Inhibition of PGs synthesis may produce:
Retention of Sodium & water
Edema
Hyperkalemia.
Interstitial nephritis with other NSAIDs , but not Aspirin
36
38. 6.Effects on Respiration:
In high doses– stimulation of Respiratory Center—hyperventilation–
respiratory alkalosis—compensated by kidney------ compensated
respiratory alkalosis
In toxic doses respiratory depression & a combination of
uncompensated respiratory & metabolic acidosis .
38
39. 7. Effects on CNS:
In large doses: Salicylism--- Vomiting ,tinnitus,
↓ hearing ,vertigo.
In Toxic Doses :Stimulation of CNS including convulsions ,followed by
depression.
Repiratory depression
Cardiotoxicity
Hyperpyrexia because salicylates uncouple the oxidative
phosphorylation. The energy normally used for production of ATP
is dissipated as heat .
39
40. 8. ↑ Risk of Reye’s syndrome:
Aspirin & other salicylates given in viral infection in young children
have been associated with an ↑ incidence of Reye’s syndrome.
In Reye’s syndrome there is fulminating hepatitis ,with cerebral
edema which may be fatal.
So Acetaminophen or Ibuprofen should be used instead of
Aspirin.
40
41. In pregnancy & during lactation:
Avoid in pregnancy & lactation
Aspirin & salicylates cross placental barrier & are secreted in breast
milk.
41
42. 10. Drug Interactions:
Corticosteroids ,other NSAIDs: ↑ GIT A/E.
With ACE inhibitors. ↓ Antihypertensive effect
With Warfarin or Heparin : ↑ GIT bleed.
With Probenecid & sufinpyrazone:
Aspirin antagonizes uricosuric action of Probenecid &
sufinpyrazone , as it inhibits tubular secretion of uric acid (in low
doses—< 2g/d). So C/I in Gout in low doses.
42
43. Displacement of PPB drugs:
As aspirin is 90-95 % PPB Aspirin can displace many drugs from
PPB sites , ie Warfarin , Phenytoin , Valproic acid ,
Sulfonylureas, Methotrexate , Indomathacin , Naproxen ,
Ketoprofen, Fenoprofen & Bilirubin ----Increased level of free
drugs/ Bilirubin– toxicity.
Aspirin ↓ diuretic action of Fursemide, Thiazides,
Spironolactone.
Aspirin blocks the active transport of Penicillin from CSF to
blood.
43
44. Contraindications / Precautions:
Peptic ulcer.
Hemophilia.
Aspirin hypersensitivity
Children with a viral illness.
Chronic liver disease.
Aspirin should be stopped one week before elective surgery.
Avoid high doses in G-6-PD deficient.
Avoid in pregnancy & lactation
Consider drug interactions.
44
45. Management of Aspirin/Salicylate Overdose
toxicity/Poisoning
Aspirin/Salicylate poisoning is a medical emergency, &
death may result.
There is no antidote.
Management begins with rapid assessment, followed
by
A(airway),B(breathing), C(circulation),
D(decontamination) approach.
Gastric Lavage , Activated Charcoal to prevent further
absorption, specially if enteric coated tablets have
been used
Measurement of serum salicylate level & pH
Correct fluid, electrolyte & acid base balance.
Maintain high urine out put.
Keep airway patent.
Lower body temperature by cold sponging.
45
46. Vit. K I/V to correct hypopthrombinemia.
Diazepam I/V for convulsions.
Promote excretion by NaHCO3 I/V to alkalinize
urine, maintain pH at 8.o.
Hemodialysis /Peritoneal dialysis in severe
acidosis & coma.
Ventilatory assistance in severe cases.
46
47. Topically used salicylates:
Methyl salicylate: As counter irritant
Salicylic acid :Topically on skin for corns ,warts
Salfasalazine , Mesalamine --- suppository & rectal
suspension enema in Inflammatory bowel disease.
47
49. Therapeutic uses:
1. Mild to moderate pain like Aspirin
2. Antipyretic
Preferred to Aspirin
In children with viral infections
In pt. with Peptic ulcer, Hemophilia
Pt. allergic to Aspirin.
Concomitantly with Probenecid & sulfinpyrazone in patients of
gout.
49
50. Pharmacokinetics of Acetoaminophen
Rapid absorption from GIT.
Significant First pass metabolism in gut wall & liver.
When given in doses up to 0.5-4g/d:
90-95% metabolized to inactive glucuronide & sulphate conjugates
which are excreted in urine.
5-10 % hydroxylated to form N- Acetyl=p benzoquinoneimine
50
51. N- Acetyl-p benzoquinoneimine is a highly reactive
metabolite which reacts with sulhydral groups.
Normally it reacts with sulhydral group Of Glutathion & forms
a non-toxic substance.
At doses above 4g/d Glutathion reserves are depleted & it can
produce toxicity– Hepatic necrosis & Renal tubular necrosis.
51
52. Toxicity: At therapeutic doses
Rash & Allergic reactions.
Drug fever.
Mild increase in hepatic enzymes.
With over dosage:
Doses above 4g may be toxic.
15g may be fatal due to metabolite N-Acetylbenzoiminoquinone which
produces:
Hepatic necrosis--- potentially fatal
Renal tubular necrosis---may occur
Hypoglycemic coma --may occur
52
54. Management of Acetoaminophen toxicity:
It constitutes a medical emergency, early diagnosis & treatment is
required.
Activated Charcoal to prevent further absorption.
Correct fluid, electrolyte & acid base balance
Antidote--N-Acetylsysteine by I/V infusion.
It provide SH-groups to neutralize the toxic metabolite.
It is life saving if given within 10 hrs of overdose.
Avoid in severe hepatic impairment.
54
55. Prevention of toxicity:
Base line & periodic estimation of hepatic enzymes
should be undertaken in patients on high dose
acetoaminophen.
55
56. B: Selective COX-2 Inhibitors (Coxibs)
Prototype—Celecoxib : A Sulfonamide
MOA: Celecoxib is 10-20 times more selective in inhibiting COX-2 than COX-
1.
COX-2
It is constitutively expressed only in brain, kidney & bone .
Its expression at other sites is increased in inflammation.
It is responsible for the elevated production of prostanoids in inflammation &
disease.
It has larger & more flexible substrate channel than COX-I .
& a large space where the Celecoxib binds..
Its expression is inhibited by Glucocorticoids
56
57. MOA of Celecoxib--- conti
Arachidonic acid is the primary precursor of Prostaglandins,
is a component of the phospholipids of cell membrane.
Free Arachidonic acid is released by cell damage mainly by
the action of Phospholipase A2 enzyme.
Arachidonic acid is converted to prostaglandins at site of
inflammation by Cyclo-oxygenase-2 (COX 2) enzyme.
It reduces PG synthesis by selectively inhibiting COX-2
enzyme induced at sites of inflammation without affecting the
actions of COX-1--- gastric cytoprotection & platelet
aggregation
Inhibition of COX-2 enzyme is time dependent & reversible.
57
60. Pharmacologic Effects :
Analgesic
Antipyretic
Anti-inflammatory effects
No inhibition of platelet aggregation. Does not
prolong bleeding time.
No inhibition of protective gastric PGs--- No gastric
irritation.
60
61. PhK:
Long half life: 11 hrs– Once or twice daily dose.
Metabolized by CYP2C9.
Excreted in feces & urine.
Can inhibit CYP2D6
Dose adjustment in hepatic dysfunction
61
62. Therapeutic uses:
Specially useful in osteoarithritis & Rheumatoid Arthritis.
Useful in Dysmenorrhea, acute gouty arthritis, acute
musculoskeletal pain & ankylosing spondylitis
Also used in Primary familial adenomatus polyposis.
Useful in patients undergoing bone repair / operation.
62
63. A/E:
Potential for increasing thrombotic events– --------Myocardial
infarction & stroke, specially in cases of Rheumatoid Arthritis Who are
at risk of myocardial infarction.
Selective COX-2 inhibitors depress PGI2 formation by endothelial cells,
without concomitant inhibition of platelets TXA2. PGI2 restrains the effects
of TXA2 on CVS, so selective COX-2 inhibitors increase the risk of
thrombosis.
Renal toxicities similar to non selective NSAIDs: depressed renal
function, edema , Hypertension.
Less GIT A/E (mediated by inhibition of COX-1)
Skin rash---because it is a Sulfonamide
63
64. D/I:
Inhibitors of CYP2C9-- Fluconazole , Fluvastatin ,& Zafirlukast may
increase the serum levels of Celecoxib
Celecoxib can inhibit CYP2D6--- may increase the serum levels of
Beta blockers , Antidepressants & Antipsychotic drugs
64
65. C/I:
Sulfonamide allergy
Anaphylactoid reaction with Aspirin.
Hepatic dysfunction.
Severe renal insufficiency
Severe heart disease
Volume depletion
65
66. Meloxicam: Related to Piroxicam. Preferentially selective COX-2
inhibitor.
Etoricoxib: Resembles diclofenac
Monitoring of hepatic functions required.
Long half life: 22 hrs
Nimesulide: new compound less gastric irritation.
Valdecoxib & Rofecoxib
Withdrawn due to. higher risk of incidence of Cardiovascular
thrombotic events----Myocardial Infarction & stroke.
66
68. Acetic Acid Derivatives
Phenylacetic acid derivative: Diclofenac , Tolmetin , ketorolac
Indomethacin , Etodolac , Sulnidac
Diclofenac: Very commonly used NSAID.
MOA: Non-selective COX inhibitor.
Good anti- inflammatory.
More potent than Indomethacin & Naproxen.
Accumulates in synovial fluid .
Drug & its metabolites are eliminated via kidney.
t1/2 --- 1.1 hrs
A/E: Nephrotoxic– Impaired renal blood flow & GF, fluid retention and
edema
Less Gastric irritation
↑ Liver enzymes
68
69. Uses & dosage forms
Diclofenac is used for long term use in Rheumatoid arthritis ,Osteoarthritis , &
Ankylosing spondylitis.
Also for short term treatment of Dysmenorhea, post operative pain, acute
musculoskeletal disorders.
Oral tablets , capsules, intramuscular Injection
Also available in combination with misoprostol & omeprazole.
Prevention of postoperative ophthalmic inflammation after intraocular lens implantation
& strabismus surgery: 1% Eye drops
Solar keratoses: 3% gel
Choice for analgesia with nausea -- rectal suppository.
Oral mouthwash.
69
70. Etodolac:
10 times more selective Cox-2 inhibitor.
Good for post-operative relief after coronary artery bypass operation.
Less gastric intolerance.
70
71. Indomethacin: Indole derivative.
Potent non selective COX inhibitor.
May also inhibit Phospholipase- A2 & C.
↓ neutrophils migration also ↓ T & B cell proliferation.
Th. Uses:
Gout, ankylosing spondylitis, PDA.
Conjunctival & gingival inflammation.
Postlaminectomy syndrome-- epidural inj.
71
72. A/E of Indomethacin:
More GIT A/E & Pancrentitis
Headache, Dizziness confusion & Depression.
Rare: Thrombocytopenia , Aplstic anemia.
Psychosis with hallucination
Hepatic abnormalities.
Renal papillary necrosis.
Tolmetin: Ineffective in gout
A/E: Thrombocytopenia.
72
73. Ketorolac:
Mainly Analgesic.Not anti-inflammatory
Can replace Morphine in post surgical pain .
More Nephrotoxic on chronic use
Sulnidac: Sulfoxide prodrug, undergoes, EHC.
DOA: 12-16 hrs.
Suppresses familial polyposis, ↓ incidence of cancer colon , breast &
prostate.
A/E: Serious
Stevens Johnsons syndrome
Nephrotic syndrome
Agranulocytosis
Hepatic toxicity.
73
74. Oxicams ( Enolic acids) : Piroxicam ,Tenoxicam
Piroxicam (Feldene): Oxicam derivative.
MOA: Non-selective Cox inhibitors
Inhibition of chemotaxis migration of polys & macrophages , Inhibits
lymphocyte function.
↓ O2 radical production.
Long t ½ - once daily dosage.
Metabolized in liver-
A/E: peptic ulcer & bleeding (at higher dose > 20 mg/d ) 9.5 times higher
than other NSAIDs.
74
76. Drugs with Analgesic & mild to moderate
anti-inflammatory effect
Propionic acid derivatives:
Ibuprofen – prototype
MOA: Like Aspirin– Non-selective COX inhibitor & also inhibits leukocyte
migration.
Good anti- inflammatory.
2400 mg = 4 g of aspirin. t ½ : 2 hrs
More effective in closure of PDA
76
77. Preparations & Uses Oral tablet, liquid , I/V : For Anti-rheumatoid
effects
For closure of PDA in pre-term infants.
Topical cream for Osteoarthritis , liquid gel for post surgical dental
pain.
A/E: Like other NSAIDs
Less Gastric irritation
Nephrotoxic —Ac. renal failure , Interstitial nephritis. Nephrotic
syndrome.
Aseptic meningitis in SLE patients
Interaction with anticoagulant uncommon.
Rare agranulocytosis & aplastic anaemia
77
78. Flurbiprofen: Non-selective COX inhibitors & also inhibits TNF-α& Nitric
oxide synthesis.
Given orally. Other preparation also available
Topical ophthalmic prep.– for inhibition of intraoperative miosis.
I/V for periopretive analgesia.
Lozenges for sore throat.
Additional A/E: cogwheel rigidity , ataxia , tremor & myoclonus.
Fenoprofen: A/E--interstitial nephritis
Ketoprofen: Also inhibits lipo-oxygenase, not superior to other NSAIDs.
78
79. Naproxen: More Toxic, rare allergic pneumonitis, vasculitis,
pseudoporphyria.
Oxaprozin: t ½: 50-60hrs. Has uricosuric effect
b. Fenamates
Mefenamic, Meclofenamic & Flufenamic acid:
Inhibit both COX & Phospholipase A2.
Have no advantages over other NSAIDs.
A/E: Severe diarrhea , inflammation of bowel , Hemolytic anemia.
79