Anti Inflammatory Drugs

ANALGESIC AND ANTIINFLAMMATORY DRUGS
PRESENTED BY S.MOHAMED ANSER II yr P.G

1
What is pain?
DEFINITION An unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage
ORAL MEDICINE BURKETS 11th EIDITION
INTRODUCTION
Algesia It is an ill-defined ,unpleasant sensation, usually evoked by an external or Internal noxious stimulus
Analgesic A drug that selectively relives pain by acting in the CNS or on peripheral pain mechanisms,without significantly altering consciousness
DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION
INFLAMMATION:
([[Latin]], ''inflamatio'', to set on fire)
DEFINITION: the local response of living tissues to injury due to any agent.
GENERAL PATHOLOGY- HARSH MOHAN
4 4
TYPES OF INFLAMMATION:
Depending upon the defense capacity of the host & duration of response, it is classified into ACUTE Short duration. Early c body reaction, Repair occurs immediaetly after reaction. Edema at the affected site. PMNs are main inflammatory cells. CHRONIC Longer duration. Stimulus persists for long duration. Characteristic feature is presence of lymphocytes, plasma cells & macrophages.
GENERAL PATHOLOGY- HARRSH MOHAN
5 5
MECHANISM OF INFLAMMATION
INTRODUCTION
Phospolipase A lipooxgynas e
Cyclooxygena se
GENERAL PHARMACOLOGY-MUNSON 4th EDITION
Classification of Analgesic & Anti-inflammatory drugs
Analgesic drugs divided in to two OPIOIDS AND NON-OPOIDS(NSAIDS)
Anti-inflammatory drugs divided in to two NSAIDS AND STERIODS
NON-STEROIDAL ANTIINFLAMMATORY DRUGS
CLASSIFICATION
Non-steriodal anti inflammatory drugs

Non selective cox inhibitors
Salicylates- aspirin,diflunisal Pyrazolone deravatives phenylbutazone, oxyphenbutazone Indole derivatives-indomethacin,sulindac Propionic acid deravatives Ibuprofen,naproxen Anthranillic acid deravativesmephenamic acid Aryl acetic acid deravatives diclofenac, Oxicam deravaties piroxicam,tenoxicam Pyrrolo pyrrole deravatives -- ketorolac
DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION 10
Preferential cox-2 inhibitors

Nimesulide,meloxicam
Selective cox-2 inhibitors

Celecoxib,rofecoxib,valedecoxib Analgesic-antipyretics with poor antiinflammatory action Paraaminophenol derivative-- paracetamol Pyrazolone deravaties metamizol,propiphenazone Benzoxazocine deravative nefopam
11
NSAIDS MECHANISM OF ACTION
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MEDICAL PHARMACOLOGY MUNSON 4TH EDITION
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MEDICAL PHARMACOLOGY MUNSON 4th EDITION
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THE SALICYLATES
ASPIRIN Asprin is acetylsalicyic acid It is one of the oldest analgesic antiinflammatory and antipyretic drug Aspirin was the first discovered member of the class of drugs known as nonsteroidal antiinflammatory drugs (NSAIDs) It inhibit the PG synthesis by inhibitng the enzyme cyclo-oxygenase
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PHARMACOLOGICAL ACTION
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ANALGESIA
ANTIPYRETIC ACTION
ANTI INFLAMMATORY ACTION
Good analgesic It relieves pain orginating from integumental structures like muscles,bone, joints
In fever ,it brings in to normal temperature By inhibiting pgs synthesis in the hypothalamus
Ineffective in visceral pain
At Higher Doses Of 46gm,Aspirin Act As An Anti Inflammatory Agent Signs Of Inflammation Like Tenderness, Sweilling All Suppressed
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DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION/ MUNSON
Respiration Production of co2 stimulates respiration It rate and depth of respiration
Acid base & Electrolytic
Cardiovascular Effects
Salicylates can cause retention of salt and water As well as acute reduction of renal function in patient with CHF,renal disease or hypovolmeia
Low Doses Of Aspirin ( 100mg) are cardioprotecti ve effects Higher doses (3g daily) circulating plasma volume it leads to cardiac out put and work
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GIT
BLOOD Inhibit the txa2 synthesis interferes with platelet aggregation Bleeding time is prolonged It decreases synthesis of clotting factors in liver(long term use)
Immunological Effects
Gastric mucosal damage Asprin gasritc secretion In acid ph of stomach salicylate remains unionised,adh ere to mucosa
Inhibition of antibodies production
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ADVERSE EFFECTS
peptic ulcer hepatic injury hypersensitivity Reyes syndrome(childr en below 12years) rare form of hepatic encephalopathy seen in children having viral infection has been noted
CONTRAINDICATION
DRUG INTRACTION
Aspirin increases toxicity of oral anticoagulants,h eparin,oral antidiabetics,phe nytoin,antiplatilet s drugs Aspirin induce sever GI bleeding when given with steroids,alcohol
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Chronic liver disease Diabetics Aspirin should be stooped 1 week before elective surgery Aspirin should be avoided by breast feeding mothers Avoided during preganancy
USES
DOSAGE
BRAND NAME
As analgesic
325-650mg/d 46hours Max 4g/day
TAB.ASPIRIN 350mg
As antipyretic
325-650mg/d 4-6 TAB.COLSPRIN hours 100,325,650mg As antiinflammatory 3-6 g/day, ECOSPIRIN doses 100,325,650 mg
Acute rheumatic fever
75-100mg/kg/day Also avaliable as i.v injection(biospiri n)
60-100mg/day postmyocardial infarction(antiplatele DRUG GUIDE CIMS- JULY 2010 t)
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Propionic Acid Derivative

IBUPROFEN Ibuprofen-was the first member of this class to be introduced in 1969 as a better alternative to aspirin. It inhibit pg synthesis,inhibit platelet functionprolong bleeding time antiiflammatory effects are lower than the high dose of aspirin
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PHAMACOLOGICAL ACTION
PHAMACOKINETICS
ADVERSE EFFECTS
Analgesic action
99% bound to plasma protein, undergoes hepatic Antipyretic action, metabolism
Ibuprofen thought to be better tolerated than aspirin
Gastric Antiinflammatory t is 2hours and discomfort, action lower than it can cross blood Nausea, vomiting, the aspirin high brain barrier, Induce asthma, dose placenta
23
Adult dosage
Analgesic & Antiinflammatory 200-400 mg every 4-6hrs;1.21.8 g/day in divided doses max 2.4 g/day Antipyretic 5-10mg/kg every 6hours(max 40mg/kg /day) Antiinflammatory 20-40mg/kg /day in 3-4 divided doses
Children dosage
Brand name
Brufen 200,400,600mg Ibugesic 100mg/5ml susp
CIMS-JULY 2010/K.D TRIPATHY
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Para-Amino Phenol Derivative
Paracetamol
The deethylated active metabolite of phenacetin Was introduced in the last cenctury but has come in to common use only since 1950 Action it has poor inhibition of PG ,Poor Ability To Cox In Presence Of Peroixide Which Is Synthesised At Inflammation Site Phamacokinetics Well abosorbed orally,only about 1/3 bound to plasma, plasma t1/2 is 2-3hours Effects after an oral dose last 3-5 hours
Good analgesic,antipyretic ,slight antiinflammatory action Action it not interfere with platelet function Gastric irritation is insignificant
Action
As antipyretic dose it is well tolerated and safe Adverse Nausea and rashes occur occasionally effect
26
Acute Paracetamol Poisioning

If a lagre dose (150mg/kg or 10g in an adult) Induce severe Hepatic toxicity In chronic alcoholics even 5-6 g/day taken for a few days can result in hepatotoxicity Early manifestation are just nausea,vomiting,liver tenderness,after 12-18 hrs hepatic necrosis and hypoglycaemia.jaundice started after 2days hepatic failure Management N-acetylcysteine (mucomix 200mg/ml inj in 1,2,5ml amps)150/mg/kg should be infused iv over 15mins , followed by next 20 hours 75mg/kg given orally 4-6 hours for 2-3days
GENERAL PHARMACOLOGY-GOODMAN-GILMAN 27
BRAND NAME
crocin(500mg,1000mg), metacin 500mg tab,125mg/5ml syrp Adult-10-15mg/kg every 4hours( max 5 doses in 4hours)
Adult Dosage
Children dosage
Age 1-3yr ;80-160mg,Age 4-8 yr; 240-320mg,Age9-12 yr 300600mg,;Infants 50mg

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CIMS-JULY 2010/DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION
Indole Derivatives
Indomethacin
It a potent anti-inflammatory, analgesic,antipyretic action It inhibit the pg synthesis and supresses neutrophil motillity It is well absorbed orally,rectal absorption is slow,90% bound to plasma protiens Plasma t1/2 is 2-5 hours It has excellent bioavaliability It partly metabolised in liver to inactive products and excreted by kidneys
GENRAL PHARMACOLOGY MUNSON 29
Dosage
Indometacin Pain and inflammation Adult 25mg tid,day For 5-7 days Child 1-2mg/kg/day in divided doses Max;3mg/kg/ day Available AS Capsule INDOCID 75mg (10cap rs.32.00) MICROCID 25mg, (10 cap-rs.23.oo)
CIMS-2010 JULY/DENTAL & GENERAL PHARMACOLOGY MUNSON
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Anthranilic Acid Derivative(fenemate)

Mephenamic acid;

An analgesic,antipyretic and antiinflammatory,which inhibit cox as well as antagnoises certain action of PGs Mephenamic acid exerts peripheral as well as central analgesic action Oral absorpion is slow but almost complete It is highly bound to plasma proteins Partly metabolized and excreted in urine as well as bile. Plasma t1/2 is 2-4hours Diarrhoea is the most important dose related side effect
Dosage
Mephenamic acid Adult Child Available As Meftal tablet 250mg ,500mg Suspension- 50mg/5ml (ponstan) Combination-mefanamic acid 500mg ,paracetamol 450mg (meftal forte)
Mild To Moderate 250 mg- 500 Pain mg tid Post-operative pain
25mg/kg daily in divided doses for up to 7 days
CIMS-JULY 2010 EDITION
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Aryl Acetic Acid Derivative

Diclofenac sodium It inhibits pg synthesis and has short lasting antiplatelet action Neutrophil chemotaxis and superoxide production at the inflammatory site are reduced It has good tissue penetrability and high concentration in synovial fluid-extended theraputic action in joints
Pharmacologica l action An analgesic antipyretic, antiinflammatory action are good
Pharmacokinetics
Adverse effects Gastric ulceration and bleeding are less common Generally mild Epigastric pain,nausea,hea dache Kidney damage is rare
It is well absorped orally,99%protien bound metabolised and excreted in urine and bile Plasma t1/2 is 2hours
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Dosage
Diclofenac
Pain and inflammation Post-operative pain
Adult
75-150 mg daily divided doses; max-150mg/day Or 75mg/3ml I.M O.D
Child
25mg/kg daily in divided doses for up to 7 days
Available As
Tab50,75,100 mg , Inj 75mg/3ml(voveran)
Rectal-75-150 Rectal; 1-2mg mg daily /kg /day in Max;150mg/day divided doses for max of 4days
CIMS-JULY2010/DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION 35
Oxicam derivatives
Piroxicam

It is a long acting potent NSAID with antiinflammatory action and good analgesic-antipyretic action It is a reversible inhibitor of cox;lowers PG concentration in synovial fluid and inhibits platelet aggregation prolong bleeding time . It also decrease the production of IgM rheuomatoid factor. Chemotaxis of leukocytes are reduced
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Pharmacological action
Good analgesic and antipyretic action Potent antiinflammatory action
Pharmacokinetics
Adverse effect
It is rapidly and completely absorbed 99% plasma protein bound Largely metabolised in liver;ecreted in urine Plasma t1/2 is long nearly 2 days
Common side effects are heart burn,nausea, and anorexia Less faecal blood loss than aspirin Edema also common
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Dosage
Piroxicam Adult Child Available As Capsule 10mg,20mgpirox, Dolonex Injection2mg/ml doloswift
pain and 20mg/day as a 10-15mg inflammaton single dose. dosess to be Followed by 10- taken once 30mg in single or daily Post divided dose operative pain 40mg/day for 2days-20mg/day for 1-2week
CIMS- JULY 2010 EDITION
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Pyrrolo-Pyrrole Derivative
Ketorolac

A novel NASID with potent analgesic and modest antiinflammatory activity In postoperative pain it has equalled the efficacy of morphine,but does not interact with opioid receptors and free of respiratory depressant It inhibits PG synthesis and is believed to relive pain by a peripheral mechanism
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Pharmacologica l action
Good analgesic Action Less antipyretic action Modest antiinflammatory action
Pharmacokinetics
Adverse effect
It rapidly absorbed after oral i.M administration It is highly bound to plasma protein excreted unchanged in urine Plasma t1/2 is 5-7 hours Metabolic pathway is glucuronidation
Nausea ,abdominal pain dyspepsia,ulcer ation ,loose stools,drowsine ss ,headache,fluid retention have been noted
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Dosage
Ketorolac Moderate to severe pain Adult Oral-10mg every 4-6hr, max;40 mg/day Max duration; 7 days Parenteral-60mg im as a single dose or 30mg i.V as a single dose max;120mg/day;max 2days Available As Tablet- ketorol 10mg (10tab-rs.32.0) Torolac 10mg tab Inj-30mg/ml
GENERAL PHARMACOLOGY MUNSON 4th EDITION
41
Preferential Cox-2 Inhibitors

Nimesulide This is newer NSAID is a relatively weak inhibitor of PG synthesis Selectively cox-2 inhibitor It action mainly by reduced generation of superoxide by neutrophils,inhibition of PAF synthesis and TNF release Recently several instances of fulminant hepatic failure have been associated with nimesulide and it has been with drawn in spain,finland,turkey;not been marketed in many countries like uk,usa,australia
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Pharmacologica Pharmacokinetics Adverse effects l action Analgesic and antipyretic action are good Short term inflammatory action Nimesulide metabolised completely absorbed orally 99% plasma protein bound, extensively metabolised and excreted in urine Plasma t1/2 of 2-5 hours Hepatic failure especially in children Heart burn,rashes,gast ric tolerability is better
43
Dosage
Nimuslide Adult Available As
Acute pain and postoperative pain
TAB-nise Oral-100mg bid 100mg (european union is susp-50mg/5ml limited to a max of 15 days) Rectal -200mg bid Topical-3% gel/cream tid for 7days -max;15 days
Acut traumatic tendinitis
Monogesic gel 10mg/1mg
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Selective Cox-2 Inhibitors

CELECOXIB Cox-2 inhibitor reduce whole body PGI2 production with out affecting platelet Txa2 synthesis Platelet aggregation in response to collogen exposure is intact and serum Txb2 levels were not reduced It is less ulcerogenic potential even in higher dose
Pharmacological action It exerts Analgesic action,antipyretic action and antiinflammatory action
Pharmacokinetics Celecoxib is slowly absorbed 97% plasma protein bound t1/2 is 11 hours
Adverse effects Tolerability of celecoxib is better than older nsaids,still abdominal pain, dyspepsia and mild diarrhoea are common
46
Dosage
Celecoxib Adult Available As
Pain and inflammation
100-200mg bid per day for 5-7days
Cap-celecap, coxib 100mg,200mg
CIMS-JULY 2010 EDITION
47
Benzoxazocine Derivative
Nefopam
It is a nonopoids analgesic which does not inhibit PG synthesis. In traumatic and postoperative pain,it acts rapidly with an efficacy approaching morphine,yet has no opioid actions Favourable results have been obtained in short lasting musculoskeletal pain not responding to other nonopoid analgesic Nefopam produces anticholinergic ,side effects, and nausea is often dose limiting
48
The mechanism of action of nefopam is not well understood, although inhibition of serotonin, dopamine and noradrenaline reuptake is thought to be involved in its analgesic effects Contraindicated in epileptics
DOSE 30-60 mg/day tid oral ;max 120mg/day 20 mg im 6 hourly Available as tablet 30mg,20mg in 1ml amp Brand name; nefomax tab 30mg
Drug Intraction With NSAIDS

Diuretics blockers ACE inhibitors Anticoagulant Sulonylureas Risk Of Hypoglycaemia
50
Diuresis Action
Antihypertensive effect Antihypertensive effect Risk Of G.I Bleeding
TOPICAL NSAID
PREPARATION DICLOFENAC 1% GEL IBUPROFEN 10% GEL NAPROXEN 10% GEL KETOPROFEN 2.5% GEL FLURBIPROFEN 5% GEL NIMESULIDE 1%GEL BRAND NAME VOVERAN EMULGEL,DICLONAC GEL RIBUFEN GEL NAPROSYN GEL NAPROSYN GEL FROBEN GEL NIMULID TRANS GEL,NIMEGESIC-T-GEL
PIROXICAM 0.5% GEL
DOLONEX GEL,MOVON GEL

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CHOICE OF NSAIDS
Mild to moderate pain with minimal inflammation Acute musculoskeletal, ostearthritic,injury associated pain Paracetamol,or low dose Ibuprofen A propionic acid derivative,diclofenac or rofecoxib
Gastric intolerance to Rofecoxib,celecoxib conventional NSAIDS and predisposed patient
Exacerbation of RMA, High dose of ankylosing aspirin,indomethacin,napr sondylitis,acute gout oxen,piroxicam Patient history of asthma nimesulide DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5 EDITION or anaphylactoid reaction
TH
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OPOIDS ANALGESIC
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INTRODUCTION
Opioids

Prototype: morphine Natural opioids occur in 2 places: 1) In the juice of the opium poppy (morphine and codeine) 2) As endogenous endorphins All other opioids are prepared from either morphine (semisynthetic opioids such as heroin) or they are synthesized from precursor compounds (synthetic opioids such as fentanyl)
GENERAL PHARMACOLOGY-GOODMAN-GILMANS 9th EDITION 54
Opioid receptors
Three Opioid Receptors Mu Kappa (k1 & k3) Delta Mu-Receptor: Two Types -1 -Located outside spinal cord ,Responsible for central interpretation of pain -2 -Located throughout CNS ,Responsible for respiratory depression, spinal analgesia, physical dependence, and euphoria
Kappa Receptor -- Only modest analgesia Mild respiratory depression Mild physical dependence Dysphoric effects Delta Receptor --It is unclear what deltas responsible for. Delta agonists show poor analgesia and little addictive potential May regulate mu receptor activity
GENERAL PHARMACOLOGY-GOODMAN-GILMANS 9th EDITION
56
Classification of opoids
Natural opium alkaloids -- morphine,codeine Semisynthetic opiates diacetylmorphine(heroin), pholcodeine Synthetic opioids -- pethidine(meperidine),fentanyl, tramadol,methadone
57
MORPHINE
Morphine is the principal alkaloid in opium and still widely used,therefore described as prototype
mechanism of action Morphine and other opoids exert their action by interacting with specific receptors (mu,kapa,delta) present on neurones in the CNS and in peripheral tissues
58
Pharmacological action
CNSdepressant effect Morphine is a strong analgesic though dull,poorly localised visceralpain is relieved better than sharply defined somatic pain Suppression of pain perception is selective,without affecting other sensation or producing proportionate generalized CNS depression Sedation Hypnotic-drowsiness and indifference to surrounding as well as to own body occurs without motor incoordination. Calming effect,feeling of detachment,lack of initiative,body warm,mental clouding
59
Mood effects
Respiration centre
Morphine depresses respiratory centre in a dose dependent manner;rate and tidal volume are both decreased
Other actions
cough centre ,temperature regulating centre,vasomotor centre fall in BP It stimulate the vagal centre can cause bradycardia; nausea and vomiting
Hypothalamic activation,short term reduction in corticosteriod and sex hormone Prolactin and GH level increased
Neuroendocrine
CVS
Morphine causes vasodilation due to Histamine release,tone of blood vessels DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5 EDITION
TH
60
GIT
Constipation direct action on intestine and in CNS increases tone and segmentation but decreases the propulsive movement and also spasm of anal sphincter
Bronchi Morphine releases histamine which cause bronchoconstriction dangerous in asthmatics Billary tract Morphine causes intrabillary pressure is increased may cause billary colic
ANS
Morphine causes mild hyperglycaemia due to central symphathetic stimulation

Action is insignificant may slightly prolong the labour
Uterus
Pharmacokinetics

The oral absorption of morphine is unreliable because of high and variable first pass metabolism; Oral bioavailability average of parenterally administered drug 30% bound to plasma proteins Distribution is widelyconcentration in liver ,spleen and kidney is higher than that in plasma Primarily metatoblized in liver by glucuronide conjugation Morphine cross the placenta and can affect foetus more than the mother Plasma t is 2-3hours Effect of a parental dose lasts 4-6 hours
Adverse effects
Side effects sedation, mental clouding,constipation is common,respiratory depression,blurring of vision,urinary retention,allergy Morphine given to mother during labour blood brain barrier of foetus is undeveloped Addiction -- Morphine is a potentially highly addictive substance. It can cause psychological dependence and physical dependence as well as tolerance
63
ACUTE MORPHINE POISOING
A morphine overdose occurs by intentionally or accidentally taking too much of it. A large overdose can cause ,shock,convulsion coma and death by respiratory depression The minimum lethal dose is 250 mg but in case of hypersensitivity 60 mg can bring sudden death. In case of drug addiction, 2-3 g/day can be tolerated Treatments include administration of activated charcoal, intravenous fluids and, laxatives and naloxone(ANTIDOTE) Naloxone 0.40.8mg i.v.repeated every 2-3 min till respiration picks up,injection should be repeated every 1-4 hrs later on,according to response
Contraindication
Bronchial asthma Patient with Respiratory insufficiency Head injury-it increases intracranial tension,severe respiratory depression Hypotensive state-morphine exaggerate fall in BP Liver and kidney disease patient are more sensitive to morphine
Uses
Analgesic-excellent analgesic for severely painful condition such as MI,fracture,post operative pain,pulmonary embolism Antitussive effective in severe cough AntiDiarrhoea opioids are effective for the symptomatic treatment of diarrhoea Preanaesthetic medicationhigh doses Special anaesthesia high doses of morphine can be used IV to produce general anaesthesia
66
Doses
Adult Oral 10 -50 mg per day in divided doses I.M or S.C 10 15mg per day I.V- 2- 6 mg / kg per day Children IM/SC: 0.1-0.2 mg/kg/dose 3-4h IV infusion: 0.02-0.06 mg/kg/hour Brand name; Morcontin 10,30,60,100mg tab
Codeine
It is a methylmorphine, occurs natural alkaloid found in opium poppy It is less potent than morphine ,also less analgesic effect than aspirin Codeine has low affinity for opoid receptors. It is more selective cough suppressant(only 1/3 as potent as morphine ) Analgesic, Antitussive, and Antidiarrheal action
68
Codeine is metabolized to codeine-6-glucuronide by uridine diphosphate glucuronosyl transferase Codeine has good activity by oral route;single dose acts for 4-6 hrs Side effects constipation is more prominent side effect Dosage ; Adult-15- 60 mg every 4hours, The maximum daily dose for the relief of pain is 240 mg/day Child-0.5 mg/kg body weight (codeine phosphate) divided into four to six doses a day Brand name; codine sulphate tab 15mg Codine Linctus syr 15mg/ml
69
Diacetylmorphine
Heroin, or diacetylmorphine , also known as diamorphine , is a semi-synthetic opioid drug synthesized from morphine, a derivative of the opium poppy It is 3 times potent than morphine. More lipid soluble enters brain more rapidly but duration of action is smillar It acts as a powerful agonist at the mu opioid receptors subtype. It has no outstanding therapeutic advantage over morphine and has been banned in most countries except u.k
GENERAL PHARMACOLOGY MUNSON
70
Central nervous system: Drowsiness,Disorientation, Delirium Psychological:Addiction (Psychological Dependence) Cardiovascular & Respiratory Bradycardia,Hypotension,Hypoventilation Bioavailability <35% (oral), 4461% (inhaled) Half-life <10 minutes uses:Powerful analgesic,Cough suppressant anti-diarrheal
GENERAL PHARMACOLOGY MUNSON 4th EDITION
71
Pethidine(meperidine)
Pethidine was synthesized as an atropine substitute in 1939 It act by interacting with opioid recptors and it action blocked by naloxon It is sedative,euphoriant and abuse potential It cause sever resperatory depression It causes less histamine release and is safer in asthmatics Bioavailability 5060% Protein binding 6575% Metabolism Liver, Excretion Renal Half-life 35 hours
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Overdose-tremors,convulsions,mydriasis Uses-used as an analgesic,preanaesthetic medication Dose; 50-100mg i.m,s.c occasionally given orally or i.v Pethidine Hcl 100mg/2ml inj Pethidine hcl ;50,100mg tab
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STEROIDS
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Corticosteroid

Corticosteroids are hormones produced in the cortex of the adrenal gland They are glucocorticoids,mineralocorticoids and a small amount of androgens Cortisol is the major glucocorticoid while aldosterone is the major mineralocorticoid The secretion of adrenal cortex is under the control of ACTH secreted by the anterior pituitary and is regulated by CRF
75
Classification
Short acting(t1/2 12hr) Hydrocortisone Cortisone Intermediate acting(t1/212-36 hr) Prednisolone Methylprednisolone Triamcinolone Long acting(t1/2 36hr) Paramethasone Dexamethasone Betamethasone
Corticosteriod Antiinflammatory Mechanism
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Pharmacological Action
Antiinflammatory action Reduce the synthesis of PGs and LTs by inhibiting the phospholipase A2 They inhibit both early and late manifestion of inflammation Inhibition of late response like capillary proliferation,collagen deposition,fibroblastic activity and scar formation may delay wound healing They inhibit migration and depress the function of the leukocytes and macrophages including the release of chemical mediators
78
Pharmacological Action
Carbohydrat e and protein metabolism Promote glycogen deposition in liver Inhibit glucose utilization by peripheral tissues Increases glucose level in blood
Fat metabolism
Calcium metabolism CVS
Promote lipolysis redistrubution of body fat occurs-moon face,fish mouth

They inhibit intestinal absorption and enhance renal excretion of calcium Restrict capillary permeability,maintain tone of arterioles79
CNS
Mild euphoria,increases the motor activity,insomnia,anxiety or depression Increase the gastric acid secretionmay aggravate peptic ulcer
GIT
Blood
Increases the number of RBC,platelet and neutrophils in circulation Decreses the lymphocytes,eosinophils and basophils
Immunologic Supress cell-mediated immunity, al prevent manifestions of allergy

Adverse Effect of Corticosteroids

RECEIVE LONG-TERM, HIGH-DOSE STEROID CUSHINGS SYNDROME-moon face buffalo hump,truncal obesity,musle wasting,thinning of the limbs Hyperglycaemia,osteoporosis,avascular necrosis,peptic ulceration,delayed wound healing ACUTE ADRENAL INSUFFICIENCY- After prolonged steriod therapy,if suddenly stopped steriod administration acute adrenal insufficiency results Steroids should be tapered before withdrawal to allow HPA axis to recover
81
USES

Rhematoid arthritis,allergic diseases,asthma,liver diseases,malignancies,organ transplanation Acute adrenal insufficiency intravenous hydrocortisone hemisuccinate 100mg bolus followed by infusion is given immediately once the patient recovers,switch over to oral preparation Chronic adrenal insufficiency(addisons disease) Oral hydrocortisone 20-40mg daily is given
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Contraindication

Peptic ulcer Hypertension Infection Diabetes mellitus Osteoporosis Epilepsy Glaucoma Renal faliure
83
GENERAL PHARMACOLOGY- GOODMAN-GILMANS 9th EDITION
84
Dosage
Glucocorticoid Hydrocortisone Hemisuccinate Prednisolone Methylprednisolo ne acetate Adult dosage 30-100mg /day Dosage form 10mg tab 50mg/ml inj IM,IV 5,10 mg tab 20mg/ml im,iv 4 mg tab 20mg/ml inj Brand name EFCORLIN
5-60mg/day 10-40mg IM /day 4-32mg/day
WYSOLONE SOLVMEDROL
Triamcinolone
Dexamethasone Betamethasone
4-20 mg/day
4mg tab 10 mg/ml inj
KENOCORT
DEXONA
0.5-5mg oral /day 0.5 mg tab 4-20mg iv/im/day 4mg/ml inj
BETNESOL 0.5-5 mg oral 0.5 mg tab /day 4 mg/ml inj DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION 4-20mg im/iv/day
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TOPICAL PREPARATIONS
PREPARATIONS AVAILABLE AS
HYRDROCORTISONE 1% TRIAMCINOLONE 0.1% DEXAMETHASONE 0.1% FLUCINOLONE ACETAMIDE 0.025% BETAMETHASONE 0.025% BECLOMETHASONE DIPROPIONATE 0.025%
LYCORTIN OINTMENT LEDERCORT ACETONIDE Oint DECADRON CREAM FLUCORT OINTMENT BETNOVATE OINT/CREAM BECLATE CREAM
CLOBETASOL PROPIONATE 0.05% CLOBESOL OINT

DENTAL USES
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CONDITION
ADMINISTRATION
Aphthous ulcer
Topical
Desquamative Gingivitis Topical,systemic Oral lichen planus Post extraction Severe allergy TMJ arthritis symptoms Oral pemphigus
GENERAL PHARMACOLOGY MUNSON 4th EIDITION
Topical,systemic Systemic Systemic
Systemic
Topical,systemic
88
REFERENCES
K.D TRIPATHI 5th EDITION--- MEDICAL PHARMACOLOGY PAUL L MUNSION PRINCIPLES OF PHARMACOLOGY GOODMAN & GILMANS 9th EDITION PHARMACOLOGICAL BASIS OF THERAPEUTICS CIMS-2010 JULY EDITION
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THANK YOU
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ANALGESIC AND ANTIINFLAMMATORY DRUGS

PRESENTED BY S.MOHAMED ANSER II yr P.G

ORAL MEDICINE BURKETS 11th EIDITION

DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION

GENERAL PATHOLOGY- HARSH MOHAN

GENERAL PATHOLOGY- HARRSH MOHAN

DENTAL & MEDICAL PHARMACOLOGY K.D.TRIPATHY 5TH EDITION

GENERAL PHARMACOLOGY-MUNSON 4th EDITION

Classification of Analgesic & Anti-inflammatory drugs

Analgesic drugs divided in to two OPIOIDS AND NON-OPOIDS(NSAIDS)