Anti Inflammatory Drugs Ppt

7/21/2019 Anti Inflammatory Drugs Ppt

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ANALGESIC AND ANTI-

INFLAMMATORY DRUGS

PRESENTED BY

S.MOHAMED ANSER

II yr P.G

1


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What is pain?

DEFINITION

An unpleasant sensory and emotional experience

associated with actual or potential tissue damage ordescribed in terms of such damage

2ORAL MEDICINEBURKETS 11thEIDITION


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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

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4

INFLAMMATION:

DEFINITION:the local response of living tissues to

injury due to any agent.

([[Latin]], ''inflamatio'', to set on fire)

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5

TYPES OF INFLAMMATION:

Depending upon the defense capacity of the host &duration of response, it is classified into

c

ACUTE

Short duration.

Early 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 ispresence of lymphocytes,plasma cells &macrophages.

5GENERAL PATHOLOGY- HARRSH MOHAN


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MECHANISM OF INFLAMMATION



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INTRODUCTION

Phospolipase A

Cyclooxygena

se

lipooxgynas

e

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Classification of Analgesic & Anti-inflammatory

drugs

Analgesic drugs divided in to two

OPIOIDS AND NON-OPOIDS(NSAIDS)

Anti-inflammatory drugs divided in to twoNSAIDS AND STERIODS

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NON-STEROIDALANTIINFLAMMATORY DRUGS

DENTAL & MEDICAL PHARMACOLOGYK.D.TRIPATHY 5THEDITION


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CLASSIFICATION

Non-steriodal anti inflammatory drugs Non selective cox inhibitors

Salicylates- aspirin,diflunisal

Pyrazolone deravativesphenylbutazone, oxyphenbutazone

Indole derivatives-indomethacin,sulindac

Propionic acid deravativesIbuprofen,naproxen

Anthranillic acid deravativesmephenamic acid

Aryl acetic acid deravativesdiclofenac, Oxicam deravatiespiroxicam,tenoxicam

Pyrrolopyrrole deravatives-- ketorolac



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Preferential cox-2 inhibitors

Nimesulide,meloxicam

Selective cox-2 inhibitors

Celecoxib,rofecoxib,valedecoxib Analgesic-antipyretics with poor antiinflammatory

action

Paraaminophenol derivative-- paracetamol

Pyrazolone deravatiesmetamizol,propiphenazone

Benzoxazocine deravativenefopam



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NSAIDS MECHANISM OF ACTION



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14MEDICAL PHARMACOLOGYMUNSON 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 anti-

inflammatory drugs (NSAIDs)

It inhibit the PG synthesis by inhibitng the

enzyme cyclo-oxygenase



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PHARMACOLOGICAL ACTION



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ANALGESIA

Goodanalgesic

It relieves pain

orginatingfromintegumentalstructures likemuscles,bone,

joints

Ineffective invisceral pain

ANTIPYRETICACTION

In fever ,itbrings in tonormaltemperature

By inhibitingpgs synthesisin thehypothalamus

ANTI -INFLAMMATORY

ACTION

At HigherDoses Of 4-6gm,AspirinAct As An

AntiInflammatoryAgent

Signs Of

InflammationLikeTenderness,Sweilling AllSuppressed

17DENTAL & MEDICAL PHARMACOLOGYK.D.TRIPATHY 5THEDITION/ MUNSON


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Respiration

Productionof co2stimulatesrespiration

It rate anddepth ofrespiration

Acid base &Electrolytic

Salicylatescan causeretention ofsalt and water

As well asacutereduction ofrenal functionin patientwithCHF,renaldisease orhypovolmeia

CardiovascularEffects

Low DosesOf Aspirin ( 100mg) arecardioprotective effects

Higher doses(3g daily) circulating

plasmavolume itleads tocardiac out

put and work



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GIT

Gastricmucosaldamage

Aspringasritc

secretion In acid ph of

stomachsalicylateremains

unionised,adhere to mucosa

BLOOD

Inhibit thetxa2 synthesisinterfereswith plateletaggregation

Bleeding timeis prolonged

It decreasessynthesis ofclotting

factors inliver(longterm use)

ImmunologicalEffects

Inhibition ofantibodiesproduction



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ADVERSE

EFFECTSCONTRAINDICATION

DRUG

INTRACTION

peptic ulcerhepatic injury

hypersensitivity

Reyes

syndrome(childr

en below

12years) rare

form of hepatic

encephalopathy

seen in childrenhaving viral

infection has

been noted

Chronic liverdisease

Diabetics

Aspirin should

be stooped 1

week before

elective surgery

Aspirin should

be avoided by

breast feedingmothers

Avoided during

preganancy

Aspirinincreases

toxicity of oral

anticoagulants,h

eparin,oral

antidiabetics,phe

nytoin,antiplatilet

s drugs

Aspirin induce

sever GIbleeding when

given with

steroids,alcohol



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USES DOSAGE BRAND NAME

As analgesic 325-650mg/d 4-

6hours

Max 4g/day

TAB.ASPIRIN

350mg

As antipyretic 325-650mg/d 4-6

hours

TAB.COLSPRIN

100,325,650mg

As antiinflammatory

doses

3-6 g/day, ECOSPIRIN

100,325,650 mg

Acute rheumatic

fever

75-100mg/kg/day Also avaliable as

i.vinjection(biospiri

n)

postmyocardial

infarction(antiplatelet)

60-100mg/day

21DRUG GUIDE CIMS- JULY 2010


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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 function-

prolong bleeding time

antiiflammatory effects are lower than the high

dose of aspirin



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PHAMACOLOGICAL

ACTION

PHAMACOKINETICS ADVERSE EFFECTS

Analgesic action

Antipyretic action,

Antiinflammatory

action lower than

the aspirin high

dose

99% bound toplasma protein,

undergoes hepatic

metabolism

t is 2hours and

it can cross blood

brain barrier,

placenta

Ibuprofen thoughtto be better

tolerated than

aspirin

Gastric

discomfort,

Nausea, vomiting,

Induce asthma,



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Analgesic & Antiinflammatory

200-400 mg every 4-6hrs;1.2-1.8 g/day in divided dosesmax 2.4 g/day

Adult dosage

Antipyretic 5-10mg/kg every6hours(max 40mg/kg /day)

Antiinflammatory 20-40mg/kg/day in 3-4 divided doses

Children dosage

Brufen 200,400,600mg

Ibugesic 100mg/5ml suspBrand name

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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



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Action

Good analgesic,antipyretic ,slight antiinflammatory action

Action

it not interfere with platelet function

Gastric irritation is insignificant

Adverseeffect

As antipyretic dose it is well tolerated and safe Nausea and rashes occur occasionally



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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 fewdays can result in hepatotoxicity

Early manifestation are just nausea,vomiting,livertenderness,after 12-18 hrs hepatic necrosis andhypoglycaemia.jaundice started after 2dayshepaticfailure

Management

N-acetylcysteine (mucomix 200mg/ml inj in 1,2,5mlamps)150/mg/kg should be infused iv over 15mins ,followed by next 20 hours

75mg/kg given orally 4-6 hours for 2-3days

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crocin(500mg,1000mg),

metacin 500mg tab,125mg/5mlsyrp

BRAND NAME

Adult-10-15mg/kg every4hours( max 5 doses in 4hours)Adult Dosage

Age 1-3yr ;80-160mg,Age 4-8yr; 240-320mg,Age9-12 yr 300-600mg,;Infants 50mg

Children dosage

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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 isslow,90% bound to plasma protiens

Plasma t1/2 is 2-5 hours

It has excellent bioavaliability

It partly metabolised in liver to inactive productsand excreted by kidneys

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Dosage

Indometacin Adult Child Available AS

Pain and

inflammation

25mg tid,day

For 5-7 days

1-2mg/kg/day

in divided

doses

Max;3mg/kg/

day

Capsule

INDOCID

75mg (10cap

rs.32.00)

MICROCID

25mg, (10

cap-rs.23.oo)

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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 centralanalgesic 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



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Dosage

Mephenamic

acid

Adult Child Available

As

Mild To Moderate

PainPost-operative

pain

250 mg- 500

mg tid

25mg/kg

daily individed

doses for

up to 7 days

Meftal tablet

250mg ,500mgSuspension- 50mg/5ml

(ponstan)

Combination-mefanamic

acid 500mg ,paracetamol

450mg(meftal forte)

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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 highconcentration in synovial fluid-extended

theraputic action in joints



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Pharmacological action

Pharmacokinetics

Adverse effects

An analgesic

antipyretic,

antiinflammatoryaction are good

It is well

absorped

orally,99%protienbound

metabolised and

excreted in urine

and bile

Plasma t1/2 is

2hours

Gastric ulceration

and bleeding are

less commonGenerally mild

Epigastric

pain,nausea,hea

dache

Kidney damage

is rare


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Dosage

Diclofenac Adult Child AvailableAs

Pain and

inflammation

Post-operativepain

75-150 mg daily

divided doses;

max-150mg/dayOr 75mg/3ml

I.M O.D

Rectal-75-150

mg daily

Max;150mg/day

25mg/kg daily

in divided

doses for upto 7 days

Rectal; 1-2mg

/kg /day in

divided doses

for max of

4days

Tab-

50,75,100

mg , Inj75mg/3ml-

(voveran)

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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

aggregationprolong bleeding time .

It also decrease the production of IgM rheuomatoid

factor.

Chemotaxis of leukocytes are reduced



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Pharmacological

action

Pharmacokinetics Adverse effect

Good analgesic

and antipyretic

action

Potent

antiinflammatoryaction

It is rapidly and

completely absorbed

99% plasma protein

bound

Largely metabolisedin liver;ecreted in

urine

Plasma t1/2 is long

nearly 2 days

Common side

effects are

heart

burn,nausea,

and anorexiaLess faecal

blood loss than

aspirin

Edema alsocommon


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Dosage

Piroxicam Adult Child AvailableAs

pain and

inflammaton

Post

operative

pain

20mg/day as a

single dose.

Followed by 10-30mg in single or

divided dose

40mg/day for2days-20mg/day

for 1-2week

10-15mg

dosess to be

taken oncedaily

Capsule -

10mg,20mg-

pirox,Dolonex

Injection-

2mg/ml

doloswift

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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

Pharmacokinetics Adverse effect

Good analgesic

Action

Less antipyretic

action

Modestantiinflammatory

action

It rapidly absorbed

after oral i.M

administration

It is highly bound to

plasma proteinexcreted

unchanged in urine

Plasma t1/2 is 5-7

hours

Metabolic pathway

is glucuronidation

Nausea

,abdominal pain

dyspepsia,ulcer

ation ,loose

stools,drowsiness

,headache,fluid

retention have

been noted



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Dosage

Ketorolac Adult AvailableAs

Moderate to

severe pain

Oral-10mg every 4-6hr,

max;40 mg/day

Max duration; 7 daysParenteral-60mg im as a

single dose or 30mg i.V

as a single dose

max;120mg/day;max

2days

Tablet- ketorol

10mg

(10tab-rs.32.0)Torolac 10mg

tab

Inj-30mg/ml

41GENERAL PHARMACOLOGYMUNSON 4thEDITION


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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 TNFrelease

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

l action

Pharmacokinetics Adverse effects

Analgesic and

antipyretic action

are good

Short term

inflammatory

action

Nimesulide

metabolised

completely

absorbed orally

99% plasma

protein bound,

extensively

metabolised

and excreted inurine

Plasma t1/2 of

2-5 hours

Hepatic failure

especially in

children

Heart

burn,rashes,gast

ric tolerability is

better


Dosage


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Dosage

Nimuslide Adult Available

As

Acute pain and

postoperative pain

Acut traumatictendinitis

Oral-100mg bid

(european union is

limited to a max of

15 days)

Rectal -200mg bid

Topical-3%gel/cream

tid for 7days

-max;15 days

TAB-nise

100mg

susp-50mg/5ml

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 Txa2synthesis

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



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Pharmacological

action

Pharmacokinetics Adverse effects

It exerts

Analgesic

action,antipyretic

action andantiinflammatory

action

Celecoxib is slowly

absorbed

97% plasma protein

boundt1/2 is 11 hours

Tolerability of

celecoxib is better

than older

nsaids,stillabdominal pain,

dyspepsia and mild

diarrhoea are

common



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Dosage

Celecoxib Adult AvailableAs

Pain and

inflammation

100-200mg bid per day

for 5-7days

Cap-celecap,

coxib

100mg,200mg

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Benzoxazocine Derivative

Nefopam

It is a nonopoids analgesic which does not inhibit PGsynthesis.

In traumatic and postoperative pain,it acts rapidly withan efficacy approaching morphine,yet has no opioidactions

Favourable results have been obtained in short lastingmusculoskeletal pain not responding to other nonopoid

analgesic Nefopam produces anticholinergic ,side effects, and

nausea is often dose limiting



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The mechanism of action of nefopam is not wellunderstood, although inhibition of serotonin, dopamineand noradrenaline reuptake is thought to be involved inits 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



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Drug Intraction With NSAIDS

Diuretics Diuresis Action

blockers Antihypertensive

effect

ACE inhibitors

Antihypertensive

effect

Anticoagulant

Risk Of G.I Bleeding

Sulonylureas Risk Of

Hypoglycaemia



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TOPICAL NSAIDPREPARATION BRAND NAME

DICLOFENAC 1% GEL VOVERAN

EMULGEL,DICLONAC GEL

IBUPROFEN 10% GEL RIBUFEN GEL

NAPROXEN 10% GEL NAPROSYN GEL

KETOPROFEN 2.5% GEL NAPROSYN GEL

FLURBIPROFEN 5% GEL FROBEN GEL

NIMESULIDE 1%GEL NIMULID TRANS

GEL,NIMEGESIC-T-GEL

PIROXICAM 0.5% GEL DOLONEX GEL,MOVON GEL


CHOICE OF NSAIDS


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CHOICE OF NSAIDS

Mild to moderate pain

with minimal

inflammation

Paracetamol,or low

dose

Ibuprofen

Acute musculoskeletal,

ostearthritic,injury

associated pain

A propionic acid

derivative,diclofenac or

rofecoxib

Gastric intolerance to

conventional NSAIDS and

predisposed patient

Rofecoxib,celecoxib

Exacerbation of RMA,

ankylosing

sondylitis,acute gout

High dose of

aspirin,indomethacin,napr

oxen,piroxicam

Patient history of asthma

or anaphylactoid reaction

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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)

54GENERAL PHARMACOLOGY-GOODMAN-GILMANS 9thEDITION

O i id t


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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



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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



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Classification of opoids

Natural opium alkaloids -- morphine,codeine

Semisynthetic opiates diacetylmorphine(heroin),

pholcodeine

Synthetic opioids -- pethidine(meperidine),fentanyl,

tramadol,methadone



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MORPHINE

Morphine is the principal alkaloid in opium andstill 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 CNSand in peripheral tissues




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CNS-

depressant

effect

Morphine is a strong analgesic though

dull,poorly localised visceralpain is

relieved better than sharply definedsomatic pain

Suppression of pain perception is

selective,without affecting other sensation

or producing proportionate generalizedCNS depression

Sedation Hypnotic-drowsiness and indifference to

surrounding as well as to own body

occurs without motor incoordination.

Mood effects Calming effect,feeling of detachment,lack

of initiative,body warm,mental clouding


Respiration Morphine depresses respiratory


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centre centre in a dose dependent

manner;rate and tidal volume are

both decreased

Other actions coughcentre ,temperature regulating

centre,vasomotor centrefall in BP

It stimulate the vagal centrecan cause

bradycardia; nausea and vomiting

Neuro-

endocrine

Hypothalamic activation,short term

reduction in corticosteriod and sex

hormone

Prolactin and GH level increased

CVS Morphine causes vasodilation due to

Histamine release,toneof blood

vessels 60DENTAL & MEDICAL PHARMACOLOGYK.D.TRIPATHY 5THEDITION

GIT Constipationdirect action on intestine and

i CNS i t d t ti b t


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in CNS increases tone and segmentation but

decreases the propulsive movement and

also spasm of anal sphincter

Bronchi Morphine releases histamine which cause

bronchoconstrictiondangerous in asthmatics

Billarytract

Morphine causes intrabillary pressure isincreasedmay cause billary colic

ANS Morphine causes mild hyperglycaemiadue to

central symphathetic stimulation

Uterus Action is insignificant may slightly prolong the

labour



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Pharmacokinetics

The oral absorption of morphine is unreliable because ofhigh and variable first pass metabolism;

Oral bioavailability average of parenterally administered

drug30% bound to plasma proteins

Distribution is widelyconcentration in liver ,spleen andkidney 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



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Adverse effects

Side effectssedation, mental clouding,constipation iscommon,respiratory depression,blurring of

vision,urinary retention,allergy

Morphine given to mother during labourblood brainbarrier of foetus is undeveloped

Addiction -- Morphine is a potentially highly addictive

substance. It can cause psychological dependence andphysical dependence as well as tolerance



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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 ofdrug 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 tillrespiration picks up,injection should be repeated every 1-4hrs later on,according to response



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Contraindication

Bronchial asthma

Patient with Respiratory insufficiency

Head injury-it increases intracranialtension,severe respiratory depression

Hypotensive state-morphine exaggerate fall in

BP

Liver and kidney disease patient are more

sensitive to morphine



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Uses

Analgesic-excellent analgesic for severely painfulcondition such as MI,fracture,post operative

pain,pulmonary embolism

Antitussiveeffective in severe cough

AntiDiarrhoeaopioids are effective for thesymptomatic treatment of diarrhoea

Preanaesthetic medicationhigh doses

Special anaesthesiahigh doses of morphine can be

used IV to produce general anaesthesia



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Doses

Adult Oral10 -50 mg per day in divided doses

I.M or S.C1015mg 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



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Codeine

It is a methylmorphine, occurs natural alkaloid found inopium 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



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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 effectsconstipation 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 Linctussyr 15mg/ml



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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

70GENERAL PHARMACOLOGY MUNSON


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Central nervous system: Drowsiness,Disorientation,

Delirium

Psychological:Addiction (Psychological Dependence)

Cardiovascular & Respiratory

Bradycardia,Hypotension,Hypoventilation

Bioavailability


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Pethidine(meperidine)

Pethidine was synthesized as an atropine substitute in1939

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 ofthe adrenal gland

They are glucocorticoids,mineralocorticoids and a small

amount of androgens

Cortisol is the major glucocorticoid while aldosterone isthe major mineralocorticoid

The secretion of adrenal cortex is under the control of

ACTH secreted by the anterior pituitary and is regulated

by CRF



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Classification

Shortacting(t1/212hr) Hydrocortisone

Cortisone

Intermediate acting(t1/212-36 hr)

Prednisolone Methylprednisolone

Triamcinolone

Longacting(t1/2 36hr)

Paramethasone Dexamethasone

Betamethasone


Corticosteriod Antiinflammatory Mechanism


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y



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PharmacologicalAction

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 theleukocytes and macrophages including the release of

chemical mediators



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Pharmacological Action

Carbohydrate and

protein

metabolism

Promote glycogen deposition inliver

Inhibit glucose utilization by

peripheral tissues

Increases glucose level in blood

Fat

metabolism

Promote lipolysisredistrubution of

body fat occurs-moon face,fish mouth

Calciummetabolism

They inhibit intestinal absorption andenhance renal excretion of calcium

CVS Restrict capillary

permeability,maintain tone of arterioles79DENTAL & MEDICAL PHARMACOLOGYK.D.TRIPATHY 5THEDITION


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CNS Mild euphoria,increases the motor

activity,insomnia,anxiety or

depression

GIT Increase the gastric acid secretion-

may aggravate peptic ulcer

Blood Increases the number of RBC,platelet

and neutrophils in circulation

Decreses the lymphocytes,eosinophils

and basophilsImmunologic

al

Supress cell-mediated immunity,

prevent manifestions of allergy


Ad Eff f C i id


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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,pepticulceration,delayed wound healing

ACUTE ADRENAL INSUFFICIENCY- After

prolonged steriod therapy,if suddenly stopped steriod

administrationacute adrenal insufficiency results Steroids should be tapered before withdrawal to allow

HPA axis to recover



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USES

Rhematoid arthritis,allergic diseases,asthma,liver

diseases,malignancies,organ transplanation

Acute adrenal insufficiencyintravenous hydrocortisonehemisuccinate 100mg bolus followed by infusion is

given immediately

once the patient recovers,switch over to oral preparation

Chronic adrenal insufficiency(addisonsdisease)

Oral hydrocortisone 20-40mg daily is given


C t i di ti


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Contraindication

Peptic ulcer Hypertension

Infection

Diabetes mellitus

Osteoporosis

Epilepsy

Glaucoma

Renal faliure



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84GENERAL PHARMACOLOGY- GOODMAN-GILMANS 9thEDITION

Dosage


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Dosage

Glucocorticoid Adult dosage Dosage form Brand name

Hydrocortisone

Hemisuccinate

30-100mg /day 10mg tab

50mg/ml inj

IM,IV

EFCORLIN

Prednisolone 5-60mg/day

10-40mg IM /day

5,10 mg tab

20mg/ml im,iv

WYSOLONE

Methylprednisolo

ne acetate

4-32mg/day 4 mg tab

20mg/ml inj

SOLVMEDROL

Triamcinolone 4-20 mg/day 4mg tab

10 mg/ml inj

KENOCORT

Dexamethasone 0.5-5mg oral /day

4-20mg iv/im/day

0.5 mg tab

4mg/ml inj

DEXONA

Betamethasone 0.5-5 mg oral

/day

4-20mg im/iv/day

0.5 mg tab

4 mg/ml inj

BETNESOL


TOPICAL PREPARATIONS


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PREPARATIONS AVAILABLE AS

HYRDROCORTISONE 1% LYCORTIN OINTMENT

TRIAMCINOLONE 0.1% LEDERCORT

ACETONIDE Oint

DEXAMETHASONE 0.1% DECADRON CREAM

FLUCINOLONE ACETAMIDE

0.025%

FLUCORT OINTMENT

BETAMETHASONE 0.025% BETNOVATE

OINT/CREAM

BECLOMETHASONE

DIPROPIONATE 0.025%

BECLATE CREAM

CLOBETASOL PROPIONATE 0.05% CLOBESOL OINT



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DENTAL USES


T i l

CONDITION ADMINISTRATION


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Aphthous ulcer

Desquamative Gingivitis

Oral lichen planus

Post extraction

Severe allergy

TMJ arthritis symptoms

Oral pemphigus

Topical

Topical,systemic

Topical,systemic

Systemic

Systemic

Systemic

Topical,systemic

88GENERAL PHARMACOLOGYMUNSON 4thEIDITION

REFERENCES


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REFERENCES

K.D TRIPATHI 5th

EDITION--- MEDICALPHARMACOLOGY

PAUL L MUNSIONPRINCIPLES OF

PHARMACOLOGY GOODMAN & GILMANS 9thEDITION

PHARMACOLOGICAL

BASISOF THERAPEUTICS

CIMS-2010 JULY EDITION

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THANK YOU

Documents

Anti Inflammatory Drugs Ppt