Analgesics and antiinflammatory drugs /certified fixed orthodontic courses by Indian dental academy

ANALGESICS AND
ANTIINFLAMMATORY
DRUGS

INDIAN DENTAL ACADEMY
Leader in continuing dental education
www.indiandentalacademy.com

PAIN (Algesia)

“Pain is an unpleasant sensory and
emotional experience associated with
actual or potential tissue damage or
described in terms of such damage”

International Association for the Study
of Pain

WHY FEEL PAIN?

• Gives conscious awareness of tissue
damage
• Protection:
– Removes body from danger
– Promotes healing by preventing
further damage
• Elicits behavioural and emotional
responses

LOCALIZATION OF PAIN

• Superficial Somatic Pain arises from
skin areas

• Deep Somatic Pain arises from
muscle, joints, tendons & fascia
• Visceral Pain arises from receptors
in visceral organs

FAST AND SLOW PAIN

• Most pain sensation is a combination of the
two types of message.
– If we prick our finger we first feel a sharp
pain which is conducted by the A fibres,
– and this is followed by a dull pain
conveyed along C fibres.

• FAST PAIN (acute)
– Occurs rapidly after stimuli (0.1
second)
– Sharp pain like needle puncture or cut
– Not felt in deeper tissues
– Larger myelinated A nerve fibers
– Velocity of 80 m/s

• SLOW PAIN (chronic)
– Begins more slowly & increases in
intensity
– In both superficial and deeper tissues
– Smaller unmyelinated C nerve fibers
– Velocity of 0.4 m/s

PAIN PATHWAY


ANALGESIC

• It is a drug that selectively relieves pain
by acting in the CNS or on peripheral
pain mechanisms,without significantly
altering consciousness


ANALGESICS

Analgesics can be:-

a) Opioid/Narcotic
b) Non opioid/Non narcotic

OPIOID ANALGESICS

Derived from opium
 It has 2 types of alkaloids:-

Phenanthrene

Benzoisoquinoline


CLASSIFICATION

1 .Natural Opium AlkaloidsMorphine,Codeine
2. Semisynthetic OpiatesDiacetylmorphine,Pholcodeine
3. Synthetic OpioidsPethidine,Fentanyl

OPIOID ANALGESICS
AND ANTAGONISTS
OPIOID DRUGS

Agonists

Mixed actions

Antagonists

Morphine

Naloxone

Heroin
Methadone
Codeine

Naltrexone
Pentazocine
Nalbuphine
Butorphan

MECHANISM OF ACTION


RECEPTORS


OPIOID RECEPTORS

• Mu opioid receptor-

Respiratory depression
Euphoria
Physical dependence
Pupil constriction

• Kappa opiod receptor-

Sedation
Spinal anaesthesia
Pupil constriction

• Sigma opioid receptor-

Hallucinations
Dysphoria
Pupil dilation

POPPY PLANT


MORPHINE

• Serturner,1806 morphine –Morpheus.
• Source- crude opium
• Prototype agonist


MECHANISM OF ACTIONa) Morphine + receptors
Hyperpolarization of nerve cells
Inhibition of nerve firing
Presynaptic inhibition(transmitter)

b) Morphine + k receptors

Reduces release of substance P
c) Morphine inhibits release of
excitatory transmitters from nerve
terminals carrying nociceptive stimuli

NOCICEPTORS

• Nociceptors are special receptors that
respond only to noxious stimuli and
generate nerve impulses which the brain
interprets as "pain".


ACTION


ACTIONS

a) Analgesia: Selective
 Raises pain threshold at spinal cord level
 Alters brain perception of pain


b) Euphoria:- stimulates ventral tegmentum
c) Respiration:d) Depression of cough reflex:e) Miosis:-


f) Emesis:g) Cardiovascular:h) G.I. tract:i) Histamine Release:j) Hormonal actions:www.indiandentalacademy.com

USES

a. Analgesia

b. Treatment of diarrhoea
c. Relief of cough

ADVERSE EFFECTS



Respiratory depression



Nausea and vomiting,constipation



Addiction potential

MEPERIDINE
• It is a synthetic opioid used for acute pain.
1.MECHANISM OF ACTION:Meperidine+k receptors
2. ACTIONS: Depression of respiration
 Dilates cerebral vessels

Contracts smooth muscle
i.v.;
in peripheral resistance
It decreases gastric motility
Dilates the pupils
3. THERAPEUTIC USES: Analgesia
Pre anaesthetic medication

5. ADVERSE EFFECTS:Large doses lead to tremors,muscle twitches
6.DRUG INTERACTIONS:It increases depression along with major neuroleptics
7.TOLERANCE:It causes dependence and cross tolerance.

METHADONE
 High oral parenteral activity ratio (1:2) and firm
binding to tissue proteins.
1. MECHANISM OF ACTION:Methadone+mu receptors
2. ACTIONS:-Analgesia
-Respiratory depression

3.THERAPEUTIC USES:a) SUBSTITUTION THERAPY OF OPIOID
DEPENDENCE;
1 mg of oral methadone for 4 mg of opioid ,2
mg of heroin,20 mg of pethidine.
b) MAINTENANCEwww.indiandentalacademy.com
THERAPY :-

5.ADVERSE EFFECTS:Dependence
Mild withdrawal syndrome


FENTANYL
It is 80-100 times more potent than morphine.
1.ACTIONS:Analgesia
Respiratory depression
2.THERAPEUTIC USES:Anaesthesia injection form exclusively
Transdermal fentanyl has become available for use
in cancer or chronic pain

Along with Droperidol,it causes NEUROLEPT
ANAESTHESIA


PROPOXYPHENE

It is a derivative of methadone

2.USES:d isomer leads to analgesia
l isomer leads to antitussive action

3.SIDE EFFECTS: Nausea,vomiting
 Toxic doses ; respiratory depression
 Used with alcohol,sedatives ;severe CNS
depression and death

CODEINE
It is a less potent analgesic than morphine having
higher oral efficacy
ACTIONS:Analgesia
Sedation
Euphoria
Depresses the cough reflex.

PENTAZOCINE

1.MECHANISM OF ACTION:It is an agonist on k receptors and weak antagonist
on mu and delta receptors.
2.USES:Analgesia
Angina


3.ACTIONS: Analgesia by activating receptors in the spinal
cord
4.ADVERSE EFFECTS:Higher dose;respiratory depression
Tolerance and dependence

BUPRENORPHINE

 It is a partial agonist acting at the mu
receptors metabolized in liver and excreted in
bile and urine.


It causes nausea,dizziness,respiratory
depression.

NALOXONE
It reverses coma and respiratory depression of
opioid overdose.
It rapidly displaces all receptor bound opioid
molecules
MECHANISM OF ACTION: It is a competitive antagonist at mu,k,delta receptors
with a ten fold affinity for mu .

NALTREXONE
 It has a longer duration of action than
naloxone and a single oral dose blocks the
effect of injected heroin for upto 48 hours.
USES: Opiate dependence maintenance
programs
 Chronic alcoholism

ANTI INFLAMMTORY DRUGS

 INFLAMMATION:It is the body’s effort to inactivate or destroy
invading microorganisms ,remove irritants
and set the stage for tissue repair.

CLASSIFICATION
DRUGS
NSAIDS GOUT ARTHRITIS ANALGESICS
(Non narcotic)


NSAIDS
1) NONSELECTIVE COX INHIBITORS :a) Salicylates- Aspirin
b) Propionic acid derivatives- Ibuprofen
c) Anthranilic acid- Mephenamic acid
d) Aryl acetic acid - Diclofenac
e) Oxicam- Piroxicam
f) Pyrrolo pyrrole- Ketorolac

g) Indole- Indomethacin
h)Pyrazolone- Phenylbutazone

2) PREFERENTIAL COX-2 INHIBITORS :- Nimesulid
- Meloxicam
- Nabumetone

3) SELECTIVE COX-2 INHIBITORS :- Celecoxib
- Etoricoxib
- Valdecoxib
4) ANALGESIC –ANTIPYRETIC WITH POOR
ANTIINFLAMMATORY:a) Para aminophenol derivative-Paracetamol
b) Pyrazolone derivative- Metamizol

c) Benzoxacine derivative:- Nefopam


SALICYLATES
ASPIRIN
 Weak organic acid
Irreversibly acetylates
Inactivates cyclooxygenase


MECHANISM OF ACTION

• Blocks Prostaglandin synthesis(Peripheral targets)
• Prevents sensitization of pain receptors
• Depresses pain stimuli at subcortical sites
(Thalamus,Hypothalamus)


PHARMACOLOGICAL EFFECTS

1. Antipyretic and analgesic effect:The two effects of aspirin are strong and rapid.
2. Anti inflammatory and anti rheumatic effect:(1) Relatively stronger
(2) Often used to the dose of tolerance

3.

Inhibits platelet aggregation and prevent
thrombosis
– Inhibits TXA2 synthetase
– Aspirin administrated in low dose can reduce
TXA2 remarkably
– Anticoagulant effect

CLINICAL USES

1. Antipyretic and analgesic: Headache,toothache,myalgia,neuralgia , fever ,
dysmenorrhoea(decreases PGE2 synthesis)
2. Anti-inflammation and antirheumatism: Diagnosis and therapy of acute rheumatic fever

3. Cariovascular applications:•
•
•
•

Stable and variant angina pectoris
Progressive myocardial infarction patients
Transient ischemic attack patients
Angioplasty, bypass transplant operations

ADVERSE REACTIONS
1.Gastrointestinal reactions:
Irritates gastric mucosa directly:
cause epigastric distress nausea and
vomiting

Irritates chemoreceptor trigger
zone(CTZ): cause nausea ,vomiting

Gastric ulcer: can cause and
deteriorate ulcer

2. Blood Coagulation Disorders:-

• In usual dose:
Inhibits platelet coagulation and prolongs the
bleeding time.
• In high dose or in long term:
Inhibits the formation of prothombin and
prolongs the prothombin time

3. Allergy urticaria, allergic shock,
angioneurotic edema.


SALICYLISM:•

≥5mg/d

•
•
•
•
•

headache, dizziness, nausea, vomiting, tin
nitus, sight and hearing failure
Severe
hyperventilation, acid-base in

Treatment:Mild;symptomatic , urinary pH
Serious; sodium bicarbonate i.v.drip
Reye’s syndrome:
Severe hepatic dysfunction with
complication of encephalopathy

DRUG INTERACTIONS

•

Replaces dicoumarol (enhances its
anticoagulation effect)

•

Replaces tolbutamide and causes
hypoglycemia


PROPIONIC ACID DERIVATIVES
IBUPROFEN
1.ACTIONSAnalgesic
Antipyretic
Antiinflammatory
2.USES Chronic treatment of rheumatoid arthritis
 Soft tissue injuries,tooth extractions,fractures

4. ADVERSE EFFECTS: Gastrointestinal
 Headache
 Tinnitus


ANTHRANILIC ACID
DERIVATIVE
MEPHENAMIC ACID
1) MECHANISM OF ACTION:Inhibits COX as well as antagonises certain actions
of prostaglandins
3)USES:Analgesic in muscle,joint and soft tissue pain
Dysmenorrhoea


ARYL ACETIC ACID
DERIVATIVE
DICLOFENAC SODIUM
1) MECHANISM OF ACTION:Inhibits prostaglandin synthesis and has short
lasting antiplatelet action.
Neutrophil chemotaxis,superoxide production
at the inflammatory site is reduced.

3)USES:Rheumatoid and osteoarthritis
Toothache
Bursitis
Dysmenorrhoea

OXICAM DERIVATIVES
PIROXICAM
1)MECHANISM OF ACTION:



Reversible inhibitor of COX
Lowers PG concentration in synovial fluid
Inhibits platelet aggregation.

3) ADVERSE EFFECTS:Heartburn
Nausea
Anorexia
Rashes
4) USES: Osteoarthritis
 Ankylosing spondylitis

PYRROLO PYRROLE
DERIVATIVE
KETOROLAC
1 MECHANISM OF ACTION:Inhibits prostaglandin synthesis
Relieves pain by peripheral action


3. ADVERSE EFFECTS:Nausea
Dyspepsia
Dizziness
Pruritus
4. USES:Postoperative dental , musculoskeletal pain
Migraine

INDOLE DERIVATIVE
INDOMETHACIN
1. MECHANISM OF ACTION:Potent inhibitor of prostaglandin synthesis
Supresses neutrophil motility.


3 ADVERSE EFFECTS:Gastric irritation
Anorexia,diarrhoea,gastric bleeding
Frontal headache, mental confusion,dizziness
4 USES:Antiinflammatory agent;ankylosing spondylitis
Hodgkin’s disease(antipyretic)
Patent ductus arteriosus

PYRAZOLONES
METAMIZOL
Derivative of amidopyrine
Potent and promptly acting analgesic
Antipyretic
Poor antiinflammatory
1.MECHANISM OF ACTION:Potent analgesic
Antipyretic

3 ADVERSE EFFECTS:Gastric irritation
Agranulocytosis


PREFERENTIAL COX 2
INHIBITORS
NIMESULIDE
1. MECHANISM OF ACTION Weak inhibitor of PG synthesis
 Inhibition of platelet activating factor
synthesis and tumor necrosis factor
release
 Inhibition of metalloproteinase activity

3. ADVERSE EFFECTS: Epigastralgia
 Pruritus
 Fulminant hepatic failure
4.USES: Sports injuries
 Dental surgery
 Dysmenorrhoea

MELOXICAM
1. MECHANISM OF ACTION:It has a COX 2:COX 1 ratio of 10
It inhibits platelet TXA production
2.ADVERSE EFFECTS:Gastric changes
Long term bleeding and perforation

3. USES:• Osteoarthritis
• Rheumatoid arthritis


SELECTIVE COX 2 INHIBITORS
They reduce prostaglandin 2 production by
vascular endothelium
CELECOXIB
Time dependent
Irreversible inhibition of COX-2

2.ADVERSE EFFECTS:Abdominal pain
3. USES:Osteoarthritis
Rheumatoidarthritis

VALDECOXIB
1.USE:Osteoarthritis
Rheumatoid arthritis
2. ADVERSE EFFECTS:In few cases severe skin reaction
Stevens-Johnson syndrome

PARA AMINO PHENOL
DERIVATIVE
PARACETAMOL
1. MECHANISM OF ACTION:It raises pain threshold but has weak peripheral
anti inflammatory component
Inhibits Prstaglandin synthesis
in CNS

3. ADVERSE EFFECTS:Acute paracetamol poisoining
Low hepatic glucuronide conjugating ability
>10 gms in an adult; serious toxicity
>250 mg/kg; fatal

Manifestations:Nausea,vomiting
After 2-18 hours,CENTRILOBULAR HEPATIC
NECROSIS and HYPOGLYCEMIA ,COMA
Mechanism:Paracetamol gives rise to metabolite, N-acetyl
p benzoquinoneimine








Very large dose is taken
Glucuronidation capacity is saturated
More of minor metabolite is formed
Hepatic glutathione is depleted
Metabolite binds covalently to proteins
Necrosis

TREATMENT: Patient brought early- GASTRIC LAVAGE
 Prevent further absorption- ACTIVATED
CHARCOAL
 Specific antidote-N-acetylcysteine i.v./oral
4 .USES: Best antipyretic
 Headache,toothache,musculoskeletal pain

DRUG INTERACTIONS

• NSAIDs + Hypotensive drugs ( β-blockers, ACEinhhibitors, diuretics ) = ↓ hypotensive effect
• NSAIDs + Ethanol = ↑ risk of bleeding from
gastrointestinal tract
• NSAIDs + Ticlopidine or Clopidogrel = ↑ risk of
bleeding

• NSAIDs + Oral antidiabetic drugs = ↑ risk of
hypoglycemia
• NSAIDs + Coumarines =↑ risk of bleeding
• NSAIDs + Corticosteroids = ↑ risk of gastropathy
and bleeding from gastrointestinal tract

• NSAIDs + Lithium = ↑ lithium toxicity
• NSAIDs + Cylosporine or ACE-inhibitors or
Tacrolimus= ↑ nephrotoxicity of drugs
• NSAIDs + Fluoroquinolons = ↑ toxic action of
fluoroquinolones on CNS
• NSAIDs + Oral antidiabetic drugs = ↑ risk of
hypoglycemia

COMBINATIONS

DEXIBUPROFEN + PARACETAMOL

Inhibits COX
Inhibits COX-3
Paracetamol; central antinociceptive
action.


 PARACETAMOL
+
DEXTROPROPOXYPHENE:greater
analgesic effect( centrally acting)


TRAMADOL+PARACETAMOL:

o Faster onset of action compared to
Tramadol alone (17 minutes)
o Longer duration of action compared
to Paracetamol alone (5 hours)

 DICLOFENAC + PARACETAMOL;

 Actions of Paracetamol set in
earlier and provides pain relief
before the effects of Diclofenac sets
in.

 ACECLOFENAC + PARACETAMOL
Inhibits synthesis
of IL-1b,PGE2 production
Positive cartilage anabolism
Modulating effect on matrix
catabolism( GAG )

 IBUPROFEN + PARACETAMOL

Potent
Antiinflammatory,analgesic
antipyretic

NIMESULIDE + RACEMETHIONINE

Scavenger

Precursor for
glutathione synthesis
Promotes production of
cartilage proteoglycans
antioxidant

TOPICAL NSAIDS









Aceclofenac
Benzydamine
Diclofenac
Ketoprofen
Naproxen
Nimesulide
Piroxicam

DISEASE MODIFYING ANTIRHEUMATIC AGENTS
A.




1.

GOLD SALTS:Are taken up by macrophages
Supresses phagocytosis
Lysosomal enzyme activity
Retards bone, articular destruction
THERAPEUTIC USES:Rheumatoid arthritis that does not respond
to SALICYLATES or other NSAIDS.

3 .ADVERSE EFFECTS:Dermatitis of skin,mucous membranes
Proteinuria
Nephrosis
ANTIDOTE:- Dimercaprol

•
•
•
•
•

CHLOROQUININE AND HYDROXY
CHLOROQUININE:It inhibits nucleic acid synthesis
Stabilizes lysosomal membranes
Traps free radicals
Reserved for RHEUMATOID ARTHRITIS that has
been unresponsive to NSAIDS
Adverse effects include headache, rashes

PENICILLAMINE: It slows the progress of bone destruction and
rheumatoid arthritis.
 Prolonged treatment leads to aplastic
anemia,nephritis
METHOTREXATE: It is used for patients with severe rheumatoid
arthritis

DRUGS FOR GOUT
COLCHICINE:It is a plant alkaloid reserved for the treatment of
acute gouty attacks
2) USE:Alleviates the pain of acute gout
within 12 hours.

ALLOPURINOL: Treats primary hyperuricemia of gout
 Hyperuricemia secondary to certain
malignancies.
1. ADVERSE EFFECTS:Hypersensitivity reactions
Nausea,diarrhoea

URICOSURIC AGENTS• PROBENECID is a general inhibitor of the tubular
secretion of organic acids and SULFINPYRAZONE
is a derivative of phenylbutazone.
• At therapeutic doses, they block proximal tubular
absoption of uric acid.


CORTICOSTEROIDS
MECHANISM OF ACTION:-(cellular level)
Corticosteroids
Bind to high affinity
Receptor protein(cytoplasmic)
Migrate into the nucleus
Transcription of m-Rna
Regulation of protein synthesis

• The most important overall mechanism appears
to be limitation of inflammatory cells at the local
site.


IMPLICATIONS IN DENTISTRY

•
•
•
•

Recurrent oral ulceration
Severe oral lesions
TMJ pain and stiffness
In case of patients who have been in recent past on
long term corticosteroid therapy,consideration has to
be given to the need for supplementary prophylactic
corticoid to cover a dental procedure.

• For traumatic procedures and those to be performed
under general anaesthesia ,supplemental steroids
may be needed,particularly if the dose and duration
of steroid therapy are such as to have caused
significant adrenal supression .


PREEMPTIVE DIASICS

 Recommended to orthodontic
patients before separator placement
IBUPROFEN(reduces pain
at 6 hours and at bedtime on the
night of separator placement)
NAPROXEN SODIUM

ORTHODONTICS
• Direct injection of prostaglandin into periodontal
ligament increases the rate of tooth movement.
• 2 types of drugs are known to depress the
response to orthodontic force and may
influence current treatment:

BISPHOSPHONATES

PROSTAGLANDIN INHIBITORS

BISPHOSPHONATES:-

• Synthetic analogues of pyrophosphate
+
Hydroxyapatite in bone,acts as specific inhibitors of
osteoclast mediated bone resorption.

PROSTAGLANDIN INHIBITORS:A) Corticosteroids and NSAIDS
B) Other agents
CORTICOSTEROIDS:Reduces PG synthesis
Both children and adults on chronic steroid
therapy- difficulty www.indiandentalacademy.com
in tooth movement.

NSAIDS
• Potent prostaglandin inhibitors like Indomethacin
can inhibit tooth movement.
OTHER AGENTS
• Tricyclic antidepressants
• Antimalarial drugs –can affect the response to
orthodontic force

• Phenytoin has been reported to decrease tooth
movement
• Some tetracycline(doxycycline) inhibits osteoclast
recruitment.


1. Acetaminophen has no effect on the rate
of tooth movement in rabbits
undergoing orthodontic tooth
movement.
2. Acetaminophen, a proven analgesic that
lacks the anti-inflammatory properties
of NSAIDS, appears to be the drug of
choice for the relief of orthodontic pain.

3. Some test subjects may have exhibited
deleterious effects on somatic growth
due either to acetaminophen toxicity or
to orthodontically induced pain.
4. Misoprostol had an insignificant
inhibitory effect on local PGE2
production; however, the degree and
rate of tooth movement was enhanced

REFERENCES
 Essentials of Pharmacology for Dentistry
K.D. Tripathi ;2005
Lippincott’s illustrared reviews
Clinical Pharmacology,8th edition
Clinical Pharmacology,9th edition
Basic and clinical Pharmaology,8th edition,Katzung
Neller’s illustrated Pharmacology
www.google.co.in
 Articles;Angle orthodontics,AJO-DO

• MANY OTHER WORKS IN
PROGRESS…


•QUESTIONS?????


THANK YOU
Leader in continuing dental education


Analgesics and antiinflammatory drugs /certified fixed orthodontic courses by Indian dental academy

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