Description: Hi. This is Dr. Amit T. Suryawanshi. Oral & Maxillofacial surgeon from Pune, India. I am here on slideshare.com to share some of my own presentations presented at various levels in the field of OMFS. Hope this would somehow be helpful to you making your presentations. All the best & your replies are welcomed!

1. AAnnaallggeessiiccss
Dr. Amit T. Suryawanshi
Oral and Maxillofacial Surgeon
Pune, India
Contact details :
Email ID - amitsuryawanshi999@gmail.com
Mobile No - 9405622455

2. CCoonntteennttss
Introduction
– Pain
– Analgesia
Analgesics
Classification of analgesics
NSAID’s
– History
– Classification of NSAID’s
– Mechanism of action
– Adverse effects
– Individual drugs

3. CCoonntteennttss
Opioids
– Classification of opioids
– Individual drugs
– Opioid receptors
– Complex action opioids and opioid antagonists
- Opioids in dental pain
Analgesics and Medical conditions
Adjuvant drugs
Future of Analgesics
References

4. IInnttrroodduuccttiioonn
PPaaiinn --
“ An unpleasant emotional experience usually
initiated by a noxious stimulus and transmitted over
a specialized neural network to the central nervous
system where it is interpreted as such ”
- Monheim’s
“Pain is whatever the experiencing person says it is
and exists whenever he says it does.”

5. GGooaallss ooff ppaaiinn mmaannaaggeemmeenntt
To relieve suffering
To increase functional capacity
To improve quality of life

6. MMeetthhooddss ooff ppaaiinn ccoonnttrrooll
1. Removing the cause
2. Blocking the pathway of painful impulses
3. Raising the pain threshold
4. Preventing pain reaction by cortical depression
5. Using psychosomatic methods

7. WWhhaatt iiss AAnnaallggeessiiaa??
The word analgesia is derived from Greek word
analgetos (an – without ; algesia – pain )
‘Analgesia simply means the absence of pain without
losing consciousness’
“The analgesia system is mediated by 3 major
components :
1. Periaquaductal grey matter
2. Nucleus raphe magnus
3. Pain inhibitory neurons

8. Analgesics
Definition -
“Analgesics are drugs that selectively relieve
pain by acting in the CNS or on the peripheral
pain mechanisms, without altering
consciousness”

9. HHiissttoorryy ooff AAnnaallggeessiiccss
 BBCC:: Ancient Greeks and Romans used salicylate
extracts derived from willow leaves as analgesics
and antipyretics
 Middle Ages: Medicinal herb gardens featured
salicylate containing wintergreen and meadowsweet
plants
 1763: Edward Stone reported on use of willow bark
powder as an anti-inflammatory agent.
 1853: Von Gerhardt synthesized a crude form of
aspirin (acetylsalicylic acid)
 1860: Felix Hoffman synthesized pure aspirin

10. continued
Opiates are one of the oldest types of drugs in history
Opium is extracted from poppy seeds (Paper
somniforum)
Undisputed reference to opium found in writings from
the third century BC
Use of Opium was first recorded in China over 2000
years ago
Greeks dedicated the Opium poppy to the Gods of Death
(Thanatos), Sleep (Hypnos), and Dreams (Morpheus)
Sixteenth Century is the first reported use of Opium for
its Analgesic qualities

11. Contnd…
 1949: The NSAID Phenylbutazone was introduced
 1963: Indomethacin was introduced
 1971: Vane and Piper demonstrated that NSAIDs inhibit
prostaglandin production
 1974: Ibuprofen was introduced
 1976: Miyamoto et al identified the COX-1 enzyme
 1989: Simmons et al identified the COX-2 enzyme
 1999: The COXIBs celecoxib and rofecoxib were introduced
 2004: Rofecoxib was banned in india due to its cardiotoxic effect .

12. CCllaassssiiffiiccaattiioonn ooff NNSSAAIIDDss
Non selective COX inhibitors (conventional NSAID’s)
– Salicylates: Asprin
– Propionic acid derivatives: Ibuprofen, Naproxen,
Ketoprofen, Flurbiprofen
– Anthranilic acid derivative: Mephenamic acid
– Aryl-acetic acid derivatives: Diclofenac
– Oxicam derivatives: Piroxicam, Tenoxicam
– Pyrrolo-pyrrole derivative: Ketorolac
– Indole derivative: Indomethacin
– Pyrazolone derivatives: Phenylbutazone,
Oxyphenbutazone

13. CCllaassssiiffiiccaattiioonn ooff NNSSAAIIDD’’ss ccoonnttdd……
Preferential COX-2 inhibitors
– Nimesulide, Meloxicam, Nabumetone
Selective COX-2 inhibitors
– Celecoxib, Rofecoxib, Valdecoxib, Etoricoxib
Analgesics-antipyretics with poor anti inflammatory
action
– Para aminophenol derivative: Parcetamol
(Acetaminophen)
– Pyrazolone derivatives: Metamizol (Dipyrone),
Propiphenazone
– Benzoxazocine derivative: Nefopam

14. NSAIDs aanndd pprroossttaaggllaannddiinn ((PPGG))
ssyynntthheessiiss iinnhhiibbiittiioonn
Prostaglandins, prostacyclin (PGI2) and thromboxane
A2(TXA2) are produced from arachidonic acid by the
enzyme cyclo oxygenase which exists in 2 forms
– (COX-1) - Cyclo oxygenase -1
– (COX-2) - Cyclo oxygenase -2
• Most NSAID’s inhibit COX-1 and COX-2
non selectively
• Some selective COX-2 inhibitors have now been
produced

15. Cellular Arachidonic Acid Metabolism
Inflammatory
Stimulus
Phospholiapase A2
Lipoxygenases
Leukotrienes

16. CCyycclloo ooxxyyggeennaassee ppaatthhwwaayy

17. BBeenneeffiicciiaall aaccttiioonnss dduuee ttoo PPGG
ssyynntthheessiiss iinnhhiibbiittiioonn
Analgesia
Anti pyresis
Anti inflammatory
Anti thrombotic

18. TTooxxiicciittiieess dduuee ttoo PPGG ssyynntthheessiiss
iinnhhiibbiittiioonn
Gastric mucosal damage
Bleeding: inhibition of platelet function
Limitation of renal blood flow: sodium and water
retention
Delay / prolongation of labour
Asthma and anaphylactic reactions in susceptible
individuals

19. AAddvveerrssee eeffffeeccttss ooff NNSSAAIIDD’’ss
Gastrointestinal
– Gastric irritation, erosions, peptic ulceration,
gastric bleeding / perforation, esophagitis
Renal
– Sodium and water retention, chronic renal
failure, interstitial nephritis, papillary necrosis
(rare)
Hepatic
– Raised transaminases, hepatic failure (rare)

20. AAddvveerrssee eeffffeeccttss ooff NNSSAAIIDD’’ss
CNS
– Headache, mental confusion, behavioural
disturbances, seizure precipitation
Haematological
– Bleeding, thrombocytopenia, hemolytic
anaemia, agranulocytosis
Others
– Asthma exacerbation, nasal polyposis, skin
rashes, pruritis, angioedema

21. NNSSAAIIDD -- GGII ttooxxiicciittyy

22. Routes of aannaallggeessiicc aaddmmiinniissttrraattiioonn
Oral
Intramuscular Injection
Intravenous Injection
Other routes
– Transdermal
• Fentanyl patch
– Sublingual
•Morphine

23. SSaalliiccyyllaatteess --AAsspprriinn
Is acetylsalicylic acid
Pharmacological actions
– Analgesic, antipyretic, anti inflammatory actions
• Analgesic action is due to prevention of PG mediated
sensitization of nerve endings
• Resets the hypothalamic thermoregulatory centre
• Anti inflammatory at high doses
– Blood
• Irreversibly inhibits TXA2 synthesis thus interferes
with platelet aggregation and BT is prolonged
• Long term use of large doses decreases synthesis of
clotting factors in liver

24. AAssppiirriinn
– Respiration
• Anti inflammatory doses – stimulates respiration
• Hyperventilation in salicylate poisoning, in doses
higher than this there is respiratory depression
– Acid-base electrolyte balance
• Adults treated with aspirin 4-6g/day stay in a state of
compensated respiratory alkalosis
• Still higher doses can cause respiratory acidosis
• Dehydration occurs in poisoning due to increased
urine output, sweating and hyperventilation
– CVS
• No direct effect in therapeutic doses

25. AAssppiirriinn
– GIT
• Aspirin irritates gastric mucosa & causes epigastric
pain, nausea and vomiting
• ‘Ion trapping’ in gastric mucosa increases gastric
toxicity
• Acute ulcers, erosive gastritis, congestion and
microscopic hemorrhages
– Metabolic effects
• Chronic use can cause negative nitrogen balance by
increased conversion of protein to carbohydrate.

26. AAssppiirriinn
Pharmacokinetics
– Absorbed from stomach and small intestine
Precautions and contraindications
– Contraindicated in patients sensitive to it and in
peptic ulcer, bleeding tendencies, & in children
suffering from chicken pox or influenza. (due to
risk of Reye’s syndrome)
– In chronic liver disease
– Asprin should be stopped 5 days before elective
surgery, dental extraction
– Pregnancy and lactating mothers

27. AAsspprriinn
Adverse effects
– Most important – gastric mucosal damage and
peptic ulceration
– Acute salicylate poisoning
– Assosiated with Reye’s syndrome
Uses
– As analgesic
– As antipyretic
– Acute rheumatic fever
– Rheumatoid arthritis
– Osteoarthritis

28. PPrrooppiioonniicc aacciidd ddeerriivvaattiivveess
Ibuprofen –
 first introduced member of this class
Anti inflammatory efficacy is lower than asprin
Inhibit Prostaglandin synthesis
Adverse effects
– Milder and better tolerated than asprin
– GI disturbances are present
– Precipitate asprin-induced asthma

29. PPrrooppiioonniicc aacciidd ddeerriivvaattiivveess
Pharmacokinetics
– Well absorbed orally
Uses
– Analgesic and Antipyretic and anti-inflammatory
– Soft tissue injuries, tooth extraction, fractures, post
operative pain.
– Rheumatoid arthritis, osteoarthritis and
musculoskeletal disorders… where pain is more
prominent than inflammation

30. AAnntthhrraanniilliicc aacciidd ddeerrvvaattiivvee
Mephenamic acid-
– Inhibits COX & antagonises certain actions of PG’s
– Exerts peripheral as well as central analgesic action
Pharmacokinetics
– Oral absorption is slow but complete
Adverse effects - Diarrhoea
Uses
– Muscle, joint and soft tissue pain
– Effective in dysmenorrhoea

31. AArryyll--aacceettiicc aacciidd ddeerriivvaattiivvee
 Diclofenac sodium
– Inhibits PG synthesis
– Has short lasting anti platelet action
– Adverse effects are mild
 Pharmacokinetics
– Well absorbed orally
– Excreted both in urine and bile
 Uses
– Toothache
– Post operative and post traumatic inflammatory conditions
– Rheumatoid arthritis and osteoarthritis

32. OOxxiiccaamm ddeerriivvaattiivveess
Piroxicam -
– Long acting NSAID
– Reversible inhibitor of COX
Pyrrolo-pyrrole derivative
Ketorolac
– Potent analgesic and moderate anti inflammatory
activity
– Used in post operative pain after surgery and acute
dental pain

33. IInnddoollee ddeerriivvaattiivvee
Indomethacin
– Potent antiinflammatory and antipyretic action
– High incidence of GI and CNS side effects.
Pyrazolones derivative
Metamizol and propiphenazone are used as analgesic
and antipyretics

34. PPrreeffeerreennttiiaall CCOOXX--22 iinnhhiibbiittoorrss
Nimesulide
– Newer NSAID
– Completely absorbed orally
– Used in patient with history of asthma and
anaphylactic reactions to other NSAIDs.
– Used for short-lasting painful inflammatory
conditions like -
- sports injuries,
- sinusitis and other ENT disorders
- fever and low back pain
Adverse effect – Hepatotoxic in pediatric patients .

35. PPaarraa--aammiinnoo pphheennooll ddeerriivvaattiivveess
Paracetamol (Acetaminophen) -
– Central analgesic action similar to asprin, i.e it raises
pain threshold
– Has weak peripheral anti inflammatory component
– Promptly acting antipyretic
Pharmacokinetics
– Well absorbed orally
– Effects after oral dose last for 3-5 hours
Adverse effects
– Acute paracetamol poisoning – children

36. PPaarraacceettaammooll ((AAcceettaammiinnoopphheenn))
Uses –
– Most commonly used drug & One of the best
antipyretic drugs
– Can be used in all age groups, also in pregnant
and lactating women
Clinical studies have found paracetamol and
asprin to be equally effective in relieving pain
after 3rd molar extraction
And it is more safer than asprin – lesser GI
disturbances and bleeding tendencies

37. OOppiiooiidd aannaallggeessiiccss

38. CCllaassssiiffiiccaattiioonn ooff ooppiiooiiddss
Natural opium alkaloids
– Morphine, codeine
Semi synthetic opiates
– Diacetylmorphine (heroin), pholcodeine
Synthetic opioids
– Pethidine (meperidine), fentanyl, methadone,
dextropropoxyphene, tramadol

39. MMoorrpphhiinnee
– Alkaloid of opium
– Widely used
Pharmacological actions
CNS
– Analgesia
• Strong analgesic
• Nociceptive pain arising from peripheral pain
receptors is better relieved than neuritic pain
• Reactions associated with intense pain –
apprehension, fear are also depressed

40. MMoorrpphhiinnee
– CNS
– Sedation
• Drowsiness and indifference to surroundings as well
as to own body , ataxia and apparent excitement also
occur
• Higher doses produce sleep and coma
– Mood and subjective changes
• Calming effect
• Loss of apprehension, feeling of detachment,mental
clouding and inability to concentrate

41. MMoorrpphhiinnee
– Respiratory and cough centres
• Depresses Repiration and Cough centre
– Temperature regulating and vasomotor centre
• Depressed
– CTZ, vagal centre & certain cortical areas are
stimulated
– GIT
• Constipation is a prominent feature

42. MMoorrpphhiinnee
Neuro-endocrine
– Enhances ADH release and so urine volume is reduced
– Causes sympathetic stimulation – mild hypoglycemia
CVS
– Causes vasodilation
– Cardiac work is consistently reduced due to decrease in
peripheral resistance

43. MMoorrpphhiinnee
Pharmacokinetics
– Oral absorption is unreliable – high and variable first
pass metabolism
– Freely crosses placenta, affects foetus more than the
mother
Adverse effects
– Mental clouding, sedation and lethargy
– constipation
– Acute morphine poisoning
• Human lethal dose is 250mg .
• Death is due to respiratory failure

44. MMoorrpphhiinnee
Tolerance and dependence
– Partly pharmacokinetic (enhanced rate of metabolism)
but mainly pharmacodynamic (cellular tolerance)
– Treated by substitution with oral methadone
Precautions and contraindications
– Infants and elderly
– Bronchial asthma
– Head injury


45. CCooddeeiinnee
Is methyl morphine
Less potent than morphine (1/10th as analgesic)
Is more selective cough suppressant

46. PPeetthhiiddiinnee
Synthesized as an atropine substitute
Interacts with opioid receptors (mu)
Similar to morphine in most of its properties
– Uses
• As analgesic (substitute to morphine)
• In pre anaesthetic medication

47. MMeetthhaaddoonnee
Chemically dissimilar but pharmacologically
similar to morphine
Used
– primarily as substitution therapy for opioid
dependence
– Also in methadone maintenance therapy

48. TTrraammaaddooll
Centrally acting analgesic
 It is believed to work through modulation of serotonin
and norepinephrine in addition to its relatively-weak μ-
opioid receptor agonism
 100mg tramadol IV is equally analgesic to 10mg
morphine IM
Uses
– Mild to moderate intensity short lasting pain due to
surgery, dental procedures, injury etc

49. OOppiiooiidd rreecceeppttoorrss
Opioids interact with specific receptors present on neurons
in the CNS and peripheral tissues
Radioligand binding studies divide receptors into
– mu, kappa and delta
Pattern of effect of particular agent depends on the nature
of its interaction with different opioid receptors and also
its relative affinity to these receptors

50. CCoommpplleexx aaccttiioonn ooppiiooiiddss aanndd ooppiiooiidd
aannttaaggoonniissttss
Agonist- antagonist
– Nalorphine
– Pentazocaine
– Butorphanol
Partial /weak agonist
– Buprenorphine
Pure antagonist
– Naloxone, naltrexone

51. PPeennttaazzooccaaiinnee
Indicated in post operative and moderately severe
pain in trauma, cancer and burns,
Naloxone
Competitive antagonist for all opioid receptors
Injected i.v (0.4- 0.8mg) it antagonizes all actions
of morphine
Drug of choice in morphine poisoning

52. OOppiiooiiddss iinn ddeennttaall ppaaiinn
Opioids are less effective and suitable than NSAID’s for
dental pain
Mostly used as additional drugs with NSAID’s to boost
their analgesic effect
Among opioids oral codeine is most suitable
Oral tramadol and pentazocine are alternatives
Injectable opioids like morphine, pethidine are limited
to intra-operative use to supplement anaesthesia and to
allay apprehension

53. AAnnaallggeessiiccss && MMeeddiiccaall ccoonnddiittiioonnss
NSAIDs should be given in 2nd triemister of
pregnancy and opioids should be avoided .
Paracetamol is the safest drug to use in pregnancy
Aspirin & Ibuprofen should not be given in
asthmatic patients
Aspirin & Paracetamol should not be given in
nephropathy.
Codein should not be used in renal dysfunction
while fentanyl & methadone are safe .

54. AAddjjuuvvaanntt ddrruuggss
To supplement the action of analgesics
To limit the side effects of analgesics
Adjuvants
– Steroids
– Anti arrythmics
– Anti depressants
– Anti epileptics
– Serotonin reuptake inhibitors
– Muscle relaxants
Adjuvant medications are mostly used for chronic pain

55. FFUUTTUURREE
Patient controlled transdermal system
Fentanyl patches
Tramadol patches
Diclofenac patches

56. RReeffeerreenncceess
GOODMAN & GILLMAN PHARMACOLOGY
 Lippincott's Pharmacology
 Rang & Dale's Pharmacology
Essentials of Medical pharmacology – KD Tripathi
Essentials of Dental pharmacology – KD Tripathi
Oral and Maxillofacial surgery –Vol. 1 - Danial Laskin

57. Thank you....