analgesics in maxillofacial surgery by dr. amit suryawanshi .oral & maxillofacial surgeon,...
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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!TRANSCRIPT
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AnalgesicsAnalgesics
Dr. Amit T. SuryawanshiOral and Maxillofacial Surgeon
Pune, India
Contact details :Email ID - [email protected]
Mobile No - 9405622455
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Contents Contents Introduction
– Pain– Analgesia
Analgesics Classification of analgesics NSAID’s
– History– Classification of NSAID’s– Mechanism of action– Adverse effects– Individual drugs
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ContentsContents 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
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Pain -Pain - “ 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.”
Introduction Introduction
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Goals of pain managementGoals of pain management
To relieve sufferingTo increase functional capacityTo improve quality of life
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Methods of pain controlMethods of pain control
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
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What is Analgesia?What is Analgesia? 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
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Analgesics
“Analgesics are drugs that selectively relieve pain by acting in the CNS or on the peripheral pain mechanisms, without altering consciousness”
Definition -
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History of AnalgesicsHistory of Analgesics BC:BC: 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
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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
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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 .
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Classification of NSAIDsClassification of NSAIDs
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
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Classification of NSAIDClassification of NSAID’’s s contdcontd……
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
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NSAIDs and prostaglandin (PG) NSAIDs and prostaglandin (PG) synthesis inhibitionsynthesis inhibition
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
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Cellular Arachidonic Acid MetabolismCellular Arachidonic Acid Metabolism
Stimulus
Phospholiapase A2
Lipoxygenases
Inflammatory
Leukotrienes
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Cyclo oxygenase pathwayCyclo oxygenase pathway
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Beneficial actions due to PG Beneficial actions due to PG synthesis inhibitionsynthesis inhibition
AnalgesiaAnti pyresisAnti inflammatoryAnti thrombotic
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Toxicities due to PG synthesis Toxicities due to PG synthesis inhibitioninhibition
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
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Adverse effects of NSAIDAdverse effects of NSAID’’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)
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Adverse effects of NSAIDAdverse effects of NSAID’’ss CNS
– Headache, mental confusion, behavioural disturbances, seizure precipitation
Haematological– Bleeding, thrombocytopenia, hemolytic
anaemia, agranulocytosis
Others– Asthma exacerbation, nasal polyposis, skin
rashes, pruritis, angioedema
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NSAID - GI toxicityNSAID - GI toxicity
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Routes of analgesic administrationRoutes of analgesic administration
OralIntramuscular InjectionIntravenous InjectionOther routes
– Transdermal• Fentanyl patch
– Sublingual • Morphine
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Salicylates -Asprin Salicylates -Asprin 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
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AspirinAspirin– 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
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AspirinAspirin
– 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.
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AspirinAspirin
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
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AsprinAsprin
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
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Propionic acid derivativesPropionic acid derivatives
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
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Propionic acid derivativesPropionic acid derivatives
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
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Anthranilic acid dervativeAnthranilic acid dervative 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
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Aryl-acetic acid derivativeAryl-acetic acid derivative 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
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Oxicam derivativesOxicam derivatives
Piroxicam -– Long acting NSAID– Reversible inhibitor of COX
Pyrrolo-pyrrole derivativeKetorolac
– Potent analgesic and moderate anti inflammatory activity
– Used in post operative pain after surgery and acute dental pain
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Indole derivativeIndole derivativeIndomethacin
– Potent antiinflammatory and antipyretic action– High incidence of GI and CNS side effects.
Pyrazolones derivative Metamizol and propiphenazone are used as analgesic
and antipyretics
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Preferential COX-2 inhibitorsPreferential COX-2 inhibitorsNimesulide
– 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 .
• Recently instances of hepatic failure have been reported
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Para-amino phenol derivativesPara-amino phenol derivativesParacetamol (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
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Paracetamol (Acetaminophen)Paracetamol (Acetaminophen)
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
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Opioid analgesicsOpioid analgesics
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Classification of opioidsClassification of opioids
Natural opium alkaloids– Morphine, codeine
Semi synthetic opiates– Diacetylmorphine (heroin), pholcodeine
Synthetic opioids– Pethidine (meperidine), fentanyl, methadone,
dextropropoxyphene, tramadol
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Morphine Morphine
– 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
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MorphineMorphine
– 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
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MorphineMorphine
– 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
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MorphineMorphine
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
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MorphineMorphine 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
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MorphineMorphine 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
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Codeine Codeine
Is methyl morphine Less potent than morphine (1/10th as analgesic) Is more selective cough suppressant
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Pethidine Pethidine
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
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Methadone Methadone
Chemically dissimilar but pharmacologically similar to morphine
Used– primarily as substitution therapy for opioid
dependence– Also in methadone maintenance therapy
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Tramadol Tramadol
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
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Opioid receptorsOpioid receptors
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
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Complex action opioids and opioid Complex action opioids and opioid antagonistsantagonists
Agonist- antagonist – Nalorphine– Pentazocaine– Butorphanol
Partial /weak agonist– Buprenorphine
Pure antagonist– Naloxone, naltrexone
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Pentazocaine Pentazocaine 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
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Opioids in dental pain Opioids in dental pain 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
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Analgesics & Medical conditionsAnalgesics & Medical conditions
NSAIDs should be given in 2nd triemister of pregnancy and opioids should be avoided .
Paracetamol is the safest drug to use in pregnancyAspirin & Ibuprofen should not be given in
asthmatic patientsAspirin & Paracetamol should not be given in
nephropathy.Codein should not be used in renal dysfunction
while fentanyl & methadone are safe .
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Adjuvant drugs Adjuvant drugs 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
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FUTUREFUTURE
Fentanyl patches Tramadol patches Diclofenac patches
Patient controlled transdermal system
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ReferencesReferences
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
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Thank you....