Analgesics and pain control in

Dentistry
Iyad Abou Rabii
DDS. OMFS. MRes. PhD
Analgesics

– Central Analgesics
– Peripheral Analgesics (NSAID)
Central Analgesics
 Central Analgesics

• Centrally acting analgesics are thought to affect

the opiate receptors in the brain and perhaps
also those in the spinal cord. (Receptors are
specialized sites with which a drug interacts to
produce its effects.)
• The most widely used and effective of these
narcotic analgesics are derived from opium
alkaloids. Morphine is one typical example
 Central Analgesics

• It is either
– opiates (natural) : morphine, codeine
– Opiates like (synthetic) : fentanyl, meperidine.
Methadone
– Endogenous opiates : enkipaline, endorphine,
endomorphine
Central Analgesics

• Opiates
– (Morphine, Heroine, Codeine, Fentanyl,
Meperidine, Tramadol, Alfetanil)
– Increase pain threshold and decrease reaction
movements
– Decreasing Respiratory Center`s sensibility for
CO2
– Some of them cause addiction
Central Analgesics

• Non-opiates
– Nevopame
– Not anti-inflamatory
– Don`t causes sleep
– Pain is reduced on the CNS level
Central Analgesics - opiates

• Morphine
Morphine receptors
• Morphine is attached to special cellular
receptors in order to perform its effects
• Three kind of receprors are been identified
– Mu µ
– Kappa κ
– Delta δ
Morphine receptors
 Morphine receptors

• Mechanism of action
Morphine is linked to theses receptors
– Activating receptor activated Potassium channels
causing rapid burst of K outside the neuron cell
(hyperpolarization)
– Decrease the voltage-gated calcium chanels
activity preventing calcium ions entrance (More
hyperpolarization)
– Hyperplorisation prevent propagation of the action
potential (electrical signals) along the axon.
 Morphines

• For sever and mild pain, two types

– Opium derived from opium plant
– Opium agonists
• Natural (Endomorphine)
• Synthetic (Methadon, meperidine, Alfantenyl))
 Morphine Agonists

• Classified to
1. Strong Agonists
1. Morphine 4 h
2. Meperidine 2h
3. Methadone24 h
4. Heroine 2 h
5. Alfentanyl 5 ‫ا‬to 45 min
 Mild Agonists (Hydropoxyphene, Codeine)
 Morphine

3. mixed agonists and antagonists

1. Pentazocaine: Agonist on κ and weak antagonist on µ and
δ
2. Nalbuphine : same as Pentozocaine but stronger afonist to
µ
3. Buprenorphine : 0.4 mg from it is equal to 10 mg of
Morphene it is partial agonist to µ and antagonist to κ
 Morphines

4. Antagonists
1. Naloxon : Rapidly emove opiums linked to the receptors µ ،
κ and δ (30 sec after inhection)
2. Naltrixone its effects are longer than naloxon (one oral
administration can block heroine effects for more than 48 h)
Morphines
Pharmaceutical effects
• Opium can affect CNS, Digestive tube, pupil,
and cardio vascular system.
• CNS
1. Prevent pain reception with a dose related effect
2. Sedation but with high doses convulsion may occur
3. Euphoria (False feeling of happiness)
4. 10 mg (IV) for mild pain
15-20 mg (IV) for severe pain (respiratory
depression is possible at this dose)
Pharmaceutical effects
• CNS (suite)
6. Decrease the RC (Respiratory Center) sensibility to
CO2 blood level. In that case no benefit of giving
pure Oxygen (apnea may develop)
7. Nausea and vomiting (Phenothiazine is
administrated to overcome these effects)
8. cough suppressant (specially Codeine)
Pharmaceutical effects
• Digestive system
1. Spasm of sphincters
2. Constipation
3. These effects can be reversed by the
administration of atropine (Acetylcholine
receptors antagonists)
Pharmaceutical effects
• Other
1. Morphine pin point pupils
2. Hypotension
3. Bronchospasme
4. ischuria (urinary retention)
Pharmacodynamic
• Can be used orally, mostly used by injection
• Analgesic for the treatment of pain (except
spasmodic origin , why?)
• Its effect starts
– IV : 7 min
– IM : 20 min
– SC (subcutaneous) : 40 min
Pharmacodynamic
• Metabolized in the liver (not to be used with
hepatic pathology)
• Eliminated by kidneys as inactive metabolites
• Also eliminated by sweat, bile, and maternal milk
(not to be administrated to breast feeding
woman)
Opium in Dentistry
1. Low to mild pain (codeine ,hydrocodone
oxycodone Propoxyphene, and tramadol)
2. For severe pain: Morphine, Pentazocaine
Butorfanol, Meperidine, and Fentanyl
Opium in Dentistry
• In most cases dental pain is accompanied or
caused by an inflammation process, so NSAIDs
is the first choice.
• Anyhow it is not uncommon to use a
combination of opium with Aspirin or other
NSAID, thus two pain control mechanisms are
combined.
 Opium in Dentistry
• Oral way is the preferred way of opium
administrations
• Most opiums have their effects appears
after 2 hours, dose cant be repeated
safely after 2 hours of the first
administration if needed
• Injection forms of opium can not be
administrated in dental clinics
Codeine
• 30 to 60 mg orally every 4-6 h
• With this dose side effects of Codeine is
negligable
• In higher dose constipation and nausee
may be noticed
• Used normally in combination with NAISD
Hydrocodone and oxycodone
• Used orally
– Hydrocodone 30 mg every 4-6 h oxycodone 5
mg every 4 to 6 h
• Pharmaceutical effects of 5 mg of
Oxycodone equal to 30-60 mg of Codeine
‫ ا‬Propoxyphene
• Some false rumors about the addiction capacity
of Codeine led to the development of
Propoxyphene
• Used for mild pain
• Its sedative action is lower than Codeine
• Normally used in combination with Paracetamol
(60 to 100mg)
Morphine
• For severe pain
• The dose for 70 kg weight patient is 10 mg
• The best sedative effect between opium
• but also side effects (constipation, nausea,
respiratory depression, addiction) are most
obvious comparing to other opiums
Non Steroidal Anti-Inflammatory
Drugs (NSAIDs)
NSAIDs

– Have analgesic, antipyretic V, and anti-

inflammatory effects
– NSAIDs are Prostaglandin Antagonist
– Prostaglandin is important mediator of
inflammation, pain and fever
Prostaglandin and Cyclooxygenases
• Prostaglandins are produced
following the sequential
oxidation of AA, DGLA or EPA
by cyclooxygenases (COX-1
and COX-2) and terminal
prostaglandin synthases:
• COX-1 is responsible for the
baseline levels of
prostaglandins.
• COX-2 produces prostaglandins
through stimulation.

(GLA) Gamma-linolenic acid

 (AA) Arachidonic acid 
(EPA) Eicosapentaenoic acid 
NSAIDs

• COX-1 and COX-2 are both located in the blood

vessels, stomach and the kidneys,
• Prostaglandin levels are increased by COX-2 in
scenarios of inflammation.
• Inhibiting COX-1 is responsible of NSAIDs side
effects
• A third form of COX, termed COX-3 is thought to
exist in the brain and may be associated with relief
of Headaches when on NSAID therapy.
 NSAIDs

• COX-2 selective inhibitor is an anti-inflammatory

drug (NSAID) that directly targets COX-2, with such NSAID
pharmaceutical effect are maximal while side effects are
minimal
NSAIDs-Pharmacodynamics

– Well absorbed in the digestive tube

– Metabolized in the liver
– Essentially eliminated by the Kidney
Paracetamol
• Most used NSAID especially when Aspirin is
contraindicated
• Inhibit prostaglandin formation in the CNS level only
(cox-3)
• Thais explains its maximal antipyretic and analgesic
effects, and minimal anti-inflammatory effects (preferred
with infection)
• 500 to 650 mg x4 daily
• Can be increased to 1000 mg X4 daily if needed
Paracetamol
• Side effects
– No side effects with therapeutic dose
– Allergy is rar
– Extensive use mais
– Excessive use of paracetamol can damage multiple
organs, especially the liver and kidney.
• Non Tetragenic, can be administrated to pregnant and
breast feeding woman.
Aspirin

• Aspirin also known as acetylsalicylic

acid abbreviated ASA
• First choice in non-infection origin dental pain
treatment (when there is no contraindication)
• Very effective in acute dental pain (650 mg of Aspirin
is more effective than 60 mg of Codeine)
• The maximum effect of aspirin is not dose related (all
or none), increasing the dose more than 650 mg is
useless
• This dose is repeated four time daily.
Aspirin
• Aspirin use has been shown to increase the risk
of gastrointestinal bleeding.
• Although some enteric coated formulations of
aspirin are advertised as being "gentle to the
stomach", in one study enteric coating did not
seem to reduce this risk.
Aspirin
• Combining aspirin with other NSAIDs has also
been shown to further increase this risk.
• Using aspirin in combination with clopidogrel or 
warfarin also increases the risk of upper
gastrointestinal bleeding.
Aspirin
• Large doses of salicylate, a metabolite of aspirin,
have been proposed to cause tinnitus
• Reye's syndrome, a severe illness characterized
by acute encephalopathy and fatty liver, can occur
when children or adolescents are given aspirin for
a fever or other illnesses or infections
•  Aspirin (or aspirin-containing products) should not
be given to anyone under the age of 12 who has a
fever
  Propionic Acid derivatives 

• Ibuprofen, fenoprofen, ketoprofen, and

flurbuprofen.
• Effective for mild pain
• Used safely with children
  Propionic Acid derivatives 

• Ibuprofen
– 400 mg X4 daily
– May be administrated preoperatively to reduce
postoperative pain
• Naproxen
– For mild pain
– 500 mg then 250 mg X3 daily
 Propionic Acid derivatives 

• Flurbuprofen
– More effctive than Ibuprofen
– 50-100 mg of it equal 400 mg of Ibuprofen in
efficacity
– Daily dose is 300 mg divided on 2 to 3
administration. (150 X2 or 100 X 3)
Etodolac
• Etodolac
– Efective dose for dental pain is 200 – 400 X3
daily
– Analgesic effect with this dose starts after 30
min and last for 4-6 h
– Daily dose shouldn`t exceed 1200 mg
Diclofenac
• Diclofenac
– Its pharmaceutics and side effects are similar
to Naproxen
– Dose is 25-50 mg X3 daily
Nimesulide
• Its side effects are minor, excellent
analgesic and anti-inflammatory effects
• Analegesic effect are stronger than
Ketoprofen (most effective propionic acid)
• Given orally 100 mg X2 daily
Possible analgesics
combinations
• Opiums + non-opiums
• Non-opiums + non-opiums
• NSAIDs + Caffeine
• NSAIDs + Sedative
 Opiums + non-opiums

 Good strategy (two pain control

mechanisms are involved)
 Most used non-opium used is Codeine
(60 mg)
 Dextropropoxyphene (65 mg) might also
be used but it is less effective than
Codeine
 NSAIDs + Sedative

• NSAIDs can be combined with sedatives

(Diphenhydramine hydrochloride)
• This help to release dental origin pain
normally accompanied with insomnia
• But increased possibility of Drug-drug
interaction should be considered when
administrated with other drugs
1. Mild Agonists: Hydropoxyphene,
Codeine
2. Strong Agonists: Morphine ,
Meperidine ,Methadone, Heroine
,Alfentanyl 5 ‫ا‬to 45 min