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 actionMorphine 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 antagonists1. 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. Antagonists1. 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.

• CNS1. 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 system1. Spasm of sphincters

2. Constipation

3. These effects can be reversed by the administration of atropine (Acetylcholine receptors antagonists)

Pharmaceutical effects

• Other1. 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

Propoxyphene ا

• 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