Use of opioid drugs in orofacial pain.pptx

Resource Faculties:
Dr. Iccha Kumar Maharjan
Dr. Pragya Regmee
Dr. Abhinaya Luitel
Department of Oral Medicine and Radiology
Common Analgesics used in
Orofacial pain - II
Presented by:
Kapil Dhungana
4th year
Roll No.: 891

Contents
Opioids
Introduction
Classification
Morphine as prototype drug
Other opioids
Opioids in dental pain
Anticonvulsants drugs
Antidepressants
Local anesthetics
Topical: Capsaicin cream
Blocks: Local and Regional
Conclusion and MCQs
Thursday, April 18, 2024 3

Opioid analgesics
Opium:
• A dark brown resinous material obtained from poppy (Papaver
somniferum) capsule.
• It contains two types of alkaloids:
1. Phenanthrene derivatives:
Morphine
Codeine
Thebaine (Non-analgesic)
2. Benzoisoquinolone derivatives:
Papaverine
Noscapine
Non-analgesic

OPIATES and OPIOIDS ?
Compounds that
are naturally
derived from
opium are called
‘opiates’.
e.g., Morphine,
Codeine, Thebaine
All those having
morphine-like
action,
irrespective of
chemical nature,
are called
‘opioids’.
e.g., Fentanyl

Morphine-prototype drug
Pharmacological actions
1. CNS:
Site specific depressant and stimulant (mu opioid receptor interaction)
• Analgesia:-
 Dull poorly localized visceral pain is relieved better
but at high doses, can mitigate even sharp somatic severe pain.
 Nociceptive pain >>> Neuropathic
 Morphine and other opioids suppress both perception of pain and its
emotional component (suffering, distress, anxiety, fear) so that pain
is no longer as unpleasant or distressing, i.e. The patient tolerates
pain better.

• Sedation:- Drowsiness, mental dullness and indifference to
surrounding as well as own body but without motor
incoordination or ataxia.
• Subjective effects and euphoria:- Prominent calming effect. Loss
of apprehension, feeling of detachment, lack of initiative, mental
clouding, inability to concentrate, kick
• Respiratory center:- Depressed in dose dependent manner, cause
of death during poisoning

• Cough center:- depressed more sensitive than respiratory center
• Temperature regulating center:- depressed, hypothermia in cold
periphery
• Vasomotor center:- depressed at higher doses and fall in BP
• Morphine stimulates CTZ (nausea and vomiting),
• But at higher doses, depress the vomiting center thus emetics should
not be used in morphine poisoning.
• Edinger Westphal nucleus (miosis). Pinpoint pupil is the tell-tale
sign of opioid use.

2. CVS:
3. GIT: Constipation due to
• Decrease propulsive movements
• Spasm of pyloric, ileocecal and anal sphincters
• Decreased GI secretions
4. Other smooth muscles:
• Biliary tract- biliary colic
• Urinary bladder- urgency and difficulty in micturition
• Bronchi- morphine causes release of histamine-
bronchoconstriction (dangerous in asthmatic)

Pharmacokinetics Of Morphine
• Oral absorption- unreliable - high and variable first pass metabolism
• Wide distribution
• Concentration in liver, spleen and kidney is higher than plasma
• Freely crosses placenta (affects fetus more than mother)
• Metabolized in liver by glucuronide conjugation
• Morphine-6-glucuronide is an active metabolite (more potent than
morphine on μ opioid receptors), which accumulates during chronic
dosing and contributes to analgesia.

Adverse Effects:
1.Side effects: sedation, mental clouding, lethargy, constipation,
respiratory depression, blurring of vision, urinary retention, fall in BP in
hypovolemic patient
2.Idiosyncrasy and allergy: rare, urticaria, itching, swelling of lips. Local
reaction at site of injection due to histamine release
3.Apnea in newborn: when given to mother during labor
(T/t: naloxone 10μg/kg injected in the umbilical cord)

. 4. Acute morphine poisoning:
• It is accidental, suicidal or seen in drug abuser.
• In non tolerant adult 50mg, i.m. produces toxicity.
• Lethal dose for human is 250 mg
• The characteristic triad of symptoms are respiratory depression,
pinpoint pupils and coma.
• Death due to respiratory failure

TREATMENT FOR MORPHINE POISONING
Respiratory support with positive pressure respiration and maintenance of
BP (I.V. Fluids, vasoconstrictors)
Gastric lavage with KMNO4
Specific antidote:- Naloxone 0.4-0.8 mg i.v. Repeated every 2-3 min till
respiration pick up.

5. Tolerance and dependence:
• Tolerance is exhibited to most actions, but not to constipating, miotic
and proconvulsant actions.
• It produces addiction and psychological & physical dependence.
• Withdrawal symptom are seen.
• Withdrawal of morphine is associated with marked drug-seeking
behavior.
Treatment:
• Consists of withdrawal of morphine and substitution with oral
methadone followed by gradual withdrawal of methadone.

PRECAUTIONS AND CONTRAINDICATIONS
1. Infants and the elderly are more susceptible to the respiratory
depressant action of morphine.
2. It is dangerous in patients with respiratory insufficiency
3. Bronchial asthma: Morphine can precipitate an attack by its histamine
releasing action. A high potency opioid with lower histamine
releasing potential (e.g. fentanyl) should be used, if unavoidable,
in an asthmatic.
4. Hypotensive states and hypovolemia exaggerate fall in BP due to
morphine.
5. Elderly male: chances of urinary retention are high.

6. Head injury: Reasons are—
• By retaining CO2, it increases intracranial tension which will add to
that caused by head injury itself.
• Even therapeutic doses can cause marked respiratory depression in
these patients.
• Vomiting, miosis and altered mentation produced by morphine
interfere with assessment of progress in head injury cases.
7. Undiagnosed acute abdominal pain:
• Morphine can aggravate certain conditions, e.g. Diverticulitis, biliary
colic, pancreatitis.
• Inflamed appendix may rupture.
• Morphine can be given after the diagnosis is established.

Drug interactions
• Actions of morphine is potentiated by:-
-Anti-Psychotics
-Tricyclic Antidepressants
-MAO Inhibitors
-Amphetamine
-Neostigmine
• Morphine retards the actions of many orally administered drugs by
delaying gastric emptying.

Hallucinogenic effects
M
U
C
A
R
D
S

CODEINE
• It is methyl-morphine, occurs naturally in opium and partly converted in
body to morphine
• Less potent than morphine (1/10th as analgesic), partial agonist of mu
receptor with low ceiling effect
• Degree of analgesia is comparable to aspirin
(60 mg of codeine = 600mg of aspirin = 10mg of Oral morphine)
• Not preferred in pediatric patients
Codeine Phosphate 10 mg + Paracetamol 500 mg
Codomol is used in patients in whom NSAIDS like ibuprofen,
naproxen are contraindicated e.g. Aspirin therapy.

HEROIN
• It is about 3 times more potent than morphine; more lipid soluble,
therefore enters the brain more rapidly, acts faster but duration of action
is similar.
• It is considered to be more euphoriant (especially on i.v. Injection) and
highly addicting.
• Because of its high potency, it has been favored in illicit drug trafficking.
• The sedative, emetic and hypotensive actions are said to be less
prominent.

PETHIDINE
• Though chemically unrelated to morphine it interact with opioid
receptors and action are blocked by naloxone.
• 1/10th of dose is as potent as morphine.
• Spasmodic action on smooth muscle is less marked – miosis,
constipation, urinary retention less prominent.
• Tachycardia due to antimuscarinic effect.

FENTANYL
• Pethidine congener, 80-100 times more potent than morphine both in
analgesia and respiratory depression.
• Produces peak analgesia in 5 min after i.v. injection
• Route of administration
Transdermal patch:
Uses: Chronic intractable pain due to cancer and other chronic pain.
Doses available: 12mcg/hr, 25mcg/hr, 50mcg/hr, 75mcg/hr, 100mcg/hr
Sites: Applied to intact, non-irritated, and non-irradiated skin on a flat
surface (eg, chest, back, flank, or upper arm)

• Transdermal fentanyl should only be used for specific
indications as it is very expensive.
• Fentanyl is indicated if a patient cannot take oral medication.
• It is also indicated in patients with renal impairment as fentanyl
is less cumulative than morphine in renal impairment

REMIFENTANIL
• This faster acting congener of fentanyl has a very brief (10–15 min)
duration of action after i.v. injection;

METHADONE
• Slow and persistent nature of action.
• Sedative and subjective effects are less intense.
• Incapable of giving a ‘kick’.
• Abuse potential is rated lower than morphine.
• Uses: Primarily used as substitution therapy for opioid dependence

TRAMADOL
• Centrally acting analgesic
• Relieves pain by opioid as well as additional mechanisms
It inhibits reuptake of Noradrenaline and Serotonin, thus activates
monoaminergic spinal inhibition of pain
• Uses:
Mild to moderate short lasting pain e.g. Injury, surgery
Chronic pain including cancer pain but not in severe pain
Recommended dosing is 50 to 100 mg orally every 4 to 6 hours,
not to exceed 400 mg in 24 hours.

• NSAIDS are more effective and more suitable than opioid analgesics.
• Opioid analgesics are typically reserved for cases where NSAIDS are
insufficient or contraindicated, and they are usually used as
adjunctive therapy with NSAIDS rather than primary treatment.
Opioids in Oro-facial pain

• When opioids are necessary, oral formulations like codeine or
tramadol are commonly prescribed due to their effectiveness in
managing mild to moderate pain and their lower risk of
dependence compared to stronger opioids like morphine or fentanyl.
• Role of injected opioids like morphine, pethidine or fentanyl in
dentistry is limited to occasional intraoperative or perioperative
use to supplement the local anesthetic and to alleviate apprehension.
• In oral medicine, opioid use is limited to cancer and Neuropathic pain.

• The primary focus in managing dental pain should be on treating the
underlying cause through appropriate local and systemic
measures, such as antiseptics, Restorations, RCT, and antibiotics when
necessary.

Mechanism of Action: enhances GABA-mediated release of Cl- channel
opening
Uses:
 Diabetic neuropathy
 Post herpetic neuralgia
 Prophylaxis in migraine
 As add on therapy in trigeminal neuralgia
 Burning mouth syndrome: Post Traumatic Neuropathic Pain
GABAPENTIN
• Gabapentin for neuropathic pain: start 300mg at night
• Increase by 300mg every 2-3 days (300mg at night >> 300mg bd>> 300mg tds >> 600mg bd)
• Maximum dose 2400mg but if no benefit after 900mg it is unlikely that it will be effective

PREGABALIN
Uses: used for neuropathic pain, such as diabetic neuropathy,
postherpetic neuralgia, complex regional pain syndrome (CRPS)
and certain other types of chronic pain.
• Pregabalin start at a dose of 50 mg three times daily or 75 mg twice daily
• Doses greater than 300 mg/day have not consistently shown additional benefit for the treatment
of neuropathic pain conditions
• Caution – renal impairment

CARBAMAZEPINE
Mechanism of Action: prolongation of Na+ channel inactivation
Pharmacokinetics:
• Carbamazepine is absorbed slowly and erratically from the GI tract
• Well distributed in the body including the cerebrospinal fluid (CSF)
• Repeated use causes enzyme induction and reduces the effectiveness
of the drug itself (autoinduction) as well as that of valproate,
phenytoin, lamotrigine, topiramate, oral contraceptive (OC) pills, etc.

Adverse effects
• Sedation, drowsiness, vertigo, ataxia, diplopia, blurred vision,
nausea, vomiting and confusion.
• Hypersensitivity reactions are skin rashes, eosinophilia,
lymphadenopathy and hepatitis.
• On chronic therapy, it may cause water retention due to the
release of Antidiuretic Hormone (ADH).
• Also possess teratogenic potential especially with valproate
combination.

OXCARBAZEPINE
• Oxcarbazepine is an analogue of carbamazepine
• Mechanism of action and therapeutic uses are similar to
carbamazepine.
• Enzyme-inducing property is much less; hence drug interactions
are very few. It is less potent and less toxic than carbamazepine.

Uses:
Trigeminal Neuralgia

TOPIRAMATE
• Weak carbonic anhydrase inhibitor
• It appears to act by multiple mechanisms,
• Phenytoin like prolongation of Na+ channel inactivation,
• Suppression of repetitive neuronal firing,
• GABA potentiation by a postsynaptic effect,
• Antagonism of certain glutamate receptors
• Neuronal hyperpolarization through K+ channels
• Topiramate has been approved for prophylaxis of migraine

Antidepressants
SSRIs: Paroxetine (20 mg/d) and Sertraline (50 mg/d) useful for
Burning Mouth Syndrome.
SNRIs: Duloxetine (20-40 mg OD or BD) used in Post Traumatic
Neuropathic Pain

Local anesthetics
Topical: Capsaicin cream
Capsaicin is a substance that is derived from red-hot chilly peppers
Capsaicin is used to help relieve diabetic peripheral neuropathy and
postherpetic neuralgia, but it will not cure the condition.
Capsaicin cream 0.025% is used for burning mouth syndrome and
Post Traumatic Neuropathic Pain
Blocks: Local and Regional
Local Anesthesia is injected to the painful site in Post herpetic neuralgia
and Regional anesthesia can be used to prevent Post Traumatic
Neuropathic Pain and CRPS

CDC Clinical Practice Guideline for
Prescribing Opioids for Pain
Informed
Discussion
Maximize
Non-Opioid
Therapies
Immediate-
Release
Opioids
Lowest
Effective
Dosage
Limited
Quantity
Regular
Evaluation
Assessment
of Risks
Review of
Prescription
History
Treatment
for Opioid
Use Disorder

Summary
Challenges in Treating Orofacial Pain:
• Subjective Nature
• Psychological overlays
• Chronic pain can cause anxiety and depression
• Complexity of anatomical region
• Opioids are the last resort for severe pain like advanced cancer
post-surgical pain or terminal illness. That's if all other classes of
medications have really failed. And even when a strong opioid
medication is considered, it is only for a short trial owing to their
potential to cause addiction.

MCQs:
1. The safe dose of morphine per day is:
a. <50 mg oral morphine equivalent/day
b. 50-100 mg oral morphine equivalent/day
c. 100-200 mg oral morphine equivalent/day
d. No dose of morphine is safe

2. A 35 year old patient complaining of severe pain along the
right side of the jaw and face; the best choice for this neuralgic
pain is:
a. Methadone.
b. Ibuprofen.
c. Carbamazepine.
d. Lorazepam.
e. Amphetamine.

The tell-tale sign of opioid use is ????
3. The opioid which wont result in pin point pupils is?
a. Morphine
b. Codeine
c. Heroine
d. Pethidine

References
• Essentials of medical pharmacology 8th ed. Edition by KD
Tripathi
• Pharmacology for medical graduates 4th edition by Tara V
Shanbhag and Smita Shenoy
• Burket's Oral Medicine by Martin S. Greenberg, Michael
Glick, Jonathon A. Ship

• https://www.researchgate.net/publication/342121970_Indian_Society_for_Study_of_
Pain_Cancer_Pain_Special_Interest_Group_Guidelines_on_Pharmacological_Manage
ment_of_Cancer_Pain_Part_I
• https://www.researchgate.net/publication/6224755_Evidence
based_approach_to_the_medical_management_of_trigeminal_neuralgia?_tp=eyJjb2
50ZXh0Ijp7ImZpcnN0UGFnZSI6Il9kaXJlY3QiLCJwYWdlIjoiX2RpcmVjdCJ9fQ
• Garcia R, Chen Q, Posadas E, et al. (March 01, 2023) Continuous Ketamine Infusion
as a Treatment for Refractory Facial Pain. Cureus 15(3): e35638.
doi:10.7759/cureus.35638
• https://emedicine.medscape.com/article/2138678 overview?form=fpf#a1

Thank
you

Unanswered Questions:

FENTANYL
• Pethidine congener, 80-100 times more potent than morphine both in
analgesia and respiratory depression.
• Produces peak analgesia in 5 min after i.v. injection
• Route of administration
Transdermal patch:
Uses: Chronic intractable pain due to cancer and other chronic pain.
Doses available: 12mcg/hr, 25mcg/hr, 50mcg/hr, 75mcg/hr, 100mcg/hr
Sites: Applied to intact, non-irritated, and non-irradiated skin on a flat
surface (eg, chest, back, flank, or upper arm)

Autoinduction
• Autoinduction in drug metabolism is a known phenomenon
observed when a drug induces the enzymes responsible for its
own metabolism.
• Some drugs which exhibit autoinduction are:
• Phenytoin
• Rifampin
• Carbamazepine

Management of Opioid Related Side Effects
• Pre-prescription counseling on opioid side effects is crucial.
• Tolerance to many side effects develops within the first few days, except
for pruritus and constipation, which may persist throughout treatment.
• Constipation can be managed with anti-emetics, fluids, fiber-rich diet,
and a combination of stool softeners and stimulant laxatives.
• Central side effects like drowsiness and dizziness typically improve
gradually but may affect driving and concentration.
• Caution is needed with sedative substances, including alcohol.
Source: https://tinyurl.com/yy39xs7v

TRAMADOL
• Centrally acting analgesic
• Relieves pain by opioid as well as additional mechanisms
It inhibits reuptake of Noradrenaline and Serotonin, thus activates
monoaminergic spinal inhibition of pain.
• Uses:
Mild to moderate short lasting pain e.g. Injury, surgery
Chronic pain including cancer pain but not in severe pain
Recommended dosing is 50 to 100 mg orally every 4 to 6 hours,
not to exceed 400 mg in 24 hours.

•Rescue dose" of Tramadol
• A "rescue dose" of tramadol typically refers to an additional dose
taken for breakthrough pain when the regular dosing schedule isn't
providing adequate relief.
• Breakthrough pain is a sudden increase in pain that may occur in
patients who already have chronic pain from cancer, arthritis,
fibromyalgia, or other conditions.
• Around 25 mg to 50 mg of immediate-release tramadol is used as
rescue dose.

Serotonin Syndrome:
• Serotonin syndrome is typically caused by the use of two or more
serotonergic medications or drugs.
• This may include
• Selective serotonin reuptake inhibitor (SSRI)
• Serotonin norepinephrine reuptake inhibitor (SNRI)
• Monoamine oxidase inhibitor (MAOI)
• Tricyclic antidepressants (TCAs)
• Amphetamines
• Pethidine
• Tramadol
• Dextromethorphan

Agitation
Confusion
Delirium
Pressured speech
Excitement
Clonus
Hyperreflexia
(lower > upper)
Tremor
Seizure
Rigidity
Hyperthermia
Tachycardia
Hypertension/hypotension
Diarrhea
Diaphoresis
Mydriasis
Shivering

Hydrocodone and oxycodone
• Oxycodone is more potent than hydrocodone and is derived from
thebaine, while hydrocodone is derived from codeine.
Some commercially available drugs combination including hydrocodone
and oxycodone

Prescription for opioids:
• In context of BPKIHS, opioid drugs are available only after
written prescription by NMC registered anesthesiologist.
• Any patient requiring opioid drugs is referred to the Pain clinic,
Department of Anesthesiology, BPKIHS.
• Opioids are available only in Government-run Pharmacies in
Nepal.

Thank
you

Use of opioid drugs in orofacial pain.pptx

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