CH6: Opioid Analgesics and antagonists slides

Learning objectives

⚫ Explain the classification, mechanism of action, and pharmacokinetics of opioids.

⚫ List and describe the pharmacologic effects and potential adverse reactions of opioids.

⚫ Discuss the addiction potential of opioid, including treatment.

⚫ Name and explain the analgesic actions of the most common opioid agonists.

⚫ Discuss the actions of and provide examples of the mixed opioids.

⚫ Summarize the mechanism of action of tramadol.

⚫ Apply the use of opioids to dentistry.

Opioids

⚫ Classified many ways by mechanism of actions, chemical structure, and efficacy.

– MOA: agonists, mixed opioids, antagonists

– Structure: morphine/codeine, methadone, morphinan, meperidine, other

– Efficacy

Mechanism of action

⚫ Bind to receptors in the CNS and the spinal cord.

⚫ Important Receptors: mu(μ), kappa(κ), delta(δ)

Mu-pain

K-anxiety

Pharmacokinetics

⚫ Absorption

– Oral, nasal, skin

⚫ Distribution

– First-pass metabolism; distributed to fetus

⚫ Metabolism

– Conjugated in the liver with glucuronic acid

⚫ Excretion

– Excreted in urine

⚫ Onset~ 1 hour; Q 4-6 H dosing

Pharmacologic effect

⚫ Analgesia

⚫ Sedation and euphoria

⚫ Cough supression

⚫ GI Effects

Adverse reactions

⚫ Respiratory Depression

⚫ Nausea and emesis

⚫ Constipation

⚫ Miosis-pupil constriction; seen in overdose

⚫ Urinary Retention

⚫ CNS

⚫ Cardiovascular

⚫ Biliary tract constriction

⚫ Histamine release

⚫ Pregnancy-C; birth defects; NO

⚫ Addiction

Overdose

Major symptom-respiratory depression

Other-coma, pinpoint pupils, shallow breathing

Treatment drug-naloxone (antagonist)

Symptoms of withdrawal

⚫ Yawning

⚫ Lacrimation

⚫ Perspiration

⚫ Rhinorrhea

⚫ Gooseflesh

⚫ Irritability

⚫ Nausea

⚫ Vomiting

⚫ Tachycardia

⚫ Tremors

⚫ Chills

Addiction treatment

⚫ Methadone Substitution

⚫ Cold Turkey

⚫ Methadone Maintenance-tolerance

⚫ Naltrexone (Trexan)-block effects (antagonist)

Opioid agonists

⚫ Morphine (MS Contin)

– Prototype (10 mg)

– Post-op care

– Terminal Illness

⚫ Oxycodone

– Percodan (also has aspirin) , Percocet (also has acetaminophen), OxyContin

– Moderate-to-severe pain

⚫ Hydrocodone

– Many combination products (APAP)

– Watch max dose of APAP

⚫ Codeine

– Most common opioid used in dentistry

– Weak analgesic

– Tylenol #3 (30 mg of codeine)

⚫ **Propoxyphene (Darvocet)

– Synthetic

– Questionable use

– Cardiotoxic metabolite

— Not available anymore

⚫ Meperidine (Demerol)

– High first-pass effect

⚫ Hydromorphone (Dilaudid)

– Effective orally

– Severe pain

– More potent than morphine

⚫ Methadone (Dolophine)

– Addict treatment

– Risks (heart, respiratory; usually seen for peeps who are new at taking opioids)

⚫ Fentanyl Products

– Duragesic, Sufenta, Alfenta

– Often used during general anesthesia

– Fentanyl patch

Mixed opioids

⚫ Pentazocine (Talwin)

– Available orally

– Can increase BP and HR

– Available with naloxone (Talwin-NX)

⚫ Butorphanol (Stadol)

– Nasal spray

⚫ Dezocine (Dalgan), nalbuphine (Nubain),

butorphanol (Stadol)

– All available parenterally

⚫ Buprenorphine (Buprenex, Subutex)

– Partial agonist

– Oral and parenteral

Know partial agonist

Opioid antagonists

⚫ Naloxone (Narcan)

– Active parenterally (IV, IM)

– Drug of choice for overdoses

⚫ Nalmefene (Revex)

⚫ Naltrexone (ReVia, Vivitrol)

– Maintenance in detoxification

– Acute hepatitis and liver failure

tramadol (ultram)

⚫ Inhibits reuptake of NE and serotonin

⚫ Adverse Reactions

– Dizziness, somnolence, headache, nausea, vomiting, diarrhea, constipation, palpitations, diaphoresis, seizures

– Withdrawal

Schedule 4 controlled substance

Dental use

⚫ Can use when NSAIDs are contraindicated

⚫ Not for chronic pain-want to know source

⚫ Prescription writing