[RHEUMATOLOGY] Analgesics - Narcotics

Narcotics

[INTRODUCTION]

These are drugs that produce narcosis, a state of stupor and insensibility.

Papaver somniferum

[GENERAL PHARMACOLOGY]

Source of MORPHINE

Papaver bracteatum

[GENERAL PHARMACOLOGY]

Source of THEBAINE

opioid receptors

[GENERAL PHARMACOLOGY]

The mechanism of action involves a mixed effect: narcotics activate _____ receptors and enhance the release of endogenous opioid peptides: endorphins, endomorphins, dynorphins, enkephalins.

● Endorphins

● Endomorphins

● Dynorphins

● Enkephalins

[GENERAL PHARMACOLOGY]

The mechanism of action involves a mixed effect: narcotics activate opioid receptors and enhance the release of endogenous opioid peptides:

● Mu (μ) receptor

● Kappa (κ) receptor

● Delta (δ) receptor

[GENERAL PHARMACOLOGY]

Different opioid receptors:

Mu (μ) receptor

[GENERAL PHARMACOLOGY]

Opioid receptors responsible for the MAJORITY of analgesic effect

Kappa (κ) receptor

[GENERAL PHARMACOLOGY]

Opioid receptors that provide additional analgesia in WOMEN

Delta (δ) receptor

[GENERAL PHARMACOLOGY]

Opioid receptors responsible for FINAL analgesia

● Analgesia

● Addiction

● Miosis

● Cough suppression

● Respiratory depression

● Convulsion

[GENERAL PHARMACOLOGY]

Central effects of narcotics:

● Cardiovascular (CVS) → Bradycardia (except Meperidine), venodilation

● Biliary tract → Contraction (except Meperidine)

● Gastrointestinal (GIT) → Constipation

● Uterine muscles → Tocolysis

● Mast cells → Anaphylactoid reaction → Pruritus

[GENERAL PHARMACOLOGY]

Peripheral effects of narcotics:

Meperidine

[GENERAL PHARMACOLOGY]

Narcotics can cause bradycardia except _______

Meperidine

[GENERAL PHARMACOLOGY]

Narcotics can cause contraction in the biliary tract except _______

● Visceral pain

● Acute pulmonary edema

● Anesthetic adjuncts (general anesthesia)

● Antidiarrheals

● Antitussive

[GENERAL PHARMACOLOGY]

Uses of narcotics:

● Somatic (musculoskeletal) pain → Treated with NSAIDs

● Visceral (internal organ) pain → Treated with narcotics

● Neuropathic (nerve) pain → Treated with anticonvulsants

[GENERAL PHARMACOLOGY]

Types of pain:

Tramadol

[GENERAL PHARMACOLOGY]

This is used for MILD visceral pain

Codeine

[GENERAL PHARMACOLOGY]

This is used for MODERATE visceral pain

Morphine

[GENERAL PHARMACOLOGY]

This is used for SEVERE visceral pain

Morphine

[GENERAL PHARMACOLOGY]

This is used in the management of ACUTE PULMONARY EDEMA.

Fentanyl IV

[GENERAL PHARMACOLOGY]

This is used as anesthetic adjuncts (GENERAL ANESTHESIA)

● Diphenoxylate

● Loperamide

[GENERAL PHARMACOLOGY]

These are used as ANTIDIARRHEALS.

Dextromethorphan

[GENERAL PHARMACOLOGY]

This is used as ANTITUSSIVE.

● Respiratory depression → Greatest threat

● Addiction → Withdrawal symptoms: frequent yawning, hyperventilation, mydriasis, rhinorrhea, enhanced hostility

● Tolerance → Chronic use > 2-3 weeks

● Anaphylactoid reaction → Epinephrine is first-line treatment

[GENERAL PHARMACOLOGY]

Toxic effects of narcotics:

● Pregnancy → Baby may become addicted

● Patients with head trauma → Risk of increased intracranial pressure

● Do not combine a partial agonist with a full agonist (BECOMES ANTAGONIST)

[GENERAL PHARMACOLOGY]

Contraindications of narcotics:

● Opiates → Natural derivatives

● Opioids → Semi-synthetic and synthetic derivatives

[SPECIFIC AGENTS]

Classification of narcotics based on sources:

● Morphine

● Codeine

● Thebaine

[SPECIFIC AGENTS]

Opiates include:

Morphine

[SPECIFIC AGENTS]

This opiate is the REFERENCE standard as ANALGESIC.

Morphine

[SPECIFIC AGENTS]

This opiate has POOR oral bioavailability (25-30%)

Codeine

[SPECIFIC AGENTS]

This opiate is the REFERENCE standard as ANTITUSSIVE.

Codeine

[SPECIFIC AGENTS]

This opiate has LESS efficacy compared from morphine.

Thebaine

[SPECIFIC AGENTS]

This opiate is the PRECURSOR in the formation of NALOXONE.

Naloxone

[SPECIFIC AGENTS]

Thebaine is the PRECURSOR in the formation of ______.

● Heroin

● Apomorphine

● Semisynthetic morphine derivatives:

● Hydromorphone

● Oxymorphone

● Semisynthetic codeine derivatives:

● Hydrocodone

● Oxycodone

[SPECIFIC AGENTS]

Semi-synthetic opioids include:

● Diacetylmorphine

● Diamorphine

[SPECIFIC AGENTS]

Heroin is also known as:

Heroin

[SPECIFIC AGENTS]

This semi-synthetic opioid has EQUAL efficacy compared to morphine.

Heroin

[SPECIFIC AGENTS]

This semi-synthetic opioid is a RECREATIONAL DRUG; DRUG OF ABUSE.

Apomorphine

[SPECIFIC AGENTS]

This semi-synthetic opioid has similar structure with morphine but NOT an analgesic as it has NO affinity to mu and any opioid receptor.

Apomorphine

[SPECIFIC AGENTS]

This semi-synthetic opioid is a DOPAMINE reuptake inhibitor which enhances dopamine effect.

Apomorphine

[SPECIFIC AGENTS]

This semi-synthetic opioid is used in the management of PARKINSONISM.

● Hydromorphone

● Oxymorphone

[SPECIFIC AGENTS]

Semisynthetic morphine derivatives include:

Semisynthetic morphine derivatives

● Hydromorphone

● Oxymorphone

[SPECIFIC AGENTS]

These semi-synthetic opioids are 8-12 times MORE POTENT than morphine - require lesser dose = same effect.

● Hydrocodone

● Oxycodone

[SPECIFIC AGENTS]

Semisynthetic codeine derivatives include:

Semisynthetic codeine derivatives

● Hydrocodone

● Oxycodone

[SPECIFIC AGENTS]

These semi-synthetic opioids are 8-12 times MORE POTENT than codeine.

● Methadone

● Meperidine

● Levorphanol

● Fentanyl

● Loperamide

● Diphenoxylate

● Tramadol

● Pentazocine

[SPECIFIC AGENTS]

Synthetic opioids include:

Methadone

[SPECIFIC AGENTS]

This synthetic opioid has the SAME efficacy with morphine but with GOOD oral bioavailability, LONG duration of action, and LESS rapid development of tolerance.

Methadone

[SPECIFIC AGENTS]

This synthetic opioid is used to wean off morphine and heroin addicts as withdrawal is NOT a problem.

Pethidine (Demerol)

[SPECIFIC AGENTS]

Meperidine is also known as:

Meperidine

[SPECIFIC AGENTS]

This synthetic opioid has NO cardiac and biliary effect and is used for ACUTE PAIN only.

Meperidine

[SPECIFIC AGENTS]

This synthetic opioid has a toxic metabolite (NORmeperidine) which can cause SEIZURES.

seizures

[SPECIFIC AGENTS]

Meperidine has a toxic metabolite (NORmeperidine) which can cause _____.

Levorphanol

[SPECIFIC AGENTS]

This synthetic opioid is 5 - 7 times more potent than morphine.

Dextromethorphan

[SPECIFIC AGENTS]

D-isomer of Levorphanol is _______

Levorphanol

[SPECIFIC AGENTS]

Dextromethorphan is the D-isomer of ______

Fentanyl

[SPECIFIC AGENTS]

This synthetic opioid is 100 times more potent than morphine and is an INTRAVENOUSLY administered general anesthetic.

● Droperidol

● Fentanyl

[SPECIFIC AGENTS]

Drugs that provide NEUROLEPT ANALGESIA:

● Droperidol

● Fentanyl

● Nitric oxide

[SPECIFIC AGENTS]

Drugs that provide NEUROLEPT ANESTHESIA:

● Diphenoxylate

● Loperamide

[SPECIFIC AGENTS]

These synthetic opioids are used as ANTIDIARRHEALS.

Loperamide

[SPECIFIC AGENTS]

This synthetic opioid is used as antidiarrheal WITHOUT addiction.

Diphenoxylate

[SPECIFIC AGENTS]

This synthetic opioid is used as antidiarrheal WITH addiction, co-administered with ATROPINE.

Atropine

[SPECIFIC AGENTS]

Diphenoxylate is used as antidiarrheal WITH addiction, co-administered with _____.

Tramdol

[SPECIFIC AGENTS]

This synthetic opioid is used for MILD pain and has WEAK Mu agonist activity.

Pentazocine

[SPECIFIC AGENTS]

This synthetic opioid is a PARTIAL KAPPA AGONIST.

● Alone = Kappa agonist

● With full agonist = Mu antagonist

● Strong full Mu (μ) receptor agonist

● Mild-moderate full agonist

● Partial agonist

● Full antagonist

[PHARMACODYNAMICS]

Classification based on Pharmacodynamics:

STRONG full Mu (μ) receptor agonist

● Morphine

● Heroin

● Hydromorphone

● Oxymorphone

● Methadone

● Meperidine

● Levorphanol

● Fentanyl

[PHARMACODYNAMICS]

These are used in the treatment of SEVERE pain:

Mild to moderate full agonist

● Codeine

● Hydrocodone

● Oxycodone

● Tramadol

[PHARMACODYNAMICS]

These are used in the treatment of MILD TO MODERATE pain:

Partial agonist

● Nalbuphine

● Butorphanol

● Buprenorphine

● Pentazocine

[PHARMACODYNAMICS]

These have drug interactions with FULL agonist (becomes antagonist)

● Naloxone

● Naltrexone

● Nalorphine

● Nalmefene

● Levallorphan

[PHARMACODYNAMICS]

Full antagonists (antidotes for narcotic poisoning):