Transcript Opioid Analgesics and Antagonists

Opioid Analgesics and
Antagonists
Carl B. Goodman, Ph.D.
Florida A&M University
College of Pharmacy & Pharmaceutical Sciences
599-3128
[email protected]
Natural Opioids
Morphine
 Codeine
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Morphine (Roxinal, MS Contin)
Prototypical opioid as an Analgesic
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Induces analgesia moderate to severe pain
Antitussive properties
Decrease in GI motility
Euphoria
Respiratory depression
Miosis
Emesis
CV effects at high doses
Histamine release
Pharmacokinetics of Morphine
Administration
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In GI tract it is slow and
erratic
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Significant first pass
metabolism of morphine
occurs in the liver (IM, SC or
IV)
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Non-medicinal purposes
taken by inhalation
Distribution
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It enter all body tissues
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Only small percentage
crosses the BBB, since it is
the least lipophilic of all
common opioids, in contrast
to Heroin and Fentanyl
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Avoid in pregnant women
and during pain in labor
Pharmacokinetics of Morphine
Fate
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Morphine is metabolized in
liver to glucuronides:
Morphine-6-glucuronide,
which is potent analgesic
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DOA is 3-6 hrs in naïve pts.
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Preferred route of
administration is IV, IM or
SQ
Excretion
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The metabolite is
mainly excreted by
kidney
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Patients with renal
dsyfunction should be
closely monitored
Drug Interaction with Morphine
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MAO Inhibitors
Absolute contraindicated with all narcotic analgesics
because of high incidence of hyperpyrexic coma
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Sedative hypnotics
Increased CNS depression, particularly respiratory
depression
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Tricyclic Anti-depressants and Antipsychotic Agents
Increase sedation, variable effects on respiratory
depression
Codeine (3-methylmorphine) (Paveral)
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Comparison to Morphine:
Less potent analgesic
Lower abuse potential and rarely induces dependence
Higher oral efficacy
Less euphoria
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Possesses good antitussive activity at doses that do not
produce analgesia (Replaced with Dextromethorphan)
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Used in combination with Aspirin or Tyrenol
Semi-Synthetic Opioids
Heroin (Diacetylmorphine)
 Hydrocodone (Hycodan)
 Meperidine (Dermerol)
 Hydromorphone (Dilaudid)
 Oxycodone (Percodan)
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Heroin
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Produced by acetylation of morphine, which produces
a 3-fold increase in its potency
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Greater lipid solubility, crosses the BBB more rapidly
and produces a more exaggerated Euphoria when
taken IV
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It is convert to morphine from 6-monoacetylmorphine,
but last about half as long
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There is no medicinal use in the USA
Meperidine (Demerol)
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Synthetically produced from Morphine
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Used for severe pain, not clinically useful for diarrhea or cough;
Produces less urinary retention than Morphine
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Well absorbed in GI tract (PO), however it is mostly given IM; DOA is 24 hrs
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*It is the preferred analgesic during labor
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It is N-demethylated in the liver and is excreted in the urine; Major
metabolite is Normeperidine
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Possesses Significant anticholinergic (antimuscarinic) effects
Hydromorphone (Dilaudid)
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Structurally a derivative of Morphine & 4-8x stronger too
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Used for relief of moderate to severe pain and painful dry
coughing
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Normally given 1-2 mg and DOA is from 3-4 hrs
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*It is one of the most used opioids in the relief of pain for the
terminally ill because of it’s minimal side effects and high
potency
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Palladone IR, Palladone SR
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Also available as a rectal suppository when oral and
parental routes are undesirable
Oxycodone (Roxicodone)
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Semi-synthetic derived from Thebaine
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Used for relief of moderate to moderately severe pain
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Controlled release (OxyContin® )
Available in 5 mg (blue), 10 mg (white), 15 mg (black), 20 mg (pink), 30 mg
(brown), 40 mg (orange), 60 mg (red), and 80 mg (green) in the U.S. and
Canada, and 160 mg (blue)
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Immediate release formulations (OxyIR®, OxyFast®)
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Pain (10-20 mg PO) (5-15mg IV)
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Used in Combination
Percodan= Aspirin + Oxycodone
Percocet= Acetominophen + Oxycodone
Tablets are available with 2.5, 5, 7.5, 10, or 15 mg of oxycodone and varying
amounts of acetaminophen
Tramadol (Ultram)
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Wide range of applications, moderate pain (4-6h), including treatment for
restless leg syndrome, acid reflux, anxiety, and fibromyalgia.
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Tramadol possesses weak agonist actions at the μ-opioid receptor, moderate
SERT inhibitor and a weak NERT inhibitor.
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Tramadol is a synthetic analog of the phenanthrene alkaloid codeine but actually
closely resembles Venlafaxine (Efflexor). Partial MOR agonist.
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Tramadol is converted to M-1 aka O-desmethyltramadol.
Side effects:
 seizure (convulsions); a red, blistering, peeling skin rash; or shallow breathing,
weak pulse.
 Less serious side effects may include: dizziness, drowsiness, weakness;
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Tramadol: Modest MOR receptor affinity and significant NERT inhibitor
Synthetic Opioids
Fentanyl (Sublimaze)
 Methadone (Dolophine)
 Propoxyphene (Darvon)
 Pentazocine (Talwin)
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Fentanyl (Sublimaze)
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Chemically related to Meperidine
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100x more potent (Analgesic) than Morphine
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Used in anesthesia (Droperidol)
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Rapid onset and short DOA (15-30 min.)
Available in the dosage forms:
 Oral transmucosal lozenges, Fentanyl "lollipops" (Actiq®)
 Buccal tablets (Fentora™)
 Transdermal patches (Duragesic®)
 Injectable formulations (IV, IM, spinally & epidurally)
Fentanyl Related Compounds
Differs in the Biodisposition and Potency
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Sufentanil (Sufenta)
• 5-7x more potent than Fentanyl
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Alfentanil (Alfenta)
• Less potent than Fentanyl
• More rapid acting & short duration of action
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Remifentanil (Ultiva)
• Rapidly metabolized in tissue by cholinesterases resulting in a
short half-life
Methadone (Dolophine)
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Is a synthetic, orally effective opioid that is equal in
potency to Morphine
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Effects mostly MOR
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Used in controlled withdrawal of addicts from Heroin
and Morphine (Given orally 5-20 mg q6-8hrs);
Patients are slowly weaned from Methadone
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It causes milder withdrawal syndrome, which
develops more slowly than seen from Morphine
Propoxyphene (Darvon, Darvon N)
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Derivative of Methadone
Dextro isomer is used as an analgesic to relieve mild to
moderate pain
Levo isomer has no analgesic properties, but has antitussive
action
Used in combination with Aspirin or Tylenol
Well absorbed orally, peak plasma level in an hour, metabolized
in the liver
Side effects: nausea, anorexia, constipation
Toxic doses: respiratory depression, convulsion, hallucinations
and confusion
Pentazocine (Talwin)
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KOR agonist and weak antagonist at MOR and DOR
Binds to Sigma receptor= Dysphoria
Used to treat moderate pain (orally or parentally)
Cause less euphoria than morphine
Higher doses: respiratory depression, decreases GI
motility, increase blood pressure, hallucinations,
nightmares, tachycardia, and dizziness
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Contraindication: in angina patients
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Tolerance and dependence can develop on repeated use
Dezocine (Dalgan)
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Structurally related to Pentazocine
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High affinity for MOR and less for KOR
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Similar efficacy to Morphine
Nalbuphine
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Kappa agonist and Mu antagonist
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IV administration
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Possesses less respiratory depression
than with Morphine, but more difficult to
control
Buprenorphine (Buprenex)
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Partial agonist at MOR, it behaves like Morphine in naïve
patients
It can antagonize Morphine
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It is administered IV and has a long DOA because of its
tight binding to the MOR (*Naloxone is ineffective)
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Metabolized in the liver and excreted in bile and urine
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Adverse effects: respiratory depression, decreases blood
pressure, nausea and dizziness
Butorphanol (Stadol)
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Analgesic is equivalent to Buprenorphine and
Nalbuphine
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More sedation
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Kappa agonist
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Only opioid currently available in the USA in a
nasal formulation
Opioid Drug Classification
Morphinelike
Agonists
Codeinelike
Agonists
Synthetic
Opioid
Partial
Agonists
Full
Mixed
Antagonists
Agonistantagonist
Hydromorphone
Dihydrocodeine
Merperidine
Burprenorphine
Pentazocine
Naloxone
Oxymorphone
Hydrocodeine
Fentanyl
Butorphonal
Naltrexone
Heroin
Oxycodone
Methadone
Tramadol
(Ultram)
Propoxyphene
THE END
Narcotic Analgesics and
Acetaminophen (Oral Route)
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Combination medicines are used to
relieve moderate pain.
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These medicines are available only
with a doctor’s prescription.
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These products are available in the
following dosage forms
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Tablet
Elixir
Suspension
Capsule
Liquid
Syrup
Solution
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APAP w/Codeine
Capital w/Codeine
Darvocet A500
Darvocet-N 100
Darvocet-N 50
Endocet
Lorcet
Lortab
Panlor-DC
Panlor-SS
Percocet
Pyregesic-C
Roxicet
Vicodin
Zerlor
Narcotic Analgesics and Aspirin
(Oral Route)
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Combination medicines are
used to relieve moderate to
severe pain on a short term
basis.
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These medicines are
available only with a doctor’s
prescription.
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These products are available
in the following dosage
forms
• Tablet
• Capsule
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Darvon Compound
Empirin w/Codeine
Endodan
Percodan
Synalgos-DC
Narcotic Analgesics Combinations
Bothersome Side Effects
 agitation
 cramps
 diarrhea
 dizziness
 headache
 lightheadedness
 loss of appetite
 nausea
 sexual dysfunction
 sleeplessness
 stomach upset
 sweating
 vomiting
Serious Side Effects
 addiction
 allergies, such as itching, hives,
skin rash, face swelling
 breathing difficulty
 heartbeat changes
 low blood pressure upon
standing
 trouble urinating
Narcotic Analgesics Combinations
Drugs to Avoid With Narcotic
Analgesic Combinations
These drugs may decrease the effects of narcotic
analgesics:
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Alcohol
Antihistamines
Antibiotics
Antidepressants
Barbiturates
Tranquilizers
Ulcer medication
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Antibacterial medicines
Medications for seizures
Nicotine, including cigarettes, cigars, and pipe
tobacco
Other pain medications
Narcotic analgesics may increase the effect of the
following medications:
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Alcohol
Antidepressants
Blood-thinning medications
Blood pressure medications
Heart medications
Seizure medications
NARCOTIC ANALGESICS
Generic Name
Common Brand Names
Codeine + Acetylsalicylic acid (ASA)
282's, 292's
Codeine + Acetaminophen
Tylenol #1, 2, 3 or 4 ; Atasol - 15 or 30
Oxycodone + Acetylsalicylic acid (ASA)
Percodan, Oxycodan
Oxycodone + Acetaminophen
Percocet, Oxycocet
Hydromorphone
Dilaudid
Morphine
MOS, Statex, M.S. Contin
Anileridine
Leritine
Levorphanol
Levodromoran