Opioid analgesics and types of opioids Drugs of choices, treatment using opioid medications.

2. What are opioid analgesics?
History
Morphine
Mechanism of opioids
Side effects
Adverse reactions
Addiction, overdose and withdrawal symptoms
Opiophobia
Opioids of abuse
Heroin
Fentanyl
Future of opioids

3. Analgesics, or pain killers, that
bind to opioid receptors which
are found principally in the:
CNS
Gastrointestinal tract

4.  Natural opiates
Alkaloids contained in the resin of the opium poppy
including morphine, codeine and thebaine
 Semi-synthetic Opiates
Created from the natural opioids such as hydromorphone,
oxycodone and diacetylmorphine (heroin)
 Fully synthetic opioids
Fentanyl, methadone and tramadol
 Endogenous opioid peptides
Proudced naturally in the body, such as endorphins,
enkephalins, dynorphins and endomorphins

6. Opioids have been the mainstay of pain treatment for thousand of years,
and they remain so today
The search for a safe, orally active, and non-addictive analgesic based on
the opiate structure is one of the oldest fields in medicinal chemistry
The opiates are perhaps the oldest drugs known to humanity
The first undisputed reference to opium is found in the writings of
Theophrastus in the third century B.C.
The use of opium was recorded in China over 2000 years ago, and
was known in Mesopotamia before that
Its use in medicine is quoted in a twelfth-century prescription:
Take opium ,mandragora, and henbane in equal parts and mix with
water. When you want to saw or cut a man, dip a rag in this and put it to
his nostrils. He will sleep so deep that you may do what you wish.

7.  Opium contains a complex mixture of 20 alkaloids,
principle one being morphine
› Responsible for analgesic activity
 Because of morphine’s poor oral bioavailability, it was little
used in medicine until the hypodermic syringe was
invented in 1853
 Morphine was used during the American Civil War and the
Franco-Prussian war.
› Due to poor understanding about:
 Safe dose levels
 Effects of long-term use
 And increased risks of addiction, tolerance and respiratory
depression
› Many casualties were either killed by overdoses or became
addicted to the drug

8. 3-D Structure of Morphine

9. In general, opioids act
upon mu-, delta-, and
kappa-receptors on CNS
neurons producing:
 Analgesia via
decreased
neuronal
transmitter
release and
decreased
nociceptive
impulse
propagation
Receptor
type
Location Effects
μ Brain,
spinal
cord
Analgesia, respiratory
depression, euphoria,
addiction, ALL pain
messages blocked
κ Brain,
spinal
cord
Analgesia, sedation, all
non-thermal pain
messages blocked
δ Brain Analgesia,
antidepression,
dependence

11.  Agonists have activity on mu and kappa
opioid receptors
 Agonist/antagonists have agonist activity in
some receptors; antagonists in others. Have
lower abuse potential than pure agonists;
because of antagonism—can produce
withdrawal symptoms
 Antagonists are antidote drugs

12.  Alfenta (alfentanil)—short duration
 Codeine
 Sublimaze or Duragesic (Fentanyl)—short duration
 Dilaudid (hydromorphone)
 Demerol (meperidine)—preferred in urinary and
biliary colic, less resp. depression newborns
 Morphine
 OxyContin

13.  Darvon (propoxyphene)
 Ultram (tramadol)
 Methadone

14. Have lower abuse potential than pure agonists
 Buprenex (buprenorphine)
 Nubain (nalbuphine)
 Talwin (pentazocine)
 Stadol (butohanol)—also in nasal spray

15.  Revex (nalmefene)—longer duration of
action than Narcan
 Narcan (naloxone)
 ReVia (naltrexone)-used in maintenance of
opiate-free states in opiate addicts

16. Depression of the respiratory centre
Constipation
Excitation
Euphoria
Nausea
Pupil constriction
Tolerance and dependence

17.  Morphine
 Pharmacological effects CNS: Analgesia:
most powerful drug available for relief of pain
 Euphoria: addict experiences a pleasant
floating sensation and freedom from anxiety
and distress.
 Sedation
 Respiratory depression:

18.  Cough suppression: suppression of cough
centre in nucleus of tractus solitarius
 • Miosis: results from stimulation of Edinger-
Westphal nucleus causing pin-point pupils.
 • Emesis: due to stimulation of brainstem
chemoreceptor trigger zone results in
nausea and vomiting

19.  CVS: No significant direct effect on CVS
Hypotension may occur if CVS is already
stressed. Due to the peripheral arterial and
venous dilation resulting from histamine
release.
 GIT: Decrease intestinal propulsive
peristalsis and stomach motility leads to
constipation
 Biliary tract: Constriction of biliary smooth
muscles leads to biliary colic

20.  Uterus: decrease uterine tone lead to
prolong labor
 • Skin: flushing and warming ,sweating,
itching due to histamine release

21.  • Analgesia for
 a. MI b. Terminal illness c. surgery d.
obstetrical procedures e. cancer f. burn •
Preanaesthetic medication

22.  Dangerous side effects are those of
tolerance and dependence, allied with the
effects morphine can have on breathing
› Most common cause of death from morphine
overdose is suffocation
› These side effects in one drug are particularly
dangerous and lead to severe withdrawal
symptoms when the drug is no longer taken

23.  Triad: • coma, pinpoint pupils, respiratory
depression
 Treatment:
 • Maintain respiration,
 • Gastric lavage should be done with Pot.
Permanganate to remove unabsorbed drug
 • Opioid antagonist, preferably iv naloxone
0.4-0.8 mg repeated every 2-3 min

25. Anorexia
Weight loss
Pupil dilation
Chills
Excessive sweating
Abdominal cramps
Muscle spasms
Hyperirritability
Lacrimation
Tremor
Increased heart rate
Increased blood
pressure

27.  Agonist Medications for Opioid Dependence
Methadone maintenance:- • The most
successful treatment for opioid addiction •
Patients receiving methadone will not
experience the ups and downs produced by
opioid. • Drug craving diminishes and may
disappear. • Neuroendocrine rhythms
eventually are restored

28.  Alpha-2-Adrenergic Agonists for
Detoxification • It moderate the symptoms of
noradrenergic hyperactivity via actions in the
central nervous system. Clonidine relieves
some signs and symptoms of opiate
withdrawal such as lacrimation, rhinorrhea,
muscle pain, joint pain, restlessness, and
gastrointestinal symptoms • associated with
fewer adverse effects

29.  The fear of prescribing opioid pain
medications is known as
"opiophobia”
 Goodman and Gillman’s
Pharmacological Basis of
Therapeutics insists that although
physical dependence and tolerance
may develop, this should not in any
way prevent physicians from
fulfilling their primary obligation to
ease the patient’s discomfort
 No patient should ever wish for
death because of a physician’s
reluctance to use adequate
amounts of effective opioids
 Physical dependence is not
equivalent to addiction

30. Heroin
2X
more
potent
Morphine

31.  First synthesized in 1874
by an English chemist
but only became popular
more than 20 years later
 From 1898 through
1910, under the name
heroin, diacetylmorphine
was marketed as a non-
addictive morphine
substitute and cough
suppressant

34. Morphine Fentanyl

35. The pharmaceutical industry has developed several analogues of
fentanyl:
 Alfentanil (Alfenta), an ultra-short acting (5-10 minutes) analgesic
 Sufentanil (trade name Sufenta), a potent analgesic (5 to 10 times more
potent than fentanyl) for use in heart surgery
 Remifentanil (trade name Ultiva), currently the shortest acting opioid, has
the benefit of rapid offset, even after prolonged infusions
 Carfentanil (Wildnil) is an analogue of fentanyl with an analgesic potency
10,000 times that of morphine and is used in veterinary practice to
immobilize certain large animals such as elephants

37. Generic Name Brand Name
buprenorphine Buprenex
butorphanol Stadol
codeine Tylenol with codeine
fentanyl Duragesic
hydrocodone Vicodin
hydromorphone Dilaudid
methadone Dolophine
morphine Astramorph
oxycodone OxyContin
porpoxyphene Darvon