OPIOIDS

1. OPIOIDS

2. OPIOIDS
drugs with depressant action on the CNS, which cause:
• analgesia
• calming anxiety
• sedation
• euphoria

3. OPIOIDS
• Opioids are natural or synthetic compounds that produce
morphine-like effects.
• The term “opiate” is reserved for drugs, such as morphine and
codeine, obtained from the juice of the opium poppy.
• All drugs in this category act by binding to specific opioid
receptors in the CNS to produce effects that mimic the action
of endogenous peptide neurotransmitters (for example,
endorphins, enkephalins, and dynorphins).
• Although the opioids have a broad range of effects, their
primary use is to relieve intense pain, whether that pain is
from surgery or a result of injury or disease such as cancer

4. Types of opioids
• endogenous opioids
• exogenous opioids - extracted from opium or produced
by synthesis

6. ENDOGENOUS OPIOIDS
Role = neuromodulators
• enkephalin
• B- endorphin
• dynorphins
• NOCICEPTIN

7. ENDOGENOUS OPIOIDS
Role = neuromodulators
• Distribution:
- central - CNS
- peripheral – intestine
1. ENKEPHALINE = pentapeptide:
It acts on miu and delta receptors
ENDORPHINE = polypeptide
Precursors = pro-opiomelanocortin (POMC)
POMC => endorphins, ACTH
It acts on miu and delta receptors

8. ENDOGENOUS OPIOIDS
3. DINORFINE = polypeptides
• Acts on Kappa receptors
4. NOCICEPTINS = polypeptides
• They have an ALGEZIC effect

9. Types of opioid receptors

10. The mechanism of action of opioid
receptors
• Opioid receptors
• Gi protein-coupled receptors
1. inhibits adenyl cyclase => decreases the intracellular
concentration of cAMP
2. open K + => hyperpolarization
3. close Ca2 channels + voltage dependent => prevent
the release of mediators

11. µ
(miu)
κ
(kappa)
δ
(delta)
Supraspinal analgesia
Sedation / Euphoria
miosis
Respiratory depression
Addiction
Constipation
Hypothermia
Spinal analgesia
Sedation / Dysphoria
miosis
Favors the action of µ
and κ

12. Classification of opioids
1. Agonists (encephalomimetics)
2. Agonists k - antagonists µ
3. Antagonists

13. OPIOUS AGONISTS
STRONG AGONISTS
• Alfentanil ALFENTA
• Fentanyl ACTIQ, DURAGESIC, FENTORA
• Heroin
• Hydrocodone various
• Hydromorphone DILAUDID
• Meperidine DEMEROL
• Methadone DOLOPHINE
• Morphine ROXANOL, CONTIN, ORAMORPH,
• KADIAN, AVINZA
• Oxycodone OXYCONTIN
• Oxymorphone OPANA
• Remifentanil ULTIVA
• Sufentanil SUFENTA
• Tapentadol NUCYNTA
MODERATE/LOW AGONISTS
• Codeine
MIXED AGONIST-ANTAGONISTS AND PARTIAL AGONISTS
• Buprenorphine BUPRENEX, SUBUTEX
• Butorphanol STADOL
• Nalbuphine NUBAIN
• Pentazocine TALWIN

14. Morphine
PHARMACOLOGICAL EFFECTS
• CNS effects
• Digestive effects
• Genitourinary effects
• Cardiovascular effects
• Lung effects
• Effects on the eye
• Effects on thermoregulation
• Neurohormonal effects
• Tolerance and dependence

15. Morphine
1. Effects on the CNS
a. Intense analgesia
• increases the threshold of painful perception
• decreases reactions to pain: screaming, fear
• changes the perception of pain - detachment from pain
• - duration of analgesia = 4 - 6 hours
• - place of action: central, bone marrow, peripheral (can be
administered for example in a joint and causes local analgesia)
b. Respiratory depression
• - is installed in parallel with analgesia
• - occurs by decreasing the sensitivity of the respiratory centers to CO2
c. Depression of the cough center
d. Behavioral change
• - euphoria, sedation, well-being
e. Vomiting - causes vomiting at low doses

16. Morphine
2. Digestive effects
• 1. decreases digestive peristalsis
• 2. decreases digestive secretions
→→constipation →antidiarrheal effect
3. spasm of the bile ducts and sphincter of Odi => in colic
is associated with antispasmodics

17. Morphine
3. Effects at the genitourinary level
• - increases the contraction of the ureters => in renal colic
is associated with antispasmodics
• - increases the tonus of the bladder detrusor
• - increases the tonus of sphincter of the bladder
→difficult urination

18. Morphine
4. Cardiovascular effects
a. vasodilation
-arterial and venous => indication in acute pulmonary
edema
-cerebral vessels => increases CSF pressure =>
contraindicated in brain trauma
- cutaneous => congestion, sweating
b. depress circulatory => orthostatic hypotension

19. Morphine
5. Effects on the lungs
• - bronchospasm - by the release of histamine
6. Eye effects – miosis
7. Effects on thermoregulation – depression
8. Neurohormonal effects
- decreases the secretion of ACTH, FSH, LH - increases
the secretion of prolactin.
9. Tolerance and dependence

20. Indications
1. Analgesia
-when there is no response to other painkillers
- in cancer pre and postoperative
2. Acute pulmonary edema
3. Colic - associated with antispasmodics
4. Diarrhea - loperamide IS better
5.Cough - better codeine or dextromethorphan

21. Contraindications and side effects
• addiction => contraindicated abusive administration
• respiratory depression => contraindicated in patients with
respiratory failure
• Sedation
• vomiting
• hypotension
• increase in intracranial pressure => contraindicated in head
trauma
• constipation
• urinary retention => contraindicated in patients with prostate
adenoma
• contraindicated in labor in administration iv => newborn
asphyxia
• contraindicated in allergies - because it causes the release of
histamine

22. Heroin
• - is a synthetic opiate produced by acetylation of
morphine
• - it is more fat soluble than morphine => it crosses the
blood-brain barrier better => it transforms into morphine
• - has a potency 2-3x higher than morphine (10 mg
morphine = 5 mg herion)
• - duration of action approx. 2 hours (½ of morphine
duration of action)
• - is not used in therapy
• - used by drug addicts

23. Meperidine( Mialgin)
• - synthetic opioid (first)
Pharmacological effects :
• analgesia 10 times lower than morphine (10 mg morphine =
100 mg meperidine)
• shorter duration of action - 2-4 hours
• sedation / euphoria - more pronounced than morphine
• respiratory depression - less than or equal to morphine
• mydriasis not miosis like morphine
• - atropine-like effect
Indications
• - Just like morphine
• - not for coughs and diarrhea

24. Methadone
• - synthetic opioid with oral administration
Pharmacological effects
• Analgesia similar to morphine after parenteral
administration, but much higher after oral administration
because it is better absorbed
• long duration of action (3 - 5 HOURS)
Indications :
1. detoxification cure - as a substitute for morphine because
it causes in abstinence syndrome slower onset and milder
than morphine due to long T / 2 (35 hours vs. 2-3 hours
morphine)
2. analgesic - orally - in chronic pain - 5-15 mg
- sc. - 5-10mg

25. . Fentanyl
• - acts predominantly on miu receptors
Pharmacological effects:
Analgesia
100 times higher than morphine
immediate action after adm. iv and short - ½ hour
Parasympathomimetic effects => bradycardia
Indications
- dissociative anesthesia together with droperidol
- treatment of neoplastic pain - transdermal devices (72 hours)

26. MIXED AGONIST-
ANTAGONISTS AND
PARTIAL AGONISTS
Buprenorphine
Butorphanol
Nalbuphine
Pentazocine

27. Pentazocine
• an agonist on κ receptors and is a weak antagonist at µ and δ
receptors.
Pharmacological effects:
• analgesic action lower than morphine
• low risk of addiction (may cause withdrawal syndrome in
morphine addicts)
• depresses the breath less than morphine
• sedative
• ATTENTION: at high doses - dysphoria, hallucinations (by
kappa stimulation)
Indications - acute and chronic pain

28. OPIOUS ANTAGONISTS
Naloxone
Use:
• Acute opioid poisoning
• Respiratory depression caused by opioids
Naltrexone
Indications :
Treatment of drug addicts after detoxification