pharmacology Dr. Mahmoud Taleb University of Al - Azhar Gaza Palestine Why Khaled Al Banna

1. Narcotic Analgesics
Dr. Mahmoud H. Taleb
Assistant Professor of Pharmacology and Toxicology
Head of the Department of Pharmacology and Medical
Sciences,
Faculty of Pharmacy- Al Azhar University
Dr. Mahmoud H. Taleb 1

2. I General Consideration
【 action mechanism 】
ligands
opioids receptor
Gi
inhibiting adenylate cyclase
increasing potassium ion efflux or reducing
calcium ion influx
impeding neuronal firing and
transmitter releaseDr. Mahmoud H. Taleb 2

3. 1.Ligands
(1)endogenous:
• endorphins from pituitary
β-endorphin
dynorphin
• enkephalins from brain
M-enkephalin
L-enkephalin
(2)exogenous: drugs
Dr. Mahmoud H. Taleb 3

4. 2.Receptor
(1)classification of opioid receptors
μ, κ, σ,δ
analgesic effect: mediated by
μ,κreceptors
(2)location of opioid receptors:
• CNS
• nerve terminals in periphery
• cells of gastrointestinal tract
.
Dr. Mahmoud H. Taleb 4

5. 【 analgesic characteristics 】
• relieving pain without affecting other
senses and consciousness.
• high potency of analgesia.
• dependence.
【 clinical use 】
intense pain.
Dr. Mahmoud H. Taleb 5

6. 【 Classification of drug 】
1.origin
• natural opiates
morphine,, codeine,, papaverine
• synthetic analgesics
meperidine, methadone, heroin fentanyl, Tramadol,,
pentazocine.
2.potency
• strong agonist
morphine,heroin,meperidine,methadone,fentanyl
• moderate agonist
codeine, propoxyphene.
• mixed agonist-antagonist
buprenorphine, pentazocine
• antagonist: naloxone, naltrexoneDr. Mahmoud H. Taleb 6

7. Ⅱ Natural Opiates
1- Morphine
【 mechanism of action 】
• Morphine activates opiate receptor to produce
analgesic effect like endogenous opiate peptides.
• high affinity for μ receptors
• varying affinities forδandκreceptors
• low affinity for σ receptors in CNS and
gastrointestinal tract.*
Dr. Mahmoud H. Taleb 7

8. Sensory neuron second neuron
sp
sp sp
E
E
Enkephalin sp=substence P
Neuron E=enkephalin
Dr. Mahmoud H. Taleb 8

9. 【 pharmacokinetics 】
• good absorption from gastrointestinal tract
• significant first-pass effect
• subcutaneous injection is commonly used.
• rapidly entering to all body tissues, including
fetuses of pregnant women.
• not used for analgesia during labor.
• duration of action is 4 - 6 h.
Dr. Mahmoud H. Taleb 9

10. 【 Pharmacologic effects 】
1. effects on CNS
(1) analgesia and sedation: prominent effect.
characteristics:
• strong analgesia
• effective on various pains
chronic dull pain, colic and acute sharp pain.
• no effect on other senses and consciousness.
• sedation
relieving anxiety and stress accompanied with
severe pain.
• analgesia with euphoria in partial patients.Dr. Mahmoud H. Taleb 10

11. (2) emesis by direct stimulation of CTZ to cause
nausea and vomiting.
(3) respiratory depression by reducing response of
respiratory centers to blood CO2
.
(4) suppression of cough by direct inhibition of cough
center.
(5) miosis by stimulating Edinger-Wesphal nucleus,
pinpoint pupils are indicative of toxic dosage.
Dr. Mahmoud H. Taleb 11

12. 2.cardiovascular effects
(1)peripheral vasodilation to cause orthostatic
hypotension
• inhibition of vasomotor center.
• promotion of histamine release from mast cells.
(2)cerebral vasodilation to increase intracranial
pressure
• depression of respiration to increase blood CO2
.
Dr. Mahmoud H. Taleb 12

13. 3. gastrointestinal effects
(1)relieves diarrhea or causes constipation
• reducing peristalsis and stomach mobility
• increasing spasmodic nonpropulsive
contraction
• decreasing biliary and pancreatic secretions
to cause indigestion.
(2)increasing biliary pressure by constriction of
Oddi's sphincter to induce biliary colic.
Dr. Mahmoud H. Taleb 13

14. 4.other effects
• bronchoconstriction by histamine.
• retention of urine by increasing sphincter tone
of bladder.
Dr. Mahmoud H. Taleb 14

15. 【 Therapeutic uses 】
1. analgesia.
• acute sharp pain(intense pain)
• anginal pectoris by analgesic, sedative and
vasodilation
• biliary and kidney colic etc., combined with
atropine
2. acute pulmonary edema
• vasodilation
• sedative
• inhibiting respiration
3. severe diarrhea.
Dr. Mahmoud H. Taleb 15

16. 【 Adverse effects 】
1.common side effects
• nausea, vomiting, constipation, biliary colic,
• respiratory depression,
• dysphoria,
• hypotension,
• acute urine retention.
2.tolerance and physical dependence
withdrawal symptoms ：
autonomic, motor and psychological
responses (insomania, dysphoria, headache,
sweating, vomiting, diarrhea, tremor,
collapse). Dr. Mahmoud H. Taleb 16

17. 【 contraindication 】
1.women in delivery and lactation.
2.patients with bronchial asthma and pulmonary
heart disease.
3.patients with cranial injury and high cranial
pressure.
Dr. Mahmoud H. Taleb 17

18. Codeine
1.codeine is 3-methyl ether of morphine.
2.pharmacologic effects are similar to
morphine,
but its analgesic potency is 1/12 of morphine,
cough depressant potency is 1/4 of morphine.
3.analgesic effect is strongr than aspirin. 30mg
of codeine is equivalent to 600mg of aspirin.
4.less sedation, respiratory depression and
fewer gastrointestinal effects.
5.use: mild to moderate pains and severe
cough by oral administration.
6.physical dependence in long administration.
Dr. Mahmoud H. Taleb 18

19. Ⅲ Synthetic Analgesics
Pethidine (Meperidine,Dolantin)
1.activating opioid receptors, particularly κ receptors.
2.pharmacologic effects are similar to morphine
• less potency and shorter duration in analgesis,
sedative and respiratory depression.
• no effect on cough, bronchial and gastrointestinal
smooth muscles.
Dr. Mahmoud H. Taleb 19

20. 3.use
• to replace morphine to relieve intense pains,
• to treat acute pulmonary edema,
• to induce artificial hibernation.
• not useful for diarrhea or cough.
4.mild adverse effects similar to morphine
5.tolerance: being cross with the other opioids.
dependence: in long use.
Dr. Mahmoud H. Taleb 20

21. Methadone
1.analgesic effect is equal to morphine in potency
and action duration, but more effective in oral
administration than morphine.
2.use:
• analgesia
• suppression of withdrawal syndrome
• treatment of heroin user.
• orally administered, methadone is substituted for
injected opioids and patient is then slowly
weaned from methadone.
3.physical dependence occurs slowly and
withdrawal syndrome is mild.
Dr. Mahmoud H. Taleb 21

22. Fentanyl
1.effects
analgesic effect is 80-100 times as effective as
morphine with short duration(15 to 30 min) and
rapid onset.
2.use
anesthesia or anesthetic adjunct.
Dr. Mahmoud H. Taleb 22

23. Alfentanil
• effects
Alfentanil has a more rapid onset of action
and shorter duration of narcotic effect than
fentanyl.
• uses
adjunct to general anesthetics
anesthetic inducing agent.
Dr. Mahmoud H. Taleb 23

24. Ⅳ Opioid Receptor Antagonists
1.partial antagonists
to precipitate a withdrawal syndrome in opioid
addicts (nalorphine, pentazocine, butorphanol,
nalbuphine, buprenorphine).
2. full antagonists
naloxone and naltrexone.
naloxone may reverse the acute poisoning
effects of opioid agonists and precipitate a
withdrawal syndrome in opioid addicts.
Dr. Mahmoud H. Taleb 24