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Narcotic analgesic
Introduction:
 Analgesic are 2 types:
1
...
Anti-pyretic analgesic (aspirin & indomethacin): No drowsiness nor dependence
...

 Supraspinal and spinal analgesia

κ (Kappa)

 Psychotomimetic (hallucinogenic) effects
 Constipation

δ (delta)

 Supraspinal and spinal analgesia
 Modulation of hormone & neurotransmitter release

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Classification of Narcotic Analgesics
According to Source & nature



Natural



Phenathrenses:
Morphine
Codeine



Benzyl isoqunilines
Narcotine
Narcetine
Papaverine

Semi-synthetic
Heroin
Apomorphine
Tramadol

According to Action



Pure Agonist
Morphine "Agonist"
Codeine "Weak"



Mixed agonist – antagonist
Pentazocin
Nalbuphine
Butorphenol
Buprenorphine

2



Synthetic
Mepridine
Fentanyl
Dextropropoxyphene
Dextromethorphame
Methadone
Lomotil (Diphenoxylate)
Loperamide (Imodium)



Pure antagonis
Naloxone
Nalmephene
Naltrexone

Natural Opium Alkaloids
1
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 In shock, used as diluted I
...
not S
...
M?
 Due to impairment in peripheral circulatiuon → poor absorption and
accumulation
 After correction of shock → Absorption of accumulated morphine → toxicity
B) Distribution: distributed all-over the body
...
During pregnancy → congenital malformations & fetal addiction
...
During labor → depresses fetal R
...
M
...
Morphine-6-glucuronide: more active than morphine
...
Morphine-3-glucronide: neuro-excitatory metabolite
...

 Gastric lavage is essential in all cases of morphine toxicity even not taken orally ??
 Pharmacodynamics: See Table
3











MOA
++ opiate receptors in C
...
S & periphery (Gi) → ‫من الرسمة‬
1
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Presynaptica: # Ca →# release of excitatory NT
3
...

It also release Histamine
Action
CNS & ANS
 ++ CIC (Bradycardia)
# Cortex (Analgesia & Narcosis)
 ++ CTZ (Vomiting)
# Cough Center (Antitussive)
 ++ EWN ??
# RC  # HRC
 # VMC
 Euphoria & Excitation
# Sympathatic (Hypotension)
 ++ Parasympathatic
# Polysynaptic reflexes
 ++ Monosynaptic reflexes
(withdrawl, defecation & mictu)
(Stretch)

Eye: Systemic due to ++ EWN → PPP, Accomodation & ↓ IOP
This action is antagonized by: Naoxone, GB & Atropine ‫ارسم‬
CVS:  S
...
D: Bradycardia & Hypotension ‫ليه بقا ؟‬
RT:  # cough center
 ↑ Histamine → Bronchospasm
 # RC→ Hypoventilation, Hypoxia & ↓ RC sensitivity to CO2
GIT: (↓Secretion “Except salivary” & Spasmognic constipation)
1
...
Biliary Tract: ↑ Inta-billiary pressure → ↑Biliary Pain
 Spasm of Bile Duct
 Spasm of Sphincter of Oddi
3
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↑pressure inside ureters → ↑ Ureteric pain ‫لسببين‬
 Spasm of ureteric wall & Spasm of Sphincter
2
...
↓ BMR→ Myxedema &↓ACTH → adrenal insufficiency
2
...
↑ ADH
Histamine release: VD, Itching & wheal Formation
Tolerance :
 Tolerance to some CNS effect e
...
analgesia & depression of R
...

 No tolerance for P
...
P, constipation & excitation
...
N
...


Morphine
Uses (SC & IM, IV & oral)
1
...
g
...

 Colic: renal or biliary colic but add atropine ?
 Post operative (except in cholecystectomy & after
eye operations?)
 Fracture (Except head injuries?)
2
...
C, HRC &VMC
...

 Post operative urine retention & constipation
...
Pulmonary edema (acute L
...

 ↓ preload (venodilatation)
 # over stimulated cough center & R
...
Primary neurogenic shock: (Analgesic)
 used by slow I
...
C or I
...
Anesthesia:
 I
...


Side effect & Contraindications
1
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Age Extremities (↓ Metabolism)
3
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Alone in biliary & Renal colic (↑ Pressure → ↑Pain)
5
...
Hypotension
7
...
Bronchial Asthma, COPD & emphysema
9
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Labor → Neonatal asphyxia (# RC)
11
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Constipation, Urine retention & Vomiting
13
...
Endocrine (Myxedema “↓BMR” Addison disease “↓ACTH”

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Acute Toxicity
Manifestations:
PPP+ 3 Hypo (oxia, tension & thermia) → Coma
Cause of Death:
# RC
Treatment of acute morphine toxicity:
1
...
Artificial respiration + respiratory stimulants (O 2 95% + CO2 5%)
3
...
Saline

Chronic toxicity (Addiction)
Course: Tolerance then psychic & physical dependence
...
N
...

 Skin: itching
...

Treatment of morphine addiction (dependence):
1
...

2
...

3
...
Gradual withdrawal of methadone Or Buprenorphine (less
withdrawal symptoms)
5
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Oral naltrexone (oral μ antagonist): prevents recurrence
...

Drug interactions
1
...
Morphine + Antidepressants → CVS depression & sedation
3
...

2- Analgesic: in mild or moderate pain ± aspirin or paracetamol
...
in the brain & Short t½ (= ½ h) → highly addictive
 less emetic
...

Apomorphine
 Direct dopamine agonist →
...

 # serotonin reuptake (main action)
 # NE reuptake
...

 Toxicity:
 seizures → CI in epilepsy
...

 Strong 80 Times than morphine
P/D (Morphine + Atropine)
 Shorter t1/2 (high addiction)
 Atropine Like action & ↑ ADH
Uses:
 Local Anasthetic
‫ما بيستخدمش لوحده بنضيف عليه حاجات وبيبقى اسمه‬
 L
...
Neuroleptic analgesia : ‫العيان فايق‬
 No PPP (Mydriasis ?)
As: Endoscope
 No Constipation
(Fentanyl + Droperidiol)
 No Drowsiness (Narcosis)
2
...
Analgesia: Visceral Pain
2
...


Members

Naloxone

Kinetics

Uses

Side effects

 Injection

1
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Neonatal Asphyxia

 If e addiction →

 Metabolized by
 Hydrxylation (phase I)

 IM to Mother B4 labor

withdrawal

 IU to infant After labor

symp
...
Diagnosis of addiction
(S
...
acute morphine toxicity

Nalmephene  Long duration (10 h)

( ttt opioid overdose)

 Naloxone derivative
Naltrexone

 Oral

1
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Morphine toxicity

 Long duration

(addiction)

Hepatotoxicity
Sedation, Nausea

Remember that:
 Agonist → produce 100% activity
 Antagonist → produce Zero activity
 Partial agonist (Mixed agonist antagonist) → produce 60 % activity
‫لو واحد مش مدمن واديته بارشيال هيسكن عنده األلم وهيشتغل كويس‬
‫ إنما لما تديله بارشيال وال هيجيب معاه نتيجة ده ممكن يظهر عليه أعراض انسحاب‬
...
C (low ceiling effect):
 ↑ dose → ↑ analgesic action
 ↑ dose → No more # RC (but, it may occurs)
If # RC occurs → very dangerous state (not
reversed by Naloxone)
Uses:
1
...
Diagnosis of Morphine addiction
Members & related Characters :
2) Pentazocine:
 Adverse effects: vomiting, night mares & anxiety
...
‫النايب بيطلع‬
4) Butorphanol:
 Adverse effects: long duration may cause sedation
...

 Used in treatment of opioid & heroin dependence

Nallorphine & Levalorphan are also Mixed agonist – Antagonist But:
No ceiling effect (#RC if used in large doses)

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