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Narcotic analgesics
► Definition:
substance, whether endogenous or
synthetic, that produces morphine-like effects that
are blocked by antagonists such as naloxone.
Receptors:
Mu: all opioid effects and ADR except dysphoria
Delta and kappa receptors
MOA:
- Decrease adenyl cyclase & cAMP in brain
- Inhibit calcium channels in pre -synaptic
neurons inhibit pain neurotransmitters
release
- Stimulate K-channels in post-synaptic neurons
hyper-polarization
Pharmacological actions
► 1.
Central effects (CNS):
► I) Depressant effects
a. Analgesia: without loss of consciousness by:
1. Inhibiting pain neurotransmitters release .
2. Modifying emotional reactions to pain (Euphoria)
b. Sedation:
c. Respiration:  Resp. depression
d. Depress cough center:
e. Hormones: decrease dopamine, CRH, ACTH,
cortisol, LH, FSH & Testosterone
f. Depress VMC: in large doses hypotension
► II)
Stimulatory effects
1. Oculomotor nucleus pin-pointed pupil
2. CTZ: Nausea, vomiting
3. Pituitary hormones: Stimulates release of
GH, prolactin and ADH
4. Cardiac center: bradycardia
► 2. Peripheral effects:
► 1. CVS:
► A. Heart: bradycardia. (central and direct)
► B. B.V: vasodilatation hypotension
- Dilate cerebral BV ONLY when Resp
depression CO2 accumulation  VD
►
2. Peripheral effects:
► 2.
GIT: Spasmogenic
Constipation through:
1. Decrease CNS perception of sensory stimuli for defecation.
2. Increase in tone in sphincters, decrease propulsive
contractions
3. Decrease in the GIT secretions.
► 3. Urinary system:
-Oliguria due to: increase ADH release + hypotension + increase
tone of ureter and the vesical sphincter.
► 4. Uterus & fetus: Is it a good analgesic for labor pain?
- Delay labor due to decrease pain sensation & spasm in uterine
muscles
-Pass placental barrier & BBB & suppress fetal respiration
-Less conjugated in fetus higher blood level
► 5. Immune system: Suppress immune system infection
► 6. Skin: increase histamine release itching, urticaria,
►
Effects of morphine
Pharmacokinetics
► A.
Absorption: Well absorbed from all sites. In
shock there is less absorption from S.C. and I.M.
► B. Distribution:
1. Highly lipid soluble drugs e.g. Heroinare
concentrated in highly perfused organs "brain" &
accumulate in fat on prolonged administration
2. Crosses the placenta, less with tramadol &
pethidine
C. Metabolism: extensive first pass metabolism
so oral dose is much higher than parenteral.
- It is conjugated with Glucoronic Acid  2
metabolites:
M3-G convulsions, M6-G (more active).
► D.
Excretion: mainly renal
Polar metabolites & small amount of free drug
are excreted in urine. Renal impairment
decrease excretion  toxicity.
► Tolerance: after 2-3 w of continuous
intake, need increase in dose up to 35
folds.
1. Marked tolerance to the depressant
effects
2. No tolerance to antagonistic or
stimulant effects EXCEPT emetic &
antidiuretic.
3. There is cross tolerance to different
opiates acting on same receptors.
Dependence
►Physical
& psychogenic dependence
►Sudden stop Withdrawal syndrome
Adverse effects
►1. CNS: Respiratory depression + dependence
► 2.
GIT: Nausea, vomiting, constipation & colic.
► 3. B.V: intracranial tension + Hypotension
 4. Muscles spasm: Urinary retention, increase
biliary and renal colic & prolongation of labor.
► 5. Histamine release: Itching, urticaria &
bronchospasm.
Therapeutic uses of Opioids
► 1.
TTT of pain
► 2. Acute left ventricular failure and
pulmonary edema.
► 3. Anesthesia (adjuvant)
► 4. Anti-diarrheal: diphenoxylate
► 5. Cough: codeine.
Contraindications & precautions
► (Explain
► 1.
WHY for each one)
bronchial asthma
► 2. Head injury.
► 3. Reduced blood volume (Induce hypotension)
► 4. Myxoedema & Addison's disease (prolong and
exacerbate response to opioids).
► 5. Advanced hepatic & renal diseases.
► 6. During pregnancy or delivery
► 7. Prostate hypertrophy. 8. Biliary & renal colic.
► 9. Undiagnosed acute abdominal pain.
Types of opioid analgesics
► A.
Pure agonists: high affinity for mu receptors
and low for kappa and delta. They include:
Morphine:
► Meperidine (pethidine)
► a. Less analgesic, less effect on cough or
resp. depression and not delay labor.
b. Has atropine & anti-H1 like action no
miosis, less constipation or urine retention,
effective in colic
► Methadone:
It is mainly used to relieve the withdrawal
symptoms of morphine or heroin
Types of opioid analgesics
► B.
Mixed agonists-antagonists:
. Agonist at k-receptors, antagonists at mu.
. They excitation, dysphoria
&hallucinations, less Resp depression
C. Opioid antagonists
► Naloxone: IV, 1h duration used in Opioid
overdose
► Naltrexone: Oral, 48h duration, used in
► Maintenance programs in treating addiction,
alcoholism