1.
Prof. Amol B. Deore
Department of Pharmacology
MVP’s Institute of Pharmaceutical Sciences, Nashik
Narcotic Analgesics and Antagonist

2.
Narcotic Analgesic
• Narcotics analgesics are drugs used to relieve moderate
to severe pain by binding to opioid receptors, which are
present in the central and peripheral nervous system.
• Narcotic refers to opium derivatives, and their semi-
synthetic or synthetic substitutes as well as cocaine and
coca leaves.
• They are only used for pain that is severe and is not
helped by other types of painkillers. When used
carefully and under a health care provider's direct care.

3.
Opioids
• Any naturally occurring, semi-synthetic or synthetic compounds that bind
specifically to opioid receptors and share the properties of one or more of the
naturally occurring endogenous opioids.
• Opium is a mixture of alkaloids from the poppy plant- Papaver Somniferum.

4.
Classification
1) Natural opium alkaloids
Ex. Morphine, Codeine, Thebaine,
2) Semisynthetic derivatives
Ex. Heroin, Hydromorphone, Oxymorphone, Oxycodone, Dextromethorphan
3) Synthetic compounds
Ex. Tramadol, Propoxyphene, Meperidine, Methadone, Levorphanol,
Loperamide, Sufentanil, Alfentanil, Fentanyl, Remifentanil,
4) Narcotic antagonists
Ex. Naloxone, Naltrexone
Narcotic Analgesics and Antagonist

5.
Mechanism of action
• As morphine binds to opioid receptors and activates
the receptors to exert certain actions.
• There are three major types of opioid receptors and
these are:
• μ receptor (Mu) – These receptors are present in the
brainstem and the thalamus, activation of these
receptors can result in pain relief, sedation and
euphoria as well as respiratory depression,
constipation and physical dependence.

6.
κ receptor (kappa) - This receptor is present in the limbic
system, the brain stem and spinal cord. Activation of this
receptor causes pain relief, sedation, loss of breath and
dependence.
δ receptor (delta) - This receptor is widely distributed in the
brain and also present in the spinal cord and digestive tract.
Stimulation of this receptor leads to analgesic as well as
antidepressant effects but may also cause respiratory
depression.

7.
Pharmacological actions of
Morphine

8.
Central Nervous System
•Analgesia: Most effective in relieving severe and
continuous pain arising from deeper structures and
less effective against superficial and sharp pain.

9.
Sedation: Drowsiness, feeling of heaviness
and difficulty in concentrating are
common. Sleep may occur with relief of
pain, but they are not true hypnotics.
Euphoria and dysphoria: Morphine and
other opioids cause a sense of fulfillment,
satisfaction and euphoria. Euphoria is the
experience of pleasure or excitement and
intense feelings of well-being and
happiness.

10.
Hallucination: Morphine and other opioids may cause
hallucinations. The hallucinations are where someone
sees, hears, smells, tastes or feels things that do not
exist outside their mind.
Hallucinations are sensations that appear real but are
created by your mind.
Tolerance and Dependence: Dependence exists when
the sudden withdrawn of an opioid, after repeated
use over a prolonged period, results in various
physical and psychological signs and symptoms. These
include; restlessness, irritability, increased salivation,
anorexia, lacrimation and sweating, muscle cramps,
vomiting and diarrhea.

11.
Cardiovascular System
• Mild bradycardia is common because of decreased
sympathetic activity and a direct effect on the SA node.
Peripheral vasodilatation caused by histamine release and
reduced sympathetic activity may result in fall in blood
pressure.
Respiratory System
• It depresses the respiratory center in medulla oblongata and
decreases rate of respiration and tidal volume. In large doses,
it produces respiratory failure and hypoxia condition.

12.
Suppression of cough
• Opioids depress the cough reflects
by depressant action on the cough
center in medulla oblongata.

13.
Gastrointestinal System
• It decreases the gastrointestinal tract secretions and peristaltic
movements. It also decreases the gastric motility thus decreasing the
gastric emptying.
• It inhibits the defecation reflex and spasm of the anal sphincters all
these effects result in the complete absorption of the water causing
drying of the stools and inability to defecate thus producing the
constipation.
• Therefore, in diarrhea opium tincture (1 to 2 ml) can be given to
produce constipation.

14.
• Preparation and doses-
• Morphine Hcl – 10 to 20 mg SC or IM
• Morphine sulfate – 10 to 20 mg SC or IM

15.
Clinical uses of morphine
• For relief of severe pain- morphine is one of the most
powerful analgesic.it is use to relieve severe pain such as
myocardial infarction, accidental pain, post-operative
pain, fracture of the long bones, severe burns, acute
pericarditis and terminal stage of the cancer that is cancer
pain
• As preanesthetic medication- morphine is used before
operation or surgery To produce sedation and anxiolytic
effect. it also reduces dose of the general Anesthetic
required.

16.
• Antitussive action– morphine can be used to suppress severe cough
but codeine is preferred.
• Antidiarrheal action: In diarrhea, morphine (tincture of opium 1 to 2
ml) can be used to produce constipation in severe diarrhea but
loperamide is preferred as the potent antidiarrheal drug.

17.
Adverse drug reactions-
• Vomiting, nausea, constipation, vertigo
• Respiratory depression
• dizziness, drowsiness
• Pin-point pupil of eye and miosis
• Urinary retention
• Euphoria, and hallucinations
• Drug tolerance
• Drug dependence
• Increased intracranial pressure
• biliary spasm

18.
Contraindications
• Head injury
• The diagnostic features of head injury are
mydriasis, vomiting and respiratory depression.
Morphine produces miosis, pin point pupil, nausea,
vomiting, respiratory depression and increases
intracranial pressure of Cerebrospinal fluid in brain.
• This may complicate the patient condition in head
injury. By producing miosis, respiratory depression
and mental clouding it may interfere with diagnosis
and assessment of head injury.

19.
Bronchial asthma
• Morphine can precipitate an acute attack of
bronchial asthma by causing bronchospasm due to
direct action on bronchial smooth muscles and
depression of respiratory centre in medulla
oblongata in CNS.

20.
Prostate enlargement
• Morphine can produce urinary retention, difficulty in urine
micturition by causing spasm of urinary sphincter of bladder.
• Morphine is strictly contraindicated in– Children, Old
patients, Pregnancy

21.
Acute Opioid Poisoning
•Causes of opioid intoxication
•Opioid intoxication occurs when someone takes
too many opioids. Opioid intoxication can occur if
someone:
•overdoses
•mixes opioids together
•takes opioids without a prescription or for longer
than prescribed

22.
Symptoms
• A cold or clammy feel to the skin,
• Bluish hue in the fingertips and lips,
• Pinpoint pupil (miosis),
• Blurry vision,
• Nausea and Vomiting,
• Severe constipation,
• Respiratory depression: irregular breathing,
• hypothermia and hypoglycaemia,
• Slow heartbeat, hypotension,
• CNS depression: Severe sleepiness,
• Loss of consciousness,
• Coma.

23.
Management
• Gastric lavage by potassium permanganate solution to
oxidise the morphine to oxymorphine (less toxic) and to
wash out unabsorbed morphine from the stomach.
• Artificial ventilator is given for breathing
• Administration of specific opioid antidote- Naloxone or
nalorphine given by intravenously.
• Administration of intravenous fluids.

24.
Morphine is good analgesic but worst drug for
addiction OR Morphine causes addiction.
• Morphine is an Opioid analgesic used to relieve very severe pain such
as cancer pain, myocardial infarction pain, accidental pain, post-
operative pain and for cough and diarrhoea.
• Morphine interacts with opioid receptors (mu, kappa, delta and
sigma) in the brain and CNS thereby producing sedation, euphoria,
mental state of well-being, pleasure, hallucinations.
• Hence, to experience positive state of mind and satisfaction,
individual continue the drug on its own therapeutic indication
(without prescription or consult). This develops tolerance and strong
degree of psychological drug dependence, which cause addiction.

25.
Morphine should be contraindicated in children, old people and
pregnant women.
• Morphine is an Opioids analgesic shows adverse drug reactions–respiratory
depression, circulatory depression, pin point pupil, difficulty in urine micturition
and prostate enlargement which cannot be tolerated by children and old people.
• The drug metabolism capacity is not completely developed in children and
become weaker in old age.
• In pregnancy, morphine crosses placental barrier and depress fetal respiration.
Therefore, Morphine is strictly contraindicated in children, old people and
pregnant women.

26.
Morphine should not be given in abdominal
pain before diagnosis.
• Abdominal pain may be due to peptic ulcer, gallbladder
stone, appendix swelling, pancreatitis and amoebiasis.
These conditions show different symptoms. Hence, their
diagnosis should be done.
• If narcotic analgesic like morphine is given, it relives
pain that interferes in the detection of the symptoms of
above mentioned diseases. This results into the faulty
diagnosis. Therefore

27.
In treatment of biliary colic, morphine is always
combined with atropine. Why?
•Biliary Colic is the condition in which there is severe
pain due to spasm (sustained contraction) in biliary
tract.
•Morphine, an opioid analgesic relieves pain while
atropine is antispasmodic which reduces spasm.
•Combination of atropine and morphine gives
synergistic effect. Therefore….

28.
• Thanking You