Pharmacology of Narcotic Analgesics.

Narcotic Analgesics.

Narcotic analgesics-

• “These are defined as pharmacological agents which relieve moderate to severe degree of pains associated with burns, multiple fractures, the terminal degree of cancer etc. by depressing CNS (Narcosis)”.
• As these agents produce narcosis (depression of CNS); hence called as narcotic analgesics.

Classification of Narcotic analgesics –

A) Natural Opium alkaloids
a) Phenanthrene derivatives: e.g. Morphine, Codeine, Thebaine
b) Benzylisoquinoline derivatives: e.g. Papaverine, Noscapine, Narcine
C) Semisynthetic Opioids: e.g. Heroine, Dextromethorphan
D) Synthetic Opioids: e.g. Pethidine, Methadone, Dextropropoxyphene, Pentazocine, Fentanyl, Tramadol

Mechanism of action of opium alkaloids (Morphine):

• Morphine is an agonist of µ (mu), k (kappa), δ (delta) opioid receptors.
• Morphine mainly exerts its action through µ-receptor.
• [µ, k, δ are receptors of opiate neurotransmitter like endorphin, enkephalin & dynorphin]

Pharmacological action of Morphine

(1) On CNS-
(a) Analgesic-

• Morphine relieves severe pain by the following mechanism…..

(1) By increasing pain threshold
(2) By decreasing perception of pain sensation

• The net result of above mechanisms is the loss of pain sensation.

(b) Euphoria, Sedation and Hypnosis-

• Morphine produces a pseudo-sensation of well-being called as euphoria.
• This effect occurs when morphine is consumed in absence of pain.
• Euphoria is a major cause of morphine addiction.
• Sedation & hypnosis is due to cortical depression.

(c) Effect on medullary center-

• Morphine produces biphasic action on medullary centre i.e. some centers get stimulated while some get depressed…..

Stimulated centers	Depressed Centers
Chemoreceptor trigger zone (CTZ) Vomiting center Vagal center Oculomotor nerve	Respiratory center Vasomotor center Cough center Temperature regulating center

(2) Eye-

• Miosis is produced due to excitatory action on oculomotor centre.
• High dose produces pinpoint miosis (pinpoint eye).
• It is an important indication for "Morphine Poisoning".

(3) Respiratory centre-

• Morphine produces respiratory depression by direct depressant action on respiratory centre.
• A cough is suppressed by the direct effect on the cough centre in medulla.

(4) Nausea & Emetic effect-

• Morphine produces nausea & vomiting due to their direct stimulant effect on CTZ & Vomiting centre.

(5) Effect on Hypothalamus-

• Morphine depresses the heat-regulating centre in hypothalamus & causes lowering of body temperature. (Hypothermia)

(6) GIT-

• Causes ilio-coliac spasm.
• Morphine decreases biliary, pancreatic & Intestinal secretion.
• Decreases peristaltic movement.
• Combined effect leads to constipation: Useful in treatment of diarrhoea.

(7) CVS-

• Morphine causes vasodilation & fall in blood pressure. (The vasodilation is due to central vasomotor depression & peripherally in response to histamine, as morphine causes liberation of histamine)

(8) Endocrine system-

• Morphine releases ADH (Anti Diuresis Hormone), decreases LH & FSH: Oliguria

(9) Other smooth muscle-

• Smooth muscles of the urinary bladder, biliary tract & bronchi are contracted.

The adverse effects of MORPHINE-

• M-Miosis
• O- Orthostatic hypotension
• R-Respiratory depression
• P-Pin-Point  Pupil
• H-Histamine release
• I-Increased intracranial pressure
• N-Nausea
• E-Emesis, other…Euphoria, constipation, drug dependence, sedation, lethargy.

Contraindications-

1. Respiratory insufficiency like bronchial asthma.( As cause release of histamine).
2. Head injury. (As increases intracranial pressure.)
3. Hypotension (As itself causes orthostatic hypotension)
4. Undiagnosed abdominal pain like biliary colic, Pancreatitis. (As interferes with the diagnosis)
5. Pregnancy (As causes depression of foetal respiration, Lady will not push the baby as labour pains are abolished due to morphine's effect this may lead to still birth.)
6. Unstable Personalities liable to be an addict. ( As such persons lacks self-control)

Drug interactions-

• 1) Phenothiazines, tricyclic antidepressants & MAO inhibitors potentiate the action of Morphine.
• 2) Morphine reduces absorption of many orally administered drug.

Therapeutic Uses-

• 1) To relieve moderate to severe types of pain associated with Myocardial infarction, fractures of long bones, burns, terminal stages of malignancy etc.
• As Pre-anaesthetic agent.
• In acute left ventricular failure.
• In the form of Tincture Opium in the treatment of diarrhoea.
• In dry irritating cough (Codeine is the best medicine.)

Dose & Preparation of Morphine-

• Morphine hydrochloride: 10-30 mg / bid/ orally
• Morphine hydrochloride: 10-30 mg /SC/IM
• Tincture Opium:3-2ml/bid/orally

Morphine Poisoning-

• Causes-

1. Clinical overdose
2. Accidental or intentional overdosing during addiction by addicts.

• Symptoms-

1. Nausea, vomiting
2. Pin- point Miosis
3. Respiratory depression
4. Cyanosis
5. Marked hypotension causing circulatory failure
6. Pulmonary oedema, apnea leading to death.

• Treatment-

1. Prompt hospitalisation.
2. Gastric lavage by potassium permanganate. ( To remove unabsorbed drug).
3. Artificial respiration to correct respiratory depression.
4. Specific anti-dote- Inj. Naloxone 0.4-0.8 mg IV or Inj. Nalorphine 3-5mg repeated every hour till respiration is improved
5. Maintenance of BP by IV fluid therapy
6. If respiration is still not improved administer respiratory stimulant like doxapram.
7. Diuretics to improve drug excretion and to correct oliguria.
8. Symptomatic treatment.