Contents:
Narcotic analgesics: Types, Uses and Treatment
PAIN
It is very difficult to define ‘Pain’, mainly because it cannot be measured objectively and it can only be felt by the person (subjective). Broadly, it can be described as an unpleasant sensation. It has two components viz. original sensation and the reaction evoked by this sensation (Psychological component). Though abolishing and/or modifying original sensation results in relief from pain but many times abolishing and/or modifying the psychological component of paining contribute more in relieving pain. Clinically, pain may be classified into three classes, viz. Acute, Chronic, and Psychogenic pain. Acute pain is temporary, severe, and has quick onset and subsidence. On the other hand, chronic pain is persistent, dull, and has gradual onset and subsistence. Psychogenic pain has no anatomical or physiological explanation and is exclusively a psychological condition :
(i) Narcotic analgesics,
(ii) Non-narcotic analgesics.
“Analgesics” are the drugs that relieve or suppress the sensation of pain by acting on the Central Nervous System (CNS) but without producing any degree of loss of consciousness. The analgesics may either decrease the pain sensation or may make the patient unaware of the existing pain. Analgesics can be divided into two types according to their structures and mechanisms of action.
Narcotic ones are analgesic drugs that possess the ability to depress the central nervous system. Thus, in addition to the analgesic effect, they also possess hypnotic and sedative actions, which further contribute to the analgesic effect.
Classification of Narcotic Analgesics :
(a) Natural opium alkaloids, e.g. Morphine, Codeine.
(b) Semisynthetic derivatives of opium alkaloids, e.g. Heroine.
(c) Synthetic morphine substitutes, e.g. Pethidine, Methadone.
NATURAL OPIUM ALKALOIDS
Opium contains two distinct types of alkaloids as under :
(i) Phenanthrin group of alkaloids, e.g. Morphine, Codeine, Thebaine. Amongst these only Morphine and Codeine have analgesic actions.
(ii) Benzyl isoquinoline group alkaloids: These include Papavarine, Noscapine, and Narceine. All three do not possess analgesic activity.
(I) Morphine: Morphine is the most important opium alkaloid used as a narcotic analgesic. In clinical practice, morphine sulfate or morphine hydrochloride is used.
Pharmacological Actions :
(1) Actions on CNS: Morphine has biphasic actions on CNS. It depresses the cerebrum while the action on the medulla is both depression and stimulation.
(a) CNS depressant actions: Morphine by its depressant action on CNS abolishes all types of severities of pain without affecting other sensations such as touch, hearing, etc. It relieves mainly dull, constant pain rather than sharp, intermittent pain. It is most effective for visceral pain.
The analgesic action of morphine is mainly due to the abolition of psychic reactions to pain (a psychological component of pain). In the thalamus, morphine raises the pain threshold and thus, impairs the perception of pain. The hypnotic action of morphine to some extent contributes to raising the pain threshold. The mood-elevating (Euphoriant) action of morphine in patients suffering from pain further decreases effective reactions to pain. Such patients will report that the pain is present but of no consequence.
Morphine depresses respiratory centre in medulla oblongata, resulting in decreased pulmonary ventillation. It also depresses a centre regulating cough reflex in medulla and thus, acts as antitussive. It depresses emetic centre in medulla making vomiting a difficult act.
It depresses the heat-regulating centre in the hypothalamus and causes lowering of body temperature.
CNS Stimulant Action: Morphine stimulates CTZ (Chemoreceptor Trigger Zone) in the medulla oblongata. It also stimulates the vagal medullary centre causing a slower pulse.
(2) Actions on the Gastro-intestinal tract (GIT): Morphine has spasmogenic action on the smooth muscles of GIT. It causes constriction of sphincters. It leads to a decrease in peristaltic movement and stagnation of intestinal contents. Stagnation of contents in the colon leads to maximum absorption of water and drying of fecal matter. Morphine also reduces the sensitivity of the defaecation reflex. This leads to constipation. This effect is of therapeutic value in the treatment of diarrhea.
(3) Other Smooth Muscle: Morphine increases the tone of the smooth muscles. Thus, there is constriction of bronchial and bladder muscles. It causes constriction of the internal bladder sphincter which leads to urine retention. Morphine constricts the pupil (miosis) by its central action rather than a peripheral action.
(4) Effects on CVS: Morphine causes vasodilation and fall in blood pressure. The vasodilation is due to central vasomotor depression and peripherally in response to histamine, as morphine causes liberation of histamine.
Absorption, Fate, and Excretion (Pharmacokinetics) :
On oral administration, the drug is absorbed but its absorption is unpredictable. Absorption from subcutaneous sites is even and quick. It is also administered by the intramuscular route. It undergoes metabolism in the liver and is excreted in the urine.
Adverse Effects :
Adverse effects include constipation, nausea, vomiting, miosis, light-headedness, dizziness, and sweating.
Tolerance and Addiction :
After repeated administration, tolerance can be developed to the respiratory depressant action but not to the other actions. Addiction can also be developed. Addiction is a major drawback of morphine therapy. The withdrawal symptoms can be severe and even fatal. The symptom finally leads to cardiovascular collapse.
Acute Morphine Poisoning:
It occurs from clinical overdosage or from suicidal intention. It is characterized by respiratory depression, cold skin, pinpoint pupils (miosis), hypotension, shock, coma and death. Death is due to respiratory depression.
Respiratory depression, pinpoint pupil and cold skin are of prognostic importance.
Treatment :
Two major lines of treatment are the administration of specific antagonists; Naloxone and gastric lavage. Naloxone 0.4 mg IV repeated every 2-3 minutes till narcotic reversal is achieved. Gastric lavage is useful to wash out the ingested drug and even when injected as it may be excreted in the stomach. The supportive treatment includes maintenance of respiration by artificial means, administration of IV fluids (5% Dextrose), and maintenance of adequate urine output.
Therapeutic Uses:
(1) Morphine is basically used for the relief of all types of pain. It is the most powerful analgesic agent for visceral pain.
(2) Morphine is also employed as a pre-anesthetic medication.
(3) Morphine is also used up to some extent to induce sleep. Hence, can be used as a sedative.
(4) Morphine is a valuable drug in acute left ventricular failure.
(5) Sometimes tincture of opium is also used to achieve symptomatic relief from severe diarrhea.
Preparations and Doses:
| Preparation |
Dose |
| 1. Powdered opium I.P. | 60 to 200 mg orally |
| 2. Tincture opium I.P. | 0.3 to 2 ml orally |
| 3. Morphine hydrochloride tablet I.P. | 8 to 20 mg orally
|
| 4. Morphine hydrochloride injection I.P. | 8 to 20 mg _ subcutaneous or intramuscular injection |
(II) Codeine : Codeine is methyl morphine. It decomposes into methane and morphine in the body. Its pharmacological actions are similar to that of morphine. But its potency, as well as addiction liability, is less than morphine. It is less constipating than morphine. It is not a powerful depressant like morphine. It depresses cough centre hence, useful in the treatment of dry cough. It has a synergistic effect with non-narcotic analgesics like aspirin. Hence, it is found in compound analgesic tablets. The major advantage of codeine is that it can be given orally.
Therapeutic Uses: Codeine is mainly used as an antitussive, a mild analgesic, and an antidiarrhoeal drug.
Preparations:
Codeine phosphate tablet B.P.
Compound codeine tablet B.P.
A.P.C. tablets B.P.
Codeine linctus B.P.C.
SEMISYNTHETIC DERIVATIVES OF OPIUM ALKALOIDS
(1) Heroine or Dimorphine Hydrochloride: Dimorphine is a semi-synthetic derivative of morphine in which both the hydroxyl groups have been acetylated. It causes similar analgesia and respiratory depression as morphine but less nausea, vomiting, constipation, and sedation. The analgesic action of dimorphine is more rapid than morphine but lasts for 2-3 hours only.
Dimorphine is very prone to cause dependence and its use is illegal in many countries.
SYNTHETIC MORPHINE SUBSTITUTES
This class includes Pethidine, Methadone, and Benzomorphans etc.
(1) Pethidine (Meperidine): Pethidine is a synthetic drug unrelated to morphine and was found in a search for a spasmolytic drug with atropine-like properties. The difference between morphine and pethidine is described here.
| Morphine
|
Pethidine
|
| 1. Absorption on oral administration is unpredictable. Administered by subcutaneous route.
|
1. Well absorbed in oral administration. Because of its irritant nature, not administered by subcutaneous route. |
| 2. Potent analgesic and narcotic.
|
2. Less potent analgesic. |
| 3. Spasmogenic
|
3. Spasmolytic. |
| 4. Depress cough centre
|
4. Does not depress cough centre. |
| 5. Constrict pupil (miosis).
|
5. No effect. |
| 6. Depress respiration in newborns hence, not useful to relieve labour pains. | 6. Comparatively less depression of respiration, hence, useful in labour pains. |
Therapeutic Uses :
(1) In the treatment of renal, biliary, and intestinal colics.
(2) In the treatment of pain in coronary thrombosis.
(3) To relieve labor pains.
Side Effects: Sweating, nausea, thirst, dizziness, dryness of the mouth. Tolerance and dependence can develop.
(2) The Benzomorphans: The best-known member of this group is phenazocine which though more potent than morphine exhibits no outstanding differences.
A more recently developed compound is the narcotic antagonist, pentazocine. This can give analgesia comparable to morphine and also produces respiratory depression. The evidence at the present time is that pentazocine does not produce dependence which, if true, makes it a very important new drug.
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