Narcosis means central nervous system depression. (CNS depression)
Narcotic analgesics are the drugs which relieve pain and also produce CNS depression.
- They are usually able to relieve severe, excruciating, acute pain arising from deeper visceral structures. These are the drugs related to the prototype “Morphine”, so they are called morphine-like drugs. Morphine was originally derived from seeds of opium plant (Poppy seeds), so these drugs are also called opioid analgesics.
- They also do have a liability for producing psychic as well as physical dependence.
- Many of them have low therapeutic index (their safety margin is low).
- They are usually used in the settings of emergencies and severe pains arising from deeper structures.
Enumerate the types of opioid receptors, and mention the mechanism of action of narcotic analgesics.
There are 3 main types of opioid receptors:
lµ (Mu), ƙ (kappa), and δ (delta).
Stimulation of receptors (agonist action of drugs) is responsible for analgesia – means those drugs which will be opioid agonists will produce relief from pain – means analgesia. So opioid analgesics are agonists of one or more of these receptors.
Opioid receptor consists of a 7 transmembrane spanning proteins coupled to inhibitory G-proteins. So stimulation of the receptor leads to –
- Inhibition of Adenyl Cyclase –> Decrease in cAMP (Cyclic AMP)
- This leads to Inhibition of voltage-gated calcium channels – Closing Ca Channels – Decreased calcium influx
- Opening and Activation of potassium channels
- This produces Hyperpolarization.
- So there is Inhibition of neuronal signaling.
- Thus the pain transmission is inhibited.
Differentiate between Narcotic analgesics and Non-narcotic analgesics.
Narcotic analgesics are opioid drugs which have a predominant central action, while Non-narcotic analgesics are analgesic-anti-inflammatory drugs whose analgesic action is mainly peripheral.
|Narcotic Analgesics||Non-Narcotic Analgescis|
|Produce CNS depression||Less CNS depression|
|Analgesic action is mainly central||Analgesic action is mainly peripheral|
|Opioid receptors||Peripheral pain receptors|
|Cardiovascular system depression||Minimal|
|Abuse liability is remarkable (Drug dependence)||No abuse liability|
|Physical dependence||No physical dependence|
|Mostly used for emergencies and severe pains||Mostly used for day to day pain relief and mild to moderate pains|
|e.g. Morphine, Buprenorphine, Pethidine, Pentazocin, Fentanyl||e.g. Aspirin, Paracetamol, Ibuprofen, Diclofenac,Naproxen, Mefenamic acid|
|Type of pain relieved|
|Severe||Mild to moderate|
|Visceral pain||Integumental; sometime also visceral|
|Deeper pain||Superficial pain|
Mention adverse effects and contraindications to morphine.
Morphine is a narcotic analgesic. It is a profound CNS depressant. It has low therapeutic index.
- Profound Central nervous system depression, drowsiness, sleep, dose-dependent increasing depression of the central nervous system
- Profound respiratory depression: It supresses all the drives of respiration.
- Hypotension: Severe fall in the blood pressure due to central nervous system depression as well as vasodilation mediated through histamine release
- Euphoria, dysphoria, mental clouding
- Nausea, vomiting, headache, vertigo, dizziness
- Increased intracranial pressure
- Increased intra-biliary pressure due to spasm of sphincter of Odi (Biliary sphincter) and abdominal distention
- Constipation, intestinal obstruction
- Pinpoint pupils and blurring of vision
- Respiratory depression in the newborn if given during labor
- Allergic skin rashes, itching, dermatitis due to histamine release
- Retention of urine – in older individuals and also post-operatively
- Tolerance – Decreased effect on long-term use. Also tissue tolerance. Means most of the tissues like CNS develop tolerance, but GIT and pupils do not develop tolerance. (This phenomenon is called tissue tolerance). This is why morphine addict has pinpoint pupils and constipation.
- Drug dependence – [Psychic (Psychological) as well as physical], and addiction
- Acute morphine poisoning: This may be fatal due to the narrow therapeutic index.
- Morphine withdrawal in morphine addicts: Withdrawal symptoms comprising of severe craving for the drug, abdominal cramps, increased heart rate and blood pressure, dilatation of pupils, Increased lacrimation, rhinorrhea, sweating, insomia, and restlessness
Contraindications to morphine:
- Extremes of age: Too young patients (Newborns and children) and too old patients
- Chronic obstructive pulmonary diseases (COPD) including chronic bronchitis, bronchiactesis, emphysema, bronchial asthma
- Patients with vertebral column deformities such as kyphosis / kyphoscoliosis, because these patients have diminished respiratory reserve and morphine may produce severe respiratory depression
- Hypothyroidism (Myxedema), Addison disease, Hypopituitarism: Diminished BMR and decreased rate of morphine breakdown
- Head injury: Because morphine increases intracranial tension, pinpoint pupils, vomiting, mental clouding, and respiratory depression
- Undiagnosed acute abodomen: Because morphine increases intrabiliary pressure and may mask the pain but worsen the underlying pathology due to its spasmodic actions on teh intestine
- Severe hepatic impairment
- Severely diminised renal function due to a renal disease
- Morphine is contraindicated during labor for the fear of respiratory depression in the newborn
- Morphine should not be used during pregnancy; it may lead to dependence and then withdrawal in the newborn
Mention uses of morphine.
Morphine is used as analgesic for acute, severe, shooting or excruciating pain arising usually from deep visceral structures.
- Pain in Terminal stages in malignancy
- Pain due to Acute Myocardial Infarction
- Pain due to severe crush injuries
- Pain due to severe multiple fractures
- Post-operative pain
Morphine dilates the blood vessels due to histamine release; thus it may decrease the preload and afterload of the heart. So it may be used (with due precautions) sometimes in cases of –
6. Acute left ventricular failure