Concept About Morphine | CHAPTER-7 | Pharmacology

Concept About Morphine – This book covers the entire syllabus of “Pharmacology” prescribed by BNMC- for a diploma in nursing science & midwifery students. We tried to accommodate the latest information and topics. This book is an examination set up according to the teachers’ lectures and examination questions.

At the end of the book, previous questions are given. We hope in touch with the book students’ knowledge will be upgraded and flourish. The unique way of presentation may make your reading of the book a pleasurable experience.

Concept About Morphine

Sir William Oslar referred to morphine as God’s own medicine the name morphine was coined alter Morpheus, the “Greek Cod of dreams”. Clinically, it is a phenanthrene derivative with two planar ring & two aliphatic ring structures.

a. Widely used analgesic for acute and chronic pain.

b. Main site of action: CNS and GIT.

c. Morphine antagonist: Naloxone.

Mechanism of action of Morphine

Morphine (opiates) inhibits neural activity by:

A. Hyper-polarisation and inhibiting presynaptic neurons (Probably by increasing K efflux).

B. Inhibition of cell firing, and

C. Pre-synaptic inhibition of neurotransmitter release (partly due to hyper polarization and partly to a reduction of the Ca++ influx into presynaptic nerve endings).

D. Morphine causes decrease in CAMP production by: activation of opioid receptor, the functional significance which is remains unclear.

Pharmacological action of Morphine On CNS:

Centers stimulated by morphine:

• Oculomotor nerve nucleus
• Vagus nerve
• Vomiting centre (CTZ)

Centre depressed by morphine

• Respiratory centre
• Cough centre
• Other centres of CNS

Depression of CNS leading to-

Analgesia Mechanism

• Morphine increases the pain threshold by acting directly on the cortex by decreasing its sensitivity to incoming pain impulses, tout aulah ibM
• Morphine acts on limbic system and reduces the psychic reaction (euphoria) to pain and so decrease perception of pain.
• Morphine depresses the activity of pain pathway.
• Morphine inhibits perception of pain in the sensory cortex and subcortical areas by hypnosis.

Respirator depression: by –

• Reducing the sensitivity of medullary respiratory centre to increase plasma CO2 concentration.
• Directly depressing respiratory centre in the medulla

➤ Cough suppression: Due to depression of cough centre in the medulla,

➤ Sedation & Hypnosis.

Stimulation of CNS Leading to –

➤ Miosis: Morphine stimulates Edinger Westphal nucleus of third cranial nerve increase pupillary respond to light

➤ Emesis: by stimulating CTZ (chemoreceptor trigger zone) of medullanishige)

➤ Truncal rigidity: by stimulating monosynaptic reflaxes spinal cord> decrease thoracic compliance > interfere with ventilation.

➤ Changes the mood and causes euphoria.

➤ Causes smooth muscle stimulation.

On CVS

➤ Orthostatic hypotension doudve sonsordinate

➤ Depress VMC (vasomotor centre) of the medulla > Decrease vasomotor tone > decrease B.P

➤ Release histamine > Vasodilatation > Decrease P.R> decrease BP.

On GIT

Morphine causes constipation & analgesia which leads to neglect the urge to defecation. So, used as anti-diarrhoeal agent.

Constipation is due to:

➤ Hardening of stool by decreasing all secretions and increasing absorption.

➤ Decrease propulsive movements by reducing motility of GIT smooth muscles increase the tone of pyloric and ileocaecal valves (e.g. increase the tone of smooth muscle sphincter).

➤ Failure to perceive sensory stimulation that elicits defecation reflex

On kidney: Release ADH > Anti-diuresis > Oliguria.

On bronchus: Constriction of bronchial muscle increases the rate and volume of respiration -> asthma.

On biliary tract .

Increases intra-biliary pressure by constricting smooth muscles of biliary tract and sphincter Oddi > spasm of biliary muscle > increase pain.

On urinary bladder

Contracts detrusor and sphincter of urinary bladder and so causes retention of urine.

On uterus: Reduce uterine tone > prolong labour.

On metabolism

Decrease activity & muscle tone > reduce 02 consumption > hyperglycaemia.

On endocrine glands

Increase ADH, prolactin and growth hormones secretion but decrease the LH secretion

On immune system

• Morphine increases N-K cell activity.
• They are chemotactic to monocytes.
• Decrease the resistance to infection.

On body temperature

Morphine has a biphasic, dose dependent effects on body temperature.

At low dose: decrease body temperature.

At high dose: increase body temperature.

On skin

Cutaneous vasodilatation secondary to histamine release can result in pruritus and sweating.

On reproduction

Morphine causes a decrease in libido, sexual drive and sexual performance.

Beneficial effects of morphine:

Analgesia & antitussive effects.

Principle pharmacological actions of morphine:

1. CNS actions Depression of CNS leading to:

a) Analgesia

b) Respiratory depression

c) Depression of cough reflex

d) Sedation

e) Stimulation of CNS leading to-

f) Miosis

g) Emesis

h) Hyperactive spinal cord reflexes

i) Convulsion

2. Changes of mood: euphoria or dysphoria. 3. Dependence: affects other systems too.

4. Smooth muscle stimulation

5. Gastrointestinal muscle spasm

6. Biliary tract spasm

7. Bronchospasm(asthma)

8. Renal tract spasm.

9. CVS: Orthostatic hypotension.

Analgesic mechanism of Morphine

Morphine

↓

Stimulation of opioid receptors (mainly mu) in the CNS

↓

Hyperpolarisation and inhibition of presynaptic neurons (probably by increasing K efflux)

↓

Inhibition of cell firing by raising the threshold for pain

↓

Elimination of pain and also allows subjects to tolerate pain.

Toxic effects of Morphine (opioid analgesics)

1. Behavioral restlessness, tremulousness, hyperactivity (in dysphoric reactions)

2. Respiratory depression

3. Nausea and vomiting.

4. Increased intracranial pressure.

5. Postural hypotension.

6. Constipation.

7. Urinary retention.

8.Itahing around the nose ustiaasia (mora fragment with parenteral administration)

Pharmacokinetics of morphine

Routes of administration; I/V, I/M, S/C, oral (Oral morphine is subject to extensive first pass metabolism; Bioavailability only 20%)

Distribution: 1/3rd drug is protein bound, can cross the placenta and depress the respiration of foetus at birth.
Plasma half-life: 2 hours.
Duration of analgesia: 4-6 hours.
Metabolism: Liver (glucoronysation), kidney. Excretion: Urine, bile,

Indications of morphine

1. As analgesic in

➤ Visceral pain

➤ Acute myocardial infarction

➤ Pain due to fracture of long bone

➤ Burm

➤ Terminal stage of malignancy

➤ Pulmonary embolism.

➤ Acute pericarditis

➤ Pleurisy with effusion

➤ Spontaneous pneumothorax

➤ post-operative pain

2. To relief anxiety in serious and frightening diseases, e.g. shock, hematemesis, heart failure.

3. Pre-anaesthetic medication.

4. Traveler’s diarrhea

5. Balance anaesthetic with morphine, pethidine, fentanyl.

6. For noctunal dyspnoea in acute left ventricular failure and pulmonary oedema

7. To control acute restlessness (rarely)

8. To produce euphoria in dying patient.

Adverse effect of morphine

1. Respiratory depression.

2. Nausea, vomiting.

3. Physical and psychological dependence.

4. Miosis (pin pointed pupil).

5. Dizziness, mental clouding and dysphoria

6. Constipation.

7. Urinary retention.

8. Biliary and urinary spasm.

9. Allergic reaction: urticaria, skin rash.

10. Hypotension > shock > coma

Contraindication of Morphine

1. Extreme of age (Below 6 years & above 60 years)

2. Head injury and following craniotomy.

3. Bronchial asthma & other hypoxic stages (e.g. emphysema)

4. Undiagnosed acute abdomen and acute pancreatitis.

5. Pregnant & lactating mother.

6. Liver disease (e.g. Cirrhosis)

7. Intestinal obstruction.

8. Myxoedema.

9. Convulsive disorder

10. Acute alcohol intoxication

11. Cardiac arrhythmias

12. Severe inflammatory bowel disease (IBS)

13. Prostatic hypertrophy, urethral stricture” etc.

Morphine Poisoning

Symptoms & signs of (acute) morphine poisoning Main features:

➤ Coma (deep unconsciousness: patient cannot he awaked)

➤ Miosis (pin pointed pupil)

➤Extreme slowing of respiration (2-4 breath a min.)

Secondary features:

➤ Cold clammy skin.

➤ Low body temperature.

➤GI Loss of skeletal muscle tone.

➤Absence of reflexes.

➤ Cyanosis.

Diagnostic features:

Triad sign

1. Respiratory depression

2. Miosis (pin-pointed pupils)

3. Coma.

Death is due to respiratory failure.

Management of Morphine Poisoning

Measures to eliminate morphine:

1. Stomach wash with worm water then with KMnO4.

2. Gastric levage.

3. Administration of activated charcoal (morphine is secreted into stomach)

4. Use of specific antidote: Naloxone (0.4-0.8 mg) I/V repeated after every 20-30 minutes.

5. Keep the patient awake by repeated pinching.

Measures to treat respiratory depression

1. Endotracheal intubation (if necessary).

2. Intermittent positive pressure ventilation (ppv)

3. 02 inhalation (if cyanosis)

4. Coramine (respiratory stimulant), if respiratory depression

5. 1000 ml of 5% glucose t/v (for shock) Hot bottle or blanket (to maintain body temp).

Morphine Tolerance & Physical Dependence

With frequently repeated administration of therapeutic doses of morphine or its surrogates, there is a gradual loss of effectiveness (I;e, tolerance). To produce the original response a larger dose must be administered. With the development of tolerance, physical dependence occurs so that continued administration of the drug becomes necessary to prevent a characteristic withdrawal syndrome.

Morphine (opiate) withdrawal:

Chronic exposure to opioids leads to adaptive changes in the endogenous opioid system and no doubt in receptor numbers, sensitivity & cellular response. Failure to continue administering the drug results in a characteristic withdrawal or abstinence syndrome. This consists largely, the opposite of normal actions of opioids.

Symptoms and signs of opiate withdrawal (narcotic abstinence syndrome)

12-16 hours after last dose of opiate

• Irritability body shakes.
• Writhing, jumping and signs of aggression.
• Sneezing, lacrimation, yawning, chills.
• Tachypnoea (hyperventilation)
• Mydriasis (pupillary dilatation)

24-72hours after last dose of opiate

• Muscular aches.
• Blood pressure crisis
• Sweating attacks (Goose pimples)
• Diarrhoea, vomiting
• Bladder spasms.
• Pain in the abdomen and limbs.

Administration of an opioid at this time suppresses abstinence signs & symptoms immediately.

Drug interaction of Morphine:

A. Morphine CNS depressant: More CNS depression, CNS depressant: such as –

• Tricyclic antidepressants
• MAO-1,
• Neostigmine
• Chlorpromazine

B. Morphine + Rifampicin: Increase metabolism. Morphine + Anti-hypertensive drug: Decrease BP.

Codeine

It is an alkaloid obtained from opium or prepared in laboratory by methylation of morphine.org

Chemically: It is 3-methyl morphine.

➤ Absorbed from the gastrointestinal tract.

➤ Route of administration: orally.

➤Half-life: 3-.4 hours.

➤Plasma protein binding capacity: 25%

➤ Metabolised in the liver by ortho and nitrodemethylation to morphine, norcodeine & normorphine. Some of codeine is conjugated with glucoronic acid codeine & its metabolites art excreted by kidney.or

Uses:

A.As an analgesic to relief cough and dianhoea.

B. It may be used as supplement to the effects of aspirin and paracetamol

Adverse effects:

1. Constipation

2. Xerostomia.

Morphine Vs Codeine

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