PHARMACO LOGY PRESENTED BY SREELAKSHMI K R 18

PHARMACO LOGY PRESENTED BY; SREELAKSHMI K. R 18 M 135

OPIOID ANALGESICS & ANTAGONISTS Adverse effect Tolerance Dependence Acute morphine poisoning Contraindication

ADVERSE EFFECTS OTHERS: • Vomiting • Drowsiness • Dizziness • Constipation • Dysphoria • Urinary retention

APNOEA: Administration of morphine to the mother in labour can cause apnoea in the new-born because morphine crosses the placenta , reaches the foetal brain , attaining high levels and causes apnoea • Naloxone injection to the umbilical cord reverses this effect. Allergic reaction including skin rashes , pruritus & wheal may be seen at the sight of injection of morphine due to histamine liberation. Rarely IV can cause anaphylaxis due to same reason

TOLERANCE: Repeated administration of morphine results in the development of tolerance to some of its effects including respiratory depression , analgesia , sedation & euphoriant effects and CNS depressant effects. Constipation and miosis show no tolerance. Though lethal dose of morphine is about 250 mg , addicts can tolerate morphine in grams. Patients in pain can also tolerate a higher dose of morphine. Cross tolerance is seen among different opioids. Tolerance is mainly pharmacodynamic where the cells adapt to the effects of the drug – at the receptor level , though pharmacokinetic mechanisms like increased metabolism also contributes.

DEPENDENCE: Opioids produce both psychological & physical dependence. Sudden cessation of opioids or administration of opioid antagonist produce significant withdrawal symptoms in such individuals like lacrimation , sweating , anxiety , restlessness , rhinorrhoea & tremors. As the syndrome progresses , fever , insomnia , abdominal colic , diarrhoea , blurring vision due to mydriasis , hyper tension , goose flesh(due to pilomotor activity; skin resembles that of a plucked turkey. Hence the word called turkey is used for the abrupt withdrawal symptoms ), palpitation , prostration & cardio vascular collapse can occur. • Not life threatening • Administration of suitable opioid completely reverses the symptoms and disappears in 7 to 10 days.

WITHDRAWAL IN THE NEWBORN: Babies born to mothers who were addicts prior to delivery will also be dependent. • Withdrawal symptomsirritability , excessive crying , tremors , etc. • Tincture of opium 0. 2 ml/Kg/3 -4 hrs is started at birth and gradually withdrawn.

MANAGEMENT OF ADDICTION: Morphine is slowly withdrawn over several days and substituted by oral Methadone. Advantages of methadone administration: • Orally effective and by this route no ‘Kick’ is experienced. • More potent , long lasting & prevents withdrawal symptoms as it is slowly released from the tissues. Dose- as per the degree of dependence— 1 mg methadone for 4 mg morphine (OD). Gradually withdrawn.

Clonidine , an alpha 2 agonist can suppress some of the autonomic withdrawal symptoms like anxiety , nausea , vomiting &diarrhoea. --given for 7 days and withdrawn over 3 -4 days. Night time sedation with a hypnotic like Diazepam is helpful. Most addicts can be completely withdrawn from opioids in about 10 days though mild tolerable withdrawal symptoms may persist like insomnia, malaise, restlessness, irritability, etc up to several months.

ACUTE MORPHINE POISONING: -May be accidental , suicidal or homicidal. -Lethal dose in non addicts is about 250 mg but addicts can tolerate grams of morphine. -Signs &Symptoms: • Shallow breathing • Pin-point pupil • Coma & death due to respiratory failure &Pulmonary edema. • Hypotension, flaccidity , shock, cyanosis.

TREATMENT: • Positive pressure respiration. • Maintenance of BP. • Gastric lavage with potassium permanganate to remove unabsorbed drug. • Specific antidote is Naloxone – 0. 4 -o. 8 mg IV repeated every 1015 min.

CONTRAINDICATIONS &PRECAUTIONS: • Avoid opioids in patients with respiratory insufficiency , COPD. • Acute bronchospasm may be precipitated by morphine in patients with bronchial asthma. • In extreme of age- more susceptible to respiratory depression. • In hypovolaemic shock , morphine further decreases the BP. • Opioids potentiate CNS depressants.

• Head injury – morphine is contraindicated because: i. CO 2 retention due to respiratory depression – increased CSF pressure thereby increasing ICP. ii. Causes marked respiratory depression. iii. Vomiting, miosis &mental clouding seen with morphine interfere with the diagnosis & assessment of progress in head injuries. • Pregnancy – opioids should be avoided.

• Undiagnosed acute abdomen – morphine relieves pain & may interfere with the diagnosis. It induces vomiting & its spasmogenic effect may add to its drawbacks. Hence it can be administered only after the diagnosis is established, if necessary. • Renal & hepatic dysfunction – opioids should be avoided or dose reduced. • Partial agonists like Pentazocine should not be mixed with pure agonist( like morphine) – reduced analgesic effect.

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