ANALGESICS

IntroductionTERMINOLOGIES

Analgesic: A drug that selectively relieves pain by acting in the CNS or on peripheral pain mechanism, without significantly altering consciousness.

Analgesia: refers to absence of pain without the loss of consciousness.

Narcotics: they are analgesic, CNS depressant, and any drug capable of causing physical dependence.

Opioid: is any drug natural, semi synthetic or synthetic that has actions similar to those of morphine.

Definitions continuedOpiates- refers to any compound present in

Opium-(alkaloids derived from opium) e.g morphine, codeine, heroin and opium.

Pain- is any unpleasant sensation ranging from mild discomfort to organized distress caused by disease, injury, or emotional sufferings that hurts the body.

Definition continued Pain can be classified as; (a) Acute- it is usually associated with trauma or

disease and has a well defined location, character and timing. It is accompanied by symptoms such tachycardia, hypertension, sweating and mydriasis.

(b) Chronic- this is pain lasting more than a few months. It may not be associated with disease or trauma or may persist after initial injury has healed. Location, character and timing are more vague in chronic than in acute pain.

Opioid Analgesics Originate from the opium poppy (plant).

Powerful pain relievers.

Opioid analgesics are the most effective analgesics and are used in the management of severe pain.

They are divided into two: weak opioid analgesics e.g. codeine, dihydrocodeine and strong opioid analgesics such as morphine pethidine, methadone.

Classified according to their chemical structure and action

Morphine-like derivatives (codeine, morphine, oxycodone, hydromorphone, oxymorphone).

Pethidine/meperidine-like derivatives (fentanyl, pethidine)

Methadone-like derivatives (methadone)

Other: tramadol 50 to 100 mg 4 hrly (no risk of physical addiction – inhibits reuptake of serotonin and norepinephrine)

Opioid receptorsThree main classes of opioid receptors, designated as mu, kappa, and delta.

From the pharmacologic perspective, mu receptors are the most important. This is because opioid analgesics act primarily through activation of mu receptors, although they also produce weak activation of kappa receptors.

As a rule, opioid analgesics do not interact with delta receptors. In contrast to opioid analgesics, endogenous opioid peptides act through all the types of opioid receptors.

Mechanism of action

Stimulate opiate receptors in the brain.

They relieve pain by mimicking the action of endogenous opioid peptides, primarily at mu receptors.

Opioid analgesics Repeated administration may cause tolerance

(patient needs increasing dose of drug to get same analgesic effect) or psychological or physical dependence.

Withdrawal signs: restless, sweating, runny eyes, runny nose, dilated pupils, can develop into muscle spasms, muscle cramps, insomnia, N, V, D, inc temp, inc BP, inc HR and RR Withdrawal symptoms reach peak at 36-72hrs after

stopping the drug and disappear over the next 5 to 14 days.

Opioids: Uses Opioids used to control moderate to severe pain

particularly of visceral origin.

Used for pain control after surgical operation.

Codeine Phosphate 30mg tab also used as cough suppressant.

Morphine Sulphate is used most widely.

Tramadol Hcl is not as effective in severe pain as other opioid analgesics.

Opioids: Side effects

The most common include nausea, vomiting, constipation, drowsiness, sedation, confusion, euphoria, urinary retention.

Larger doses produce respiratory depression and hypotension.

Convulsions and worsening of asthma may occur.

Tolerance and physical dependence may occur.

Drowsiness affects performance of skilled labour and it is increased by presence of alcohol.

Opioids: Contraindications Known medicine allergy.

Severe asthma.

Used with caution in:– Patients with severe head injuries (mask level of

consciousness).– Morbid obesity with respiratory disturbances when

asleep (apnoea).– Bowel paralysis – opioids tend to slow bowel

movements and can cause constipation.

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Opioids

Medicine Formulation Dosage

Adult Child

Morphine Sulphate

Tablet 10mg 5 – 20mg (or more) every four hours (chronic pain)

2.5-5mg every four hrs prn

10mg/30mg/60mg (Slow release)

Daily dose in two divided doses

Adjusted as needed

Inj 10mg in 1ml amp 10mg every 4hrs (acute pain)

Syrup 10 mg / 5 ml Adjusted as needed 2.5-5mg as needed

Dyhydrocodeine (DF118)

Tab: 15 mg ,30 mg (phosphate).

15-30mg every four hours

0.5-1mg/kg every four hours.

Opioids: Toxicity When used in overdose, opioids are toxic.

Signs and symptoms: Coma Respiratory depression Pinpoint pupils

Antidote used is Naloxone.

It acts by blocking the effects of opioids including CNS and respiratory depression.

Therapeutic outcome is reversal of signs of opioid toxic effects.

Antidote: Naloxone

Dosage form 400mcg/ml injection

Dose: IV injection, ADULT: 0.4-2mg repeated at intervals of 2-3 minutes up to a maximum of 10mg. CHILD: 10mcg/kg, subsequent dose of 100mcg/kg if no response.

Points to note Opioids are controlled medicines and should

only be supplied on prescription by qualified medical practitioner.

Prescribing of these medicines are subject to legal requirements.

Strict legal requirements require detailed recording of dispensing and issue of these medicines.

Points to note Drug intxn: other CNS depressants i.e. Alcohol,

antihistamines, antidepressants (TCAs)

If someone is on chronic pain treatment with opiates, need to also be on drugs for prophylaxis of constipation. Start opiate and the drug for constipation at the same time i.e. Can use a stool softener (docusate calcium/sodium) PLUS bisacodyl daily

Patient can develop tolerance to nausea side effect of opiates, but will NEVER develop tolerance to constipation, therefore need to PREVENT constipation when starting chronic opiate use

Morphine sulphate Indications - severe pain, pulmonary oedema, and pain

associated with heart attack, during major surgery and postoperative analgesia, Myocardial infarction, Sickle cell crisis, Chronic pain(cancer).

Contraindication: Acute respiratory depression, Known hypersensitivity to morphine, Acute alcoholism, Head injury

Dose – 10mg initially, reduce to 5mg in the elderly; children 100mcg/kg

Adverse Reactions- severe respiratory depression, constipation.

Codeine/dihydrocodeine Uses - allergy, cold and cough remedies, antitussives, opioid

analgesics

Side Effects - confusion, sedation, hypotension, constipation.

Contra-indications: Respiratory depression, Obstructive airway disease, Hypersensivity to codeine, Acute alcoholism, Raised intracranial pressure or head injury, Risk of paralytic ileus

Usually supplied in combination with other analgesics

Dosing: 10-60mg every four hours.

PETHIDINE Indications: Pre-operative medication, Acute

analgesia, Post-operative, Moderate to severe acute pain, Obstetric analgesia.

Contra indications: Severe renal impairment, Acute respiratory depression, acute alcoholism, Head injury, Severe liver disease, Avoid injection in phaeochromacytoma, Known hypersensitivity to pethidine.

Side effects: Confusion, Spasm of urinary tract.

TRAMADOLMOA: It inhibits reuptake of noradrenalin and 5HT, and thus activates monoaminergics spinal inhibition of pain.

Indications: Moderate to severe pain, Postoperative pain, Neuropathic pain, Cancer pain, Low back pain,Pain associated with orthopedic disorders.

Contraindications: known hypersensitivity to tramadol, Acute intoxication with alcohol,Severe renal impairment

TRAMADOL Side effects: Weakness, Fatigue, Diarrhea, Headache,

Hypotension, Sweating, Constipation, Dizziness, Hallucination, Nausea and vomiting, Dry mouth, Urticaria.

PrecautionsAvoid rapid IV injection since it associated with a higher

incidence of side effectsInform a patient that tramadol causes dizziness and

drowsiness which may impair the ability to perform activity require mental alertness

Avoid alcohol and other medications that cause sedation

NONNARCOTIC ANALGESICS

INTRODUUCTION

•They do not depress CNS

•They do not produce physical dependency

•Have no abuse liability and weaker analgesics

•Most of these drugs can produce three clinical effects: suppression of inflammation; relieve of pain and reduction of fever.

Mechanism of action

Inhibition of cyclooxygenase, an enzyme require for the biosynthesis of prostaglandins and related metabolites of arachidonic acid (prostacyclin and thromboxane A2)

Non-Opioid analgesics Paracetamol/Acetaminophen.

Salicylates (Anti-inflammatory medicine)- acetylsalicylic acid (Aspirin) prototype for class.

Non-Steroidal Anti-Inflammatory medicines (NSAIDS) e.g. Ibuprofen, diclofenac sodium, naproxen sodium, aceclofenac.

All these substances also reduce fever.

Paracetamol/Acetaminophen Action: Blocks central pain impulses (cyclo-oxygenase 3 inhibitor). Note: Acetaminophen does not block the prostaglandin synthesis

in the peripheral tissues but instead produces pain relief through central mechanisms.

Uses: Treatment of mild to moderate pain, to lower elevated body temperature., Treatment of Gout i.e. Aetaminophen+probenicid.

Contraindications: Medicine allergy, liver disease.

Cautions: Hepatic impairment, renal impairment, alcohol dependence.

Side effects: Rare, but rashes, blood disorders, liver damage. Dose: By mouth, 0.5–1 g every 4–6 hours to a max. of 4 g daily.

Paracetamol: Toxicity Ingestion of large amounts of paracetamol, as in

acute overdose, or even chronic unintentional misuse can cause liver damage.

Acute ingestion of doses of 150 mg/kg or more may result in severe hepatic toxicity, dizziness and disorientation.

Treatment: Liver damage is minimized by administering Acetylcysteine (Mucomyst)

Action: Aspirin provide analgesia by blocking prostaglandins synthesis, that sensitize the peripheral pain receptors to send a pain signal to the central nervous system (CNS). i.e. Non-selective cyclo-oxygenase inhibitor.

Use: Mild to moderate pain including dysmenorrhoea, headache, acute migraine attack and pyrexia (fever). It prevents platelets aggregation (Thromboembolic disorders, Prophylaxis in myocardial infarction).

Cautions: Asthma, allergic disease.

Contra-indications: Children and adolescents under 16 years and in breast-feeding, previous or active peptic ulceration, haemophilia, Pregnancy, gout.

Acetysalicylic acid (ASPIRIN)

Acetysalicylic acid

• Dose: by mouth 300-900mg every 4-6 hours when necessary. Maximum dose 4g per day.

• Side effects:– GI ulceration: Gastric acidity GI protection– Bleeding.– Renal elimination.– Uterine contractions during labour.

Reyes Syndrome The acetic class of medicines e.g. aspirin is

contraindicated in children.

It is associated with Reyes syndrome - a fatal disease affecting many organs especially the brain and liver.

Symptoms include vomiting and rashes.

Manage fever in children with paracetamol and not with acetylsalicylic acid.

Diclofenac sodium• Use: Anti-inflammatory, analgesic, and antipyretic. Treatment

of Acute gout, Rheumatoid arthritis, Migraine, Renal colic pain, Tendonitis, Strains and sprain, Post operative pain.

• Cautions: Asthma, allergic disease.

• Contra-indications: Children and adolescents under 16 years and in breast-feeding, previous or active peptic ulceration.

• Dose: – By mouth, 25–100 mg every 8 -12 hours when necessary; max.

100mg daily.– IM 75mg daily.

Ibuprofen Use: anti-inflammatory, analgesic, and antipyretic. Used in

treatment of gout. Cautions: asthma, allergic disease.

Contra-indications: children and adolescents under 16 years and in breast-feeding, previous or active peptic ulceration and pregnancy.

Dose: By mouth,400mg three times daily max 1.8 g daily. doses preferably after food; increased if necessary to max. 2.4 g daily.

IndomethacinIndications

Treatment of rheumatoid arthritis, osteoarthritis, tendonitis

ContraindicationsCardiac dysfunction, Hypertension, Decreased

renal/hepatic function, Epilepsy, Concurrent anticoagulant therapy.

Adverse effects Severe frontal headache, Dizziness, Vertigo, Confusion

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