Drugs used in the management of pain

 Non opioid analgesics

 Opioid analgesics
 NSAIDS

Pain
"Pain is an unpleasant sensory and emotional experience associated with actual or potential
tissue damage, or described in terms of such damage." In medical diagnosis, pain is a
symptom.Pain motivates the individual to withdraw from damaging situations, to protect a
damaged body part while it heals, and to avoid similar experiences in the future. Pain that lasts
a long time is called chronic or persistent, and pain that resolves quickly is called acute.

For Mild pain, Paracetamol (acetaminophen), or a non steroidal anti-inflammatory drug

(NSAID) such as ibuprofen.

For Mild to moderate pain,Paracetamol, an NSAID and/or paracetamol in a combination

product with a weak opioid such as tramadol.

1.Non-opioid analgesics
Non-opioid analgesics with anti-inflammatory activity include salicylates such as acetylsalicylic
acid and other nonsteroidal anti-inflammatory drugs such as ibuprofen. Non-opioid analgesics
with little or no anti-inflammatory activity include paracetamol.

Acetylsalicylic acid
The principal effects of acetylsalicylic acid are anti-inflammatory, analgesic, antipyretic and
antiplatelet. Oral doses are absorbed rapidly from the gastrointestinal tract; rectal absorption is
less reliable but suppositories are useful in patients unable to take oral dosage forms.

Uses: mild to moderate pain including dysmenorrhoea, headache; pain and inflammation in
rheumatic disease and other musculoskeletal disorders (including juvenile arthritis); pyrexia;
acute migraine attack ; antiplatelet .

Contraindications: hypersensitivity ,haemophilia and other bleeding disorders;not for

treatment of gout
Precautions: asthma, allergic disease; impaired renal or hepatic function pregnancy ;
breastfeeding ; elderly; G6PD-deficiency; dehydration; interactions:

Dosage: Mild to moderate pain, pyrexia, by mouth with or after food, ADULT 300–900 mg
every 4–6 hours if necessary; maximum 4 g daily; CHILD under 16 years not recommended Mild
to moderate pain, pyrexia, by rectum , ADULT 600–900 mg inserted every 4 hours if necessary;
maximum 3.6 g daily;

Adverse effects: gastrointestinal discomfort or nausea, ulceration with occult bleeding

(occasionally major haemorrhage); also other haemorrhage (includingsubconjunctival); hearing
disturbances such as tinnitus (rarely deafness), vertigo, confusion, hypersensitivity reactions
(angioedema, bronchospasm and rash); increased bleeding time; rarely oedema, myocarditis,
blood disorders (particularly thrombocytopenia)2

2Paracetamol

Paracetamol is similar in analgesic and antipyretic efficacy to acetylsalicylic acid. It is used for
mild to moderate pain including headache and acute migraine attacks and for reducing fever,
including post-immunization pyrexia. Paracetamol is particularly useful in patients in whom
salicylates or other NSAIDs are contraindicated,. Unlike acetylsalicylic acid and other NSAIDs,
paracetamol has little anti-inflammatory activity which limits its usefulness for long-term
treatment of pain associated with inflammation; however it is useful in the management of
osteoarthritis, a condition with only a small inflammatory component.

Uses: mild to moderate pain including dysmenorrhoea, headache; pain relief in osteoarthritis
and soft tissue lesions; pyrexia including post-immunization pyrexia; acute migraine attack .

Precautions: hepatic impairment ; renal impairment; alcohol dependence; breastfeeding ;

overdosage: .; interactions:

Dosage2Post-immunization pyrexia, by mouth , INFANT 2–3 months, 60 mg followed by a

second dose.

Mild to moderate pain, pyrexia, by mouth, ADULT 0.5–1 g every 4–6 hours, maximum 4 g
daily; CHILD under 3 months see note below, 3 months–1 year 60–125 mg.

Adverse effects: rare but rashes and blood disorders reported; important: liver damage
(and less frequently renal damage) following overdosage 2

22.Opioid analgesics
Includes :
 STRONG AGONISTS3-
Morphine3,Meperidine3,Methadone3,Fentanyl3,Sufentanil, alfentanil, and
remifentanil3,Heroin3
 MODERATE/LOW AGONIST3:Codeine3,
 MIXED AGONIST-ANTAGONISTS AND PARTIAL
AGONISTS3:Pentazocine3,Buprenorphine3,Nalbuphine and butorphanol3,
 ANTAGONISTS3:Naloxone3,Naltrexone3
 OTHER ANALGESICS3:Tramadol3,Tapentadol3
Opioids interact stereospecifically with protein receptors on the membranes of certain cells in
the CNS, on nerve terminals in the periphery, and on cells of the gastrointestinal (GI) tract and
other anatomic regions.

Morphine
Morphine is the major analgesic drug contained in crudeopium and is the prototype strong
agonist. Codeine is present in crude opium in lower concentrations and is inherently less
potent, making codeine the prototype of theweak opioid agonists. Morphine and several other
opioids have high affinity for µ receptors, whereas other agents have varying affinities for δ and
κ receptors.3

Mechanism of action: Morphine acts at κ receptors in laminae I and II of the dorsal horn of
the spinal cord, and it decreases the release of substance P, which modulates pain perception
in the spinal cord. Morphine also appears to inhibit the release of many excitatory transmitters
from nerve terminals carrying nociceptive (painful) stimuli.

Actions:
Analgesia: Morphine causes analgesia (relief of pain without the loss of consciousness).

Euphoria:

Respiration: Morphine causes respiratory depression by reduction of the sensitivity of

respiratory center neurons to carbon dioxide. Miosis: The pinpoint pupil, characteristic of
morphine use, results from stimulation of µ and κ receptors.
Uses: severe pain (acute and chronic); myocardial infarction, acute pulmonary oedema;
adjunct during major surgery and postoperative analgesia ,cancer pain.

Contraindications: acute respiratory depression, acute alcoholism, where risk of paralytic

ileus; raised intracranial pressure or head injury (interferes with respiration, also affects
pupillary responses vital for neurological assessment); avoid injection in phaeochromocytoma

Precautions: renal and hepatic impairment ; reduce dose or avoid in elderly and debilitated;
dependence (severe withdrawal symptoms if withdrawn abruptly); hypothyroidism; convulsive
disorders; decreased respiratory reserve and acute asthma; hypotension; prostatic
hypertrophy; pregnancy and breastfeeding; overdosage: interactions.

Dosage: Acute pain, by subcutaneous injection (not suitable for oedematous patients) or by
intramuscular injection ADULT 10 mg every 4 hours if necessary (15 mg for heavier well-
muscled patients); INFANT up to 1 month 150 micrograms/kg, 1–12 months 200
micrograms/kg; CHILD 1–5 years 2.5–5 mg, 6–12 years 5–10 mg Chronic pain, by mouth or by
subcutaneous injection (not suitable for oedematous patients).

Adverse effects: nausea, vomiting ,constipation; drowsiness; also dry mouth, anorexia,
spasm of urinary and biliary tract; bradycardia, tachycardia, palpitations, euphoria, decreased
libido,

Meperidine
Meperidine is a synthetic opioid structurally unrelated to morphine. It is used for acute pain.

Mechanism of action: Meperidine binds to opioid receptors, particularly µ receptors. It also

binds well to κ receptors.

Actions: Meperidine causes a depression of respiration similar to that of morphine, but it has
no significant cardiovascular action when given orally. On IV administration, meperidine
produces a decrease in peripheral resistance and an increase in peripheral blood flow, and it
may cause an increase in cardiac rate. As with morphine, meperidine dilates cerebral vessels,
increases CSF pressure, and contracts smooth muscle (the latter to a lesser extent than does
morphine). Meperidine does not cause pinpoint pupils but, rather, causes the pupils to dilate
because of an anticholinergic action.

Adverse effects: anxiety, tremors, muscle twitches, and, rarely, convulsions, due to the
accumulation of normeperidine,hyperactive reflexes.

4Codeine phosphate
The analgesic actions of codeine derive from its conversion to morphine by the CYP450 2D6
enzyme system, whereas the drug’s antitussive effects are due to codeine itself. Thus, codeine
is a much less potent analgesic than morphine. Codeine’s analgesic potency is approximately 30
percent that of morphine. Codeine shows good antitussive activity at doses that do not cause
analgesia.

Uses: mild to moderate pain; diarrhoea

Contraindications: respiratory depression, obstructive airways disease, acute asthma

attack; where risk of paralytic ileus

Precautions: renal and hepatic impairment ; dependence; pregnancy breastfeeding ;

overdosage: interactions:

Dosage: Mild to moderate pain, by mouth , ADULT 30–60 mg every 4 hours when necessary to
a maximum of 240 mg daily; CHILD 1–12 years, 0.5–1 mg/kg every 4–6 hours when needed

Adverse effects: constipation ,dizziness, nausea, vomiting; difficulty with micturition;

ureteric or biliary spasm; dry mouth, headaches, sweating, facial flushing;

Tramadol
Tramadol is a centrally acting analgesic that binds to the µ-opioid receptor. The drug
undergoes extensive metabolism via CYP450 2D6, leading to an active metabolite that has a
much higher affinity for the µ receptor than the parent compound. In addition, it weakly
inhibits reuptake of norepinephrine and serotonin. It is used to manage moderate to
moderately severe pain. Its respiratory-depressant activity is less than that of morphine.
Naloxone (see below) can only partially reverse the analgesia produced by tramadol or its active
metabolite. Anaphylactoid reactions have been reported. Toxicity through drug-drug
interactions with medications, such as selective serotonin reuptake inhibitors and tricyclic
antidepressants, or in overdose, leads to CNS excitation and seizures. Tramadol should also be
avoided in patients taking MAOIs. 5

3.5NSAIDs (nonsteroidal anti-inflammatory drugs)

NSAIDs, including ibuprofen , have analgesic, anti-inflammatory and antipyretic properties. In
single doses NSAIDs have analgesic activity comparable to that of paracetamol. In regular full
dosage, they have a lasting analgesic and antinflammatory effect, which makes them useful for
continuous or regular pain due to inflammation.
Ibuprofen
Ibuprofen Is used in the treatment of mild to moderate pain and in the management of pain
and inflammation in rheumatoid arthritis and juvenile arthritis.

Uses: pain and inflammation in rheumatic disease and other musculoskeletal disorders
including juvenile arthritis; mild to moderate pain including dysmenorrhoea, headache; pain in
children; acute migraine attack.

Contraindications: hypersensitivity to acetylsalicylic acid or any other NSAID; active peptic

ulceration.

Precautions: renal and hepatic impairment ; peptic ulceration; cardiac disease; elderly;
pregnancy and breastfeeding ; coagulation defects; allergic disorders.

Dosage: Mild to moderate pain, pyrexia, inflammatory musculoskeletal disorders, by

mouthwith or after food, ADULT 1.2–1.8 g daily in 3–4 divided doses.

Adverse effects: gastrointestinal disturbances , gastrointestinal haemorrhage;

hypersensitivity angioedema, bronchospasm; headache, dizziness, nervousness, depression,
drowsiness, insomnia, vertigo, tinnitus, photosensitivity, haematuria; fluid retention .