ANALGESICS

• Pain is one of the major sufferings of mankind.

• An analgesic is a drug that results in the
abolition of sensation of pain.
• An anaesthetic is an agent that causes
abolition of all modalities of sensation.
• E.g morphine is an analgesic drug that makes
the patient unable to appreciate the sensation
of pain.
• Athough he/she can still appreciate the
sensation of touch/ heat.
• Local anaesthetic( e.g. procaine) when
injected near the nerve causes loss of
sensations- but only in a localised area.
• Pain, touch, heat and all other sensations are
lost- hence cant be a local analgesics.
• Pain is relieved by
• Treating the cause
• Interrupting the conduction of pain
• Centrally acting drugs which increase pain
threshold. E.g, non narcotic & narcotic
analgesics.
• A narcotic- induces drowsiness, sleep, stupor
or insensibility in a patient. They act on the
CNS.
• It produces drug dependence. Many of these
• Drugs produce euphoria.
• These drugs differ from hypnotics as they
produce sleep as well as analgesia.
 NARCOTIC ANALGESICS
• CLASSIFICATION OF NARCOTIC DRUGS
• Natural- opium & its alkaloid( morphine,
codeine)
• Semisynthetic derivatives- of morphine &
codeine. E.g. pholcodeine, oxycodone, diacetyl
morphine( heroin)
• Synthetic derivatives- pethidine, methadone,
pentazocine.
• ENDOGENOUS OPIOID PEPTIDE RECEPTORS
• Opioid peptides, endorphins, encephalins,
dynorphins and beta endorphins are present
in brain, pituitary, spinal cord & the gut& the
opioid receptors ( mu, kappa & delta
receptors) are also present. Opium alkaloids
act through these receptors.
• Mu receptor stimulation produces
• Supraspinal analgesia.
• Respiratory depression
• Reduction in gut motility
• Increase in tone of smooth muscles.
• Sedation & euphoria
• Physical dependence.
• Kappa receptors stimulation leads to
• Spinal analgesia
• Dysphoria
• Sedation.
• Delta receptor stimulation leads to
• Analgesia& changes in emotional behaviour.
• MORPHINE
• Derived from poppy
• ACTIONS OF MORPHINE
• A) ON CNS
• Depression of
• Respiration centre
• Vasomotor centre
• Cough centre- antitussive
• Thermoregulatory center – fall in body.
• Cortical areas- produces sleep
• Relieves pain by increasing threshold of pain
perception.
• STIMULATES
• CTZ- hence induces vomiting
• Vomiting centre.
• Vagal centre in brain & produces bradychardia.
• Oculomotor center- causes constriction of
pupils.
• EXTRA CNS EFFECTS
• Causes contraction of smooth muscles of
bronchi, gut & sphincters. Hence causes.
• Constipation
• Retention of urine
• Precipitation of asthma.
• USES OF MORPHINE
• To relieve pain
• In cardiac asthma( left ventricular failure)- to
release anxiety & make patient breathe more
easily.
• As post operation medication
• ADVERSE EFFECT
• It induces n&v.
• Produces constipation
• Precipitates bronchial asthma
• Produces acute retention of urine.
• Depresses respiration
• Rarely, allergic reactions.
• TREATING MORPHINE TOXICITY
• Keep airway patent & give artificial
respiration.
• Naloxone- an antagonist is injected.
• Gastric lavage.
• CONDITIONS NOT TO GIVE MORPHINE
• Head injury
• Prostatic hypertrophy
• Bronchial asthma & emphysema
• Undiagnosed acute abdominal pain.
• TOLERANCE
• 60mg- can kill a normal man
• 100mg- morphine addict can tolerate without
danger.
• DRUG DEPENDENCE
• Withdrawal symptoms- tremors, dryness of
the mouth, diarrhoea.
• CODEINE
• Its chemically known as methyl morphine
• Is a less potent analgesic, longer duration of
action, is an anti-tussive( suppresses cough)
• USES
• AS an antitussive- found in cough mixtures
• For controlling diarrhea, & as an analgesic +
NSAIDS.
• PETHIDINE
• Is a synthetic opiate.
• More dose is required than morphine.
• Differs from morphine in the following
• Is less potent,
• Has quick onset but short duration of action
• Does not suppress cough
• Can be given orally
• Produces mydriasis( dilation of pupil)
• Produces tachycardia
• Is less constipating.
• It is preffered in most clinical situations.
• USES
• Analgesic- in short time surgical intervention
e.g cystoscopy, gastroscopy.
• As pre anaesthetic medication
• During labour for relieving pain. Preffered over
morphine as it doesn’t interfere with uterine
contractions.
• OTHERS
• Methadone
• Heroin
• Propoxyphene
• PARTIAL OPIOID AGONISTS
• Pentazocine
• Buprenorphine
• Nalbuphine
• Butorphenol
• Tramadol hydrochloride.
• NARCOTIC ANTAGONISTS
• There are two types of these
• Pure antagonists- e.g naloxone
• Partial antagonists- nalorphine.
• NON NARCOTIC ANALGESICS.
 Nonsteroidal Anti-inflamatory Drugs
(NSAIDS)

• In the prostaglandin synthesis pathway, an enzyme

cyclooxygenase (COX) converts arachidonic acid
into:
– Prostaglandins
• Depending on the tissues where they are
produced, some are important for a variety of
normal physiologic processes, while others
serve as mediators of inflammation
– Thromboxane:
• Causes platelet aggregation
– Prostacyclin:
• Produced in endothelial cells; causes
vasodilation
• The cyclooxygenase (COX) enzyme exists in two
isoforms: COX 1 and COX 2
– COX-1 is primarily expressed in
noninflammatory cells. Prostaglandins
synthesized in this pathway perform
important homeostatic functions:
• cytoprotection in the gastrointestinal tract
• autoregulation of renal function.
– COX-2 is expressed in activated lymphocytes,
polymorphonuclear cells, and other inflammatory
cells;
• Prostaglandins produced in this pathway are
important mediators of inflammation
• NSAIDS exert their effects by inhibiting COX;
• Some NSAIDS non selectively inhibit both cox1 and
cox2 while others are selective inhibitors of cox2,
hence their classification into two groups
 CLASSIFICATION OF NSAIDS

– 1) Nonselective NSAIDS:
• Inhibit both cox 1 and cox 2
• Drugs:
-Acetylsalicylic acid (Asprin), -Piroxicam
-ibuprofen, -ketorolac
-naproxen, -Sulindac
-ketoprofen, -Tolmentin
-indomethacin,
-diclofenac,
 Cont…

– 2) Selective NSAIDS:
• Selectively inhibit cox2
• Drugs:
• celecoxib,
• meloxicam (slightly COX-2-selective),
• rofecoxib and
• valdecoxib (currently withdrawn because of
cardiovascular toxicity)
 Effects of NSAIDS

– 1) Anti-inflammatory effect
• reduce the manifestations of inflammation,
although they have no effect on underlying
tissue damage or immunologic reactions
– 2) Analgesia:
• Mechanism not well understood; reduced
production of prostaglandins (resulting from
injury) is thought to diminish activation of
peripheral pain sensors
 CONT…

– 3) Antipyretic:
• Suppression of pyrogen stimulated
prostaglandin synthesis in the CNS, thus
reducing fever
– 4) Disruption of prostaglandin mediated
homeostatic functions:
• cytoprotection in the gastrointestinal tract
• autoregulation of renal function.
– 5) Antiplatelet effect:
• Aspirin and nonselective NSAIDs inhibit both cyclooxygenase
isoforms
– Hence decreasing prostaglandin and thromboxane
synthesis throughout the body;
– Thromoxane is required for platelet aggregation
• Aspirin differs from other NSAIDs in that
– It acetylates and thereby irreversibly inhibiting
cyclooxygenase
– On the other hand, other NSAIDs produce reversible
inhibition
 TOXICITY

– Aspirin
• GIT effects:
– Gastric upset: The most common adverse effect from
therapeutic anti-inflammatory doses of aspirin
– gastric ulceration,
– upper gastrointestinal bleeding,
• renal effects
– acute failure
• Increases in bleeding time; the non selective inhibition of cox 1
and 2 leads to reduction in thromboxane which is required for
platelet aggregation
• Hypersensitivity reactions:
• High doses of aspirin may lead to:
– ,tinnitus, vertigo, hyperventilation, and respiratory
alkalosis are observed. At very high doses, the drug
causes metabolic acidosis, dehydration,
hyperthermia, collapse, coma, and death.
• Reye's syndrome:
– a rare but serious syndrome of rapid liver
degeneration and encephalopathy occuring in
Children with viral infections who are treated with
aspirin
 Acetaminophen/Paracetamol

• Acetaminophen is not classified as an NSAID;

– it’s a non–anti-inflammatory analgesic
commonly available
– Phenacetin, a toxic prodrug that is
metabolized to acetaminophen, is still
available in some other countries.
• Mechanism of Action
– analgesic action of acetaminophen is not
clearly understood.
– The drug is only a weak COX-1 and COX-2
inhibitor in peripheral tissues,
• Thus lacking anti-inflammatory effects.
 – There is evidence that acetaminophen may
inhibit a third enzyme, COX-3, in the CNS.
• Effects
– Acetaminophen has both analgesic and
antipyretic effects;
• It does not have anti-inflammatory or
antiplatelet effects.
 Pharmacokinetics and Clinical Use
• Except for inflammatory conditions,
acetaminophen shares the same indications as
intermediate-dose aspirin, thus providing a
substitute in patients with ASPIRIN/NSAIDs
contraindication or intolerance
• DOSE- 300-600 mg/ 4 times a day.
 CONT…
• Toxicity
– acetaminophen has negligible toxicity in
therapeutic doses.
– In cases of overdose or in patients with
severe liver impairment,
• the drug causes serious hepatotoxicity.