Analgesics

Definition Analgesic: Drugs that relieve pain also they named

painkillers, pain medications, pain relievers.

Classifications of Analgesics: They are classified into:

I- Analgesic antipyretic: e.g. Aspirin

II- Narcotic (Opioid) analgesic: e.g. Morphine

These are drugs that relieve pain but with repeated use they leads
to tolerance and addiction.
 Comparison between Opioid (Narcotic) analgesic
and Analgesic antipyretic
Characters Narcotic (Opioid) Analgesic antipyretic
analgesic
Type of pain All types of pain Low intensity pain like
treated except etching pain toothache or bone ache and
and biliary colic headache
Site of analgesic Cerebral Cortex Subcortical and peripheral
action
Relief of pain is Euphoria or Antipyretic and anti-
accompanied by drowsiness inflammatory but No Euphoria
or drowsiness
Addiction Addictive with Non Addictive with frequent
frequent use use
Effect on body No effect Normalize elevated body
temperature temperature
Example Morphine Aspirin
I- Analgesics antipyretic include the following groups:
- Salicylates : Acetyl salicylic acid (Aspirin)
- Aniline derivatives: e.g. Acetaminophen (paracetamol).
- Pyrazolone derivatives: e.g. Phenylbutazone
- Indole derivatives: e.g. Indomethacin.
- Phenyl acetic acid derivative: Diclofenac (voltaren).
- Ibuprofen: Brufen
- Oxicam: Piroxicam
- Fenamic acid derivatives: Mefenamic acid

All these groups have the main following actions :

Analgesic - Antipyretic - Anti-inflammatory
so they are named Non Steroidal Analgesic Anti-inflammatory
drugs (NSAIDs) except aniline derivative that has minimal anti-
inflammatory effect as it inhibits PGs centrally only
Mechanism of action of NSAIDs:
NSAIDs act through inhibition of prostaglandins (PGs) synthesis which are
the main mediators of inflammation, pain and fever.
Inhibition of prostaglandins (PGs) synthesis occurs through Inhibition of
cyclooxygenase (COX) enzyme at the site of injury
There are 3 types of COX enzymes, COX-1 and COX-2, COX3
- COX-1 is always active (Useful) as is responsible for:
Stomach - Kidney(Maintenance of renal function) - Platelets (stop bleeding)
While
- COX-2 is not always active and is only activated by with tissue injury and is
responsible for production of
Inflammatory - Sensitization of pain receptors - Fever
- COX3: Centrally only is responsible for production of: Pain & Fever
Traditional NSAIDs -- both COX 1,2 &3 (Nonselective COX
inhibitor)
Block of COX2 = Useful (relief inflammation and pain)
Block of COX1 = Side effects of NSAID as peptic ulcer and
nephrotoxicity
So, selective COX2 inhibitor as: celecoxib (Celebrex) and its
rofecoxib (Vioxx)) has marked less side effect than the
nonselective COX inhibitors
NB: There is no selective COX1 inhibitor
Selective COX3 inhibitor as: Acetaminophen (paracetamol) has
the least harmful effect on stomach.
Acetyl salicylic acid (Aspirin)
It is the prototype of analgesic antipyretic group.

Pharmacokinetics:
- It is absorbed after oral and parenteral administration.
- Salicylic acid is highly plasma protein bound.
- Salicylates passively diffuse to all tissues, including breast milk
and the CNS.
- It is metabolized in the liver and excreted in the kidney.
- Its excretion increase in alkaline urine.

Pharmacodynamics:
Aspirin has the following actions:
 Analgesic: to mild and moderate pain like headache or toothache
- (mechanism: -- of PGs synthesis central → analgesia and
antipyretic & peripheral →↓ inflammatory reaction
 Anti-inflammatory:
Mechanism:
- The antiplatelet effect of aspirin continues for 10 days
a) Inhibition of prostaglandin synthesis at site of inflammation
b) Inhibition of bradykinin synthesis (increases permeability of
blood vessels)
c) Inhibition of fibrinolysin

 - Antipyretic: Normalize the elevated body temperature

regardless cause of fever.
Mechanism: -- of PGs synthesis in heat regulating center in CNS
▬► Increase heat loss through:
- Dilatation of cutaneous blood vessels
- Increase sweating.
 - Small dose of aspirin has anti-platelets effects (Through
irreversible inhibition of thromboxane enzyme TXA2).
N.B: The antiplatelet effect of aspirin continues for 10 days
Therapeutic uses of Aspirin: (Local & systemic)
Local uses:
Salicylic acid is applied topically as:
- Keratolytic agent for removal of corns and warts
- Fungistatic in combination with benzoic acid
- Hyperhedrosis 2-4% with talcum powder.
- Methyl salicylic acid is used as counterirritant externally for
painful muscle or joints.
Systemic uses of Aspirin:
1- Fever
2-Analgesic of dull aching pain e.g. toothache and bone ache.
The analgesic dose of acetyl salicylic acid is 0.3- 1 G orally.
- Children dose is 50- 75 mg/Kg/day in divided doses
3- Common cold: to reduce fever, relieve headache, and muscle aching.
4-Acute rheumatic fever:
Salicylates relieve fever and arthritis but don't affect cardiac
complications , chorea and subcutaneous nodules
Dose: 5- 8 G orally divided at four hours intervals.
NB: Sodium salicylate is contraindicated in cases of acute rheumatic
fever complicated with heart failure (sodium increase blood volume)
5- Rheumatoid arthritis. 3-6 G orally daily
6- Gout (large dose > 5 G/day)
N.B. Large dose of aspirin increase secretion of uric acid while
small dose i.e. less than 5gm inhibit secretion of uric acid from
kidney.
7- Ischemic heart disease as it reduces the risk of thrombosis
(due to its antiplatelet effect) Dose: 75 mg/day
Side effects:
1- Gastric irritation: Epigastric discomfort, heartburn and nausea.
2- Gastrointestinal bleeding due to ulceration.
3- Salicylism: these symptoms are reversible on cessation of the drug.
4- Reye’s syndrome.
5-Hypersensitivity reactions:
Aspirin allergy manifest in the form of bronchospasm and urticaria.
Aspirin produce bronchospasm in susceptible patients.
Contraindications of aspirin:
- Peptic ulcer - Hypersensitivity to aspirin
- Bleeding tendencies e.g. haemophilia, hypobrothrombonemia
- Patients taking anticoagulants - Children with viral infection.
Aniline derivatives: e.g. Acetaminophen (paracetamol).
- Acetaminophen is not related to salicylates or NSAIDs.
- It is rapidly and completely absorbed from the gastrointestinal tract.
- Acetaminophen is metabolized by the liver.
- Acetaminophen acts through – PGs centrally only so, it is used for
its analgesic and antipyretic effects.
Therapeutic doses have no effect on the cardiovascular and
respiratory system. It does not have any real gastrointestinal effects.
Uses:
- Acetaminophen is used for its analgesic and antipyretic effects. It is
useful in patients having hypersensitivity to aspirin or NSAID or
have peptic ulcer.
- It is useful for children because it is not known to cause Reye
syndrome.
Adverse Effects
- Hepatotoxicity
Can occur after the ingestion of a single toxic dose (10-15 g) or after
long term use of therapeutic doses.
- Nephrotoxicity: It has been associated with long-term use.