CHAPTER FIVE
NON-NARCOTIC ANALGESICS &
RELATED DRUGS AND DRUGS USED
IN GOUT
BY: TESFAYE.N (B.Sc,B.Pharm,M.Sc)
HARAMBEE UNIVERSITY,2022
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OUTLINE
5.1 Non-narcotic analgesics
i. Salicylates
ii. p-aminophenol derivatives
iii. 5-pyrazolone derivatives
iv. 3,5-pyrazolidinedione derivatives
v. Miscellaneous agents
5.2 Drugs used in the treatment of gout
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5.1 Non-narcotic Analgesics
NSAIDs are a class of drugs that relieve pain, reduce inflammation
(redness and swelling) and bring down a high temperature (fever).
NSAIDs are used to treat a wide range of conditions: Headaches,
painful periods, toothache, sprains and strains infections, such as
the common cold or the flu inflammation of the joints (arthritis)
and other tissues
NSAIDs work by blocking the production of prostaglandins,
chemical messengers that often are responsible for the pain and
swelling of inflammatory conditions.
Narcotic analgesics—the analgesics that have CNS effect. Non-
Narcotics—the analgesics that do not have CNS effect
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i. Salicylate Derivatives
Salicylates are derived from Salicylic acid which is a
monohydroxybenzoic acid, and are nonsteroidal anti-
inflammatory drugs.
They inhibit the synthesis of prostaglandin and other mediators in
the process of inflammation
have anti-inflammatory, antipyretic and analgesic properties.
The salicylates are strong organic acids and readily form salts with
alkaline materials.
Note that the carboxyl group is substantially more acidic (and
ionizes readily at physiologic pH) than the phenolic hydroxyl 4
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Cont…
Salicylic acid (2-Hydroxybenzoic acid)
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Cont…
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Structure Activity Relationship of Salicylates
• Hydroxyl group should be ortho with respect to carboxylic group
• Halogen substitution enhances activity however make them
toxic as well
• Substitution with hydrophobic aryl groups at the 5- position of
the ring improves anti inflammatory activity
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ii. Para-amino Phenol Derivatives
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Synthesis of Paracetamol
The nitro group on 4-nitrophenol was reduced with sodium
borohydride.
The resultant 4-aminophenol is then acetylated with acetic
anhydride
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iii. 5-Pyrazolone Derivative
is 1-phenyl-2,3-dimethyl-3-pyrazolin-5-one and derivatives
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iv.3,5-Pyrazolidinedione Derivatives
is1,2-diphesnylpyrazolidin-3,5-dione derivatives
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Cont…
Pyrazolone Derivative - Dipyrone (Novalgene, Metamizole
sodium)
A drug that has analgesic, anti-inflammatory, and antipyretic
properties.
Associated with acute condition involving a severe and
dangerous leukopenia (lowered white blood cell count)
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Cont…
Pyrazolidinedione Derivatives - Phenylbutazone
Phenylbutazone is a nonsteroidal anti-inflammatory drug
(NSAID) effective in treating fever, pain, and inflammation
in the body.
Phenylbutazone has analgesic and antipyretic effects with
similar potency as aminophenazone and phenazon.
It has enhanced antiinflammatory effects and is used to
treat rheumatoid arthritis.
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SAR for Pyrazolidinediones (and phenylbutazone)
The butyl group of carbon 4 may be replaced by propyl
or allyl and show similar activity.
The meta substitution of the aryl ring are inactive but para
substitution such as CH3, Cl, NO2 or OH retains activity.
Replacement of nitrogen in pyrazolidines with oxygen yield
isoxazole analog which is as active as pyrazolidine derivatives.
Decreasing pKa values of phenyl butazone analogs have shorter
half lives decreasing anti inflammatory activity
Substitution of Hydrogen at C-4 by methyl group or others destroys
anti inflammatory activity since it is important to have a dicarbonyl
group that could be enolized.
If pyrazolidine ring is replaced with cyclopentane or cyclopenten
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V. Miscellaneous Agents
Aniline or Paracetamol (acetaminophen), Acetanilide,
Phenacetin,
Indole & related drugs: Indomethacin, Sulindac.
Phenyl acetic acid derivatives: Diclofenac.
Propionic acid derivatives: Ibuprofen, Naproxen, Fenoprofen,
Ketoprofen.
Fenamates: Mefenamic acid.
Oxicams derivatives : Piroxicam, Tenoxicam, Meloxicam.
Sulfonanilide derivatives: Nimesulide.
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5.2 Drugs Used in The Treatment of Gout
Gout is usually characterized by recurrent attacks of acute
inflammatory arthritis with red, tender, hot and swollen
joints.
Pathogenesis: Deposits of sodium urate crystals in articular,
periarticular, and subcutaneous tissues
Gout was historically known as "the disease of kings" or
"rich man's disease."
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Cont…
The uric acid is a waste product formed from the degradation
of purines. Xanthine oxidase
Purines → xanthine → uric acid
If there is abnormal production and/or execration of uric acid
it will cause deposition of Monosodium Urate Crystals(MUC)
in joints and this will initiate the inflammation and cause gout.
lowering the uric acid level below the saturation point (6mg/dl)
can be achieved by:
i. interfering with uric acid synthesis with allopurinol, Febuxostat.
ii. increasing uric acid excretion with probenecid or
sulfinpyrazone.
iii. inhibiting leukocyte entry into the affected joint with colchicine.
iv. administration of NSAID.
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Cont…
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NSAIDs
• NSAIDs are the most commonly used first-line treatment
• Head-to-head studies show few differences between drugs
• Full doses of NSAID should be initiated immediately
• and tapered after resolution of symptoms
• Should be avoid in:
GI ulcer
Bleeding or perforation
Renal insufficiency
Heart failure
Use of oral anticoagulants
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steroids
• Corticosteroids are a good alternative where NSAIDs
• and colchicine cannot be used or in refractory cases
• Studies showed equal efficacy between corticosteroid
• and NSAIDs, with no reported side-effects with
• short-term use of corticosteroids
• In elderly people, patients with liver or hepatic impairment, IHD
(ischemic heart disease ), PUD (Peptic ulcer disease),
hypersensitivity to NSAIDs
• Route of administration : Intra articularly (preferred route if one
or two joints affected) Orally Intramuscularly or intravenously
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Allopurinol
• Management of hyperuricemia of gout
• Uric acid stones or nephropathy
• It is a drug of choice in patients with both gout & ischemic heart
disease
• Severe tophaceous deposits (uric acid deposits in tissues)
• Management of hyperuricemia associated with chemotherapy
• Prevention of recurrent calcium oxalate kidney stones
• Metabolism: it is metabolized by xanthine oxidase into alloxanthine
which is pharmacologically active
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Febuxostat
Indicated for the management of hyperuricemia in patients
with gout (as it reduces serum uric acid levels)
* Chemically distinct from allopurinol (non purine)
* Can be used in patients with renal disease
* Oral specific xanthine oxidase inhibitor
Given orally once daily
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