Other NSAIDs Case Studies

Ibuprofen

(Naproxen contains same features)

contains one chiral centre

two possible enantiomers, exists in a racemic form

Diclofenac

does not contain a chiral centre

does not exits in racemic form

(D)

Using a Single Enantiomer

• reduced activity

• some enantiomers associated with toxicity

• more predictable pharmacokinetics

(as opposed to using a racemic mixture)

Ibuprofen

• R enantiomer less active than S enantiomer, but can be converted in vivo

• sold as a racemic mixture as a result

Naproxen

its R enantiomer is associated with liver toxicity

Carboxylic Acid

can form salts using these groups

• salts readily ionise in water, improving solubility and absorption

Dexketoprofen

the S enantiomer of Ketoprofen, possesses beneficial pharmacological activity

Mefenemic Acid

does not possess a chiral centre

does not exist in racemic form

(MA)

Aromatic Rings

increase lipophilicity and are non-polar

Amines

allow for ionic interactions with acidic residues due to their basicity

can be converted into salts

Ketones

can function as hydrogen bond acceptors

Diclofenac Potassium

allows for:

• faster dissolution

• faster absorption

• faster onset of action

• used for acute pain

Diclofenac Sodium

allows for:

• slower onset of actions

• sometimes a longer duration

• used for chronic inflammatory conditions

Ibuprofen

• NSAID

• reversibly inhibits COX, reducing prostaglandin synthesis

Codeine Phosphate

relieves moderate pain not controlled by simple analgesics

• acts via mu opioid receptors in CNS

• low receptor affinity

• pharmacologically inactive until metabolised in the liver and converted to morphine

Migraine Pain

• anti-emetics

• triptans

• propanolol

Etofenamate

active ingredient in Etoflam gel

• classified as a flufenamic acid derivative

Etoflam

• prescription only medicine

• mild to moderate pain (musculoskeletal, etc.)

• inhibits cyclooxygenase enzymes

Selective COX 2 Inhibitors

• fewer side effects than non selective NSAIDs

• type of NSAID

• Celecoxib and Etoricoxib

Etoricoxib

selective inhibitor of COX 2

• favours platelet aggregation

• indicated for symptomatic relief of rheumatoid arthritis

• can increase risk of thrombotic effects

Benzydamine

active ingredient in Difflam spray

• relieves pain, swelling, redness in throat and mouth

• anti-inflammatory and analgesic effect at site of application, rather than COX inhibition

• sodium channel blockade

• reduced vascular permeability