Drug Examples: Anti-inflamm to Statins

Question 1

Steroidal anti-inflammatory example:
Oral
Inhalable
Topical

Answer 1

Oral: Prednisone
Inhalable: Fluticasone (Flixotide)
Topical: Prednisone, Dexamethasone

Question 2

Non-steroidal anti-inflammatory example:

Answer 2

Aspirin

Ibuprofen

Question 3

Mechanism of NSAIDS

Answer 3

Inhibits COX activity to prevent formation of prostaglandins (Inflammatory mediator)

Question 4

Aspirin

Answer 4

Inhibits COX1 irreversibly

Also inhibits TXA2 release by platelets (antithrombotic)

Associated with significant GI side effects

Question 5

Paracetamol

Answer 5

Good antipyretic / analgesic. Ineffective antiinflammatory

Reduces prostaglandin synthesis

Relatively weak cox1/cox2 inhibitor

Metabolised in liver to toxic intermediate (serious liver damage)

Question 6

Non-selective NSAIDS

Answer 6

Ibuprofen, Naproxen, Diclofenac

Question 7

Adverse effects of NSAIDS

Answer 7

GI
Renal
Increased clotting time (inhib of thromboxame production)

Complications largely associated with cox-1 inhibition

Question 8

Cox2 selective inhibition

Answer 8

Celecoxib, Refoecoxib (vioxx)

Have not proved test of time

Leave COX1 (maintenance/protective) uninhibited, target inflammation associated COX2

Reduce GI irritation and ulceration, useful for chronic long-term pain management

Question 9

Unexpected effects of Cox2 selective inhibitors

Answer 9

Celecoxib assoc with ACUTE CARDIOVASCULAR EVENTS
Rofecoxib increased risk of thrombotic events
Increased BP
Renal impairment perhaps?

Global rofecoxib withdrawal

Question 10

Quinine

Answer 10

FIRST malaria treatment, Cinchona bark
Active against erythrocytic stages of parasite

Mode MAY involve binding to DNA, stopping synth of nucleic acids, inhibition of haem digestion

Question 11

Pamaquine

Answer 11

SYNTHETIC (first) WWI

Active only against avian malaria, not falciparum, main human form
Toxic to humans, however found effective against vivax relapses

Question 12

Chloroquine

Answer 12

Based on quinine
Accumulates in food vacuole of parasite, interferes with haem digestion
Effective against blood stages
Safe
RESISTANCE

Question 13

Amodiaquine

Answer 13

effective against blood stages and in some resistant P falciparum strains BUT liver/granulocyte toxicity

Question 14

Primaquine

Answer 14

Active against LIVER of P.Vivax

Mechanism may invplve oxidative stress in parasite
Effective against other stages BUT too toxic (causes haemolysis and methaemoglobinaemia)

Question 15

Mefloquine

Answer 15

PRETTY GOOD
Minor side effects (nausea, dizzy)
Not recommended if known allergo, epilepsy, cardiac conduction abnormalities

Question 16

Pyronaridine

Answer 16

Potential Chloroquine replacement
TOO EXPENSIVE ($3-4 per course)
Requires new synthesis route

(structure is combination of everything)

Question 17

Proguanyl

Answer 17

PROPHYLACTIC use as too slow for cure
Prodrug requires metabolism to cycloguanyl
Effective against liver and erythrocytic stages of P.Falciparum

Inhibits dihydrofolate reductase and hence DNA synthesis

Question 18

Sulfonamides (Sulphone)

Answer 18

eg Dapsone and Sulphadoxine
INHIBIT dyhydropterate synthase
(ie DNA synthesis as invplved in folate)

Act too slowly on their own but act synergistically with proguanyl and pyrimethamine because all act in different parts of the SAME pathway
- always used in combination therapy

Question 19

Artemesin Derivatives

Answer 19

Highly effective, rapid, cheap, limited toxicity

Inappropriate use leads to resistance and toxicity