Anti-inflammatory drugs

Question 1

Antihistamine

Answer 1

• Inverse agonists
• Shift dose response curve to the right
• Look like competitive antagonists

Question 2

Inverse agonists

Answer 2

Reduce receptor activity below basal levels observed in absence of any ligand

Question 3

First generation antihistamines

Answer 3

Diphenhydramine (OTC), Chlorpheniramine (OTC)

Question 4

MOA of first and second generation antihistamines

Answer 4

-Blockade of H1, muscarinic, alpha adrenergic, serotonin receptors.

Question 5

Diphenhydramine and chlorpheniramine distribution

Answer 5

-Well absorbed orally, wide distribution (+CNS), not recognized by P-glycoprotein in CNS and so not pumped out of CNS

Question 6

Elimination of first and second generation antihistamines

Answer 6

-Transformed to inactive metabolites in liver and excreted in urine

Question 7

Diphenhydramine and chlorpheniramine general side effects

Answer 7

• Sedation
• Drying of secretions
• GI disturbances
• Some anticholinergic activitya
• Acute poisoning: treatment symptomatic and supportive, resembles atropine poisoning (exciation, hallucinations, incoordination, convulsions, flushed face, dilated pupils etc.) Terminaly can cause coma and cardiorespiratory collapse

Question 8

Diphenhydramine additional info

Answer 8

-Low GI side effects
-Sedation!
If you want sedative actions as well, use this

Question 9

Chlorpheniramine additional info

Answer 9

Most suitable for daytime use

Question 10

Newer (2nd gen) antihistamines

Answer 10

Cetirizine
Fexofenadine
Loratadine

Question 11

2nd generation antihistamines and distribution

Answer 11

• Only small amounts cross BBB and cause less sedation

- Affinity for P-glycoprotein (pumped out of CNS)

Question 12

Are the current 2nd gen antihistamines cardiotoxic?

Answer 12

No. But the original 2nd gen drugs were.

Question 13

Therapeutic uses of H1 antihistamines

Answer 13

• Allergy (allergic rhinitis, urticaria, atopic dermatitis)
• Not for asthma use!!
• Motion sickness use (older antihistamines…like diphenhydramine)
• Sleep aid (Diphenhydramine)

Question 14

H2 antihistamine properties

Answer 14

Inhibit histamine, gastrin, pentagastrin-induced gastric acid secretion and decreasing muscarinic agonist-induced gastric acid secretion

Question 15

H2 antihistamine uses

Answer 15

Ulcers and gastric hypersecretory states

Question 16

NSAIDS

Answer 16

Inhibit COX

Question 17

Shared therapeutic activities of COX-1 and COX-2 inhibitors

Answer 17

• Analgesia
• Antipyretics
• Anti-inflammatory

Question 18

Aspirin

Answer 18

Irreversibly acetylates COX (inhibits)

Question 19

What are the traditional NSAIDs?

Answer 19

Ibuprofen, naproxen, ketorolac, ketoprofen, indomethacin, sulindac, piroxicam

Question 20

Selective COX2 inhibitor still in use, advantages and disadvantages

Answer 20

Celecoxib (celebrex)

-Doesn’t cause prevention of platelet aggregation

Question 21

Ibuprofen

Answer 21

Fewer GI side effects than aspirin

Question 22

Ketorolac

Answer 22

Promoted primarily for analgesia, also anti-inflammatory

Question 23

Ketoprofen

Answer 23

Related to Ibuprofen

Question 24

Indomethacin

Answer 24

Most potent NSAID, severe frontal headache and blood disorders

Question 25

Piroxicam

Answer 25

Once a day admin, can cause dose related serious GI bleeding

Question 26

Acetaminophen

Answer 26

• Not a NSAID
• Weak COX inhibitor
• Analgesic, antipyretic, NOT anti-inflammatory
• Inhibits COX in brain, but not at inflammation sites.
• Overdoses can cause significant hepatic injury.
• No data that 1000 mg better than 650 mg in treating everyday causes of pain

Question 27

Adverse effects of COX inhibitors

Answer 27

• Gastric or intestinal ulceration (less likely in COX2 inhibitors)
• Prolongation of gestation
• Renal function
• Hepatic function
• Increased bleeding time (not in COX2 inhibitors)
• Aspirin hypersensitivity (less likely in COX2 inhibitors)

Question 28

Aspirin hypersensitivity

Answer 28

3-10% of asthmatics
Atopic individuals primarily
Can be caused by other NSAIDS
Rhinitis, urticaria, asthma, laryngeal edema

Question 29

Probable mechanisms of aspirin hypersensitivity

Answer 29

1. COX blockade shifts arachidonate utilization to lipoxygenase pathway–>increased leukotriene production and symptoms of hypersensitivity.
2. Inhibition of COX1, decling PGE2 synthesis. Removing eliminates blocking effects on 5-Lipoxygenase, allowing rapid leukotriene synthesis.

Question 30

Why is aspirin not recommended for use in children?

Answer 30

Can cause Reye syndrome (encephalopathy and fatty liver) following viral infection in children. Anti-inflammatory doses for aspirin are close to toxic doses

Question 31

Leukotriene inhibitors and leukotriene modifiers (names and use)

Answer 31

Used in treatment of bronchial asthma. (Chronic not acute).
Zileuton
Zafirlulast and montelukast

Question 32

Zileuton

Answer 32

Inhibits 5-lipoxygenase and prevents synthesis of LTB4 and peptide leukotrienes

• Metabolized by cytochrome P450 and may cause drug interactions
• May decrease beta-agonist use in asthma
• modestly effective in maintenance treatment of chronic asthma
• Need to monitor for hepatic toxicity

Question 33

Zafirlukast

Answer 33

Leukotriene receptor antagonists (LTD4 receptor, Cys LTR1).

Inhibits Cytochrome P450 isoenzyme and may cause significant drug interactions

Question 34

Montelukast

Answer 34

Prescribed more than zafirlukast because of once daily admin w/o meal restrictions
Used in asthma
Leukotriene receptor antagonists (LTD4 receptor, Cys LTR1)