Regal Drugs

Question 1

Mediator that causes redness, heat, swelling and airway constriction but not chemotaxis.

Answer 1

Histamine

Question 2

Vasodilate, increase vascular permeability and cause pain

Answer 2

PGE2 and PGI2

Question 3

What two things cause bronchoconstriction?

Answer 3

PGD2 and thromboxane

Question 4

What causes platelet aggregation?

Answer 4

TXA2

Question 5

What opposes platelet aggregation?

Answer 5

PGI2

Question 6

Kinins (bradykinin and kallidin) are very strong what?

Answer 6

Vasodilator!

Question 7

Which way do antihistamines shift the agonist dose-response curve?

Answer 7

Right (competitive antagonist)

Question 8

Which histamine receptor is responsible for most clinically relevant symptoms like bronchoconstriction, contraction of GI smooth muscle, increased capillary permeability (wheal), pruritis and pain, and release of catecholamines?

Answer 8

H1 receptor

Question 9

Describe how old antihistamines (classical, first generation antihistamines) work.

Answer 9

Block H1, Muscarinic, alpha adrenergic, and serotonin receptors, widely distributed (including CNS), not recognized by p-glycoprotein.

Side effects: Sedation, drying of secretions (due to anticholinergic properties), GI disturbances

Question 10

Name the 2 first gen antihistamines we need to know and when to use them.

Answer 10

Diphenydramine (good for sedation) and Chlorpheniramine (suitable for daytime).

Question 11

How are the newer antihistamines different than the first generation ones?

Answer 11

Minimal anticholinergic properties, DO NOT cause sedation

Question 12

Which newer antihistamines do we need to know?

Answer 12

Cetirizine, Fexofenadine, Loratadine

Question 13

Why don’t the newer antihistamines cause sedation?

Answer 13

B/c pumped out of CNS as they have a high affinity for p-glycoprotein.

Question 14

Why were the new antihistamines created?

Answer 14

B/c original had cardiotoxicity with overdosage.

Question 15

Which COX is constitutively expressed in most cells, protects gastric mucosa, and is found in platelets?

Answer 15

COX-1

Question 16

COX-2

Answer 16

NOT in platelets, induced by serum factors, cytokines, and growth factors!

Question 17

What causes pain?

Answer 17

Prostaglandins

Question 18

Which drugs inhibit COX-1 and COX-2? What are their shared therapeutic activities?

Answer 18

NSAIDs: ANALGESIA: pain of low to moderate intensity, no addiction, lower maximal effects than opioids, block prostaglandin synthesis, ANTIPYRETICS: reduce body temp, ANTI-INFLAMMATORY-reduce redness, swelling, heat, and pain.

Question 19

Which drugs are NSAIDs?

Answer 19

Aspirin (irreversible)
Ibuprofen
Naproxen
Ketorolac (promoted for analgesia)
Ketoprofen 
Indomethacin (most potent, severe frontal headache, blood disorders)
Sulindac
Piroxicam (can cause dose-related GI bleeding)

Question 20

What selective COX-2 Inhibitor is still on the market?

Answer 20

Celecoxib

Question 21

What drug is analgesic, antipyretic, NOT anti-inflammatory, and is not an NSAID? (also overdosage can cause serious hepatic injury).

Answer 21

Acetaminophen

Question 22

Why is acetaminophen better than NSAIDs for headaches?

Answer 22

Because it inhibits COX in the brain but not at sites of inflammation.

Question 23

What is the only drug that irreversibly inhibits COX1 in the platelet (preventing aggregation and TX formation)?

Answer 23

Aspirin

Question 24

What are the symptoms and what is the cause of aspirin hypersensitivity?

Answer 24

Rhinitis, urticaria, asthma, and laryngeal edema.
Blockade of COX shifts arachidonic acid utilization to the lipoxygenase pathway. The end result is increased leukotriene production and the symptoms of hypersensitivity.

Question 25

Risk with COX-2 inhibitors?

Answer 25

Reduction of prostacyclin production by endothelial cells thus a concern for increased risk of thrombotic cardiovascular events

Question 26

LTC4, LTD4, and LTE4 are most effect at causing what?

Answer 26

Bronchoconstriction

Question 27

LTB4 is effective at causing what?

Answer 27

Chemotaxis of WBCs

Question 28

What drugs are used for the treatment of chronic asthma?

Answer 28

Leukotriene inhibitors

Question 29

Tell me about Zileuton:

Answer 29

inhibits LOX, thus preventing synthesis of LTB4 as well as peptide-leukotrienes.
Metabolized by CYP 450 (think drug interactions)
Maintenance of Chronic asthma

Question 30

Zafirlukast

Answer 30

Leukotriene receptor antagonist (LTD4, Cys LTR1), inhibits a CYP450 isoenzyme and may cause significant drug interactions
Used in asthma

Question 31

Montelukast

Answer 31

Leukotriene receptor antagonist (LTD4, Cys LTR1) Prescibed more than Zafirlukast because of once daily administration without restrictions with regard to meals.
Used in asthma

Question 32

Sirolimus

Answer 32

Binds FKBP to inhibit mTOR (blocking cell cycle progression from G1 to S).
Used in combination therapy for organ transplant rejection.

Question 33

Mycophenolate Mofetil

Answer 33

A metabolite inhibits IMPDH (enzyme in pathway of guanine nucleotide synthesis). B and T cells are highly dependent on this pathway.

Question 34

Difference between dosing strategy for cancer vs. immunosuppression?

Answer 34

Immunosuppression: low daily dose. Cancer: Pulses of high dose

Question 35

Anti-thymocyte globulin

Answer 35

binds to thymocytes in circulation resulting in lymphopenia and impaired T cell immune response.

Question 36

Muromonab-CD3

Answer 36

anti-CD3 antibody that causes TCR to become internalized and no further recognition of antigen can occur!

Question 37

Daclizumab or Basiliximab

Answer 37

Anti-IL2R (anti-CD25) antibodies used in organ transplantation. Only binds IL-2R on activated T cells to block IL-2 mediated activation events.