Regal Drugs Flashcards
Mediator that causes redness, heat, swelling and airway constriction but not chemotaxis.
Histamine
Vasodilate, increase vascular permeability and cause pain
PGE2 and PGI2
What two things cause bronchoconstriction?
PGD2 and thromboxane
What causes platelet aggregation?
TXA2
What opposes platelet aggregation?
PGI2
Kinins (bradykinin and kallidin) are very strong what?
Vasodilator!
Which way do antihistamines shift the agonist dose-response curve?
Right (competitive antagonist)
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?
H1 receptor
Describe how old antihistamines (classical, first generation antihistamines) work.
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
Name the 2 first gen antihistamines we need to know and when to use them.
Diphenydramine (good for sedation) and Chlorpheniramine (suitable for daytime).
How are the newer antihistamines different than the first generation ones?
Minimal anticholinergic properties, DO NOT cause sedation
Which newer antihistamines do we need to know?
Cetirizine, Fexofenadine, Loratadine
Why don’t the newer antihistamines cause sedation?
B/c pumped out of CNS as they have a high affinity for p-glycoprotein.
Why were the new antihistamines created?
B/c original had cardiotoxicity with overdosage.
Which COX is constitutively expressed in most cells, protects gastric mucosa, and is found in platelets?
COX-1
COX-2
NOT in platelets, induced by serum factors, cytokines, and growth factors!
What causes pain?
Prostaglandins
Which drugs inhibit COX-1 and COX-2? What are their shared therapeutic activities?
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.
Which drugs are NSAIDs?
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)
What selective COX-2 Inhibitor is still on the market?
Celecoxib
What drug is analgesic, antipyretic, NOT anti-inflammatory, and is not an NSAID? (also overdosage can cause serious hepatic injury).
Acetaminophen
Why is acetaminophen better than NSAIDs for headaches?
Because it inhibits COX in the brain but not at sites of inflammation.
What is the only drug that irreversibly inhibits COX1 in the platelet (preventing aggregation and TX formation)?
Aspirin
What are the symptoms and what is the cause of aspirin hypersensitivity?
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.
Risk with COX-2 inhibitors?
Reduction of prostacyclin production by endothelial cells thus a concern for increased risk of thrombotic cardiovascular events
LTC4, LTD4, and LTE4 are most effect at causing what?
Bronchoconstriction
LTB4 is effective at causing what?
Chemotaxis of WBCs
What drugs are used for the treatment of chronic asthma?
Leukotriene inhibitors
Tell me about Zileuton:
inhibits LOX, thus preventing synthesis of LTB4 as well as peptide-leukotrienes.
Metabolized by CYP 450 (think drug interactions)
Maintenance of Chronic asthma
Zafirlukast
Leukotriene receptor antagonist (LTD4, Cys LTR1), inhibits a CYP450 isoenzyme and may cause significant drug interactions
Used in asthma
Montelukast
Leukotriene receptor antagonist (LTD4, Cys LTR1) Prescibed more than Zafirlukast because of once daily administration without restrictions with regard to meals.
Used in asthma
Sirolimus
Binds FKBP to inhibit mTOR (blocking cell cycle progression from G1 to S).
Used in combination therapy for organ transplant rejection.
Mycophenolate Mofetil
A metabolite inhibits IMPDH (enzyme in pathway of guanine nucleotide synthesis). B and T cells are highly dependent on this pathway.
Difference between dosing strategy for cancer vs. immunosuppression?
Immunosuppression: low daily dose. Cancer: Pulses of high dose
Anti-thymocyte globulin
binds to thymocytes in circulation resulting in lymphopenia and impaired T cell immune response.
Muromonab-CD3
anti-CD3 antibody that causes TCR to become internalized and no further recognition of antigen can occur!
Daclizumab or Basiliximab
Anti-IL2R (anti-CD25) antibodies used in organ transplantation. Only binds IL-2R on activated T cells to block IL-2 mediated activation events.
