Dr. K. Crawford
| AUTOCOIDS, ANTI-MOTION SICKNESS AND NONSTEROIDAL ANTIINFLAMMATAORY DRUGS |
1. Histamine
 | Distribution and storage |
| Synthesis and release (immunologic and nonspecific) |
| Metabolism and elimination |
| Receptors (H1 and H2) - signal transduction (eg. phosphoinositide turnover, adenylate cyalase) |
| Pharmacologic actions: (GI: bronchiolar : vasculature) smooth muscle, exocrine glands, cardiovascular, and sensory nerve endings |
Drugs to consider: Agonist
| HISTAMINE |
| betazole |
| Impromidine |
2. Antihistaminic drugs
| Mechanisms of action: Receptors (H1 and H2) |
| Pharmacological properties and side effects (desirable/adverse) - alternate receptor systems involved |
| Therapeutic uses |
Drugs to consider:
H1-antagonists: H2 antagonists:
doxylamine clemastine
brompheniramine triprolidine CIMETIDINE
CHLORPHENIRAMINE famotidine
DIPHENHYDRAMINE NIZATIDINE
PROMETHAZINE RANITIDINE
2nd generation: H1-antagonists:
Loratidine Levocobastine
Cetirizine Acravastine
3. Anti-motion sickness drugs
Understand the mechanisms of motion sickness and the differences in mechanism and action between the phenothiazine neuroleptics and those drugs that affect the vestibular pathway.
Drugs to consider:
| cyclizine |
| DIMENHYDRINATE |
| meclizine |
| promethazine |
| scopolamine
|
Inhibitors of Histamine Release
CROMALYN
NEDOCROMIL
Eicosanoids
| Synthesis of prostaglandins, thromboxanes, and leukotrienes from arachidonic acid. Know which are the key enzymes in the overall pathway and what drugs affect each enzyme. |
| Pharmacological actions of PGE2, PGF2, PGI2 (prostacyclin), TXA2, and the (LTB4 and peptidyl leukotrienes) leukotrienes (LTA4 thru LTB4): vascular, airway, uterine, and GI smooth muscle; microvascular permeability; platelet function; sensory nerve ending; gastric and intestinal secretions; temperature regulating center. |
| Indications and mechanisms of leukotriene antagonists. |
Inhibitors of Leukotriene Synthesis Peptide Leukotriene Antagonists
Zileuton zafirlakast
montelekast
Drugs to consider:
| carboprost |
| dinoprotone |
| alprostadil |
| dinoprost |
| misoprostol |
Bradykinin
| Synthesis and metabolism of kinins: know what pathophysiological factors trigger kinin formation and how bradykinin can influence the eicosanoid pathway. |
| Pharmacological actions: compare and contrast with actions of histamine and eisosanoids. |
Drugs to consider:
| BRADYKININ |
| aprotinin |
Analgesic, antipyretic, antiinflammatory drugs
| Antipyretic-analgesic drugs |
a) Understand the physiological basis of body temperature control and peripheral sensory pain fibers.
b) Understand the role of eicosanoids and bradyknin in causing local pain, edema and fever.
c) Understand the difference in mechanisms of action between acetaminophen and aspirin. How pharmacology relates to indications.
d) Understand how aspirin has dual effects on cyclooxygenase (PGH synthase) compared to other salicylates and NSAIDS. How are the effects of aspirin relevant to platelet function?e) Understand the metabolism of acetaminophen, the role of cytochrome P450, and the mechanism of acetaminophen toxicity as well as its reversal by N-acetylcysteine.
f) Understand the adverse effects of aspirin as well as the acute toxic effects of aspirin overdose.
g) Understand the dose-dependent vs. independent elimination of aspirin (doses where first order/zero elimination are displayed).
h) Understand the hepatic metabolism of aspirin.
i) Understand the adverse drug interactions possible with aspirin (coumarin anticoagulants, oral hypoglycemic drugs, alcohol, others).
j) Understand the principles of treatment of salicylate intoxication.
Drugs to consider:
| ACETAMINOPHEN |
| ASPIRIN and related salicylates |
| non-steroidal antiinflammatory drugs other than aspirin |
B. Non-steroidal antiinflammatory drugs (NSAID)
a) Understand the pathophysiology of acute and chronic inflammation.
| vasoactive anunes |
| eicosanoids |
| bradykinins |
| complement system |
| macrophage-derived |
| oxygen radicals |
| + proteolytic enzymes |
| inducible NOS |
| immune system |
| (T-lymphocytes, B-lymphocytes, cytokines) |
b) Understand the adverse effects and potential adverse drug interactions associated with inhibition of the cyclooxygenase pathway.
c) Understand the mechanism of NSAID-induced acute renal failure and which pts. are at risk.
d) Understand differences in function, antomical locations of COX-1 vs. COX-2. Understand the basis for COX-selectivity in drug design, toxicity, platelet and endothelial function.
Drugs to consider:
| ASPIRIN and salicylates meclofenamate |
| Celecoxib |
| DICLOFENAC SODIUM |
| NAPROXEN |
| Rofecoxib |
| fenoprofen |
| phenylbutazone |
| Meloxicam |
| IBUPROFEN |
| piroxicam |
| Namebutone |
| INDOMETHACIN |
| sulindac |
| KETOPROFEN |
| tometin |
C. Special drugs for rheumatoid arthritis
a) Understand that these drugs have no analgesic, antipyretic, or antiinflammatory activity; their mechanisms of action are unknown.
b) Understand that their onset of action is very long and the drugs are very toxic.
c) Understand the mechanism of newer agents for rheumatic and inflammatory diseases.
Drugs to consider:
| HYDROXYCHLOROQUINE |
| chloroquine |
| gold salts (auranofin, aurothioglucose) |
| D-penicillamine |
| cyclophosphamide and azathioprine |
| methotrexate |
| chlorambucil |
D. Drugs used to treat gout
a) Understand the causes and pathophysiology of acute gouty arthritis and chronic tophaceous gout.
b) Compare and contrast the mechanisms of action of colchicine, allopurinol, probenecid, and sulfinpyrazone.
c) Understand the dangerous side effects of colchicine.
d) Understand the cause and treatment of acute gouty flare-ups associated with the use of allopurinol or probenecid in treating chronic tophaceous gout.
e) Understand the NDAID's except aspirin may be used as substitutes for colchicine. Why is aspirin contraindicated?
f) Understand the potential adverse drug interactions with allopurinol (i.e. 6-mercaptopurine).
Drugs to consider:
| COLCHICINE |
| ALLOPURINOL |
| NSAID (except aspirin) PROBENECID |
| SULFINPYRAZONE |
Drug to be considered:
| +ACETAMINOPHEN |
| cyclizine meclofenamate |
| +ACETYLSALICYCLIC ACID CYCLOPHOSPHAMIDE misoprostol |
| (aspirin) +DICLOFENAC SODIUM +NAPROXEN |
| ALLOPURINOL |
| dinoprost |
| NIZATIDINE |
| aprotinin |
| dinoprostone |
| D-PENICILLAMINE |
| auranofin (oral gold) |
| DIMENHYDRINATE |
| phenylbutazone |
| AUROTHIOGLUCOSE |
| DIPHENHYDRAMINE |
| +piroxicam |
| azothioprine |
| +famotidine |
| PROBENECID |
| BRADYKININ |
| fenoprofen |
| +promethazine |
| betazole |
| HISTAMINE |
| +RANITIDINE |
| brompheniramine hydroxychloroquine |
| scopolamine |
| carboprost |
| +IBUPROFEN SULFINPYRAZONE |
| CHLOROQUINE INDOMETHACIN |
| +sulindac |
| +CHLORPHENIRAMINE |
| +KETROPROFEN |
| tolmetin |
| +CIMETIDINE |
| meclizine |
| +CLEMASTINE |
| COCHICINE |
PRIMARY DRUGS - All capital letters
SECONDARD DRUGS - Small letters
+ Indicates that drug is listed in the 200 most commonly prescribed drugs in 1989 (National Prescription Audit). All of the first 100 and most of the second 100 of the top 200 drugs prescribed are included in this document.