by Seetal K Dhaliwal H.

S 1

Section VI Flash cards by Seetal K. Dhaliwal H. S

 2
Histamine:

↑ nasal & bronchial mucus production, contraction of bronchioles, pruritus & pain.

↑ gastric acid secretions  gastrointestinal ulcers.

by Seetal K Dhaliwal H. S
 Antihistamines (Anti-H1):
3
Drug M Block Sedation Antimotion Other characteristics

Diphenhydramine/ +++ +++ +++ Widely used OTC drug (used

diphenhydrinate orally)

Scopolamine ++ 0 +++ Transdermal antimotion patch

Promethazine +++ +++ ++ Some α block & local anesthetic

action
Chlorphenoramine ++ ++ ++ Possible CNS stimulation

Meclizine ++ ++ ++++ Highly effective in antimotion

sickness

Hydroxyzine ++ +++ ++ Commonly used as sedative

Loratidine +/- 0 0 No CNS entry

Fexofenadine +/- 0 0 No CNS entry

by Seetal K Dhaliwal H. S
 4
Drugs used in Peptic Ulcer Disease (PUD):

by Seetal K Dhaliwal H. S
Drugs used in Peptic Ulcer Disease (PUD): 5

 H2 Antagonist:
 Cimetidine, Ranitidine, Famotidine, Nizatidine “take H2 blockers before u DINE. Table for
2”
 Reversible block of H2 receptors  ↓ H+ secretion by parietal cells
 Used in peptic ulcers, gastritis, mild esophageal reflux.
 Toxicity: Cimetidine is CYP450 inhibitor & has antiandrogen effects (prolactin release,
gynecomastia, impotence, ↓ libido in males); can cross BBB (confusion, dizziness, headaches)
& placenta. Cimetidine & Ranitidine ↓ Renal excretion of creatinine.

 Proton Pump Inhibitors:

 Omeprazole, Lansoprazole; Irreversibly inhibit H+/K+ ATPase in stomach parietal cells.
 Used for peptic ulcers (better than H2 blockers), gastritis, esophageal reflux, Zollinger-
Ellison syndrome.

 Bismuth, Sucralfate:
 Binds ulcer, protecting it from acid & pepsin.
 Used in ulcer healing & traveler’s diarrhea.
 BMT triple H.pylori thearapy: Bismuth, Metronidazole, Tetracycline (or Amoxicillin)
by Seetal K Dhaliwal H. S
Drugs used in Peptic Ulcer Disease (PUD): 6

 Misoprostol:
 A PGE1 analog. ↑ mucus & ↑ HCO3-, and ↓ HCl.
 Used to prevent NSAID-induced peptic ulcers; maintenance of PDA (Alprostradil); also used
to induce labor.
 Toxicity: Diarrhea. Contraindicated in childbearing women (abortifacient).

 Muscarinic Antagonists:
 Propantheline, Pirenzepine; Block M1 receptors on ECL cells (↓ histamine secretion) & M3
receptors on parietal cells (↓ H+secretion).
 Used for peptic ulcers (rarely). Caused tachycardia, dry mouth, difficulty focusing eyes.

 Metoclopramide:
 D2 receptor antagonist. ↑ resting tone, contractility, LES tone, motility. Does NOT influence
colon transport time.
 Used in Diabetics & post-surgery gastroparesis.
 Toxicity: ↑ parkinsonian effects. Restlessness, drowsiness, fatigue, depression, nausea,
diarrhea. Drug interaction with Digoxin & Diabetic agents. Contraindicated in patients with
small bowel obstruction
by Seetal K Dhaliwal H. S
Drugs used in Peptic Ulcer Disease (PUD): 7

 Infliximab:
 A monoclonal Ab to TNF, proinflammatory cytokine.
 Used Crohn’s disease (IBD), rheumatoid arthritis.
 Toxicity: Respiratory infection (including activation of latent TB), fever, hypotension.
 Sulfasalazine:
 A combination of Sulfapyridine (antibacterial) & 5-aminosalicylic acid (anti-inflammatory).
Activated by colonic bacteria.
 Used ulcerative colitis (IBD) & Crohn’s disease (IBD).
 Toxicity: malaise, nausea, sulfa allergy, reversible oligospermia.
 Laxatives:
 MgSO4: water retaining – ↑ intraluminal pressure.
 Bisacodyl: direct intestinal wall stimulant.
 Methylcellulose: collects water & swells – ↑ bulk.
 Docusate: detergent – stool softener
 Mineral oil: lubricant
 Lactulose: hyperosmotic (also indicated for systemic encephalopathy)
by Seetal K Dhaliwal H. S
Drugs used in Peptic Ulcer Disease (PUD): 8

 Antacids: (all cause hypOkalemia)

 Can affect absorption, bioavailability or urinary excretion of other drugs by altering
gastric & urinary pH or by delaying gastric emptying.
 ↑ Oral absorption of weak bases (quinidine); ↓ oral absorption of weak acids (warfarin),
azoles, fluoroquinolones & tetracylines (via chelation by Ca carbonate)
 Overuse can also cause the following problems:
1. Aluminium Hydroxide  Constipation & hypOphosphatemia; proximal muscle weakness,
osteodystrophy, seizures.
2. Magnesium Hydroxide  Diarrhea, hyporeflexia, hypotension, cardiac arrest.
3. Calcium carbonate  Hypercalcemia, rebound acid ↑.

 Antidiarrheals:
 Loperamide & diphenoxylate (with atropine) are opioids that are poorly absorbed
 Adsorbants: kaolin, pectin

by Seetal K Dhaliwal H. S
 Antiemetics:
9
 5-HT3 antagonist:
 Ondansetron (caused headache & constipation), and Granisetron
 DA antagonists:
 Prochlorperazine & Metoclopromide
 H1 antagonists:
 Diphenhydramine, Meclizine, Promethazine
 Muscarinic antagonists:
 Scopolamine
 Cannabinoids:
 Dronabinol
 NK1-receptor antagonist:
 Aprepitant (NK1 is a receptor to substance P)
by Seetal K Dhaliwal H. S
 Drugs acting on Serotonergic systems:
10
 5-HT1(a-h):
 Found in CNS (inhibitory) & smooth muscle (excitatory/inhibitory)
 BUSPIRONE (agonist of 5-HT1a)  anxiolytic & GAD.
 SUMATRIPTAN (agonist of 5-HT1d)  ↓ migraine pain.
 5-HT4:
 TEGASEROD (agonist of 5-HT4)  used in IBS when associated with
constipation)
 5-HT2 (a-c):
 Found in CNS (excitatory) “too (2) excited”
 OLANZEPINE (antagonist at 5-HT2a)  ↓ psychosis symptoms.
 CYPROHEPTADINE (antagonist at 5-HT2)  used in carcinoid
tumors, postgastrectomy & anorexia nervosa. Also has H1 blocking
action (used in seasonal allergies).
 5-HT3:
 ONDANSETRON (antagonist at 5-HT3)  antiemesis. by Seetal K Dhaliwal H. S
 Drugs used in migraine headaches:
11

 Ergot alkaloid:
Ergonovine:
 Ergotamine: Causes uterine
 Partial agonist at α & 5-HT2 receptors. smooth muscle
contraction.
 Vasoconstrictive actions – ↓ pulsation in cerebral vessels Given IM after
 Used in acute migraine attacks placental delivery.
 Side effects: GI distress, prolonged vasoconstiction 
ischemia & gangrene, abortion near term.
 Analgesics:
 ASA, other NSAIDs, acetaminophen, oral or injectable opioid
analgesics & butorphanol (spray).
 Prophylaxis:
 Propanolol, verapamil, amitriptyline, valproic acid.

by Seetal K Dhaliwal H. S
 12

Eicosanoid
Pharmacology:

by Seetal K Dhaliwal H. S
 Eicosanoid Pharmacology: 13

 Aspirin:
 Irreversibly inhibits COX  ↓ TXAs & PGEs
 Low dose (<300 mg/day) to ↓ platelet aggregation; intermediate dose (300 – 2400
mg/day) as antipyretic & analgesia; high dose (2400 – 4000 mg/day) as anti-
inflammatory.
 Toxicity: gastric upset. Chronic use  acute renal failure, intestinal nephritis, & upper GI
bleeding. Reye syndrome in children with viral infection (use Acetaminophen instead).
 NSAIDs:
 Ibuprofen, Naproxen, Indomethacin, Ketorolac, Sulindac (causes Steven-Johnson Syndrome).
 Reversibly inhibits COX-1 & COX-2. Block PGE synthesis.
 Used as antipyretic, anti-inflammatory. Indomethacin to close PDA.
 Toxicity: renal damage (except Sulindac), fluid retention, aplastic anemia, GI distress,
ulcers.
 Acetaminophen:
 Reversibly inhibits COX (mostly in CNS). Inactivated peripherally.
 Used as antipyretic, analgesia. Lack anti-inflammatory properties.
 Toxicity: hepatic necrosis (depleted GSH). N-acetylcysteine is antidote – regenerates GSH.
by Seetal K Dhaliwal H. S
 Eicosanoid Pharmacology: 14

 COX-2 inhibitors (celecoxib):

 Reversibly inhibits COX-2  helps maintain gastric mucosa.
 Used in RA and OA.
 Toxicity: ↑ risk of thrombosis. Sulfa allergy.
 Anti-leukotrienes (LTs):
 Zileuton – a 5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to LTs.
 Zafirlukast, montelukast – block LT receptors. Especially good for aspirin-induced asthma.
 Prostaglandins (PGs):
 PGE1  Misoprostol (used in NSAID-induced ulcers); Alprostadil (Maintain PDA open &
causes vasodilation in male impotence)
 PGE2  Dinoprostone (causes cervical “ripening” – used as abortifacient)
 PGE2α  Carboprost (abortifacient); Latanoprost (tx of glaucoma – ↓ IOP)
 PGI2 (prostacyclin)  Epoprostenol (platelet stabilizer – used in pulmonary HTN)
 PGE2 & PGE2α  Both ↑ in primary dismenorrhea.
 Thromboxanes (TXAs):
 TXA2  Platelet aggregator & causes bronchoconstriction & vasoconstriction.
by Seetal K Dhaliwal H. S
 Drugs used in treatment of Gout:
15

 Acute Gout:
 Colchicine:
 Binds & stabilizes tubulin to inhibit polymerization, impairing leukocyte chemotaxis &
degranulation. GI side effects, especially if given orally (Note: Indomethacin is less toxic
& is also used in acute gout).
 Chronic Gout:
 Probenecid:
 Inhibits reabsorption of uric acid in PCT (also inhibits secretion of penicillin – synergistic).
 Allopurinol:
 Inhibits xanthine oxidase, ↓ conversion of xanthine to uric acid. Also used in lymphoma &
leukemia to prevent tumor lysis – associated urate nephropathy. ↑ concentrations of
azathioprine & 6-MP (both normally metabolized by xanthine oxidase).
Probenecid & Allopurinol should not be used to treat acute gout.
Do not give salicylates. All but the highest doses depress uric acid clearance. Even high
doses (5 – 6 g/day) have only minor uricosuric activity.
by Seetal K Dhaliwal H. S
 16
Drugs used in RA:
Drug Mechanism(s) Side Effects
Hydroxychloroquine Stabilizes lysosomes & ↓ GI distress, dizziness, blurred vision,
chemotaxis tinnitus, pruritus (cinchonism), hemolysis
in G6PD def.
Methotrexate Cytotoxic to lymphocytes Hemototoxic, mucositis, crystalluria
Sulfasalazine Sulfapyridine  ↓ B-cell functions; GI distress, rash, hemolysis in G6PD def,
5-ASA possibly inhibits COX SLE-like syndrome.
Glucocorticoids ↓ LTs, Ils, & PAF ACTH suppression, cushingoid state,
osteoporosis, GI distress, glaucoma.
Gold Salts ↓ lysosomal & macrophage Dermatitis, hematotoxic, nephrotoxic.
functions
Penicillamine Supresses T cells & circulating Proteinuria, hematotoxic, autoimmune
Rheumatoid factor disease
Etanercept Binds TNF Hypersensitivity, injection site reaction,
infections.
Infliximab Monoclonal Ab to TNF Infusion reactions, infections
Leflunomide Inhibits DHOD  ↓ UMP  ↓ Alopecia, rash, diarrhea, hepatotoxic,
ribonucleotides  arrests rarely Steven-Johnson Syndrome.
lymphocytes in G1
Anakira IL-1 receptor antagonist Infection, injection-site reaction.
by Seetal K Dhaliwal H. S
 17

Glucocorticoids:
Drugs Glucocorticoid Mineralocorticoid Duration
Activity Activity
Cortisol 1 1 Short
Prednisone 4 0.3 Medium
Triamcinolone 5 0 Intermediate
Betamethasone 25 0 Long-acting
Dexamethasone 30 0 Long-acting

 ↓ the production of LTs & PGs by inhibiting phospholipase A2 & expression of

COX-2.
 Used in Addison disease, inflammation, immune suppression, asthma.
 Side effects: iatrogenic Cushing’s syndrome – buffalo hump, moon facies, truncle
obesity, skin thinning & easily bruised, osteoporosis, adrenocortical atrophy,
peptic ulcers & even diabetes (with chronic use). Also cause ↑ in IOP.
by Seetal K Dhaliwal H. S
 Drugs used to treat asthma:
18

by Seetal K Dhaliwal H. S
 19
Drugs used to treat asthma:
 Non-specific β-agonist:
 Isoproterenol  relaxes bronchial smooth muscle (β2); adverse effect is
tachycardia (β1)
 β2-agonist:
 Albuterol  relaxes bronchial smooth muscle (β2); use during acute attack !!
 Salmeterol  long-acting for prophylaxis; adverse effects: tremors & arrhythmia.
 Methylxanthines:
 Theophylline  causes bronchodilation by inhibiting PDE, thereby ↓ cAMP
hydrolysis. Narrow therapeutic index (cardio- & neurotoxicity). Metabolized by
CYP450. Blocks action of adenosine.
 Muscarinic antagonist:
 Ipratropium bromide  competitive muscarinic block, prevents
bronchoconstriction. Also used in COPD.
by Seetal K Dhaliwal H. S
Drugs used to treat asthma: 20

 Cromolyn & Nedocromil:

 Prevents release of mediators from mast cells. Effective ONLY for ASTHMA
PROPHYLAXIS (not during acute attack). Toxicity is rare.

 Corticosteroids:

 Beclomethasone, prednisone  inhibits the synthesis of virtually all cytokines.

Inactivates NF-κB, the transcription factor that induces the production of TNF-α,
among other inflammatory agents. 1st line therapy for chronic asthma.

 Antileukotrienes:

 Zileuton  A 5-lipoxygenase pathway inhibitor. Blocks conversion of arachidonic

acid to LTs.

 Zafirlukast, montelukast  Blocks LT receptors. Especially good for aspirin-

induced asthma.
by Seetal K Dhaliwal H. S
 by Seetal K Dhaliwal H. S 21

Section VII Flash cards by Seetal K. Dhaliwal H. S

 Anticoagulants: 22

Heparin Warfarin
Structure Large anionic, acidic polymer Small lipid-soluble molecule
Route of Parental (IV, SC) Oral
administration
Site of action Blood Liver
Onset of action Rapid (seconds) Slow. Limited by t1/2 of normal
clotting factors.
Mechanism of action Activates antithrombin, ↓ which Impaires synthesis of vit K-
action of IIa (thrombin) & Xa dependent factors II, VII, IX & X.
Duration of action Acute (hours) Chronic (days)
Inhibits coagulation YES NO
in vitro
Treatment of acute Protamine sulfate IV Vitamin K & Fresh frozen
overdose plasma
Monitoring PTT (intrinsic) “HEPAR IN our PT (extrinsic) “WAR happens
body” EXTRINSICally”
Crosses placenta NO YES (teratogenic)
by Seetal K Dhaliwal H. S
Anticoagulants: 23

 Heparin:
 Immediate anticoagulant for pulmonary embolism, stroke, acute coronary syndrome, MI,
DVT. Used during pregnancy, does not cross placenta. Follow PTT.
 Toxicity: bleeding, thrombocytopenia (HIT), osteoporosis, drug2 interactions.
 Newer LMW Heparins (enoxaparin) act more on Xa, have better bioavailability & 2 – 4
times longer t1/2. Can be administered SC & without laboratory monitoring.
 HIT  heparin binds to platelets, causing autoantibody production that destroys platelets &
overactivates the remaining ones, resulting in a thrombocytopenic, hypercoagulable state.

 Lepirudin, Bivalirudin:
 Hirudin derivatives, directly inhibit thrombin. Used as an alternative to Heparin for
anticoagulating patients with HIT.

 Warfarin (Coumadin):
 Interferes with normal γ-carboxylation of vit K-dependent clotting factors II, VII, IX, X, and
protein C & S (in protein C deficiency  hypercoagulability occurs  dermal vascular
thrombosis & skin necrosis). Metabolized by CYP450.
 Used in chronic anticoagulation. Not used in pregnancy (crosses placenta).
 Toxicity: bleeding, teratogenic, skin/tissue necrosis, drug2 interactions.
by Seetal K Dhaliwal H. S
 24

Thrombolytics (or fibrinolytics):

 Streptokinase, urokinase, alteplase (tPA), APSAC (anistreplase)
 Mechanism of action:
 Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves
thrombin fibrin clots. ↑ PT & ↑ PTT, no change in platelet count.
 Clinical use:
 Early MI, early ischemic stroke.
 Toxicity:
 Bleeding. Contraindicated in patients with active bleeding, history of intracranial
bleeding, recent surgery, known bleeding diatheses, or severe HTN.
 Antifibrinolysins (antidote for thrombolytic overdose):
 Aminocaproic acid or tranexamic acid.
by Seetal K Dhaliwal H. S
 25
Platelet aggregation ↓ by: PGI2, cAMP, ASA, ticlopidine, Clopidogrel, gp IIb/IIIa blockers.
Platelet aggregation ↑ by: ADP, 5HT, TXA2, thrombin, α2 agonists.

 Aspirin (ASA):
 Acetylates & irreversibly inhibits COX to prevent conversion of arachidonic acid to TXA2
(platelet aggregator). ↑ bleeding time. No effect on PT & PTT.
 Antipyretic, analgesic, anti-inflammatory, anti-platelet drug (used especially post-MI).
 Toxicity: gastric ulceration, bleeding, hyperventilation, Reye’s syndrome, tinnitus (CN VIII).
 Ticlopidine & Clopidogrel:
 Inhibit platelet aggregation by irreversibly blocking ADP receptors. Inhibit fibrinogen
binding by preventing glycoprotein IIb/IIIa expression..
 Used in acute coronary syndrome, coronary stenting. ↓ incidence or recurrence of
thrombotic stroke.
 Toxicity: neutropenia (ticlopidine).
 Abciximab, eptifibatide, & tirofiban:
 Monoclonal Ab binds gp IIb/IIIa on activated platelets, preventing aggregation.
 Used in acute coronary syndromes, percutaneous transluminal coronary angioplasty.
 Toxicity: bleeding, thrombocytopenia. by Seetal K Dhaliwal H. S