Pharmacology - Exam 1 - Road Map 2

Front 1

General properties of H1 blocking drugs

Back 1

1. used in treatment of hayfever and urticaria, and a few IgE-mediated allergies.
2. toxicities reflect their effects on the ANS and CNS

Front 2

General properties of H2 blocking drugs

Back 2

1. used in treatment of acid-peptic disease, especially heartburn and peptic ulcer
2. toxicities (almost exclusively cimetidine) include:
a. inhibition of hepatic CYP450
b. antiandrogenic action

Front 3

Examples of typical H2 blockers

Back 3

1. cimetidine
2. famotidine
3. nizatidine
4. ranitidine

Front 4

Examples of H3 blockers

Back 4

1. clobenpropit
2. abt-239 (nootropic)
3. ciproxifan
4. ciprilisant

Front 5

In which cells is serotonin stored?

Back 5

1. platelets
2. neurons
3. enterochromaffin cells
4. cells in the gut

Front 6

What is the main metabolite of serotonin?

Back 6

1. hydroxyindoleacetic acid (HIAA)
2. is increased in urine of patients with carcinoid tumor

Front 7

Effects of increased serotonin (and other substances) produced by carcinoid tumor include

Back 7

1. diarrhea
2. bronchospasm
3. variable changes in blood pressure
4. flushing of the skin

Front 8

Serotonin's effects are mediated by a large number of receptors, four of which are of clinical importance. Which ones?

Back 8

1. 5-HT 1D (GPCR)
2. 5-HT2 (GPCR)
3. 5-HT3 (ion channel)
4. 5-HT4 (GPCR)

Front 9

Clinical value of serotonin?

Back 9

Serotonin itself is of no value as a drug, but two more selective agonists are used:
1. 5-HT 1D (e.g., sumatriptan) for migraine. Toxicities include coronary vasospasm
2. 5-HT4 agonists (e.g., tegaserod and cisapride) increase the release of ACh in the gut--> increased motility. Toxicities include tosade de pointes arrhythmia and diarrhea.

Front 10

What is the standard treatment of migraine headache?

Back 10

1. Simple analgesics, with sumatriptan or a similar "triptan" drug, or with ergotamine
2. Prophylaxis is partially successful using propranolol, amitriptyline, calcium channel blockers, and others

Front 11

H1 receptor functions:

Back 11

1. Gq coupled
2. increased IP3 and DAG, smooth muscle contraction (EXCEPT vessels), increased secretion
3. located in smooth muscle, gland cells, some nerve endings

Front 12

H2 receptor functions:

Back 12

1. Gs coupled
2. Increased cAMP, increased acid secretion, cardiac stimulation
3. located in parietal cells (stomach) and heart

Front 13

H3 receptor functions

Back 13

1. Gi coupled
2. decreased cAMP, modulates transmitter release
3. presynaptic autoreceptor in nerve endings

Front 14

Histamine H1 antagonists can be divided into three groups. What are they? And what are their uses?

Back 14

1. First generation, older - allergy, sleep aid, motion sickness, nausea of chemotherapy
2. First generation, newer - allergy
3. Second generation - allergy

Front 15

Examples of first generation, older, H1 antagonists

Back 15

1. Diphenhydramine
2. dimenhydrinate

Front 16

Examples of first generation, newer, H1 antagonists

Back 16

1. chlorpheniramine
2. cyclizine

Front 17

Examples of second generation H1 antagonists

Back 17

1. fexofenadine
2. loratadine
3. desloratadine
4. cetrizine

Front 18

Toxicities of first generation, older antihistamines

Back 18

1. strong alpha and muscarinic block
2. strongly sedative

Front 19

Toxicities of first generation, newer antihistamines

Back 19

1. much reduced sedative and ANS effects

Front 20

Toxicities of second generation antihistamines

Back 20

negligible CNS and ANS effects

Front 21

Location and function of 5-HT1D receptors

Back 21

1. Located in neurons, perhaps other places
2. mediates increased IP3, DAG

Front 22

Location and function of 5-HT2 receptors

Back 22

1. smooth muscle, other?
2. increased IP3 and DAG, smooth muscle contraction

Front 23

Location and function of 5-HT3 receptors

Back 23

1. chemoreceptors in the central and peripheral nervous system
2. nasuea and vomiting

Front 24

Location and function of 5-HT4 receptors

Back 24

1. neurons in the gut
2. increased GI motility

Front 25

Some notes on 5-HT2 antagonists

Back 25

5-HT2 antagonists, such as ketanserin, have been developed for the treatment of carcinoid tumors. However, older drugs with overlapping effects (e.g., phenoxybenzamine [5-HT+alpha blocker] or cyproheptadine [5-HT+H1 blocker]) appear to be just as useful. In addition ketanserin has been used to treat HTN in Europe.

Front 26

Indications for 5-HT3 antagonists?

Back 26

Extremely useful antinauseants and antiemetics for patients undergoing general anesthesia or chemotherapy

Front 27

Examples of 5-HT3 antagonists

Back 27

1. ondansetron
2. granisetron
3. tropisetron
4. dolasetron

Front 28

Other serotonin related drugs

Back 28

1. ergot alkaloids (complex partial agonists at 5-Ht, alpha, and dopamine receptors)
2. ergotamine (for migraine) - natural
3. ergonovine (oxytocic agent) - natural
4. bromocriptine (used in hyperprolactinemia and parkinsonism) - semisynthetic
5. pergolide (parkinsonism) - semisynthetic
6. LSD - semisynthetic. no meidcal use, powerful hallucinogenic

Front 29

Effects and clinical uses of endogenous PGE2

Back 29

1. vasodilation, bronchodilation, oxytocic
2. oxytocic (as dinoprostone)

Front 30

Effects and clinical uses of PGE1 analog misoprostol

Back 30

1. increased bicarbonate and mucus secretion in stomach
2. prevention of NSAID-induced ulcers

Front 31

Effects and clinical uses of PGE1 analog alprostadil

Back 31

1. smooth muscle relaxation
2. erectile dysfunction

Front 32

Effects and clinical uses of endogenous PGF2alpha

Back 32

1. vasoconstriction, bronchoconstriction, oxytocic
2. no clinical uses

Front 33

Effects and clinical uses of PGF2alpha analog latanoprost

Back 33

1. increased aqueous humor drainage
2. chronic glaucoma

Front 34

Effects and clinical uses of prostacyclin (PGI2)

Back 34

1. prevents platelet aggregation, vasodilation
2. severe pulmonary hypertension (as epoprostenol)

Front 35

Effects and clinical uses of thromboxane (TXA2)

Back 35

1. facilitates platelet aggregation
2. no clinical uses

Front 36

Effects and clinical uses of LTB4

Back 36

1. leukocyte chemotaxis
2. no clinical uses

Front 37

Effects and clinical uses of LTC4

Back 37

1. bronchoconstriction
2. no clinical uses

Front 38

Effects and clinical uses of LTD4

Back 38

1. bronchoconstriction
2. no clinical uses

Front 39

Difference between NSAIDs and steroids?

Back 39

Steroids are powerful anti-inflammatory agents, whereas NSAIDs have weaker anti-inflammatory actions, but are more suitable for long-term therapy because they are less toxic

Front 40

Older NSAIDs include

Back 40

1. aspirin
2. salicylate

Front 41

Newer non-COX selective NSAIDs include

Back 41

1. indomethacin
2. ibuprofen
3. diclofenac
4. indomethacin
5. ketorolac
6. naproxen
7. piroxicam

Front 42

Selective COX-2 inhibitors include

Back 42

1. celecoxib
2. valdecoxib
3. other members of this drug

Front 43

Half-life and comments on aspirin

Back 43

1. 15 minutes (but active metabolite has a half life of 3-15 hours)
2. Widely used for pain, fever, inflammation, and antiplatelet action

Front 44

Half-life and comments on celecoxib

Back 44

1. 11 hours
2. selective COX-2 inhibitor; a sulfonamide

Front 45

Half-life and comments on diclofenac

Back 45

1. 1.1 hours
2. general use in inflammation, pain

Front 46

Half-life and comments on ibuprofen

Back 46

1. 2 hours
2. general use in inflammation, pain

Front 47

Half-life and comments on indomethacin

Back 47

1. 4-5 hours
2. general use in inflammation, pain

Front 48

Half-life and comments on ketorolac

Back 48

1. 4-10 hours
2. parenteral use in pain; an opioid substitute

Front 49

Half-life and comments on naproxen

Back 49

1. 12 hours
2. longer action

Front 50

Half-life and comments on piroxicam

Back 50

1. 20 hours
2. longest action

Front 51

Half-life and comments on salicylic acid

Back 51

1. 3-15 hours
2. active metabolite of aspirin, zero order elimination at high concentrations

Front 52

What sets aspirin apart from all other NSAIDs?

Back 52

It irreversibly blocks COX, especially in platelets. Its antiplatelet effect is, therefore, longer in duration (24-48 hrs) than its anti-inflammatory and analgesic action (4-6 hours)

Front 53

Toxicities of the NSAIDs include

Back 53

1. GI upset
2. peptic ulcers with or without bleeding
3. renal damage
4. diversion of arachidonic acid metabolism to the leukotriene pathway (may rarely present with anaphylaxis)

Front 54

Pros and cons of COX-2 selective inhibitors

Back 54

1. Pro: lower risk of GI bleeding
2. Con. increased risk of cardiovascular events (stroke and MI)

Front 55

Comments on acetaminophen

Back 55

1. similar analgesic and antiypritic effect to aspirin
2. weak COX inhibitor
3. little or no anti-inflammatory effect
4. metabolites of acetaminophen may cause hepatic necrosis (overdose)

Front 56

What is gout?

Back 56

1. chronic metabolic disease characterized by an elevated body load of uric acid.
2. manifested by depositus of urate crystals in soft tissue and joints
3. in the joints, these crystals trigger episodes of acute painful arthritis

Front 57

Which classes of drugs are used in the treatment of gout?

Back 57

1. anti-inflammatory agents (mainstay of therapy)
2. uricosuric agents (increases excretion of uric acid)
2. inhibitor of uric acid synthesis (allopurinol)

Front 58

Which anti-inflammatory drugs are are often used in the treatment of acute joint pain?

Back 58

1. ibuprofen and indomethacin
2. colcichine (highly selective for gouty arthritis) - but is usually restricted to low-dose prophylactic therapy because of GI and hepatic toxicity

Front 59

Which uricosuric agents are normally used in the treatment of gout?

Back 59

1. probenecid
2. sulfinpyrazone

They inhibit the uric acid reabsorption transporter in the straight segment of proximal tubules

Front 60

Mechanism of action of allopurinol

Back 60

1. inhibits xanthine oxidase
2. reduces concentration of insoluble uric acid
3. increases concentration of uric acid precursors, xanthine and hypoxanthine

Front 61

Clinical correlations on the treatment of gout

Back 61

1. acute attacks require strong anti-inflammatory drugs, strong analgesics, or both
2. indomethacin and ketorolac are often used. ketorolac may be used parenterally
3. uricosurics may precipitate an immediate attack and should always be used in conjunction with colcichine or other agents initially
4. allopurinol's benefits are slow in onset and are suitable only for long-term therapy

Front 62

In addition to the obvious cardiovascular events that hypertriglyceridemia may cause, it may also contribute to an incresed risk of

Back 62

acute pancreatitis

Front 63

Drugs used in hypercholesterolemia include

Back 63

1. statins
2. resins
3. ezetimibe
4. niacin
5. fibrates

Front 64

Mechanism of action of statins

Back 64

(e.g., levostatin and atorvastatin)
1. inhibitors of cholesterol synthesis (HMG-CoA reductase inhbitors)
2. reduced cholesterol concentrtion results in increased LDL-binding receptors on liver cells, which increases clearance of LDL from blood
3. most statins only reduce cholesterol, but atorvastatin reduces both cholesterol and triglyceride levels

Front 65

Mechanism of action of resins

Back 65

(e.g., cholestyramine and colestipol)
1. nonabsorbable macromolecules, bind to and prevent reabsorption of cholesterol and bile acids
2. resins tend to increase triglycerides

Front 66

Mechanism of action of exetimibe

Back 66

new drug that reduces the absorption of cholesterol from the intestines, the exact mechanism is unknown

Front 67

Mechanism of action of niacin

Back 67

(nicotinic acid and vitamin b3)
1. the exact mechanism is not fully understood.
2. high doses cause a decrease in secretion of VLDL from the liver into blood, and thus decreased LDL.
3. is also effective in hypertriglyceridemia and may cause increase in HDL

Front 68

Mechanism of action of the fibrates

Back 68

(e.g., gemfibrozil and fenofibrate)
1. activate peroxisome proliferator-activator receptor alpha (PPAR-a)
2. increases synthesis of lipoprotein lipase and other enzymes
3. serum triglyceride concentrations are reduced, may be a reduction in LDL

Front 69

Toxicities of statins

Back 69

1. may cause serious skeletal muscle or liver damage
2. may interfere with myelination in growing infants.

These drugs are contraindicated in pregnancy

Front 70

Toxicities of niacin

Back 70

1. high doses causes a transient uncomfortable flushing with itching (may be reduced with aspirin)
2. may rarely cause elevation of:
a. liver enzymes
b. hyperuricemia
c. glucose intolerance

Front 71

Toxicities of resins

Back 71

1. unpleasant gritty taste
2. may cause GI discomfort (including bloating and constipation)
3. impaired fat-soluble vitamin and drug absorption

Should be avoided in hypertriglyceridemia

Front 72

Toxicities of fibrates

Back 72

1. nausea
2. skin rash
3. increased effect of antiplatelet drugs
4. increased risk of gall stones

Front 73

Anticoagulants include

Back 73

1. warfarin (oral; blocks reactivation of vitamin K epoxide; monitor with PT and INR)
2. heparin (parenterally, binds factor Xa and AT III)

Front 74

Heparin is available in both HMW and LMW forms. The differences

Back 74

1. HMW - binds Xa and AT III. AT III in this bound form is activated 1000-fold --> immediate clotting inhibition. The response is variable, must monitor.
b. LMW - inhibit factor Xa, but less effect on AT III. Response is predictable and so does not require monitoring.

Front 75

Examples of LMW heparins

Back 75

1. enoxaparin
2. dalteparin

Front 76

Major clinical application of heparins and warfarin are

Back 76

in the prevention and treatment of venous clotting, especially DVT

Front 77

Toxicities of heparins and warfarin

Back 77

1. bleeding
2. warfarin is a teratogen
3. heparin causes dose-dependent thrombocytopenia, but occasionally causes a more severe loss of platelets

Front 78

Most important antiplatelet drugs include

Back 78

1. aspirin
2. clopidogrel - blocks ADP receptor on platelets
3. ticlopidine - blocks ADP receptor on platelets
4. fiban drugs (eptifibatide and tirofiban) - IIb/IIIa blocker
5. abciximab - IIb/IIIa blocker

Front 79

Most important clinical use of fibrinolytics

Back 79

intravenous administration for pulmonary embolism and myocardial infarction

Front 80

Most important fibrinolytic drugs

Back 80

1. streptokinase - may cause allergic response, bleeding
2. alteplase (tPA), reteplase - bleeding
3. urokinase - bleeding

Front 81

Anemia results from

Back 81

1. inadequate dietary iron
2. inadequate vitamin intake
3. inadequate RBC production
4. accelerated RBC breakdown

Front 82

What is anemia?

Back 82

a deficiency of red blood cells (RBCs) or hemoglobin

Front 83

For simple iron deficiency anemia, oral supplementation is effective. In what form is iron given?

Back 83

1. ferrous sulfate
2. ferrous gluconate

ferric iron salts are poorly absorbed

Front 84

Iron is irritating to the stomach, annd some patients cannot tolerate the doses required for rapid correction of severe deficiency. What options do these patients have?

Back 84

1. iron dextran
2. iron sucrose complex
3. iron gluconate complex

all parenteral iron

Front 85

Manifestations of iron poisoning include

Back 85

1. vomiting
2. abdominal pain
3. diarrhea
3. necrotizing enteritis, followed by shock, lethargy, metabolic acidosis, death

Front 86

How do you treat iron poisoning?

Back 86

Prompt diagnosis and an iron chelator, such as deferoxamine

Front 87

Growth factor used for anemia

Back 87

1. epoetin (human recombinant erythropoietin)
2. increases RBC production
3. may cause HTN, thrombotic events

Front 88

Growth factor used for granulocytopenia (F)

Back 88

1. filgrastim (human recombinant GM-CSF)
2. increases neutrophil production
3. may cause bone pain

Front 89

Growth factor used for granulocytopenia (S)

Back 89

1. sargramostim (human recombinant G-CSF)
2. stimulates most marrow precursors, but increases neutrophil production the most
3. may cause fever, myalgia, peripheral and pulmonary edema

Front 90

Growth factors used for thrombocytopenia

Back 90

1. oprelvekin (human recombinant IL-11)
2. stimulates platelet production
3. may cause fatigue, headache, dizziness

Front 91

Definition of asthma

Back 91

asthma is a chronic inflammtory airway disease, with superimposed transient episodes of bronchoconstriction

Front 92

Therapy of asthma consists of

Back 92

1. bronchodilators - control of symptoms
2. anti-inflammatory drugs - prophylaxis

Front 93

Bronchoconstriction in asthma is mediated mostly by

Back 93

1. leukotrienes
2. other smooth muscle activators from mast cells and eosinophils in the airways

Front 94

Bronchodilators consist of

Back 94

1. beta2-selective agonists
2. muscarinic blockers
3. theophylline

Front 95

Drug of choice in acute episodes of asthmatic bronchoconstriction

Back 95

1. beta2-selective agonists, such as:
a. albuterol
b. metaproterenol
2. they are physiologic leukotriene antagonists (and others increasing cAMP)
3.

Front 96

Toxicities of beta2-selective agonists

Back 96

1. tremor
2. tachycardia

However, do not limit the drug during an acute attack: uncontrolled bronchoconstriction can be fatal

Front 97

The most important muscarinic antagonists used in asthma are atropinelike. Their names are

Back 97

1. ipratropium
2. tiotropium

*not as effective as SABAs

Front 98

Toxicities of ipratropium and tiotropium

Back 98

1. dry mouth
2. tachycardia (rarely)
3. cycloplegia (rarely)

Front 99

Toxicities of theophylline include

Back 99

1. GI disturbances
2. tremor
3. arrhythmias
4. convulsions

Front 100

Third kind of bronchodilator

Back 100

1. theophylline - is related to caffeine and theobromine, but more effective than either
2. inhibits phosphodiesterase -->increased levels of cAMP
3. not active when inhaled

Front 101

Which anti-inflammatory drugs are used in asthma?

Back 101

1. corticosteroids
2. mast cell stabilizers
3. leukotriene antagonists

Front 102

Most important prophylactic agent for asthma

Back 102

corticosteroids - given by metered-dose inhaler when possible

Front 103

Which steroids are most commonly used in asthma?

Back 103

1. beclomethasone
2. fluticasone
3. uhm... others...

Front 104

How do corticosteroids help in asthma?

Back 104

inhibit leukotriene and inflammatory cytokine production and release

Front 105

Toxicities of inhaled corticosteroids include

Back 105

1. temporary retardation of growth young children
2. candidal yeast infection of larynx

Front 106

Mast cell stabilizers used in asthma include

Back 106

1. cromolyn
2. nedocromil

highly insoluble compounds that can be administered by metered-dose inhalation with practically no systemic toxicity

Front 107

How do mast cell stabilizers work?

Back 107

Probably by inhibiting mast cell release of inflammatory and allergic mediators, including leukotrienes, cytokines, and histamine

Front 108

Leukotriene receptor antagonists used in asthma

Back 108

1. zafirlukast
2. montelukast

orally active (advantageous in young children and others who can't use inhalers)

Front 109

Downside of leukotriene receptor antagonists?

Back 109

1. not as effective as corticosteroids
2. no value in acute bronchospasm