Pharmacology: Block 5: Drugs For Respiratory Disorders

Front 1

Histamine: what is it?

Back 1

"a biologic amine"

Front 2

Histamine: what does it do?

Back 2

- Modulation of allergic and inflammatory reactions
- Stimulation of gastric acid secretions
- Neurotransmitter in the CNS
- Chemotaxis of WBC?

Front 3

Histamine: where are they synthesized/stored?

Back 3

- Mast cells
- Basophils
- CNS neurons
- Enterochromaffin-like cells of the stomach.

Front 4

Histamine: synthesized from what?

Back 4

Synthesized from L-histidine by histidine decarboxylase

Front 5

What is a good way to search for a histamine secreting tumor?

Back 5

Look for metabolites of histamine:

- N-methylhistamine
- N-methyl-imidazole-acetic acid
- Imidazole-5-acetic acid

Front 6

What drugs can release histamine from mast cells wtihout degranulation or mast cell injury?

Back 6

Morphine, tubocurarine - these "displace" histamine without degranulation.

Front 7

What are some substances that can cause degranulation/mast cell injury?

Back 7

- Polypeptides
- Bradykinin
- Substance P
- Venoms
- Radiocontrast agents
- ABX (vancomycin)

Front 8

Histamine: effects on gastric secretions?

Back 8

stimulates

Front 9

Histamine: non-vascular smooth muscle?

Back 9

vasoconstricts

Front 10

Histamine: vascular beds?

Back 10

vasodilates. Low doses stimulate H1 receptors and release NO. High doses activate H2 receptors on vascular smooth muscle.

Front 11

Histamine: cardiac effects?

Back 11

Causes reflex tachycardia and H2 receptors up (???)

Front 12

Histamine: CNS effects?

Back 12

wakefulness, decreased appetite

Front 13

H2 receptors: effects on gastric mucosa?

Back 13

stimulate secretion

Front 14

H2 receptors: effects on bronchial smooth muscle?

Back 14

weak relaxation

Front 15

H2 receptors: effects on cardiac muscle?

Back 15

generalized stimulation

Front 16

Histamine: clinical uses?

Back 16

- Used for allergy skin tests.

- Used to be used for airway hyperreactivity, but it has largely been replaced by methacholine.

- Used to be used for gastric secretory capacity.

Front 17

H1 receptor blocker

Back 17

Fexofenadine (Allegra)

Front 18

H2 receptor blocker

Back 18

Cimetidine

Front 19

What is one clinically relevant function that H1 receptor blockers do not block?

Back 19

Histamine induced gastric secretion.

Front 20

c/c the three different generations of histamine blockers: sedation

Back 20

- 1st generation agents have prominent CNS sedative effects (can cross BBB)

- 2nd and 3rd generation agents are much less sedating

Front 21

Name 7 H1 receptor blockers

Back 21

1. Chlorpheniramine (Chlor-trimeton)
2. Diphenhydramine (Benadryl)
3. Dimenhydrinate (Dramamine)
4. Promethazine (Phenergan)
5. Cyproheptadine (Periactin)
6. Hydroxyzine (Atarax, Vistaril)
7. Meclizine (Antivert)

Front 22

Name 2 H2 receptor blockers

Back 22

1. Loratadine (Claritin)
2. Cetirizine (Zyrtec)

Front 23

Name 2 histamine releasing drugs

Back 23

1. Morphine
2. Vancomycin

Front 24

Name a histamine release inhibitor

Back 24

Cromolyn (Intal)

Front 25

Name 4 decongestants

Back 25

1. Phenylephrine (Neo-synephrine)
2. Pseudoephedrine (Sudafed)
3. Oxymetazole (Afrin)
4. Ipratropium (Atrovent)

Front 26

Name 2 expectorants

Back 26

1. Guaifenesin (Mucinex, Tussin)

2. Acetylcysteine (Mucomyst)

Front 27

Name 3 cough supressants

Back 27

1. Codeine
2. Dextromethorphan
3. Hydrocodone

Front 28

Dimenhydramine

Back 28

Strong anticholinergic activity. Marked sedation, anti-motion sickness activity.

(Dramamine), ethanolamine

Front 29

Diphenhydramine

Back 29

Strong anticholinergic activity. Marked sedation, anti-motion sickness activity.

(Benadryl), Ethanolamine

Front 30

Hydroxyzine

Back 30

Undetermined anticholinergic effects. Marked sedation. Injectable used as a tranquilizer.

(Atarax), Piperazine derivative

Front 31

Meclizine

Back 31

Very little anticholinergic activity. Slight sedation, anti-motion sickness activity.

(Bonine), Piperazine derivative

Front 32

Chlorpheniramine

Back 32

Slight anticholinergic activity. Common component of OTC "cold" medication.

(Chlor-Trimetron), Alkylamine

Front 33

Promethazine

Back 33

Lots of anticholinergic activity. Marked sedation, antiemetic, alpha block, D2 receptor block.

(Phenergan), Alkylamine

Front 34

Cyproheptadine

Back 34

Slight anticholinergic activity. Moderate sedation, also has anti-serotonin activity.

(Periactin)

Front 35

What was the problem with the first 2nd generation H2 blockers?

Back 35

They caused QT prolongation

Front 36

Some "H1 antagonists" may actually be what?

Back 36

Inverse agonists

Front 37

Antihistamines: uses

Back 37

- Treatment of acute allergies
- Treatment of allergic dermatoses
- Treatment of serum sickness/allergic drug reactions
- Treatment of motion sickness and vertigo (1st generation)
- As sedatives (1st generation)

Front 38

Antihistamines: AE

Back 38

- Sedation, fatigue
- Dizziness, tinnitus
- Blurred vision
- Dry mouth, GI distress
- Weight gain
- Excitation
- Overdoses may lead to convulsions - especially in children!
- Drug allergies may develop when these agents are applied topically.

Front 39

Dextromethorphan

Back 39

Robatussin
NMDA receptor antagonists - PCP like effects. Inhibit brainstem cough reflex.

Front 40

Guaifenesin

Back 40

- Reduces viscosity of respiratory secretions

- AE: nephrolithiasis, nausea

Front 41

Acetylcysteine

Back 41

- Reduces disulfide bonds in mucus, increasing fluidity

- SE: nausea, bronchospasm, hypersensitivity.

Front 42

What are three different types of medications that you would give to someone who is having an asthma attack?

Back 42

Bronchodilator
Oxygen
Antiinflammatory corticosteroid

Front 43

Name three "short term relievers" of contracted airways.

Back 43

1. β-agonists
2. Theophylline
3. Antimuscarinics

Front 44

Name four anti-inflammatory "long term controllers" for asthma.

Back 44

1. Inhaled corticosteroids
2. Inhaled mast-cell stabilizers
3. Leukotriene pathway inhibitors
4. Anti-IgE MAB

Front 45

Inhalation route: dose at target organ? Total dose amount? AE? Duration of onset? What is important about the design of inhaled drugs?

Back 45

High dose at target organ, but total dose patient takes is much lower. Lower systemic exposure = lower AE. Generally has a very rapid onset (usually 5-10 min w/ inhalation, about as good as IV!). Particle size is very important.

Front 46

Nebulization: pros and cons

Back 46

Pros: good for infants and unconscious patients.

Cons: slow, high drug dose, exact dose pt received unknown

Front 47

Metered dose inhaler: pros and cons

Back 47

Pros: portable, dose is low, rapid onset.

Cons: need education about proper use. Sometimes need to use spacer to get uniform dosing.

Front 48

Dry powder inhaler: pros and cons.

Back 48

Pros: No CFCs, portable, rapid

Cons: dose depends on pt's ability to take a quick and deep breath. Specific ways to use. Feels like breathing rocks. Drug can be sensitive to humidity.

Front 49

c/c albuterol and theophylline: mechanism of bronchodilation.

Back 49

Albu

Front 50

Elevated levels of cAMP do what to the bronchi?

Back 50

Dilate

Front 51

Elevated levels of acetylcholine do what to the bronchi?

Back 51

Constrict

Front 52

Name 2 "short acting" beta 2 agonists for asthma

Back 52

Albuterol, Terbutaline

Front 53

Terbutaline

Back 53

"Short acting" beta 2 agonist (3-4) hours, used for asthma rescue. Oral, injection

Front 54

Salmetrol

Back 54

Slow onset (12-24 hrs) beta 2 selective agonist used for long term control of asthma.

Front 55

Formetrol

Back 55

Somewhat fast onset beta 2 selective agonist. Not labeled for rescue, but has faster onset than salmetrol. 25x more potent than albuterol.

Front 56

Beta 2 agonists: AE

Back 56

Tremor
Tachycardia
Palpitations
Dizziness
Bronchoconstriction (paradoxical effect)
Heartburn
Hypokalemia (K+ goes into skeletal muscle?)
Prolonged QT
Sudden cardiac death - Black box warning (esp long-acting agonists)

Front 57

Name 2 antimuscarinics that are used as bronchodilators

Back 57

Ipratropium bromide, Tiotropium.

Front 58

Ipratropium bromide

Back 58

Antimuscarinic, very insoluble quaternary ammonium atropine derivative. Not intended for rescue, but fairly rapid action. 2-4x daily.

AE: urinary retention, glaucoma, blurry vision

Front 59

Tiotropium

Back 59

Antimuscarinic used for bronchodilation.

1x daily, selective M1, M3 antagonism, because dissociates from prejunctional M2 receptor faster.

AE: urinary retention, glaucoma, blurry vision.

Front 60

Name three methylxanthines that are used for bronchodilation

Back 60

1. Theophylline
2. Aminophylline
3. Caffeine

Front 61

Theophylline

Back 61

Oral, Inhibits PDE4, adenosine antagonist (causing bronchodilation), anti-inflammatory action.

AE: Low theraputic index - must monitor plasma levels.
CNS stimulation
Tremor, seizure
Decreased sensitivity to CO2
GERD/heartburn/nausea
Muscle activity
Diuresis

Front 62

Name 3 important corticosteroids used for anti-inflammation in asthma/COPD

Back 62

1. Fluticasone, MDI, PDI
2. Budesonide, MDI, PDI
3. Trimacinolone, MDI

Front 63

What should you do immediately after using steriod inhalers?

Back 63

Rinse your mouth!

Front 64

Inhaled corticosteroids for asthma: AE

Back 64

AE:
Candidal infections
Esophagitis
Vocal chord changes
Glaucoma, cataracts
Adrenal suppression

Front 65

What are "leukotriene modulators used for"?

Back 65

As anti-inflammatory agents in COPD

Front 66

Name 2 Leukotriene modulators (LTD4 receptor antagonists)

Back 66

1. Montelukast (Singulair)
2. Zafirlukast

Front 67

Montelukast

Back 67

Leukotriene modulator (LTD4 receptor antagonist)

Oral 1x daily, children above 6 years. AE: drowsiness

Front 68

Zafirlukast

Back 68

Leukotriene modulator (LTD4 receptor antagonist)

Oral 2x daily. AE: drowsiness.

Front 69

Name a 5-lipoxygenase inhibitor used for anti-inflammation in asthma

Back 69

Zileuton

Front 70

Zileuton

Back 70

5-lipoxygenase inhibitor. Used for anti-inflammation in asthma.

SR oral, 2x daily

Not that popular, less efficacious than corticosteroids

AE: liver injury (reversible if you catch it in time)

Front 71

Name a mast cell stabilizer used for treatment of asthma

Back 71

Cromolyn.

Front 72

Cromolyn

Back 72

A mast cell stabilizer used for treatment of asthma.

Inhibit the early response to allergen change and mast cell degranulation by altering the function of a delayed chloride channel.

Very effective but not rapidly acting.

Used for allergic rhinitides.

Inhalation.

AE: throat irritation, dry mouth, cough
SAE: dermatitis, myositis, gastroenteritis.

Front 73

Name an IgE monoclonal antibody used in the treatment of asthma

Back 73

Omalizumab

Front 74

Omalizumab

Back 74

An IgE monoclonal antibody used in the treatment of asthma.

Inhibits IgE binding to mast cells. 2x week for 10 weeks.

Resevered for patients with poor pulmonary function and whose asthma cannot be controlled with corticosteroids.

Very expensive!

Front 75

Beta blocker use in COPDers?

Back 75

"Usually ok" (???)

Front 76

NSAIDs: cause asthma how often? What other symptoms to they cause?

Back 76

10-15%
Sampter's triad: asthma, aspirin sensitivity, and nasal polyp (usually seen in Haitians in their 20s???)