EXAM #5: ANTIHISTAMINES

Question 1

What is cytolytic histamine release?

Answer 1

Histamine release in response to damage of the mast cell membrane e.g.

• Skin damage
• High concentrations of certain drugs

Question 2

What is noncytolytic histamine release?

Answer 2

• Immune mediated release of histamine
• Non-immunological response caused by some polypeptides
• Displacement of histamine from mast cells by certain drugs

Question 3

Describe the mechanism of histamine release in an allergic response.

Answer 3

1) Initial contact with allergen leading to T-cell induced B-cell production of IgE
2) Plasma-cell released IgE antibodies that bind to mast cells
3) Subsequent exposure to allergen causes mast cell degranulation/ histamine release

Question 4

Where are H1 receptors primarily located?

Answer 4

1) Smooth muscle cells i.e. respiratory and GI
2) Vascular endothelial cells
3) CNS neurons
4) Peripheral sensory nerves

Itching

Question 5

Where are H2 receptors located?

Answer 5

1) Gastric parietal cells
2) Cardiac muscle
3) CNS neurons

Question 6

What G-protein subunit is H1 associated with?

Answer 6

Gq

PLC, IP3, Ca++

Question 7

What G-protein subunit is H2 associated with?

Answer 7

Gs

adenylyl cyclase, cAMP, PKA

Question 8

What is the function of histamine in the CNS?

Answer 8

1) Controls release of pituitary hormones
2) Wakefulness
3) Appetite/ satiety

Also responsible for some itching

Question 9

What is the effect of histamine in the vascular system?

Answer 9

1) Vasodilation
2) Increased vascular permeability–>edema

(hypotension and reflex tachycardia)

Question 10

What histamine receptor is primarily responsible for increased vascular permeability?

Answer 10

H1

Question 11

What histamine receptor is responsible for itching?

Answer 11

H1 in the epidermis

Question 12

What are the H1 effects of histamine in the respiratory system?

Answer 12

1) Elevated secretion of airway fluid

2) Bronchoconstriction

Question 13

What histamine receptor predominates in the heart itself?

Answer 13

H2

Question 14

What are the H2 effects on the heart?

Answer 14

1) Positive ionotrope

2) Positive dromotrope

Question 15

What are the actions of histamine in the immune system?

Answer 15

Facilitates the accumulation of immune cells at the site of infection or damage

Question 16

What are the classes of antihistamines?

Answer 16

1) Physiologic antagonists– reverse physiologic EFFECTS of histamine
2) Release inhibitors–block degrandulation
3) Receptor antagonists

Question 17

What is the difference between a 1st and 2nd generation antihistamines?

Answer 17

1) Specificity
- 2nd generation are more specific for H1 only
2) CNS penetration
- 2nd don’t penetrate the BBB as much as 1st

Question 18

Generally, what conditions are treated with 1st generation antihistamines?

Answer 18

1) Allergic rhinitis
2) Allergic conjunctivitis
3) Urticaria
4) Motion sickness
5) Anti-emetic

Question 19

Why can antihistamines be used as anti-emetics?

Answer 19

Vomiting center in the medulla contains H1 receptors

Question 20

What is the MOA of the H1 antihistamines?

Answer 20

“Inverse agonist” which means that they:

• Binds receptor
• Stabilizes the receptor in the inactive confirmation

Question 21

What are the major side effects of the 1st generation antihistamines?

Answer 21

1) CNS depression (H1)
2) Anticholinergic (M) effects
- Dry mouth
- Urinary retention
3) Increased appetite and weight gain (5-HT)
4) Dizziness and postural hypotension (Alpha-1)

Also can lead to paradoxical excitation and seizures in neonates and young children

Question 22

List the first generation antihistamines.

Answer 22

Chlorpheniramine 
Diphenhydramine
Pyrilamine 
Hydroxyzine 
Meclizine 
Promethazine 
Cyproheptadine

Question 23

What is the unique indication for Diphenhydramine?

Answer 23

Extrapyramidal sx. of antipsychotics

Question 24

What is the unique indication for Cyproheptadine?

Answer 24

Reversal of Serotonin Syndrome

Question 25

List the H1 antihistamines with the strongest antiemetic effects.

Answer 25

Diphenhydramine
Promethazine
Hydroxyzine
Meclazine

Question 26

List the H1 antihistamines with the highest sedative effects.

Answer 26

Diphenhydramine
Hydroxyzine
Promethazine

Question 27

Which H1 antihistamines have the strongest anticholinergic effects?

Answer 27

Diphenhydramine

Promethazine

Question 28

Which H1 antihistamine has the strongest alpha-1 antagonism?

Answer 28

Promethazine

Question 29

Which H1 antihistamine has the strongest anti-5HT effects?

Answer 29

Cyproheptadine

Question 30

How do the 2nd generation antihistamines differ from 1st generation?

Answer 30

1) Noncompetitive H1 inhibitors
2) Reduced lipophilicity i.e. less CNS penetration
3) Higher H1 selectivity

Question 31

List the 2nd generation antihistamines.

Answer 31

Fexofenadine 
Loratadine 
Desloratadine 
Levocetirizine 
Cetirizine 
Azelastine

Question 32

Which of the 2nd generation antihistamines have a higher sedative effect compared to the others?

Answer 32

1) Cetirizine

2) Levocetrizine

Question 33

What do you need to remember about Fexofenadine clinically?

Answer 33

1) Decrease dose in renal dysfunction

2) Avoid taking with antacids

Question 34

What is the MOA of Cromolyn and Nedocromil?

Answer 34

Stabilization of mast cells and inhibition of mast cell degranulation

Question 35

What are the indications for Cromolyn and Nedocromil?

Answer 35

1) Allergic rhinitis
2) Allergic conjunctivitis
3) Exercise induced asthma

Question 36

What is Omalizumab?

Answer 36

IgE monoclonal antibody

Question 37

What are the indications for Omalizumab?

Answer 37

1) Chronic urticaria

2) Asthma

Question 38

What is Doxepin?

Answer 38

TCA that is useful for treating chronic urticaria

Question 39

What is Ketotifen?

Answer 39

H1 antihistamine that has additional mast cell and basophil stabilizing properties

Available as ophthalmic preparation

Question 40

What is Ketotifen used to treat?

Answer 40

Allergic conjunctivitis