Module 4 - Antihistamines

Question 1

What is histamine, and what role does it play in allergic reactions?

Answer 1

Histamine is a compound that is produced locally in the body and plays a significant role in allergic reactions. It contributes to various allergy symptoms, including rhinitis (runny or stuffy nose), itching, and localized edema (swelling).

Question 2

Which receptors are primarily responsible for the symptoms of mild allergies?

Answer 2

The symptoms of mild allergies, such as rhinitis, itching, and localized edema, are largely related to the activation of Histamine-1 receptors.

Question 3

How are these allergic symptoms managed?

Answer 3

Common drugs are used to block Histamine-1 receptors, which helps alleviate allergy symptoms. These drugs are known as antihistamines.

Question 4

What compounds are involved in allergic reactions?

Answer 4

Allergic reactions are mediated by compounds such as histamine, prostaglandins, leukotrienes, and tryptase.

Question 5

How is the intensity of an allergic reaction determined?

Answer 5

The intensity of an allergic reaction is determined by the specific mediator involved.

Question 6

Which symptoms of mild allergy are primarily caused by histamine?

Answer 6

Mild allergic symptoms like rhinitis (runny nose), itching, and localized edema (swelling) are largely caused by histamine acting on H1 receptors.

Question 7

Are mild allergic conditions generally responsive to a specific type of therapy?

Answer 7

Yes, mild allergic conditions such as hay fever, acute urticaria (hives), and mild transfusion reactions are typically responsive to antihistamine therapy.

Question 8

What are the various effects of histamine in the body?

Answer 8

Histamine has effects such as dilating small blood vessels, increasing capillary permeability, causing bronchoconstriction in the bronchi, stimulating stomach acid secretion, and acting as a neurotransmitter in the central nervous system.

Question 9

What is the clinical use of histamine?

Answer 9

The clinical use of histamine is primarily limited to diagnostic procedures.

Question 10

Despite its limited clinical use, why is histamine still of interest in medicine?

Answer 10

Histamine remains of interest in medicine because it plays a crucial role in two common pathological conditions: allergic disorders and peptic ulcer disease.

Question 11

In which tissues is histamine present, and where are its levels notably high?

Answer 11

Histamine is found in practically all tissues, with notably high levels in the skin, lungs, and the gastrointestinal (GI) tract. Plasma contains a low histamine content.

Question 12

Where is histamine synthesized and stored in the periphery of the body?

Answer 12

in the periphery, histamine is synthesized and stored in two types of cells: mast cells, which are present in the skin and soft tissues, and basophils, which are present in the blood. Histamine is stored in secretory granules within these cells.

Question 13

Which part of the brain is responsible for producing histamine in the central nervous system (CNS), and where do the neurons project?

Answer 13

In the CNS, histamine is produced by neurons with cell bodies located in the posterior hypothalamus. These neurons project axons to various regions of the brain, including the frontal and temporal cortices.

Question 14

What triggers the release of histamine from mast cells and basophils, and through what mechanisms?

Answer 14

Histamine release from mast cells and basophils can be triggered by both allergic and nonallergic mechanisms. Allergic release involves the production of immunoglobulin E (IgE) antibodies after exposure to specific allergens. Nonallergic release can be induced by certain agents (such as drugs or cell injury).

Question 15

What is the initial requirement for allergic release of histamine?

Answer 15

The initial requirement for allergic release of histamine is the production of antibodies of the immunoglobulin E (IgE) class.

Question 16

How are these IgE antibodies generated?

Answer 16

IgE antibodies are generated after exposure to specific allergens, such as pollens, insect venoms, or certain drugs.

Question 17

Once produced, where do these IgE antibodies become attached?

Answer 17

IgE antibodies become attached to the outer surface of mast cells and basophils.

Question 18

What happens when an individual is reexposed to the allergen?

Answer 18

When an individual is reexposed to the allergen, the allergen becomes bound by the IgE antibodies attached to mast cells and basophils.

Question 19

What is the outcome of allergen binding to adjacent IgE antibodies?

Answer 19

Binding of the allergen to adjacent IgE antibodies creates a bridge between these antibodies.

Question 20

What cellular events follow this bridging process?

Answer 20

The bridging process mobilizes intracellular calcium.

Question 21

How does calcium mobilization affect histamine-containing storage granules?

Answer 21

Calcium mobilization causes the histamine-containing storage granules to fuse with the cell membrane and release their contents into the extracellular space.

Question 22

Can an allergic reaction occur during the initial exposure to an allergen?

Answer 22

No, an allergic reaction cannot occur during the initial exposure to an allergen; prior sensitization is required for allergic release of histamine.

Question 23

What triggers nonallergic release of histamine?

Answer 23

Nonallergic release of histamine can be triggered by several agents, including certain drugs, radiocontrast media, and plasma expanders.

Question 24

Is prior sensitization required for nonallergic release of histamine?

Answer 24

No, prior sensitization is not needed for nonallergic release of histamine.

Question 25

What can also cause direct release of histamine?

Answer 25

Cell injury can also lead to the direct release of histamine.

Question 26

What are the two main types of histamine receptors?

Answer 26

The two main types of histamine receptors are histamine-1 (H1) and histamine-2 (H2) receptors.

Question 27

How does the response produced by histamine depend on these receptors?

Answer 27

The response produced by histamine depends on which of these receptors (H1 or H2) is involved.

Question 28

What does the activation of histamine-1 (H1) receptors cause in the vascular system?

Answer 28

Activation of H1 receptors causes vasodilation of small blood vessels (arterioles and venules).

Question 29

Where is vasodilation prominent when H1 receptors are activated?

Answer 29

Vasodilation is prominent in the skin of the face and upper body.

Question 30

What happens when H1 receptors are activated regarding capillary permeability?

Answer 30

Activation of H1 receptors increases capillary permeability, leading to the contraction of capillary endothelial cells and the creation of openings between these cells.

Question 31

What can escape through the openings created by H1 receptor activation in capillary endothelial cells?

Answer 31

Through the openings created by H1 receptor activation, fluid, protein, and platelets can escape.

Question 32

What is the result of fluid and protein escaping into the interstitial space due to H1 receptor activation?

Answer 32

The escape of fluid and protein into the interstitial space produces edema.

Question 33

What potential effect on blood pressure can occur if there is substantial loss of intravascular fluid due to H1 receptor activation?

Answer 33

If there is substantial loss of intravascular fluid, blood pressure may fall.

Question 34

What effect does activation of histamine-1 (H1) receptors have on the bronchi?

Answer 34

Activation of H1 receptors causes constriction of the bronchi.

Question 35

What can happen if histamine is administered to an individual with asthma?

Answer 35

If histamine is administered to an individual with asthma, severe bronchoconstriction will follow.

Question 36

Is histamine the primary cause of bronchoconstriction during a spontaneous asthma attack?

Answer 36

No, histamine is not the primary cause of bronchoconstriction during a spontaneous asthma attack.

Question 37

Are antihistamines useful for treating asthma?

Answer 37

Antihistamines are not useful for treating asthma.

Question 38

In the central nervous system (CNS), what roles do H1 receptors play?

Answer 38

H1 receptors in the CNS have roles in cognition, memory, the sleep-wake cycle, seizure suppression, modulation of neurotransmitter release, and regulation of energy and endocrine homeostasis.

Question 39

What happens when H1 receptors on sensory nerves are activated?

Answer 39

Activation of H1 receptors on sensory nerves produces itching and pain.

Question 40

What effect does H1 activation have on the secretion of mucus?

Answer 40

H1 activation promotes the secretion of mucus.

Question 41

What is the major response to activation of histamine-2 (H2) receptors?

Answer 41

The major response to activation of H2 receptors is the secretion of gastric acid in the stomach.

Question 42

What mediates allergic reactions in the body?

Answer 42

Allergic reactions are mediated by histamine and other compounds, including prostaglandins, leukotrienes, and tryptase.

Question 43

What determines the intensity of an allergic reaction?

Answer 43

The intensity of an allergic reaction is determined by the specific mediator involved.

Question 44

Which symptoms of mild allergy are primarily caused by histamine?

Answer 44

Symptoms of mild allergy, such as rhinitis, itching, and localized edema, are largely caused by histamine acting at H1 receptors.

Question 45

Are mild allergic conditions typically responsive to a specific type of medication?

Answer 45

Yes, mild allergic conditions like hay fever, acute urticaria, and mild transfusion reactions are generally responsive to antihistamine therapy.

Question 46

What are the two basic categories of antihistamines?

Answer 46

Antihistamines are categorized into two main groups: H1 receptor antagonists and H2 receptor antagonists.

Question 47

What is the primary use of H1 receptor antagonists (H1 blockers)?

Answer 47

H1 blockers are primarily used to treat mild allergic disorders.

Question 48

What is the primary use of H2 receptor antagonists (H2 blockers)?

Answer 48

H2 blockers are mainly used for the treatment of gastric and duodenal ulcers.

Question 49

Can H2 receptor antagonists be used to treat allergies?

Answer 49

No, H2 antagonists do not block H1 receptors and, therefore, are not effective for treating allergies.

Question 50

What are H1 antagonists, also known as antihistamines?

Answer 50

H1 antagonists are a group of drugs that block the effects of histamine at H1 receptors in the body.

Question 51

How are the terms "antihistamines," "H1 blockers," and "H1 antagonists" used?

Answer 51

These terms are often used interchangeably to describe the same group of drugs that block histamine's effects at H1 receptors.

Question 52

Do all H1 antagonists have identical actions and side effects?

Answer 52

While H1 antagonists have similar actions in blocking histamine, they can differ significantly in terms of side effects.

Question 53

Is there a single prototype drug that represents all H1 antagonists?

Answer 53

No, there is no single prototype drug that represents the entire group, as individual antihistamines have distinct characteristics and side effects.

Question 54

How are H1 antagonists classified?

Answer 54

H1 antagonists (antihistamines) are classified into two major groups: first-generation H1 antagonists and second-generation H1 antagonists.

Question 55

What distinguishes the first-generation H1 antagonists from the second-generation ones?

Answer 55

The primary difference between these groups is that first-generation antihistamines are highly sedating, while second-generation antihistamines are not typically sedating.

Question 56

How do H1 blockers (antihistamines) work?

Answer 56

H1 blockers selectively bind to H1-histaminic receptors, blocking the actions of histamine at these specific sites. They do not block H2 receptors or histamine release from mast cells or basophils.

Question 57

Can H1 blockers also interact with other receptors besides H1-histaminic receptors?

Answer 57

Yes, some antihistamines can bind to and block muscarinic receptors, which can lead to certain side effects.

Question 58

What is the primary mechanism of action of H1 blockers (antihistamines)?

Answer 58

H1 blockers primarily work by preventing histamine's actions at H1 receptors.

Question 59

How do H1 blockers affect blood vessels in the skin?

Answer 59

H1 antagonists inhibit histamine-induced dilation of blood vessels in the skin, reducing localized flushing.

Question 60

What effect do antihistamines have on capillary permeability?

Answer 60

Antihistamines prevent histamine-induced increases in capillary permeability, reducing edema.

Question 61

How do H1 antagonists reduce itching and pain?

Answer 61

Antihistamines block histamine at sensory nerves, which reduces itching and pain.

Question 62

What is the impact of H1 blockers on mucus secretion?

Answer 62

H1 antagonists suppress mucus secretion by blocking H1 receptors in mucous membranes.

Question 63

What kind of effects can antihistamines have on the central nervous system (CNS)?

Answer 63

Antihistamines can cause CNS depression, leading to slowed reaction time, decreased alertness, and drowsiness, particularly at therapeutic doses.

Question 64

Do all antihistamines have the same degree of CNS depression?

Answer 64

No, the degree of CNS depression can vary among different antihistamines, with some causing more pronounced effects than others.

Question 65

What can antihistamine overdose lead to in terms of CNS effects?

Answer 65

Antihistamine overdose can produce CNS stimulation, often resulting in seizures, especially in young children who are highly sensitive to this effect.

Question 66

What other pharmacologic effects can certain antihistamines have due to their interactions with receptors?

Answer 66

Some antihistamines can block muscarinic cholinergic receptors, causing typical anticholinergic responses. They can also act as antiemetics to suppress nausea and vomiting, particularly in motion sickness.

Question 67

What patient care concern is associated with infants and antihistamines?

Answer 67

Antihistamines can cause sedation in infants, so caution should be exercised. They can be used in small doses in children older than 6 months.

Question 68

Can antihistamines be safely used in children and adolescents?

Answer 68

Yes, antihistamines can be used safely in children, but in smaller doses. Side effect profiles are similar to those of adults. Promethazine should be avoided in children younger than 2 years due to the risk of deaths.

Question 69

Is it advisable for pregnant women to use antihistamines?

Answer 69

There has been debate regarding whether antihistamines cause fetal harm when used in pregnancy. Many of these drugs are classified as Pregnancy Risk Category C by the U.S. FDA and should be avoided unless absolutely necessary.

Question 70

What should breastfeeding women be cautious about when using antihistamines?

Answer 70

Occasional, small doses of antihistamines do not appear to cause sedation in infants. However, caution should be exercised.

Question 71

Why should older adults be cautious when using antihistamines?

Answer 71

Many antihistamines are listed within the Beers Criteria and should be avoided in older adults. Smaller doses should be used initially due to the potential for sedation. Additionally, these medications can worsen conditions like glaucoma or benign prostatic hyperplasia.

Question 72

What conditions can antihistamines be used to treat?

Answer 72

Antihistamines are useful in treating allergic disorders, including mild allergies.

Question 73

What symptoms of mild allergies can antihistamines help reduce?

Answer 73

Antihistamines can reduce symptoms such as sneezing, runny nose, itching of the eyes, nose, and throat, as well as redness and edema.

Question 74

How do antihistamines work in alleviating these symptoms?

Answer 74

Antihistamines work by blocking H1 receptors, which play a role in allergic reactions.

Question 75

Which specific antihistamines are labeled for use in treating motion sickness?

Answer 75

Some antihistamines, such as promethazine (Phenergan) and dimenhydrinate (Dramamine), are labeled for use in motion sickness.

Question 76

How do these antihistamines provide benefits in treating motion sickness?

Answer 76

The benefits of these antihistamines in treating motion sickness come from blocking H1 receptors and muscarinic receptors in the neuronal pathway that goes from the inner ear's vestibular apparatus to the vomiting center in the medulla.

Question 77

How can antihistamines affect a person's drowsiness?

Answer 77

Antihistamines like diphenhydramine and pyrilamine can induce drowsiness.

Question 78

How have antihistamines been utilized in treating insomnia?

Answer 78

Antihistamines have been used in over-the-counter (OTC) sleep aids to take advantage of their drowsiness-inducing effects.

Question 79

Are the doses of antihistamines in OTC sleep aids always effective for treating insomnia?

Answer 79

No, the doses of antihistamines in many OTC sleep aids are often too low to effectively treat insomnia.

Question 80

Can H1 blockers cause adverse effects?

Answer 80

Yes, all H1 blockers can produce undesired effects.

Question 81

Are the adverse effects of H1 blockers typically serious?

Answer 81

Generally, the adverse effects are more of a nuisance than a source of serious discomfort or danger.

Question 82

Do side effects of H1 blockers usually go away with continued use?

Answer 82

Yes, frequently side effects subside as you continue to use the drug.

Question 83

How can adverse responses to H1 blockers be minimized?

Answer 83

Adverse responses can be reduced by selecting the right antihistamine, as different ones have varying side effect profiles.

Question 84

What is the most common side effect of antihistamines?

Answer 84

Sedation is the most common side effect.

Question 85

Can sedation from antihistamines be severe?

Answer 85

Yes, sedation from antihistamines can be severe and lead to significant impairment.

Question 86

Is it safe to drive or do hazardous activities while taking antihistamines?

Answer 86

Patients should exercise extreme caution when driving or performing hazardous activities while taking antihistamines due to potential impairment.

Question 87

How can patients minimize daytime sedation from antihistamines?

Answer 87

Daytime sedation can be minimized by taking the entire daily dose of antihistamines at night.

Question 88

Do second-generation antihistamines cause sedation?

Answer 88

No, second-generation antihistamines typically do not cause sedation.

Question 89

Why do first-generation antihistamines cause sedation?

Answer 89

First-generation antihistamines can cause sedation because they can cross the blood-brain barrier and have a high affinity for brain H1 receptors.

Question 90

what can patients who experience severe sedation with first-generation antihistamines do?

Answer 90

Patients who experience disabling sedation with first-generation antihistamines can try switching to second-generation (nonsedating) antihistamines.

Question 91

Besides sedation, what other central nervous system effects can antihistamines cause?

Answer 91

Antihistamines can also cause dizziness, incoordination, confusional states, and fatigue.

Question 92

Who is particularly sensitive to the central nervous system effects of antihistamines?

Answer 92

Older patients are especially sensitive to these effects.

Question 93

What is paradoxical excitation in the context of antihistamines?

Answer 93

Paradoxical excitation refers to unusual reactions, such as insomnia, nervousness, tremors, and even seizures, that can occur in some patients taking antihistamines.

Question 94

When is CNS stimulation most common with antihistamines?

Answer 94

CNS stimulation is most common in children and after an overdose of antihistamines.

Question 95

What are some common gastrointestinal effects associated with antihistamines?

Answer 95

Gastrointestinal effects can include nausea, vomiting, loss of appetite, and diarrhea or constipation.

Question 96

How can one minimize gastrointestinal disturbances when taking antihistamines?

Answer 96

Administering antihistamines with food can help reduce these gastrointestinal reactions.

Question 97

**Question 1:** What are anticholinergic effects associated with H1 antagonists (antihistamines)?

Answer 97

**Answer 1:** Anticholinergic effects can include drying of mucous membranes in the mouth, nasal passages, and throat, as well as urinary hesitancy, constipation, and palpitations.

Question 98

**Question 2:** How can one alleviate the discomfort caused by dry mouth resulting from anticholinergic effects of antihistamines?

Answer 98

**Answer 2:** Discomfort from dry mouth can be minimized by using hard sugarless candy and frequently sipping on liquids.

Question 99

**Question 3:** In which patients should antihistamines be used with caution due to their anticholinergic effects?

Answer 99

**Answer 3:** Antihistamines should be used with caution in patients with conditions that can be worsened by muscarinic blockade, such as asthma, urinary retention, benign prostatic hyperplasia, and hypertension

Question 100

How can alcohol and other CNS depressants interact with H1 antagonists (antihistamines)?

Answer 100

Alcohol and other CNS depressants can intensify the depressant effects of H1 antagonists.

Question 101

What should patients be advised regarding the consumption of alcoholic beverages while taking H1 antagonists?

Answer 101

Patients should be advised against drinking alcoholic beverages when using H1 antagonists.

Question 102

What adjustment may be necessary when combining medications with CNS-depressant properties with H1 blockers?

Answer 102

When combining medications with CNS-depressant properties with H1 blockers, the dosage of the depressant medication may need to be lowered.

Question 103

**Question 1:** What are the two major groups of H1 antagonists?

Answer 103

**Answer 1:** The two major groups of H1 antagonists are first-generation H1 antagonists and second-generation H1 antagonists.

Question 104

**Question 4:** How can H1 antagonists be administered?

Answer 104

**Answer 4:** H1 antagonists can be administered orally (by mouth) and, in some cases, parenterally, by nasal spray, or by rectal suppository.

Question 105

**Question 3:** What is the notable difference between first-generation and second-generation H1 antagonists regarding sedation?

Answer 105

**Answer 3:** Second-generation H1 antagonists cause little to no sedation.

Question 106

**Question 2:** Which group of H1 antagonists can cause significant sedation?

Answer 106

**Answer 2:** The first-generation H1 antagonists can cause significant sedation.

Question 107

**Q1:** What are first-generation histamine-1 antagonists?

Answer 107

**A1:** First-generation histamine-1 antagonists are a group of antihistamine drugs that can block the effects of histamine at H1 receptors.

Question 108

**Q6:** What should be considered if a patient experiences excessive sedation with an alkylamine antihistamine?

Answer 108

**A6:** If sedation remains excessive with an alkylamine antihistamine, a second-generation antihistamine should be considered.

Question 109

**Q5:** Which category of first-generation antihistamines is associated with the least sedation?

Answer 109

**A5:** The alkylamines category (e.g., chlorpheniramine) is associated with the least sedation among the first-generation antihistamines.

Question 110

**Q4:** Which category of first-generation antihistamines is known for causing the most sedation?

Answer 110

**A4:** Among the first-generation agents, ethanolamines (e.g., diphenhydramine) and phenothiazines (e.g., promethazine) are known for causing the most sedation.

Question 111

**Q3:** What are some common side effects associated with first-generation antihistamines?

Answer 111

**A3:** Common side effects of first-generation antihistamines include sedation, muscarinic blockade (anticholinergic effects), dry mouth, and urinary hesitancy.

Question 112

What distinguishes second-generation (nonsedating) histamine-1 antagonists from first-generation antihistamines in terms of sedation?

Answer 112

Second-generation antihistamines produce much less sedation compared to first-generation agents.

Question 113

Why do second-generation antihistamines produce less sedation?

Answer 113

Second-generation antihistamines produce less sedation because they (1) poorly cross the blood–brain barrier and (2) have a low affinity for H1 receptors in the central nervous system (CNS).

Question 114

What should be avoided when using second-generation antihistamines?

Answer 114

Although the sedative effects of second-generation antihistamines are low, combined use with alcohol and other CNS depressants should be avoided.

Question 115

What is the primary advantage of second-generation antihistamines?

Answer 115

Second-generation antihistamines are largely devoid of anticholinergic actions, making them more tolerable in terms of side effects.

Question 116

How can the initial selection of second-generation antihistamines be made?

Answer 116

Initial selection of second-generation antihistamines can often be based on price. If a cheaper agent proves ineffective, a more expensive one can be tried.

Question 117

What is Fexofenadine approved for in terms of therapy?

Answer 117

Fexofenadine (Allegra, Allegra Allergy) is approved for oral therapy of seasonal allergic rhinitis and for chronic idiopathic urticaria.

Question 118

How does Fexofenadine compare to other second-generation antihistamines in terms of efficacy and safety?

Answer 118

Among the second-generation antihistamines currently available, fexofenadine appears to offer the best combination of efficacy and safety.

Question 119

What is the half-life of Fexofenadine, and how is it eliminated from the body?

Answer 119

Fexofenadine has a half-life of 14.4 hours and is excreted unchanged in the urine.

Question 120

In what formulations is Fexofenadine available?

Answer 120

Fexofenadine is available in standard tablets (30, 60, and 180 mg), a suspension (6 mg/mL), marketed as Allegra Children's Liquid, and orally disintegrating tablets (30 mg), marketed as Allegra Children's Meltable Tablets.

Question 121

What precaution should be taken regarding fruit juices when using Fexofenadine, and why?

Answer 121

Certain fruit juices (e.g., apple juice, orange juice, grapefruit juice) can reduce fexofenadine absorption, possibly reducing therapeutic effects. This occurs because these juices inhibit organic anion transporting polypeptides, which contribute to the absorption of fexofenadine from the GI tract. To ensure fexofenadine absorption, patients should avoid drinking fruit juices within 4 hours before dosing or 1 to 2 hours after dosing.