Antihistamines

Question 1

What is the normal physiological effect of antihistamine release?

Answer 1

Vasodilation

Bronchoconstriction

Eryhtema

Oedema

dermatitis

rhinitis

Conjunctivitis

Question 2

What is a type 1 and 2 hypersensitivity reaction? (what is, what mediated by?)

Answer 2

Type 1 = immediate or anaphylaxis –> w/in minute, mediated by IgE

Type 2 = antibody dependent –> involves IgG or IgM-directed activation of complement system, lysis of normal cells (autoimmune response)

Question 3

What is a type 3 and 4 hypersensitivity reaction? (what is, what mediated by?)

Answer 3

Type 3 = complex-mediated –> aka serum sickness, antigens form complex w/ IgG in blood vessels –> fever, swollen lymph nodes

Type 4 = cell-mediated, basis for skin reactions, involves T-lymphocytes

Question 4

What is the role of the H2 and H3 receptors?

Answer 4

H2 = inc gastric acid secretions, inc HR, inc contractility

H3 = in peripheral tissue, on nerve terminals

Question 5

What are the second generation antihistamines?

Answer 5

Cetirizine

Desloratadine

Fexofenadine

levocetrizine

loratadine

Question 6

How do second and first generation antihistamines differ in terms of duration of action?

Answer 6

Most first generation antihistamines are shorter acting, max 12 hours

- chlorpheniramine, hydroxyzine, dexchlorpheniramine = 6 hrs 
- cyproheptadine, dimenhydramine, doxylamine, diphenhydramine = 8hrs 
- promethazine, meclizine = 12 hours

Second generation antihistamines are longer acting, most are 24 hrs except fexofenadine which is 12 hours

Question 7

How do first and second generation antihistamines differ in terms of sedative effects?

Answer 7

First generation, all have high sedative effect (cross BBB) except for chlorpheniramine, dexchlorpheniramine, meclizine

Whist second generation all have low (cetirizine) or very low sedating effects (dont cross BBB)

Question 8

How do first and second generation antihistamines differ in terms of antiemetic effects?

Answer 8

Most first generation have high (promethazine, meclizine, hydroxyzine) antiemetic effects whilst the rest are medium or none (chlorpheniramine, dexchlorpheniramine)

All of the second generation antihistamines have no anti-emetic effects

Question 9

How do first and second generation antihistamines differ in terms of anticholinergic effects? (this is good, can be beneficial)

Answer 9

All second generation antihistamines have very low anticholinergic effects

There is a spread of low and high anti-chol effects in the first gen group

- high = dimenhydrinate, diphenhydramine, doxylamine, promethazine 

- medium = meclizine, hydroxyzine, dexchlorpheniramine, chlorpheniramine 

- low = cyproheptadine

Question 10

What are the direct and indirect effects of histamine antagonism?

Answer 10

H1 block = Dec allergic inflam, itching, sneezing, rhinorrhoea, whealing

H1 mediated inhibition of NF-KB = dec Ag presentation, expression of cell adhesion molecules, chemotaxis, pro-inflam cytokines

Question 11

Which generation is of antihistamine is more likely to prolong the QT interval? (give drug examples)

Answer 11

Second generation, esp astemizole and terfenadine (fexofenadine pro-drug)

Question 12

What are some ADRs associated with antihistamine mediated H1-R blocking?

Answer 12

Dec neurotransmission in CNS

Inc sedation, dec cognitive and psychomotor performance

Inc appetite

Question 13

Why may people on antihistamines long term gain weight/have inc appetite?

Answer 13

H1-R block, block the serotonin receptor

Question 14

What are some ADRs associated with antihistamine effect of muscarinic receptors (blocks)?

Answer 14

Inc dry mouth

urinary retention

sinus tachycardia

Question 15

What are some ADRs associated with antihistamine effect on alpha-adrenergic receptors?

Answer 15

HTN

dizziness

reflex tachycardia

Question 16

What are some ADRs associated with antihistamine effect on cardiac ion channels (ca2+)?

Answer 16

Prolonged QT intervals –> can cause ventricular arrhythmias