PED1003/L22 Antihistamines

Question 1

What does the term ‘autocoid’ mean?

Answer 1

Self remedy

Question 2

Give 3 reasons why histamine is released from mast cells.

Answer 2

Acute inflammatory response
Hypersensitivity
Physical destruction

Question 3

Describe how acute inflammatory response triggers histamine release. (3)

Answer 3

Complement component
C3a and C5a receptors
Mast cell releases histamine

Question 4

Describe how hypersensitivity leads to histamine release. (3)

Answer 4

Immunoglobulin IgE
Cell fixed antibody
Mast cell releases histamine

Question 5

Describe when the arousal pathway releases histamine.

Answer 5

Spontaneously active and release histamine during wakefulness

Question 6

When does the emetic centre trigger histamine release? (3)

Answer 6

Histaminergic neurones in TMN receive input from vestibular centre in inner ear and other sensory inputs
Mismatch between inputs activates histaminergic neurones
& emetic (vomiting) centre in medulla

Question 7

Give the 2 types of histamine receptors.

Answer 7

H1 coupled to phospholipase C
H2 coupled to adenyl cyclase

Question 8

What does the H1 receptor trigger? (3)

Answer 8

Myosin phosphorylation
Vascular permeability
NFkB activation

Question 9

What does the H2 receptor trigger? (2)

Answer 9

Proton pump function
Gastric acid secretion

Question 10

Give 3 effects of the H1 receptor.

Answer 10

CNS neuronal activation
Smooth muscle contraction
Sensory nerve endings
Capillary permeability and dilation
Nasal and bronchial mucus secretion
Inotropic
Chronotropic
Proinflammatory cytokine secretion

Question 11

Give 3 effects of the H2 receptor.

Answer 11

Inotropic
Chronotropic
Stimulation of gastric acid secretion

Question 12

Describe allergic rhinitis. (4)

Answer 12

Inflammation inside nose in response to allergen e.g., pollen, dust
Sensory nerve ending stimulation
Increased nasal secretions
Capillary permeability and dilation

Question 13

Describe urticaria (hives).

Answer 13

Skin rash in response to allergen or toxic substance e.g., nettle sting, latex
Sensory nerve ending stimulation
Capillary permeability and dilation

Question 14

Give 2 other effects caused by moderate allergic reaction.

Answer 14

Tummy pain, diarrhoea
Wheezing, chest tightness, shortness of breath

Question 15

What kind of drugs are most 1st generation antihistamines?

Answer 15

H1 receptor antagonists
Hydroxyzine
Promethazine
Diphenhydramine

Question 16

Give 2 advantages to 1st generation antihistamines.

Answer 16

Inexpensive and effective
Cross BBB so can prevent motion sickness
Can cause sedation
Not very H1 selective so extra wanted effects

Question 17

Give 2 disadvantages to 1st generation antihistamines.

Answer 17

Cross BBB - unwanted sedation
Unwanted adverse effects

Question 18

Give 3 unwanted effects of 1st generation antihistamines.

Answer 18

Pupil dilation (blurred vision)
Increased cardiac output
Decreased exocrine gland secretion (dry mouth)
Decreased bladder contraction (urinary retention)

Question 19

Which other receptors can 1st generation antihistamines block?

Answer 19

A1-adrenoceptor
Causes vasodilation (hypotension, dizziness)

Question 20

What is the difference in 2nd generation antihistamines? (3)

Answer 20

Add carboxyl groups so more polar
Do not cross BBB as easily
Less unwanted sedation
Less anticholinergic effects

Question 21

Give an example of a 2nd generation antihistamine.

Answer 21

Ceterizine
Loratidine
Fexofenadine

Question 22

What is the oral Cmax of antihistamines?

Answer 22

1-2 hours

Question 23

Describe the distribution of 1st and 2nd gen antihistamines.

Answer 23

1st - all tissues
2nd all tissues except CNS

Question 24

Describe the metabolism of 1st and 2nd gen antihistamines.

Answer 24

1st - cytochrome P450s
2nd - most cytochrome P450s

Question 25

What is the average half-life of antihistamines?

Answer 25

4-6 hours

Question 26

Describe how H2 receptor agonists lead to increased gastric acid secretion. (4)

Answer 26

Histamine activates H2 receptor
Increased cAMP
Activated protein kinase
H+ and Cl- excreted from cell

Question 27

Give 2 advantages to H2 receptor antagonists.

Answer 27

All 4 effective for H. pylori peptic ulcers
Effective for heartburn
Inexpensive
Relatively safe

Question 28

Give 2 disadvantages to H2 receptor antagonists.

Answer 28

Peptic ulcer recurrence common if H. pylori present and untreated
Not as effect treating and preventing NSAID induced peptic ulcers
Heartburn onset of action 45 mins
Reduce efficacy of drugs requiring acidic environment for absorption
Cimetidine affects metabolism of other drugs

Question 29

Describe how prodrugs work.

Answer 29

Acid resistant coating removed in duodenum
Absorbed and transported to parietal cell
Metabolised to active drug
Binds H+/K+ ATPase
Decrease gastric acid secretion
18 hours to resynthesise