Antihistamines

Question 1

What is the mast cell source of histamine?

Answer 1

Histamine is stored in vesicles in mast cells and basophils (WBC) - involved in allergy and immunological responses against pathogens

Histamine is released immunologically from mast cells in type 1 (IgE-mediated) hypersensitivity reactions.

Question 2

What is the source non-mast cell histamines (2)?

Answer 2

• Histamine is synthesized and stored in granules in the CNS and stomach.
  a. CNS: Histamine is released from histaminergic neurons → alertness (during the day) and emesis (in motion sickness).
  b. Stomach: Enterochromaffin-like cells mediate stomach acid (H+) secretion.

Question 3

What are the types of histamine receptors?

Answer 3

H1 and H2

Question 4

What do H1 receptors do?

Answer 4

Histaminergic nerves in daytime activities - alertness
* In motion sickness
In allergy: contraction s. muscle (bronchial contraction), vasodilation (headache), increased vasc. Permeability - edema, stim CNS pain, itch

Question 5

What do H1 receptors do in pregnancy?

Answer 5

Histamine released from uterine mast cells stimulates H1 to mediate nausea, vomiting, hives

Question 6

What do H2 receptors do?

Answer 6

Secrete stomach acids

Question 7

What are first generation H1 antihistamines?

Answer 7

Lipophilic and cause sedation due to penetration to the CNS.

Some of them have other actions (e.g., anti-muscarinic and local anesthetic properties).
* Remember: doxylamine thought to be dangerous wasn’t
Safe for preg and lactation

Question 8

What are second generation H1 antihistimines?

Answer 8

• Less sedative effects because they are hydrophilic (e.g., cetirizine, loratadine) and have less anti-muscarinic effects.
• Remember: Cetrizine
  Likely Safe for preg and lactation

Question 9

What are H1 antihistamines used for (4)?

Answer 9

relieve hypersensitivity,
prevent nausea/vomiting in motion sickness and pregnancy,
local anaesthetic,
sleep aid

Question 10

Side effects of H1 antihistamines (4) ?

Answer 10

sleepiness, dry mouth, constipation, urinary retention

Question 11

What is the main cause of peptic ulcer disease?

Answer 11

• PUD is a break in mucus layer of stomach an is due to too much HCl secreted in stomach (imbalance b/w secretion HCl and defense factors (mucus)

helicobacter pylori (helicopter pyloric sphincter (butt))

Long-term use of NSAIDS (suppression of COX1 to decrease the synthesis of prostaglandins). most common

GERD

Gastrin-secreting tumor.

Question 12

What are treatments of peptic ulcer disease in pregnancy?

Answer 12

1) Safe - antacids, Sucralfate
2) Likely safe H2 antihistamine (famotidine)
3) Use with caution proton pump inhibitor
Not safe - misoprostal

Question 13

What does Angiotensin II naturally do (3)?

Answer 13

Constrict arterioles and veins and convers into Aldosterone which increases renal absorption of Na - increases blood volume / BP
Activates AT 1 and AT 2 receptors

Question 14

What does AT1 and AT2 receptors do (3) & (1)?

Answer 14

AT1 - Mediate actions of ANG II - increase SNS, increase aldosterone and Na+ absorption and increases Cell growth of blood vessels and heart

AT2 - in fetal and injured tissue - growth and re-development

Question 15

What do blockers of ANG system do (2)?

Answer 15

1) ACEI (enalapril) - decrease formation of ANG II
2) ARB (losartan) - block action of ANG II on AT1 receptors

Question 16

What are ANG blockers used for clinically (3)?

Answer 16

Hypertension, chronic renal failure, heart failure

fetotoxic in 2nd and 3rd trimester (cross the placenta

Question 17

How do ACEI and ARB work clinically (4) ?

Answer 17

Vasodilation → decrease total peripheral resistance → decrease BP.
- ↑ Renal blood flow and glomerular filtration (dilate renal artery).
- Decrease Synthesis of aldosterone → renal Na+ loss → decrease blood volume/BP.
- Improve heart function in heart failure ( decrease BP, blood volume and heart size)