Antihistamines

Question 1

H1 (tissue and signaling)

Answer 1

• Smooth muscle cells (vascular, respiratory, GI)
• Vascular endothelial cells
• CNS neurons
• peripheral sensory nerves

Gq –> PLC-IP3-Ca2+

Question 2

H2

Answer 2

• Gastric parietal cells
• Cardiac muscle
• CNS neurons

Gs

• increase adenyl cyclase
• increase cyclic AMP-PKA

Question 3

Histamine function in NS

Answer 3

• found in hypothalamus
• released in circadian pattern (increase during day and decrease during night)
  
  • controls release of pituitary hormones, wakefulness, and appetitie/satiety
• peripheral and central nervous system histamine receptor mediate itch

Question 4

Describe organ system effects of histamine on endothelial

Answer 4

• VASODILATION
• decreased total peripheral resistane and fall in systemic blood pressure (can cause REFLEX TACHYCARDIA)

Question 5

Histamine effects of vascular permeability

Answer 5

• INCREASED VASCULAR PERMEABILITY
• H1-medaited increase permeability of post capillary venules leads to edema

Question 6

H1 effects on peripheral neurons and lung

Answer 6

• H1 in peripheral neurons
  
  • activation in EPIDERMIS causes itch
  • activation in DERMIS causes pain
• H1 in lung smooth muscles cells causes ELEVATED SECRETION of wairway fluid and electrolytes and BRONCHOCONSTRICTION

Question 7

Histamine effects on cardiac muscle

Answer 7

• H2 activation on cardiac muscle
  
  • increased Ca+ leads to increase FORCE OF CONTRACTION
  • Speeds up SA-node depolarization which INCREASE HR

Question 8

Histamine effects on immune system

Answer 8

• Faciliates the accumulation of immune cells at the site of infection or damage
  
  • HISTAMINE INCREASES
    
    • vascular permeability
    • immune cell adhesion molecules (P-selectin)
    • Chemotaxis of eosinophils and neutrophils
    • Increase release of inflammatory cytokines
    • increases antigen presentation from APC cells

Question 9

What are disease that increase histamine levels

Answer 9

• Myelogenous leukemia
  
  • significant increase in basophil numbers
  • high levels of histamine that may contribute to chronic pruritus
• Gastric carcinoid tumors secrete histamine
  
  • can cause episodes of vasodilation
• Systemic mas cell disease
  
  • Mast cell leukemia –> pruritus and flushing, diarrhea, GERD and anaphylactoid rxns

Question 10

what are some common conditions currently treated with first gen H1-antihistamines

Answer 10

• allergic rhinitus, conjunctivitis, urticaria
• nausea/ vomiting
• motion sickness
• sedatives
• sleep aids
• acute extrapyramidal symptoms associated with certian antipsychotic drugs
• cough
• common cold (anti-mucarinic effects

Question 11

strongest antiemetic effects

Answer 11

diphenhydramine

promethazine

hydrozyine

maclazine

Question 12

antihistamiens with highest sedatives effects

Answer 12

diphenhydramine

hydroxyzine

promethazine

Question 13

Anticholinergic drugs

Answer 13

diphenhydramine and promethazine

• dry mouth, urinary retention, sinus tachycardia

Question 14

drug interactions with 1st generation H1 antihistamines

Answer 14

• MAOI’s may prolong and intensify the anticholinergic effects of antihistamines
• additive sedative effects with opiods, alcohol and other sedatives
• additive anticholinergic effects
• overdose with diphenhydramine (max dose of 300mg/day
  
  • extreme drowsiness, delirium, coma, respiratory depresion
  • sinus tachycardia, prolongation of QT inteval and ventricular arrhythmias