antihistamines (H1)

see also:

• histamine physiology, receptors and antihistamines
• allergy and hypersensitivity reactions
• H2-type antihistamines

• 1st discovered 1937 but useful ones in 1950;
• The “classical” antihistamines have similar activity:
  • decr. most smooth muscle response to histamine;
  • decr. rapid vasodilatory action via endoth.cells;
  • decr. his. induced capill.perm. ⇒ decr. oedema/wheal;
  • decr. his.induced itch;
  • stimulate or depress CNS (except newer ones):
  • ethanolamines (diphenhydramine) esp. ⇒ sedation;
  • some pts or OD or infants ⇒ stim. ⇒ convulsions;
  • In addition, these tend to have anticholinergic effects which may be beneficial in motion sickness or in drying secretions;
  • Promethazine in high [] has LA effect > procaine!

• diphenhydramine (Benadryl)
• signif. antichol. & CNS decr., good for motion sickness;
• may reverse extrapyramidal phenothiazine reactions;
• may cause cardiotoxicity as also blocks HERG K+

• pyrilamine
• more specific, but still some CNS decr. & GIT problematic;

• chlorpheniramine (Sinutab/Polaramine/Demazin)
• pheniramine (Avil)
• less sedative & more CNS incr., but still some sedation;

• hydroxyzine (Atarax)
• cyclizine (Migral)
• meclozine (Ancolan)
• Atarax prolonged action & CNS decr. ⇒ good antipruritic;
• good for motion sickness, decr. sedative but less effective;
• Ancolan may help in vestibular vertigo;

• promethazine (Phenergan)
• most have anticholinergic, sedative, antiemetic;
• good for motion sickness;
• see also phenothiazines

• these poorly cross BBB and hence are relatively non-sedating;
• relatively devoid of anticholinergic actions
• loratadine (Claratyne) - rapid onset <1hr, once daily;
• acrivastine (Duact)
• cetirizine (Zyrtec)
  • also has anti-inlammatory effect via suppression of the NF-κB pathway
• bilastine (Allertine)
• cardiotoxic H1-antihistamines:
  • terfenadine (Teldane) - twice daily, rapid onset;
  • astemizole (Hismanal) - once daily but slow onset up to 3 days
  • mizolastine - only cardiotoxic in very high doses or those at risk
  • may delay action potential repolarization by blocking HERG1 K+ channels, thus predisposing the individual to prolonged QTc & the occurrence of torsade de pointes VT particularly if plasma levels are high as in overdose or if impaired hepatic metabolism, combined with predisposing factors such as IHD, other drugs that prolong QTc.