Antihistamines

Serotonin Agonists

Histamine Antagonists

• H 1 receptors• inhibit smooth muscle

contraction• decrease wheal,

flare,and itch• decrease secretions:

salivary and lachrymal• CNS: sedation

• H 2 receptors• inhibit gastric acid

secretion• decrease content and

volume of gastric juice• fasting, food

stimulated and nocturnal

H 1 antagonists

• Relief of manifestations of immediate-type hypersensitivity reactions– allergic rhinitis– cold remedies

• newer agents “selective” for peripheral H 1 receptors– less sedation (dose dependant)

Antihistamine Products

• sedating– diphenhydramine

(Benadryl)

– chlorpheniramine (Chlor-Trimeton)

• non-sedating– fexofenadine (Allegra)

– loratadine (Claritin)

– cetirizine (Zyrtec)*

• * metabolite sedating

Sedation

• dose related even for newer agents

• most common ingredient in OTC sleep aids

Children’s Formulations

• Most available as syrups

• Allegra– 30 mg tab

• Claritin– 10 mg Redi-tab (fast dissolve)

Role of Antihistamines in the Treatment of Allergic Rhinitis

Nasal Steroids vs. Antihistamines

UCDHS Adult Allergic Rhinoconjunctivitis Guidelines

Trea tm en t F a ilu resE va lu a te p a tien t com p lian ce an d in h a le r tech n iq u e

C on s id er a lte rn a tive n asa l s te ro idcon tin u e A lleg ra "as n eed ed "

2 sp rays each n os tril b id (R h in ocort), q d (N ason ex)A lleg ra 6 0 m g b id fo r two weeks

th en "as n eed ed "n ap h azo lin e op th a lm ic "as n eed ed "

M od era te S eason a l o r M od era te P eren n ia lA lle rg en A vo id an ce

R h in ocort , o r N ason ex: N asa l In h a la tionn on -sed atin g an tih is tam in e , ocu lar m ed ica tion "as n eed ed "

R E F E RTO

A L L E R G IS TIM M U N O TH E R A P Y

F or Tream en t F a ilu resE va lu a te p a tien t com p lian ce an d in h a le r tech n iq u e

U se a lte rn a tive n asa l s te ro idsevere rh in orrh ea : A troven t N asa l 2 sp rays each n os til 3 -4 x d ay

R h in ocort 2 -4 sp rays each n os tril tw ice a d ay,N ason ex 2 sp rays each n os tril d a ily

w ith A lleg ra 6 0 m g tw ice a d ay an d if n eed edlod oxam id e (A lom id e)1 -2 d rop s a ffec ted eye(s ) 4 x d ay

S evere L on g S eason a l o r S evere P eren n ia lA lle rg en A vo id an ce an d N asa l S te ro id s w ith

D a ily n on -sed atin g an tih is tam in etop ica l an tih is tam in e fo r con ju n c tivit is if n eed ed

Rhinitis D e fin itionNasa l D ischarge

BlockageS neeze /Itch

HealthNet: Nasonex, Nasacort

Pacificare: Rhinocort, Nasonex, Nasarel

WHA: Rhinocort, Nasonex, Nasacort AQ

Approved UCDMG P&T Committee January 2001

Reviewed by: T. Albertson S. Teuber, M. E. Gershwin, R. Mowers, J. Fischer

January 2001

HealthNet Jan-Jun 2002Label_name Data TotalALLEGRA Average of Ing_cost 63.59

Sum of Ing_cost 246,090.63Number of Rx 3,870

ALLEGRA-D Average of Ing_cost 55.34Sum of Ing_cost 3,209.82Number of Rx 58

CLARINEX Average of Ing_cost 54.37Sum of Ing_cost 69,318.89Number of Rx 1,275

CLARINEX TAB 5MG Average of Ing_cost 55.63Sum of Ing_cost 278.13Number of Rx 5

CLARITIN Average of Ing_cost 76.42Sum of Ing_cost 267,921.14Number of Rx 3,506

CLARITIN-D 12 HOUR Average of Ing_cost 78.77Sum of Ing_cost 12,131.11Number of Rx 154

CLARITIN-D 24 HOUR Average of Ing_cost 80.74Sum of Ing_cost 19,862.94Number of Rx 246

FLONASE Average of Ing_cost 53.52Sum of Ing_cost 73,590.60Number of Rx 1,375

NASACORT Average of Ing_cost 51.04Sum of Ing_cost 9,237.88Number of Rx 181

NASACORT AQ Average of Ing_cost 47.78Sum of Ing_cost 44,821.44Number of Rx 938

NASALIDE Average of Ing_cost 42.63Sum of Ing_cost 255.77Number of Rx 6

NASAREL Average of Ing_cost 24.26Sum of Ing_cost 121.30Number of Rx 5

RHINOCORT Average of Ing_cost 37.46Sum of Ing_cost 13,074.74Number of Rx 349

RHINOCORT AQUA Average of Ing_cost 55.24Sum of Ing_cost 5,192.84Number of Rx 94

ZYRTEC Average of Ing_cost 50.21Sum of Ing_cost 41,826.46Number of Rx 833

ZYRTEC-D Average of Ing_cost 49.40Sum of Ing_cost 493.99Number of Rx 10

Total Average of Ing_cost 62.57Total Sum of Ing_cost 807,427.68Total Number of Rx 12,905

other routes of administration

• azelastine (Astelin)– nasal spray

– allergic rhinitis

– decrease side effect profile

• Bitter amine taste

• sedation (systemic absorption)

• olopatadine (Patanol)• emedastine (Emadine)• ophthalmic antihistamine

H 1

• allergic conjuctivitis and itching

• headache, taste perversion, abnormal dreams

H 2 Antagonists

• Therapeutic Indications– duodenal and gastric ulcer– gastroesophageal reflux disease (GERD)– erosive esophagitis– hypersecratory conditions– heart burn, indigestion, sour stomach– multidrug regimen for the eradication of

H.Pylori in peptic ulcer disease

UC Davis Primary Care Adult Tx: GERD

A p p rove fo r lon g te rmm ain tan ce th erap y

P P I

S u rg ery

S evere G E R D(E ros ive esop h ag it isB arre tt 's esop ag u s ,

esop h ag ea l s tric tu re )

d iscon tin u e d ru gcon tin u e H 2 m ain tan ce

R e-eva lu a te p a tien t sym p tom sat 1 6 w eeks to ta l th erap y

R ed u ce to m a in tan ce d osec im etid in e 4 0 0 m g h sran it id in e 1 5 0 m g h s

Im p rovm en t

d iscon tin u e d ru g th erap ych an g e to H 2 m ain tan ce th erap y

Im p rovem en t

R efe r to G I S p ec ia lis t

N o Im p rovem en t

R e-eva lu a te p a tien t sym p tom sat 1 6 w eeks to ta l th erap y

P ro ton ix 4 0 m g d a ilyA c ip h ex 2 0 m g d a ilyP revac id 3 0 m g d a ily

P rilosec /N exiu m 2 0 m g d a ily

N o Im p rovm en t

c im etid in e 8 0 0 m g b idran it id in e 1 5 0 m g b id

8 weeks th erap y"S tep U p " S ta rt w ith H ig h D ose H 2

M ild to M od era te G E R D(R eflu x esop h ag it is )

D ia gnosisG a stroesophogea l R eflux D isea se

Drug AWP/eaProtonix® 40 mg 3.00Aciphex® 20 mg 3.70 Prevacid® 30 mg 3.88Nexium® 20 mg 3.99Prilosec® 20 mg 4.15

Reviewed by; T. Albertson, J. Lee, J. Fischer, R. Mowers

UCDMC P&T Committee January 2002

June 2001

Beck IT et al. The Second Canadian Consensus Conf. on Management of Patients with GERD. Can J Gastroenterol 1997;11 suppl B 7-20.

Katz PO. Treatment of GERD: Use of Algorithms. Am J Gastroenterol 1999;94(11)suppl:3-10.

HealthNet Jan-Jun 2002Label_name Data TotalACIPHEX Average of Ing_cost 119.73

Sum of Ing_cost 275,734.11Count of Pt_first_name 2303

CIMETIDINE Average of Ing_cost 8.96Sum of Ing_cost 7,179.47Count of Pt_first_name 801

CIMETIDINE HCL Average of Ing_cost 38.36Sum of Ing_cost 191.82Count of Pt_first_name 5

FAMOTIDINE Average of Ing_cost 27.44Sum of Ing_cost 2,908.76Count of Pt_first_name 106

NEXIUM Average of Ing_cost 115.34Sum of Ing_cost 7,843.10Count of Pt_first_name 68

PREVACID Average of Ing_cost 119.92Sum of Ing_cost 17,627.56Count of Pt_first_name 147

PRILOSEC Average of Ing_cost 139.62Sum of Ing_cost 73,021.10Count of Pt_first_name 523

PROTONIX Average of Ing_cost 88.35Sum of Ing_cost 172,897.16Count of Pt_first_name 1957

RANITIDINE TAB 150MG Average of Ing_cost 6.69Sum of Ing_cost 100.31Count of Pt_first_name 15

RANITIDINE TAB 300MG Average of Ing_cost 7.57Sum of Ing_cost 30.29Count of Pt_first_name 4

RANITIDINE HCL Average of Ing_cost 10.26Sum of Ing_cost 21,961.43Count of Pt_first_name 2140

Total Average of Ing_cost 71.82Total Sum of Ing_cost 579,495.11Total Count of Pt_first_name 8069

Adverse Reactions

• low incidence of side effects

• headache and fatigue - 1%

• cimetidine– highest incidence of gynecomastia (1- 4%)– P450 drug interactions

• decrease digoxin levels

• increase flecainide activity

Serotonin 5-HT1 agonists

• Treatment of Migraine with or without aura.

• Acute treatment of Cluster headaches.

• Drugs are combination of 5-HT (1A, 1B, 1D, 1E, 1F, 7)

• No activity at 5HT 2-4 receptors, adrenergic, muscarinic, dopaminergic

Mechanism of Action

• Stimulation 5HT-1 receptors in extracerebral and intracranial blood vessels results in vasoconstriction. Also seen is an inhibition of neuropeptide release and decreased transmission in trigeminal pain pathways.

• It is thought cranial vessel dilation induced by release of vasoactive peptides from sensory nerve endings in an active trigeminal system my be a root cause of Migraine.

Prototype agents

• sumatriptan (Imitrex)– Tablets, nasal spray, injection

• rizatriptan (Maxalt)

• Several others

Common adverse events

• Generally well tolerated

• Events with 5% rate: paresthesia, nausea, dizzsiness, fatigue, dry mouth, headache, flushing

• Rare but serious events: cardiac events with fatalities, cerebrovascular events with fatalities (hemorrhage, stroke, others)

Rebound headache

• The risk of rebound headaches increases with the number of doses taken.

• Patient information:– Take as soon as possible– Second dose may be taken if no response in 2

hours– Limit injections to 2 per 24 hours– Contact MD before taking additional doses if

no response

• Other drugs for Migraine Treatment

• Ergot alkaloids such as dihydroergotamine (Migranal, DHE 45)

• Migraine Prophylaxis– Beta blockers– Calcium channel blockers– NSAID– Valproate