• Mast cell
• Basophils 
• CNS + peripheral nerves
• Enterochromaffin-like cells of the stomach 

• Bronchoconstriction 
• Increased capillary permeability 
• Exocrine excretion
• Intestinal smooth muscle contraction 
• Nerve stimulation

What is the MOA by which H1 receptor activation works?

Where are these H1 receptors located?

• ↑Phosphoinositol (PI3) hydroslysis → increased intracellular Ca 

Smooth muscle 

Endothelial cells

Brain 

• Increased Gastric Secretions (predominant effect) 
• Cardiac effects
• Vasodilatory effects
• Can actually reduce histamine release from mast cells 

How does the activation of H2 receptors cause cellular changes?

MOA...

Distribution of H2 receptors 

• Stimulation of adenylate cyclase → increased cAMP 

Gastric mucosa 

Heart 

Mast cells 

Brains

Presynaptic auto-recetpros on histamine-containing neurons 

Produce feedback inhibition of histamine release 

Found on eosinophils + mast cells 

Involved in chemotaxis 

• Role in allergy/anaphylaxis/inflammation 
• Cardiovascular system 
• Non-vascular smooth muscle
• Exocrine glands 
• Nervous system 

Contributes to hypersensitivity phenomena and includes:

• Urticaria (hives)
• Pruritis
• Allergic rhinitis (rhinorrhea, sneezing, itching) 

Anaphylactic shock:

Inflammation:

• Mast cells release histamine → cuase local dilation  + increased blood flow in inflamed area 

Cardiac:

• Increased force + rate of contraction (physiologic importance is minimal) 

Vasculature:

• Capillary dilation (mainly in the peripheral capillary bed)
• Local edema 
• Arteriodilation + venodilation 
• Venoconstriciton of large vessels (only at specific sites) 
• "histamine headache" 
• "histamine shock" 

1)  Localized red-spots:

• This is local dilation 
• Appears w/in seconds

2)  "Flush" or "flare"

• This is an axon reflex

3)  Wheal:

•  Local edema 
• W/in 1-2 minutes 

GI tract contraction: 

• Leads to diarrhea

Bronchioles:

• Constriction (mostly seen in asthmatics)

Other effects are negligible:

What is the effect of histamine on the excroine glands?

What is the effect of histamine on the nervous system?

Exocrine glands:

• Gastric acid secretion

Nervous system:

• Peripheral:  Stimulates sensory nerve endings → causes pain, itching, flare of triple response 
• Central:  Fucntions as neurotransmitter 

• Immunological release 
• Drug/chemmical induced release:  Morphine, organic bases (antibiotics) can cause release 

• Histamine itself i used seldomly clinically.  But histamine-agonists can sometimes be used for diagnostic purposes.  Some of their uses are listed below:

-Diseases of allergy:  Help with desensitization (not successful)

-Assessment of bronchial reactivity (histamine in aerosol form), but usually use methacholine challenge instead 

-Assessment of gastric acid secretion (pentagastrin, impromidine) 

H1-receptor antagonists (antihistamines)

Structure activity relationship

• Most contain substituted ethylamine moiety  
• There are serveral sub-classifications 

H1-receptor antagonists 

Pharmacokinetics

Absorption 

Distribution 

CNS penetration 

Metabolization

Duration of action

• Rapidly absorbed 
• Widely distributed 
• 2nd generation drugs penetrate into the CNS very poorly (Cetirizine has some sedative effects b/c it is an active metabolite of the 1st generation drug hydroxyzine) 
• Metabolized in the liver
• DOA:  4-6 hours and 12-24 for long acting 

H1-receptor antagonists 

Pharmacodynamics 

(effects)

Antagonize most of the effects of histamine
However they do NOT block gastric acid secretion or histamine release b/c this is H2 receptor mediated 

The effects that are seen from H1-receptor antagonists are INDEPENDENT of their H1-blockade (these are going to be seen in 1st generation anti-histamines).  These effects include:

• Sedation:  Caused by an anti-muscarinic effect of the drug.  This is going to be minimal in the newer H1 blockers 
• Anti-emesis/anti-nausea:  This is going to be caused by Na-channel blockage by the drugs 

H1-antagonists 

Clinical indications

Allergic conditions:

• DOC for allergic rhinitis 
• DOC for urticaria 
• Allergic conjunctivitis 
• This is inneffective in bronchial asthma 
• This is going to be given as adjunctive to epinephrine in anaphylactic reactions 

• Diphenhydramine
• Dimenhydrinate 
• "zines" 

• Sedation- this is the msot common SE but seen mainly in older generation anti-histamines
• CNS effects:  Dizziness, tinnitus, nervousness, insomnia, fatigue, blurred vision
• GI effects:  Vomiting + reduced appetite 
• Anti-muscarinic effects:  Dryness of the mouth and nasal passage + urinary retention
• Hypersensitivity 

Central effects:

• In children-excitation 
• Hallucinations + ataxia + incoordination + convulsions 

Fixed dilated pupils + flushed face + fever

Deepening coma w/cardiorespiratory collapse + death (terminally) 

Azelastine hydrochloride 

Use 

Metabolism 

Half-life

SE

Cost 

• Use:  Nasal spray that has been approved for the treatment of seasonal allergic rhinitis. Clinical trials have shown it to be more effective than Cetirizine.  
• Metabolism:  Metabolized to desmethylazelastine which is also active.  
• Half-Life:  22-54 hours 
• Adverse effects:  Somnolence, bitter taste, nasal burning, sore throat, dry mouth 
• Cost:  About the same as a 2nd generation 

• Ethanolamines 
• Dimenhydrinate 
• Diphenhydramine (benadryl) 
• Doxylamine 
• Ethylenediamines
• Tripelennamine (PBZ)
• Piperazine derivatives (cyclizine) 
• Meclizine 
• Alkylamines (brompheniramine) 
• Chlorpheniramine
• Phenothiazine derivatives (promethazine) 
• Cyproheptadine

Dimenhydrinate 

SE

Use 

• SE:  Sedation 
• Use:  Anti-motion sickness

Diphenhydramine 

SE

Use 

• SE:  Sedation
• Use:  Anti-motion sickness activity 

Doxylamine 

SE

Use

• SE:  Sedation
• Use:  Only in OTC "sleep aid" 

Ethylenediamines

SE

Use 

• SE:  Sedation
• Use:  OTC sleep aid 

Piperazine derivate example 

SE

Use 

Cyclizine 

SE = slight sedation 

Use = Anti-motion sickness 

Meclizine 

SE

Use

SE = sedation

Use = anti-motion sickness activity 

Alkylamines example 

SE

Brompheniramine 

SE = Sedation 

Chlorpheniramine 

SE

Use 

SE = Sedation 

Use = common componenet of OTC cold medication 

Phenothiazine derivate example 

SE

USE

Promethazine 

SE = sedation

Use = antiemetic + antimuscarinic activity 

Cyproheptadine 

SE

Use 

SE = sedation

Use = anti-serotonin activity 

• Ethanolamines (carbinoxamine)
• Dimenhydrinate 
• Diphenhydramine 
• Phenothiazine derivatives (promethazine) 

• Doxylamine 
• Ethylenediamines (pyrilamine)

• Dimenhydrinate 
• Diphnhydramine 
• Peperazine derivative (cyclizine) 
• Meclizine 

• Piperidines (fexofenadine) 
• Loratadine 
• Desloratadine (active metabolite of loratadine)
• Cetirizine (more sedating than other 2nd generation H1 blockers)
• Levocetirizine (enantiomer of cetirizine) 

• Use:  Treatment of GI disease 

Cimetidine 

Ranitidine

Famotidine

Nizatidine

H2-receptor antagonists 

Elimination 

MOA 

• Elimination:  Via kidneys

• MOA:  Reversible competitive blocker of H2-receptors → causes a decrease in secretion gastric acid.  Also block acid secretion stimualted by gastrin + cholinergic agonists + vagal stimulation of food + insulin + caffeine 

• Peptic ulcer
• Gastric ulcer 
• Zollinger-Ellison Syndrome 
• Reflux disorder 

• Anti-androgenic effects:  Caused by cimetidine. Leads to gynecomastia + galactorrhea 
• GI problems:  Constipation + nausea/vomiting + diarrhea (cimetidine) 
• CNS problems:  Headache + dizziness + hallucinations 
• Hematologic:  Agranulocytosis + thrombocytopenia 
• Liver toxicity

• Cimetidine:  Inhibits P-450. So monitor drugs that are metabolized P-450

Oral alpha-1 adrenergic agonists examples

Topical intranasal alpha-1 adrenergic agonists examples

Ohter alpha-1 adrenergic agonist examples

Use 

MOA

Give with

• Oral:  Pseudoephedrine 
• Topical:  Phenylephrine 
• Other:  Oxymetazoline 

• MOA:  Cause vasoconstriction in nasal mucosa = causes a decrease in edema and causes decongestion.  These are ONLY effective for nasal congestion and do NOT help sneezing, itching, or discharge
• Give with: H1-antihistamine, analgesics, cough suppressants, or expectorants 

Alpha-1 adrenergic agonists

AE

• AE:  Insomnia + excitability + headache + nervousness + palpitations + tachycardia + hypertesnion + nausea + vomiting + urinary retention 

**Topically cause less systemic effects than oral**

• Do NOT give for more than 3 days to avoid rebound congestion
• Also with prolonged use, rhinitis medicamentosa can occur with chronic use. Cocaine abuse will also have this effect. 
• Chronic nasal obstruction + nasal inflammation → beefy red nasal membranes on PE  

• They are the most effective drugs for prevention + relief of allergic rhinitis symptoms 

What are the corticosteroid drugs?

Note that all of these come in aqueous solution/pump spray formulations EXCEPT QNASL

• Beclomethasone dipropionate (this is called QNASL and is the first dry powder aerosol nasal corticosteroid) 
• Budesonide 
• Ciclesoinde 
• Flunisolide 
• Fluticasone propionate 
• Mometasone furoate 
• Triamcinolone acetonide 

• Reduce sneezing 
• Reduce itching
• Reduce discarge (rhinitis)
• Reduce congestion 

Steroids

Onset 

Onset is usually going to take 1-2 day to up to a week 

The maximal response is going to be w/in 1-2 weeks 

Ciclesonide produces a theraputic reponse in 1-2 days

Ciclesonide

Acts w/in 1-2 days

Most of the intra-nasal corticosteroids are going to end up being swallowed.  

Which one has has the highest GI absorption 

Which one has a moderate GI absorption 

• Highest:  Beclomethasone (44%)
• Moderate:  Budesonide (10% is absorbed in the GI tract and 34% is absorbed via the nasal mucosa
• Lowest: Fluticasone, ciclesonide, mometasone (1%) 

Contraindications for corticosteroids 

Long term use AE 

• Suppresses wound healing so avoid after surgery or trauma 
• Long term AE:  Growth suppression in children with beclomethasone but not with mometasone or fluticasone

Ipratropium bromide 

Molecular makeup 

MOA 

Use

AE

• Molecular makeup:  Quaternary ammonium (permanent charge)
• MOA:  Muscarcinic receptor antagonist (LAMA)
• Use:  Inhaled bronchodilator, mostly used for COPD. However, given as a nasal spray is used for nasal discharge especially triggered by irritants or the cold. Does NOT releive itching, sneezing, or nasal congestion 
• AE:  Dry nose + mouth, pharyngeal irritation + urinary retention 

Cromolyn sodium 

MOA 

Application

Use

• MOA:  Mast cell stabilizer (anti-inflammatory)
• Application:  Only applied topically to nasal mucsoa 
• Use:  Given before allergen exposure to prevent early and late phase allergic reponses.  But it is not as effective as corticosteroids but has no local or systemic toxicity