Sympathomimetics, Antihistamines and ENT products
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Response to organ depends on
o Specificity of the agonist/antagonist at a given receptor
o The absolute number of receptors in that organ or organ system
o Ratio of receptors (which is prominent)
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Alpha 1 = primary receptor for EENT indications:
o Stimulation causes:
 Smooth muscle contraction (lining blood vessels)
 Vasoconstriction (can help control blood flow) @ a local level (causes vasoconstriction)
 Decrease in mucous membrane secretions (decongestants)
Beta 1 = cardiac stimulation (heart’s a beating)
Beta 2 = smooth muscle relaxation (lungs are breathing)
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SYMPATHOMIMETICS
 Adrenergic agonists
o Mixed acting
 combine with receptor and produce a response AND:
 cause NE release or
 block NE uptake
 ex: pseudoephendrine
 ex: phenylpropanolamine (was in Dimetapp but now off the market bc <3 toxicity)
o Alpha 1 agonist
 ex: phenylephrine (decongestant)
common uses of sympathomimetics:
o Hemorrhage
 Alpha 1
 Epinephrine (Epi) – causes superficial vasoconstriction = controls capillary bleeding;
***used in nasal surgery
o Combined with local anesthetics
 Alpha 1
 Epi – causes local vasoconstriction = decreased blood flow which slows absorption and localizes affect
of anesthetic
Sympathomimetics, Antihistamines and ENT products
o Nasal decongestants
 Alpha agonists
 Applied locally or orally
 Constricts swollen (edematous) vessels/tissue
 Relieves mucosal congestion
o Anaphylaxis (acute allergic rxn)
 Epi
 Alpha 1 = relieves swelling
 Beta 1 = some cardiac stimulation (USE WITH CAUTION)
 Beta 2 = relaxes constricted bronchial smooth muscle
o Hypotension – hypotensive crisis (beta one helps in a crisis)
 Alpha agonists
 Increased blood pressure via vasoconstriction
 Causes:
o Ischemia in extremities, organs with prolonged administration
o Withdraw – taper off agent slowly to prevent recurrence
o EENT indications:
 Nasal preparations
 Ophthalmic preparations
 Otic preparations
 Oral preparations
Sympathomimetics, Antihistamines and ENT products
Nasal preparations
 Used to relieve nasal congestion associated with common cold, allergic rhinitis and sinusitis
 Topical – use as vasodilator (used LOCALLY; not systemically)
o Oxymetazolone – active ingredient in afrin; one strength
o Phenylephrine – various strength so low doses used for children
 Sprays
o Preferred in adults
o Better coverage of nasal mucosa
o Easier self administration
 Drops
o Preferred in children
o Nostrils are smalle – easily administered by adults
o Use lowest strength in children – not for <2 yo
 Systemic absorption if minimal
o Slightly more with drops due to swallowing excess
 ADRs
o Local irritation (burning, stinging, sneezing, dryness)
o RHINITIS MEDICAMENTOSA (rebound congestion)
 Caused by using decongestants for more than 3-4 days; use short term as directed
 Receptors become desensitized
 Contraindicated with monamine oxidase inhibitors [MAO-Is]
 (breaks down catecholamine = severe tachycardia & HTN)
 Increase in heart rate
 Can be caused by both oxymetazolone and phenylephrine
 Patient uses for >3-4 days, desensitization of receptors; does not get relief
 Starts with bid then tid then qid then 5xd etc.
 Rebound can be worse than original congestion
Sympathomimetics, Antihistamines and ENT products
Opthalmic preparations
 Oxymetazolone
 Phenylephrine
 Tetrahydrozaline
 Naphazoline
 CAUTIONS:
o Contact lens – drops need to be compatible
o Narrow angle glaucoma = contraindicated
o Greater chance of systemic absorption with eye drops
 Due to relatively high concentration of medication contained in solution
 Drug absorbed directly into the tear duct
 To avoid/lessen the absorption, instruct pt to press on the tear duct when instilling eye drop
Sympathomimetics, Antihistamines and ENT products
Systemic Preparations: Oral (systemic)
 Related to amphetamine
o Pseudoephedrine (isomer of ephedrine – Sudafed)
o Ephedrine (appetite suppressant – CNS stimulation)
o Phenylpropanolamine (off the market now; <3 toxicity)
 Was an excellent decongestant
 Used in appetite suppressants (dexitrim)
o Phenylephrine – also available as an injection
 Available as single agents
o Pseudoephedrine (Sudafed)
o Phenylephrine (Sudafed PE)
 Availavle as combo agents:
o Anti-histamine (with brompheniramine in Dimetapp)
o APAP (tylenol cold and sinus)
o Ibuprofen
o Anti-tussive
******* comb of all the above = “complete cold” formulas
 ADRs
o Binding to alpha receptors
 Systemic effects:
 Increased HR, BP, palpitations
 Agitation – irritability
 Restlessness
 Insomnia
 Nervousness
 Appetite suppression (CNS stimulation
 Euphoria (~ effects as amphetamines)
 CNS stimulation – prominent aspect of amphetamines (indirect acting)
 Tolerance to stimulant properties – leading to drug dependence, especially w/ amphetamines
Sympathomimetics, Antihistamines and ENT products
Antihistamines
 Histamine
o Produced primarily by mast cells and basophils
o Abundant in skin, GI, respiratory tract
 GI – paracrine cells in fundus (lining) stimulates gastric secretion by parietal cells
o CNS neurotransmitter
o Released from mast cells by IgE (cromolyn NA blocks this action)
o Mast cell degranulation can be caused by : bacterial toxin and drugs (morphine and tubocurarine) – results in flushing
and vasodilation when these are given
o NORMAL PHYSIOLOGIC EFFECTS
 Primitive reflex – protective mechanism
 Vasodilation = decrease BP (relaxation of arteriolar smooth muscle and benules) = hypotension
 Increased vascular permeability = edema (promotes fluid and plasma out of blood into extracellular spaces)
 Heart (tachycardia & increased contractility
 Bronchoconstriction – in lungs (body trying to decrease the amount of allergens entering the lungs)
– protective mechanism
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ANTI-HISTAMINE RECEPTORS
o H1 receptor effects
 Mediates allergic rxns
 Used in dermatitis, rhinitis, conjunctivitis
 Activation in skin and mucous membranes causes
 Vasodilation, increased vascular permeability, erythema, congestion, edema, inflammation
 Mucocutaneous nerves – pruritis, cough
 Histamine in circulation – decreased BP, anaphylactic shock
o H2 receptor effects
 GI acid secretions – primarily
 Allergic reactions
 H1 and H2 blockers may be used in combo for some allergic reactions (diphenhydramine + famotidine)
 H2 receptors in heart
 Increased HR and increased contractility
Sympathomimetics, Antihistamines and ENT products
o H1 receptor antagonists
 Block the action of histamine by competitive inhibition at the receptor site
 Most are capable of crossing the BBB and entering the CNS causing sedation
 These antihistamines have many other effects NOT due to the histamine receptor
 There chemical structure is similar to other endogenous agents so they are capable of combining with
other receptors in the body to produce a variety of SEs
 Some effects may be desirable (therapeutic) and others undesirable
o EFFECTS OF ANTI-HISTAMINES
 Therapeutic effects
 Treatment of allergies
 Treatment of motion sickness (scopalomine – anti-muscarinic; H1 receptors in vestib. apparatus)
 Anti-nausea & anti-emetic: central chemotrigger inhibition
o Phenothiazines – stimulation of antihistamine to target trigger zone
 Treatment of insomnia due to sedative side effects
 ADRs
 SEDATION
 Anticholinergic effects (blocks muscarinic receptor causing anti SLUDGE effects)
 Adrenergic blockade causing orthostatic hypotension (alpha 1 blocker)
o Phenothiazines
o ANTIHISTAMINES FOR EENT INDICATIONS
 CAUTION IN THE ELDERLY – ANTICHOLINERGIC SEs
 Nonselective lipid soluble; cross BBB
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FIRST GENERATION – used for seasonal or allergic rhinitis
 Piperazines
o Mexlizine – not used for allergic rhinitis; used for vertigo
o Hydroxyzine – very sedating
 Phenothiazines
o Promethazine – very sedating; anticholinergic; antiemetic
 Similar structure binds to other systems = SEs
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Sympathomimetics, Antihistamines and ENT products
FIRST GENERATION ADRs
 Sedation most common ADR
 May get paradoxical excitation in children and infants
 Do not use antihistamine to get a child to sleep
 Atropine-like ADRs (anti-SLUDGE)
o Dry mouth, blurred vision, tachycardia, urinary retention
 Anticholinergic toxicity – manifestation of overdose
o Administer physostigmine (cholinesterase inhibitor)
SECOND GENERATION – used for seasonal or allergic rhinitis
 do not block muscarinic receptors or alpha 1 receptors
 do not cross BBB
 MOA = block H1 receptor or stabilize mast cell (prevent release of histamine)
 Selective for H1 receptor therefore little or no sedative activity
 Piperidines
o Loratadine (Claritin)
o Desloratadine (clarinex)
o Fexofenadine (Allegra)
 Piperazines
o Cetirizine
o Levocetirizine – isomer of cetirizine
***** brand name + D = has pseudoephedrine
SECOND GENERATION ADRs
 The 2nd generations’ advantage over the first is that they are relatively specific for the H1 receptor and
therefore have little or no sedative activity
 HOWEVER, significant DDIs
(don’t memorize):
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Alkylamines
 Brompheniramine
 Chlorpheniramine
 Triprolidine – cause the least amount of sedation (may even cause CNS stimulation)
Ethanolamonies
 Clemastine
 Diphenhydramine (Benadryl) – VERY sedating, anticholinergic
Sympathomimetics, Antihistamines and ENT products
o ANTIHISTAMINES EENT EFFICACY:
 More effective in preventing histamine-mediated effects than reversing these effects
 Most effective when taken 1-2 hours prior to anticipated exposure of offending allergen
o ANTIHISTAMINES EENT KINETICS
 Well absorbed PO, large Vd, liver metabilism
Zyrtec and Claritin Eye Drops
 Active ingredient is ketotifen
o Not cetirizine or loratadine; it has antihistamine and mast cell stabilizing effects
 Indicated for itchy eyes due to pollen, ragweed, grass, animal hair and dander
Cough and cold preparations in kids
 April 2009: FDA updated the Public Health Advisory recommending that OTC couch and cold products not be used in infants
and children less than 2 years (specifically referring to antihistamines, decongestants and dextromethorphan)
Topical antihistamines
 CAUTION IN THE ELDERLY – ANTICHOLINERGIC SEs
 Nonselective lipid soluble; cross BBB
 Also considered 2nd generation – used for seasonal or allergic rhinitis
o Levocabastine
o Aselastine
o Olopatadine – mast cell stabilizer and antihistamine (blocks H1 receptor)
Miscellaneous agents (EENT)
 Cromolyn – stabilizes mast cell membranes and thereby preventing degranulation and release of histamine
 Montelukast – used for seasonal allergic rhinitis in adults and children over 2 years old
o Leukotrine receptor antagonist; inflammatory mediator
Other agents for Rhinitis
 Intranasal steroids
o Very efficacious, also good if pt also has asthma
o Less systemic ADRs
 Ipratropium nasal spray
 Saline nasal preps
Sympathomimetics, Antihistamines and ENT products
Miscellaneous Otic preparations
 Otic antibiotics; PO approach; systemic
 Neomycin containing preparations
o Neomycin, polymixin B and hydrocortisone
 Used for otitis externa
 Solution may be more irritating due to acid content
 Poor compliance due to frequency (tid; qid)
Miscellaneous Otic antibiotics (fluoroquinolones) for otitis externa
o Ciprofloxacin & hydrocortisone
o Ciprofloxacin & dexamethasone
o Ofloxacin
o Carbamide peroxide (debrox)
 Used to emulsify ear wax
 Tilt head sideways and instill 1-10 drops in ear bid for 4 days
 Must keep drops in ears for several minutes by keeping head tilted and placing cotton in ear
o Analgesics
 Used to treat acute pain associated with certain ear conditions (otitis media and externa)
 Antipyrine/benzocaine
Miscellaneous Oral Preps & Sprays
o Benzocaine
o Local anesthetic
o May be combined in other anesthetics in different products