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Antitussives:
inhibit cough thru either central or peripheral mech, or a combo of the 2.
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Antitussives.
Central acting drugs:
- Guaifenesin and codeine (Cheratussin AC)- schedule V
- dextromethorphan
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Dosing for Guaifenesin and codeine (Cheratussin AC):
- Cough: 10 ml PO q 4-6h prn
- Dosage forms: 10/100/ 5 mL
- 10 codeine, 100 guaifenesin, in every 5 mL
- Max daily dose (MDD) required on Rx
- Dose should be decreased for renally impaired
- Does have alcohol in it
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Antitussives.
Peripherally acting drugs:
- Camphormenthol
- eucalyptus oil
Benzonatate (Tessalon)
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How does Benzonatate (Tessalon) act peripherally?
by anesthetizing the stretch receptors located in the respiratory passages & lungs
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WARNINGS of Antitussives:
- Severe hypersensitivity reactions (including bronchospasm, laryngospasm and cardiovascular collapse) have been reported
- Possibly related to local anesthesia from sucking or chewing the capsule instead of swallowing it
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MOA of centrally acting antitussives:
- Inhibit the cough center in the brain
- Exact mechanism not well understood
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MOA of peripherally acting antitussives:
- Anesthetize local nerve endings
- Act as demulcents (soothing agents)
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How does a cough occur? not sure this will be on exam...
- Lower pharynx, larynx, trachea & small airways of respiratory system are innervated by vagus & glossopharyngeal nerves
- Stimulation of sensory receptors of these nerves leads to cough
- Irritant leads to cough
- Receptors relay info to cough center in brain (medulla)
- A reflex motor response occurs; results in contraction of muscle to close glottis & muscles of expiration
- Leads to an increase in intrathoracic pressure, followed by relaxation of the glottis
- This results in rapid expulsion of air
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Indications of antitussives:
cough
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kinetics of codeine (says FYI...?)
- Onset occurs in 15–30 minutes. Peak antitussive effects within 1–4 hours.
- Rapidly distributed into various body tissues.
- Distributed into milk. Readily crosses the placenta.
- Metabolized in liver, principally by CYP3A4, to O-demethylated morphine, the active metabolite.
- genetic differences in drug metabolism affect drug response
- Excreted mainly in urine
- Half-life: about 2.5–3 hours
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Kinetics of Dextromethorphan (FYI..?):
- Onset of action is 15-30 minutes·
- Duration is 3-6 hours
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kinetics of camphor or menthol (FYI...?):
- Used topically (vapors inhaled)
- inhaled through a vaporizer
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SE of Dextromethorphan:
- Drowsiness
- nausea
- dizziness
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SE of Benzonatate:
- Sedation
- HA
- dizziness
- Can numb mouth
- Warn patients: Do not chew or dissolve in the mouth when used as an antitussive
- Why? temporary, potentially life-threatening local anesthesia of the oral mucosa, choking, or severe hypersensitivity reactions could occur.
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SE of Codeine; hydrocodone:
- Lightheadedness
- nausea
- sedation
- constipation
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CI of antitussives:
- Dextromethorphan and MAOI inhibitors (selegiline, tranylcypromine, phenelzine, isocarbozazid) use within 14 days;
- Why? MAOI directly inhibit this enzyme, increases the amount in the synapse-increased risk of serotonin syndrome- confusion, uncoordination, agitation
- Ppl are abusing unexpected OTC & rx meds
- -dextromethorphan taken in high doses can create euphoria
- OTC cough & cold med in children:
- -lifestyle modifications are 1st line of tx: humidifiers, saline, & nose suctioner
- -encourage parents to avoid using vicks, can make it worse
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Expectorants:
facilitate the removal of mucous from the respiratory tract
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expectorant drugs:
Guaifenesin (Robitussin) (Mucinex)
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Indication for expectorants:
chest congestion
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MOA of expectorants:
Increases volume & decreases viscosity of respiratory secretions, resulting in increased flow & clearance of irritants (“loosens” phlegm)
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kinetics of expectorants:
half-life is 1 hr
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Dosing for Cheratussin AC (codeine/guaifenesin):
- 10/100/5ml
- contains alcohol
- 20 mg codeine PO q4-6h prn.
- Adjust dose amount in renal impairment
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20 mg is = ___ mL
20 mg= 10 mL
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2 categories of Decongestant drugs:
- Direct alpha-1 agonists
- Indirect alpha-1 agonists
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Direct alpha-1 agonists drugs:
- Phenylephrine (Dimetapp)- not very effective be it is poorly absorbed
- Oxymetazolone
- Naphazoline
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Indirect alpha-1 agonist drugs:
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MOA of decongestants:
all nasal decongestants are vasoconstrictors
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Indication of decongestants:
- nasal congestion; reduces "stuffiness"
- ocular congestion
- -temporary relief of conjunctival congestion, itching, & minor irritation
- -used alone or in fixed combo c/ antihistamines &/or astringents
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Naphazoline is:
Naphcon, Visine A
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Kinetics of decongestants:
- orally, topically, and ophthalmics
- Pseudoephedrine: (oral) onset c/in 30 mins
- Nasal decongestion may persist for 8 hours following oral administration of 60 mg and up to 12 hours following 120 mg of the drug in extended-release capsules.
- Presumed to cross the placenta
- About 0.5% of an oral dose is distributed into milk over 24 hours.
- Incompletely metabolized in the liver·
- Excreted in urine·
- Half-life is 9-16 hours; decreased excretion in alkaline urine
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SE of decongestants:
Imp SE of inhaled decongestants:
- Inhaled: Rhinitis medicamentosa- rebound congestion
- What can you do it pt has this? Taper them off it
- CNS stimulation ; Anxiety, agitation, insomnia; take it during the day(Pseudophedrine)
- Dizziness
- Palpitations
- increased blood pressure
- urinary retention
- Topical agents may cause stinging, burning & dryness
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CI of decongestants:
- Severe HTN
- CAD
- MAOI use c/in 14 days (may lead to hypertensive crisis)
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What were the legal requirements put in place for Pseudoephedrine?
- Combat Methamphetamine Epidemic Act of 2005
- The act bans OTC sales of cold meds that contain the ingredient pseudoephedrine
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H1 antagonists (antihistamines):
antagonize the allergic responses & other effects mediated by histamine
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H1 antagonists. First generation drugs:
- Diphenhydramine (Benadryl)
- Chlorpheniramine (Chlor-Trimeton)
- Brompheniramine
- Promethazine (Phenergan)
- Hydroxyzine (Vistaril)
- Meclizine (Antivert) (Dramamine)
- Clemastine (OTC & Rx) (Tavist Allergy)
- Cyproheptadine (Rx) (Periactin)- DC'd
- (Die C B Penis c/ Horrible and Mighty Condylomata & Chlamydia)
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H1 antagonists. Second generation drugs:
- (Claritin)(Alavert) Loratadine - 10 mg·
- (Zyrtec)Cetirizine
- (Allegra) Fexofenadine
- (Astelin) Azelastine (nasal)
- (Optivar) Azelastine (ophthalmic)
- (Clarinex) Desloratadine
- (Xyzal) Levocetirizine
- (Patanase) Olopatadine (nasal)
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Dosing and indication for Diphenhydramine (Benadryl)
- Moderate to severe allergic rxns: 25-50 mg q 2-4 hrs.
- not to exceed 400 mg/day
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Dosing for Loratadine (Claritin)
10 mg
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Dosing for Cetirizine (Zyrtec)
5-10 mg PO once daily
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Dosing for Fexofenadine (Allegra)
- 60 mg PO 2x daily OR
- 180 mg PO once daily
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Main indications for H1 histamine:
allergic rxns
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Main indication for H2 histamine
- to reduce gastric acid
- Cimetidine (Tagamet)
- Ranitidine (Zantac)
- Famotidine (Pepcid)
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Histamine is primarily synthesized in
mast cells
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An immune response mediated by histamine may lead to:
- Bronchoconstriction
- Vasodilation
- Nerve sensitization
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MOA of H1 antagonists:
- Antihistamines competitively antagonize histamine at the H1 receptor; altering the immune response to an allergen: (opposite of:)
- -Bronchoconstriction
- -Vasodilation
- -Nerve sensitization
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Rhinitis:
inflammation of the mucous membrane
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Allergic rhinitis:
- Due to mucous membrane exposure to an inhaled allergen; results in a specific response mediated by immunoglobulin E (IgE)
- Response is characterized by sneezing, itchy, runny nose, & often nasal congestion & postnasal drip. Itchy eyes, ears and throat frequently accompany allergic rhinitis.
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Indications for H1 antagonists:
- Allergic symptoms
- Allergic reactions
- Urticaria
- Motion sickness prevention
- Nausea
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approaches for H1 antagonists:
- allergen avoidance
- pharmacotherapy to prevent or treat symptoms
- specific immunotherapy
- Antihistamines are more effective in preventing, rather than reversing, the actions of histamine.
- Reversal of symptoms is probably due, in part, to the anticholinergic effects of the drugs.
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Symptoms that oral antihistamines control
- Sneezing,runny nose, itching, conjunctivitis
- For seasonal. Begin tx before allergen exposure
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Symptoms that ophthalmic antihistamines control:
Conjunctivitis
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Symptoms that intranasal antihistamines control:
Sneezing, runny nose, nasal itchiness
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Kinetics of H1 antagonists:
- Well absorbed
- Large volume of distribution
- Metabolized by liver
- Older agents are lipid soluble
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SE of H1 antagonists:
- Anticholinergic (drying) effects: (first generation)
- Dry mouth
- Difficulty urinating
- Constipation
- Changes in vision
- Drowsiness (less of a problem with second generation)
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Cautions of H1 antagonists:
patients <6 and >65 years old, CNS depressant use, increased intraocular pressure, hepatic or renal disease, hypertension, asthma, COPD, peptic ulcer disease, BPH, hyperthyroidism
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