Pharmacology and Therapeutics





Antimicrobials



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  • The reader is directed to Chapter 9: Antimicrobial Therapy for review of antibiotics, antivirals, and antifungal medicinal therapies.





Chemotherapy



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  • The reader is directed to Chapter 46: Chemotherapy for Head and Neck Cancer for review of chemotherapeutic drugs and their applications and indications.





Perioperative Drugs



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  • The reader is directed to Chapter 4: Anesthesia for Head and Neck Surgery for review of local anesthetics, narcotics, sedatives, and the various other perioperative drugs.





Allergy Medications



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  • The reader is directed to Chapter 59: Immunology and Allergy for review of antihistamines, decongestants, corticosteroid, mast cell stabilizers, leukotriene antagonists, and the treatment of anaphylactic conditions.





Biologic Agents



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  • Medicinal agents originating from biologic sources used to prevent and treat cancers or autoimmune diseases, which includes the use of antibodies, interleukins, and vaccines.




Cetuximab





  • Recombinant humanized monoclonal antibody approved for squamous cell carcinoma (SCCA) of the head and neck.



  • Mechanism includes selective binding of epidermal growth factor (EGF) receptor to competitively inhibit EGF resulting in cell growth inhibition, cellular apoptosis, and reduction of vascular endothelial growth factor (VEGF) production.



  • Indicated in the initial treatment of locally or regionally advanced SCCA and recurrent or metastatic SCCA.



  • May be used as monotherapy after platinum-based therapy for metastatic disease or in combination with platinum-based therapy or with radiation therapy.



  • Most common side effects include rash, fatigue, and hypomagnesemia.




Rituximab





  • Humanized monoclonal antibody used for the treatment of granulomatosis with polyangiitis (GPA) (Wegener granulomatosis) and Non-Hodgkin lymphoma.



  • Mechanism of action involves binding of CD20 surface protein on B cells, which allows natural killer (NK) cell-mediated destruction of B cells through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity.



  • It also promotes CD20+ cell apoptosis.



  • Indicated in the treatment of moderate to severe forms of GPA and has generally replaced the use of methotrexate and cyclophosphamide as the secondary treatment of this disease.



  • Generally well tolerated by patients but may include leukopenia, thrombocytopenia, and neutropenia with increased infection rates.




Infliximab





  • Recombinant human-mouse IgG monoclonal antibody used to treat relapsing polychondritis.



  • Mechanism through the neutralization of TNF-α thereby reducing pro-inflammatory cytokine production, reduction of endothelial permeability, and reducing adhesion molecule release.



  • Up to 50% of patients may have formation of antinuclear antibodies with use.




Tocilizumab





  • Recombinant humanized monoclonal antibody targeting the interleukin-6 receptor, which inhibits transduction of inflammatory mediators that summon T and B cells.



  • Initiated with glucocorticoid therapy as the glucocorticoid is tapered until Tocilizumab is used as long-term monotherapy.



  • Used to treat inflammatory autoimmune diseases, it is indicated for giant cell arteritis (temporal arteritis), which is a large-vessel vasculitis that can also affect medium and small arteries.




Asthma Related Biologic Agents:





  • Biological agents offer an opportunity to manage poorly controlled asthma by interfering in the Th2 inflammatory cascade related to IgE-mediated disease.



  • Eosinophilic airway inflammation is a key component to asthma and provides an obvious target for biologics in the treatment of this disease.



  • Omalizumab




    • Humanized anti-IgE monoclonal antibody that exclusively binds circulating blood and interstitial IgE resulting in immunoglobulin depletion and FcεRI (high-affinity IgE receptor) expression on key cells.



    • Cumulative result is diminished inflammatory mediators and recruitment of eosinophils into the airway with results shown to prevent progression or reverse changes in airway remodeling.



    • Indicated in the United States for treatment of patients over 12 years with severe persistent allergic asthma with serum IgE levels between 30 to 700 IU/mL.



    • Clinical trials have suggested severe allergic rhinitis patients also benefit from omalizumab.



    • Dosing is weight and IgE-level based and injections are every 2 or 4 weeks in frequency.



    • Adverse effects are rare but include possible anaphylaxis, local site reaction, and arteriothrombotic effects.



  • Mepolizumab




    • Humanized anti-IL-5 monoclonal antibody that inhibits the bioactivity of IL-5 by preventing the binding of IL-5 to the eosinophilic surface.



    • The result is impaired eosinophil differentiation, maturation, migration, and survival.



    • The drug is indicated for the use of severe asthma and eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome).



    • Outcome studies have shown fewer severe asthma exacerbations and improved quality of life for asthmatics.



    • It has the potential for anaphylaxis and angioedema.





Corticosteroids



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  • Utilized in the treatment of a variety of inflammatory and immune-mediated disorders (eg, sarcoidosis), which can be administered topically or systemically.



  • Common systemic corticosteroids include prednisone and dexamethasone.



  • Unless systemic use is less than 5 days, a taper is typically required to prevent adrenal insufficiency from hypothalamic-pituitary-adrenal (HPA) axis suppression.



  • Fluticasone and mometasone are commonly used topical corticosteroids, which do not require tapering despite prolonged use because there is little impact on the HPA axis.



  • Available corticosteroids have differing potencies with the equi-efficacious doses listed below:



  • Prolonged systemic corticosteroid use can lead to hypertension, Cushing disease, blood sugar dyscrasias, mental status changes (anxiety, insomnia), glaucoma, cataract (posterior subcapsular) formation, decreased bone mineral density, avascular necrosis (AVN) most commonly of the femoral head, and peptic ulcer formation.




    • AVN is the most commonly litigated corticosteroid complication and is associated with doses in excess of 290 mg of prednisone.



  • Topically administered corticosteroids typically have few or no systemic adverse effects due to lack of systemic absorption.



  • Intranasal corticosteroids (INCS)




    • Local adverse effects include epistaxis and rarely nasal septum perforation with intranasal administration.



    • Research has shown no significant effect on cataract formation or intraocular pressure.



    • INCS are indicated for the treatment of inflammatory conditions of the nose and paranasal sinuses including allergic and nonallergic rhinitis, vasomotor rhinitis, and chronic rhinosinusitis (CRS).



    • Multiple studies have demonstrated the efficacy of nasal corticosteroid sprays in the treatment of nasal polyposis, though only two carry formal indications.



  • Otologic topical steroids




    • Several antibiotic and corticosteroid otic drops formulations are available.



    • Indicated in the treatment of infectious otitis externa or as single modality therapy for eczematous otitis externa.



  • The table below lists and compares several commonly employed topical nasal corticosteroids:



  • Preoperative systemic steroid use has been shown to decrease intraoperative bleeding during sinus surgery and improve surgical field visualization (prednisone 30 mg PO daily for 4 to 7 days before surgery).





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Hydrocortisone 1
Prednisone 4
Prednisolone 4
Methylprednisolone 5
Triamcinolone 5
Dexamethasone 25





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Drug Youngest approved age Possible growth suppression in children Nasal polyposis indication Pregnancy approved Scent
Beclomethasone propionate 6 Yes No No Yes
Budesonide 6 N/A Yes Yes No
Ciclesonide 6 N/A No No No
Flunisolide 6 N/A No No Yes
Fluticasone propionate 6 No No No Yes
Fluticasone furoate 2 No No No No
Mometasone 2 No Yes No No





Anticholinergics



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  • Muscarinic acetylcholine receptor antagonists (parasympatholytics) are the most commonly employed anticholinergics in head and neck conditions.



  • Available in both topical and systemic formulations.




Nasal preparations





  • Ipratropium bromide




    • The only available anticholinergic nasal spray, available in 0.03% and 0.06% preparations. Decreases parasympathetic-mediated nasal secretions.



    • Rapid onset and low systemic absorption.



    • Indications include conditions with elevated nasal secretions including virally mediated rhinitis, allergic and nonallergic rhinitis, and especially vasomotor rhinitis.




Systemic Preparations





  • Utilized for motion sickness, systemic secretions reduction, treatment of vagal reactions, and as part of advanced cardiac support during code events.



  • Scopolamine




    • Commonly employed in the treatment of motion sickness by blocking vestibular input to the central vestibular system that is responsible for the vegetative symptoms. See later in antiemetic section.



    • Both systemic and transdermal formulations have demonstrated efficacy with prophylaxis; neither has literature support for active symptom management and may impair central nervous system recovery from vestibular dysfunction.



  • Glycopyrrolate




    • Quaternary amine (does not cross the blood-brain barrier) and is commonly used to reduce oral, pharyngeal, and respiratory secretions prior to endoscopy without significant central effects.



  • Atropine




    • Typically used in the treatment of bradycardia or cardiac arrest events.



    • Adverse effects are mediated by the blockage of normal parasympathetic activity resulting in tachycardia, flushing, blurred vision, urinary retention, decreased gastrointestinal motility and constipation, mental status changes (decreased arousal), and xerostomia.



    • “Blind as a bat, mad as a hatter, hot as a hare, dry as a bone” is one mnemonic to remember these adverse effects.



Apr 30, 2020 | Posted by in OTOLARYNGOLOGY | Comments Off on Pharmacology and Therapeutics
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