Pharmacological Management in Voice and Laryngeal Care

Drugs In Laryngology

Medications are prescribed. Antibiotics and anticoagulants are given for prophylactic

Purposes. Anticoagulants are given to a patient planned for surgery as blood loss during surgery is expected. Anticoagulants are not started before the surgery. It is given to patients expected to be bedridden for a prolonged period after surgery. For e.g. heparin, LMWH is prescribed in immobile patients to avoid DVT after surgery such as major head and neck surgery, laryngectomy, or flap reconstruction. Whereas antibiotics are given before surgery. Prophylactic medications do not mean they should be given before surgery. It can also be given post-surgery.

For therapeutic purposes in the management, medications are given to treat infections, steroids are given for immune conditions, and therapy for voice throat problems such as anti-reflux, and allergy along with voice rest and other precautions.

Antiplatelet Drugs

Whenever there is a tissue injury, there is clot formation. There are 3 steps in clot formation. These are adherence, activation, and aggregation. The first step in clot formation is adherence. Whenever there is a trauma, the basement membrane is ruptured, and underlying collagen is exposed and releases the Von Willebrand factor which will slow down the movement of platelets and attract the platelet towards the area of injury and adhere to the underlying collagen by two molecules GP2b3a and GP1b V/IX. GP2b3a is the major molecule that helps in adherence of underlying tissue directly and GP1b V/IX helps the adherence indirectly.

The second step in clot formation is activation. The activation occurs via arachidonic acid pathway. There is a release of arachidonic acid from the cell membrane phospholipids. The arachidonic acid is initially converted to prostaglandins via cyclooxygenase. Prostaglandins give two molecules thromboxane and prostacyclin. Thromboxane is a vasoconstrictor and platelet aggregator whereas prostacyclin has a reverse effect. The platelet after activation secretes adenine nucleotide peptides. These will act on the platelet and activate them further with the help of two molecules P Y complex and the 2 1 P Y complex. 2 12. P Y initiates the platelet activation and P Y completes 2 1 2 12 platelet activation.

The activation of platelets attracts more platelets and aggregation. Over some time there is clot formation. The antiplatelet drugs on the molecules that help in adhesion, activation, or aggregation.

Antiplatelet drugs reduce platelet aggregation and thereby thrombus formation in the arterial circulation where thrombi are primarily composed of platelets with little fibrin. These drugs are given to patients with the possibility of thrombosis.

Aspirin, clopidogrel, and dipyridamole are often encountered in ENT patients with comorbidities to prevent atherosclerotic and thromboembolic events. The decision to stop these preparations before surgery is based on the balance of risk of bleeding versus the risk of thrombus formation.

These drugs can be continued with minor surgeries but they should be discontinued in major surgeries where there is a chance of excessive bleeding.

Anticoagulants

Anticoagulants are drugs that act on the coagulation pathway but not on the platelet pathway.

There are two pathways for coagulation i.e. the intrinsic pathway and extrinsic pathway. 

In the intrinsic pathway, there is factor XII which is converted to factor XIIa, and factor XIIa acts on factor XI to convert it into activated factor XIa. The activated factor XIa acts on factor IX to convert into IXa and IXa works on factor X to form activated Xa. The activated Xa converts

prothrombin to thrombin and thrombin works on fibrinogen to form fibrin.

In the extrinsic pathway, factor VII is converted to activated factor VII. Activated factor VII acts on factor X to form activated Xa. The activated Xa converts prothrombin to thrombin and thrombin works on fibrinogen to form fibrin. Factor Xa inhibitors such as apixaban, edoxaban, and rivaroxaban are extrinsic pathway inhibitors. Heparin inhibits factor Xa as well as thrombin. Warfarin has multiple sites of action. It can inhibit factor IX, factor X, prothrombin, and factor VII. Direct thrombin inhibitors are argatroban and dabigatran.

Antibiotics 

Antibiotics given as prophylaxis in major head and neck surgery to prevent infection. Antibiotic prophylaxis for laryngectomy is a preoperative dose given to allow a high tissue level at the time of surgery and three postoperative doses of cephalosporin and metronidazole. Antibiotic prophylaxis in patients with artificial heart valves or cardiac valve disease, Amoxicillin 3g orally or 1g intramuscularly can be given 1 hour before surgery and 6 hours postoperatively.

Throat Lozenges and Pastilles 

Lozenges and pastilles are both used to deliver medicaments of local effect, either to soothe or treat infections. Lozenges consist of medicaments incorporated into a flavored base that dissolves or disintegrates slowly in the mouth. Pastilles consist of medicaments in a base containing gelatin and glycerol or a mixture of acacia and sucrose. Sodium benzoate and citric acid monohydrate may be used as a preservative and antioxidant respectively. Flavorings such as lemon oil may be incorporated to make it more palatable and compliant for patient use.

Treatment of Dry Mouth 

Dry mouth is a common side effect of radiotherapy or a disease affecting the salivary glands.

Artificial saliva can be useful in relieving dry mouth. These preparations should be of neutral pH and contain electrolytes approximating the composition of saliva. Artificial saliva is available as oral sprays, lozenges, and pastilles. Pilocarpine (Salagen) is a muscarinic drug and can stimulate any residual salivary gland function. The side effects of pilocarpine relate to the muscarinic action. It is contraindicated in those with significant respiratory and cardiovascular disease, angle closure glaucoma, pregnancy, and breastfeeding.

Cough Medicines

Management of Stridor 

Heliox is a mixture of helium and oxygen. Heliox is useful in an acute situation but antibiotics,

adrenaline, steroids, and antihistamines may be required as may surgery. Helium is a colorless, odorless, tasteless gas that when mixed, with one volume of helium to two volumes of air,

diffuses more rapidly than air itself. Breathing such a mixture requires less effort due to the lower density. This is administered in patients with labored breathing. An air-helium mixture or a mixture of 21 volumes of oxygen and 79 volumes of helium (heliox) has been used in the

management of stridor.

Drug Therapy in Angioneurotic Edema 

Angioneurotic edema can be allergic type and non-allergic type. For allergic-type angioneurotic edema, antihistamines and corticosteroids are prescribed. In life-threatening conditions, 1ml/1:1000 adrenaline can be administered subcutaneously or intramuscularly. For non-allergic type results from a serum deficiency of the C1 esterase inhibitor protein. This is treated with an intravenous injection of 1000 units of C1 esterase inhibitor protein that is derived from human plasma. This can also be given before surgery for prophylaxis. Conestat alfa and icatibant are also licensed to treat acute attacks of hereditary angioedema in adults with C1 esterase Inhibition. Conestat alfa is contraindicated in patients allergic to rabbits. Long-term prophylaxis is done with epsilon aminocaproic acid or its derivative tranexamic acid or with androgen methyltestosterone or its derivative danazol. These stimulate the production of the C1 esterase inhibitor protein.

Collagen Injection of Paralyzed Vocal Cords 

Collagen injection is used for paralyzed vocal cords especially when planning to adduct the cord. Collagen is a purified bovine dermal glutaraldehyde crosslinked collagen and has been used in genuine stress incontinence. A skin test must be done before administration. 0.1ml collagen and lignocaine is injected intradermally into the volar surface of the forearm and should be carried out 4 weeks before the treatment. It is contraindicated in patients with hypersensitivity to the ingredients, with a positive skin test, in pregnancy and lactation, and patients with autoimmune disease or a history of multiple severe allergies.

Liothyronine 

Liothyronine has a shorter half-life, more rapid onset, and shorter duration of action. 20 mcg of liothyronine is equivalent to 100 mcg of thyroxine sodium. It can also be given intravenously.

A pretherapy ECG should be performed since hypothyroidism can produce changes resembling ischemia. The starting dose of liothyronine is 10-20 m every 8 hours. The usual maintenance dose is 60 m daily in three divided doses. Sometimes it is co-administered with carbimazole to treat thyrotoxicosis.

It may be used in severe hypothyroid states when a rapid response is required and is used in patients awaiting radioactive iodine scans following thyroid surgery. These thyroid hormones must be used with caution in patients with

• Hypertension
• Diabetes mellitus is an insipidus
• Cardiovascular disorders
• Angina
• The elderly
• Lactation
• Pregnancy
• Adrenal insufficiency

Drugs used in Hyperthyroidism 

Antithyroid drugs are used for hyperthyroidism either preoperatively or for long-term management. Carbimazole (neo-mercazole) is the most commonly used drug in hyperthyroidism. Propyluracil is used in patients sensitive to carbimazole. Carbimazole is rapidly converted to methimazole in vivo.

Treatment of Reflux Oesophagitis and Laryngopharyngeal Reflux

H2 Receptor Antagonist

H2 receptor antagonists such as cimetidine, and ranitidine should be used with caution in patients with liver or renal disease, in pregnancy, and breastfeeding. The side effects are diarrhea, altered liver function tests, rashes, hypersensitivity reactions, AV block, and blood dyscrasias. Cimetidine causes gynaecomastia and it binds to cytochrome P-450 reducing the hepatic metabolism of drugs such as warfarin.

Proton Pump Inhibitors 

Proton pump inhibitors such as rabeprazole, and pantoprazole react with sulfhydryl groups in the H+/K+ ATPase (proton pump) responsible for the transportation of H+ ions out of the parietal cells. Its use is well-established in the treatment of reflux oesophagitis.

Chemotherapeutic Agents 

These drugs are used either alone or in combination with surgery and/or radiotherapy to cure or palliate cancer. They inhibit the mechanisms of cell proliferation and rely upon malignant tumors having a greater proportion of cells undergoing division than in normal proliferating cells.

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