Respiratory PharmacologyWeek 6

Inhaled SteroidsMode of action at the tissue level

◦Restoration of epithelium◦Reduction of thickening of basement

membrane◦Reduction of mucosal edema◦Reduction of leukocyte infiltrate◦Reduction of mast cell number

Inhaled SteroidsMode of action at the molecular

level:◦Blockage of active sites of pro-

inflammatory genesMode of action at the cellular

level:◦Inhibition of release of pro-

inflammatory molecules

Inhaled CorticosteroidsMode of action

◦ Modify response of the cell in order to inhibit inflammatory response of the airway

◦ May require hours to days to gain full benefits

◦ Daily compliance is essential to maximizing effects

Inhaled CorticosteroidsIndications

◦ Anti-inflammatory maintenance therapy of persistent asthma and COPD

◦ Control of seasonal allergic or non-allergic rhinitis

◦ May be administered as orally inhaled aerosol or intranasal aerosol

◦ http://www.youtube.com/watch?v=LcM7f1iwOGo

Flovent: DPI/MDI. 3 doses.

Asmanex: twisthaler, grey or pink depending on dose

Qvar: 40/80 ug dose

Aerobid is now Aerospan

Pulmicort: turbahaler or respules

Advair: MDI or DPI, 3 doses, combo drug

Symbicort: 2 doses, combo drug

Inhaled Corticosteroids

Adverse effects

◦ Decrease type and severity of side effects compared to systemic administration

◦ Adrenal insufficiency

◦ Acute asthma

Inhaled Corticosteroids

Adverse effects (systemic mostly)

◦ Osteoporosis

◦ Growth suppression

◦ Oropharyngeal infections

Inhaled Corticosteroids

Adverse effects

◦ Dysphonia

◦ Cough

◦ Bronchoconstriction

Corticosteroids Used in Aerosol Administration

Beclomethasone dipropionate

QVAR MDI: 40 and 80 µg/puff.Adults > 12 years: 40 to 80 µg twice daily, or 40 to 160 µg twice dailyChildren > 5 years: 40 to 80 µg twice daily

Triamcinolone acetonide(No longer made)

Azmacort

MDI: 100 µg/puff.Adults > 12 years: 2 puffs three times of four times dailyChildren > 6 years: 1 or 2 puffs three or four times daily

Flunisolide(No longer made)

Aero-Bid MDI: 250 µg/puffAdults and children > 6 years: 2 puffs twice daily; adults no more than 4 puffs; children < 15 years no more than 2 puffs daily

Corticosteroids Used in Aerosol Administration

Fluticasone propionate

Flovent MDI: 44, 110, and 220 µg/puffAdults > 12 years: 88 µg twice daily; 88 – 220 µg twice daily; or 880 µg twice dailyChildren 4 – 11 years: 88 µg twice dailyDPI: 50, 100, and 250 µgAdults: 100 µg twice daily; 100 – 250 µg twice daily; or 1000 µg twice dailyChildren 4 – 11 years: 50 µg twice daily

Budesonide Pulmicort

DPI: 200 µg/actuationAdults: 200 – 400 µg twice daily; 400 – 800 µg twice dailyChildren > 6 years: 200 µg twice dailySVN: 0.25 mg/2 ml; 0.5 mg/2 mlChildren 1 – 8 years: 0.5 mg total dose once daily or twice daily in divided doses 1 mg given as 0.5 mg twice daily or once daily

Corticosteroids Used in Aerosol Administration

Fluticasone propionate/ salmeterol

Advair Diskus

Advair HFA

DPI: 100 µg fluticasone / 50 µg salmeterol 250 µg fluticasone / 50 µg salmeterol 500 µg fluticasone / 50 µg salmeterolAdults and children > 12 years: 100 µg fluticasone / 50 µg salmeterol, one inhalation twice daily, about 12 hours apartChildren > 4 years: 100 µg fluticasone / 50 µg salmeterol, one inhalation twice daily, about 12 hours apartMDI: 45 µg fluticasone / 21 µg salmeterol 115 µg fluticasone / 21 µg salmeterol 230 µg fluticasone / 21 µg salmeterolAdults and children > 12 years: 2 inhalations twice daily, about 12 hours apart

Budesonide / formoterol fumarate

Symbicort MDI: 80 µg budesonide / 4.5 µg formoterol 160 µg budesonide / 4.5 µg formoterolAdults and children > 12 years: 160 µg budesonide / 9 µg formoterol twice daily; maximum daily: 640 µg budesonide / 18 µg formoterol

Advair Advair Diskus combines an inhaled corticosteroid and

an inhaled long-acting bronchodilator in one easy-to-use device. Advair Diskus does not replace fast-acting inhalers for sudden symptoms. Advair Diskus effectively treats the two main components of asthma at the same time: constriction, the tightening of the muscles around the airways, and inflammation, the swelling and irritation of the airways. Constriction and inflammation cause the airways to narrow and reduce airflow into the lungs, which may result in symptoms such as wheezing, coughing, chest tightness, or shortness of breath. The combination of fluticasone (Flovent-steroid) and salmeterol (Serevent-bronchodilator) is used to prevent wheezing, shortness of breath, and breathing difficulties caused by asthma, but also be prescribed for COPD.

Advair Generic Name: fluticasone propionate and

salmeterol xinafoate Trade Name: Advair (Advair Diskus) How should Advair Asthma Medication be Used?

1. OPEN Hold the DISKUS in one hand and put the thumb of your other hand on the thumbgrip. Push your thumb away from you as far as it will go until the mouthpiece appears and snaps into position. 2. CLICK Hold the DISKUS in a level, horizontal position with the mouthpiece towards you. Slide the lever away from you as far as it will go until it clicks. The DISKUS is now ready to use. Every time the lever is pushed back, a dose is ready to be inhaled. This is shown by a decrease in numbers on the dose counter.

Advair To avoid releasing or wasting doses:

• Do not close the DISKUS. • Do not tilt the DISKUS. • Do not play with the lever. • Do not advance the lever more than once. 3. INHALE Before inhaling your dose of Advair Diskus, breathe out as far as is comfortable, holding the DISKUS level and away from your mouth. Remember, never breathe out into the DISKUS mouthpiece. Put the mouthpiece to your lips. Breathe in quickly and deeply through the Advair Diskus, not through your nose.

CombosSymbicort (Contains formoterol, a long-acting

beta2-adrenergic agonist (LABA) and budesonide (steroid); given BID, two doses 160/4.5 mcg, 80/4.5 mcg; MDI)

Dulera (mometasone furoate/ formoterol fumarate dihydrate, BID, 100/5 or 200/5 mcg dose MDI)

Non-Steroidal Anti-Asthma Drugs

Mast cell stabilizers

◦ Indicated for prophylactic control of mild to moderate asthma

◦ Inhibits degranulation of mast cells in response to allergic and non-allergic stimuli

◦ Used typically as alternatives to inhaled corticosteroids, especially in children

Non-Steroidal Anti-Asthma Drugs

Leukotriene inhibitors

◦ Indicated for prophylactic control of mild to moderate asthma

◦ Used in combination with inhaled steroids to reduce the dose of the steroid

Non-Steroidal Anti-Asthma Drugs

Cromolyn sodium

Intal

Nasalcrom

MDI: 800 µg / actuationAdults and children > 5 years: 2 inhalations four times dailySVN: 20 mg / ampule or 20 mg / 2 mlAdults and children > 2 years: 20 mg inhaled four times dailySpray: 40 mg / ml (4%)Adults and children > 2 years: 1 spray each nostril, 3 to 6 times daily every 4 – 6 hours

Nedocromil sodium

Tilade MDI: 1.75 mg / actuationAdults and children > 6 years: 2 inhalations four times daily

Zafirlukast Accolate Tablets: 10 and 20 mgAdults and children > 12 years: 20 mg twice daily, without foodChildren 5 – 11 years: 10 mg twice daily

Non-Steroidal Anti-Asthma Drugs

Montelukast Singulair Tablets: 10 mg; 4 and 5 mg chewable; 4 mg packet of granules:Adults and children > 15 years: one 10 mg tablet dailyChildren 6 – 14 years: one 5 mg chewable tablet dailyChildren 2 – 5 years: one 4 mg chewable tablet dailyChildren 6 – 23 months: one 4 mg packet of granules daily

Zileuton Zyflo Tablets: 600 mgAdults and children > 12 years: one 600 mg tablet four times per day

Aerosolized Anti-Infective Agents

Pentamidine isethionate (Nebupent)

◦ Indicated for the prevention of Pneumocystis carinii pneumonia (PCP)

◦ Not recommended for use in treatment of PCP (however typically given)

Pentamidine Isethionate (Nebupent) Action: The drug interferes with protozoal

nuclear metabolism inhibitionof DNA, RNA, phospholipid and protein synthesis. It is known to have activity against pneumocystis carinii.

Indication: Prevention of Pneumocystis carinii pneumonia (PCP) in high risk, HIV-infected patients.

Dosage: 300mg once every 4 weeks (nebulized)

Pneumocystis pneumonia (PCP) Pneumocystis pneumonia (PCP) form of

pneumonia, caused by the yeast-like fungus (which had previously been erroneously classified as a protozoan) Pneumocystis jirovecii

Pneumocystis is commonly found in the lungs of healthy people, but being a source of opportunistic infection it can cause a lung infection in people with a weak immune system.

Pneumocystis pneumonia is especially seen in people with cancer, HIV/AIDS and the use of medications that affect the immune system.

also known as Pneumocystis jiroveci[i] pneumonia

Pentamidine Isethionate

Adverse effects◦ Cough

◦ Bronchial irritation, bronchospasm

◦ Shortness of breath

◦Given using a scavenger nebulizer/SPAG

Pentamidine Isethionate

Adverse effects◦ Fatigue

◦ Pharyngitis

◦ Chest Pain

Aerosolized Anti-Infective Agents

Ribavirin (Virazole)

◦ Indicated as anti-viral agent to treat respiratory syncytial virus (RSV)

◦ Administered via small particle aerosol generator (SPAG)

Ribavirin-injectionRibavirin is also used with an interferon

medication to treat hepatitis C in people who have not been treated with an interferon before.

Ribavirin is in a class of antiviral medications called nucleoside analogues. It works by stopping the virus that causes hepatitis C from spreading inside the body. It is not known if treatment that includes ribavirin and another medication cures hepatitis C infection, prevents liver damage that may be caused by hepatitis C, or prevents the spread of hepatitis C to other people.

Ribavirin

Adverse effects

◦ Skin rash

◦ Eyelid erythema

◦ Occlusion of endotracheal tube

◦ Deterioration of pulmonary function

Aerosolized Anti-Infective Agents

Tobramycin (Tobi)

◦ Indicated for management of chronic infection with Pseudomonas

aeruginosa; typically seen with CF and

immune suppressed patients

◦ Treat or prevent colonization

TobiAction: Aminoglycoside antibiotic

disrupts protein synthesis eventually resulting in cell death (gram negative organisms).

Dosage: One 5 mL ampule contains 300mg of tobramycin. Given B.I.D. / Q12 with recommended nebulizer (Pari type neb)

Tobramycin

Adverse effects

◦ Ototoxicity and tinnitus

◦ Bronchospasm

◦ Fetal harm (deafness)

Aerosolized Anti-Infective Agents

Zanamivir (Relenza)

◦ Indicated for treatment of uncomplicated illness due to influenza virus

Relenzaused in the treatment and prophylaxis of

influenza caused by influenza A virus and influenza B virus.

The bioavailability of zanamivir is 2%. After inhalation, zanamivir is concentrated in the lungs and oropharynx, where up to 15% of the dose is absorbed and excreted in urine.

Dosing is limited to the inhaled route. This restricts its usage, as treating asthmatics could induce bronchospasms

Zanamivir

Adverse effects

◦ Bronchospasm

◦ Under treatment of bacterial infection appearing as viral infection

Aerosolized Anti-Infective Agents

Amphotericin B

◦ Indicated for the treatment of fungal infections, especially in lung transplants

amphotericin Bamphotericin B binds the main

component of fungal cell membranes, forming a transmembrane channel that leads to monovalent ion (K+, Na+, H+ and Cl−) leakage, which is the primary effect leading to fungal cell death.

Amphotericin B

Adverse effects

◦ Nausea

◦ Vomiting

◦ Bronchoconstriction

Aerosolized Anti-Infective Agents

Pentamidine isethionate

Nebupent

300 mg powder in 6 ml sterile water, once every four weeks

Ribavirin Virazole 6 g powder in 300 ml sterile water (20 mg / ml solution); given every 12 – 18 hr / day for 3 – 7 days by SPAG

Tobramycin TOBI 300 mg / 5 ml ampule:Adults and children > 6 years: 300 mg bid, 28 days on drug, 28 days off drug

Zanamivir Relenza DPI: 5 mg / inhalation:Adults and children > 7 years: 2 inhalations (one 5 mg blister / inhalation) bid, 12 hours apart for 5 days

Amphotericin B

Fungizone

10 mg three times per day for six to 8 weeks

Nitric Oxide

Indicated for the treatment of pulmonary hypertension in neonates

Causes relaxation of vascular smooth muscle, producing pulmonary vasodilation

Nitric Oxide

Contraindicated in neonates with right to left shunts

Nitric Oxide

Adverse effects

◦ Hypotension

◦ Formation of Methemoglobinia

◦ Withdrawal