Primary function of Resp system is to bring O2 in and remove CO2 Ventilation vs respiration (Books says PERFUSION) Ventilation – mechanical process of air coming in and out of lungs Respiration(PERFUSION)- process by which gases are ACTUALLY exchanged in the lungs Inspiration → diaphragm contracts, creating neg pressure in lung, air comes in Expiration → diaphragm relaxes, air goes out Normal RR rate 12-20 , rate is set by neurons in the brainstem but can fluctuate d/t emotions, fever, stress, blood PH, and certain meds. Alveoli(the tiny sacs at the end of the bronchial tree)- have no smooth muscle, but highly rich in capillaries, air leaves through alveolar membrane and is exchanged for CO2. Perfusion- blood flow through the lung Bronchioles (the little tree) – their diameter varies w contraction or relaxation of smooth muscle Sympathetic branch- activates beta 2 adrenergic receptors (Works on LUNGS ), causes bronchiolar smooth muscle to RELAX , airway diameter to INCREASE, and BRONCHODILATION to occur – improved breathing Parasympathetic branch- cause bronchiolar smooth muscle to CONTRACT, airway diameter to NARROW and BRONCHOCONSTRICTION to occur. Bronchodilators- will enhance breathing and tx pulm disorders Bronchoconstrictors- result in more labored breathing and SOB Admin of pulmonary drugs via INHALATION Method provides RAPID and EFFICIENT mechanism to deliver drugs Instantaneous onset of action d/t > surface area and blood supply of bronchioles and alveoli Aerosol therapy is used Aerosol- a suspension of miniature liquid droplets or fine solid particles In a gas Major advantage is that it delivers drugs to IMMEDIATE SITE OF ACTION → < systemic s/e Immediate relief fro bronchospasm: acute condition in which bronchiole smooth muscle rapidly contracts causing sob Drugs also loosen viscious mucus Drugs CAN still produce systemic effects bc some absorption still happens in capillaries; ex: anesthetics nitrous oxide anda isoflurane (forane) ; solvents and paints also absorbed systemically , can cause death
Chances of systemic toxicity is < if admin is CORRECT Nebulizer - machine that vaporizes a liquid med into a fine mist for inhalation, uses mask or HHD DPI(dry powder inhaler) – ex: fluticasone; if drug is solid use this device that’s activated during inhalation to deliver fine powder directly to bronchiole tree MDI (Metered dose inhaler) – MOST COMMON type of device to deliver respiratory drugs; have a propellant inside a canister filled w medication. Canister is depressed while inhaling a slow deep breath. An exact measured dose of med is delivered during each breath Disadvantages: diff to measure exact med bc pts breathing patterns vary and may not use inhalers correctly Only 10-50% of med reaches lower resp tract Instruct pt not to swallow residual/excess med in mouth → will cause systemic s/e ASTHMA Chronic pulmonary disease w inflammatory and bronchospasm components More common in peds Characterized by acute bronchospasms- cause intense breathlessness, coughing, gasping for air (NARROW the airway) Acute inflammatory response- stimulates histamine release and other inflammatory mediators → which > mucus and edema in airways (PLUG the airway) ^^ BOTH CONTRIBUTE TO AIRWAY OBSTRUCTION ^^ Astma pts can have ACUTE or CHRONIC s/s Some pts get attacks d/t triggers (air poullutants, allergens, chemicals and food, respiratory infections, stress) Others get attacks d/t EXERCISE INDUCED ASTHMA Status asmathicus- SEVERE, PROLONGED form that is unresponsive to drug tx → leads to RR failure. Pharmacotherapy for asthma focuses on 1 out of 2 mechanisms: 1) TERMINATE acute bronchospasms – tx w acute relief meds SABA 2) REDUCE the frequency of attacks – tx w long term control meds LABA QUICK RELIEF MEDS- short, immediate acting beta 2 adrenergic agonists, anticholinergics and systemic corticosteroids (po) LONG TERM MEDICATIONS - inhaled corticosteroids, mast cell stabilizers, leukotriene modifiers, long acting beta 2 adrenergic agonists, methylxanthines, immunomodulators.
BRONCHODILATORS FOR TX ASTHMA Beta 2 adrenergic agonists (beta agonists) are effective bronchodilators for management of asthma and other pulm diseases. First line drugs for tx of ACUTE VASOCONSTRICTION Active SNS → bronchodilation Have no anti-inflammatory properties (other drugs have to be given also to tx imflammation of CHRONIC asthma) Act on B1 or B2 receptors – heart or lungs On both = non selective On B2 only- selective Beta 2 adrenergic agonists have largely replaced older non selective drugs bc they have LESS CARDIAC EFFECTS * (BYPASS the heart, only work on the LUNGS*) SABAS – short acting beta adrenergic agonists ex: albuterol, levoalbuterol, metaproterenol, and SQ terbulatine have RAPID ONSET OF ACTION (usually mins) ; most FREQUENTLY prescribed for acute asthma attacks ; AKA RESCUE DRUGS ; LAST 2-6 HRS ; usually are PRN meds for ACUTE EPISODES LABAS - long acting beta agonists : arfirmoterol , albuterol, formoteol, olodaterol , salmeterol- therapeutic effect can last → 12HRS . LONG ACTING* /LONG DURATION OF ACTION; LABAS have → BLACK BOX WARNING: use is associated w increased r/o asthma related deaths. LABAS have slow onset of action and will not be effective or reverse ACUTE BRONCHOSPASM LABAS should only be used as adjunct therapy for pts who cannot be controlled w other meds → such as inhaled corticosteroids, or pts w severe asthma that require 2 meds for tx BETA ADRENERGIC agonists are avail in PO, inhaled, parenteral formulations; inhalation is MOST COMMON → have less systemic toxicity PO → longer duration but more systemic a/e Chronic use can = tolerance to the bronchodilation effect and duration of action will shorten → will need > dose or secondary aadjunct drugs added Need for > use of these meds → means condition is deteriorating ; seek help ALB(2)UTEROL (ProAir HFA, Proventil HFA, Ventoline HFFA, VoSpire ER) Bronchodilator ; beta 2 adrenergic agonist SABA used to tx acute bronchospasms in asthma
Rapid onset + safe = preferred tx for acute bronchospasms Facilitates mucus drainage Inhibit release of inflammatory chemicals from mast cells Inhale 15-30 mins prior to physical activity - can PREVENT EXERCISE INDUCED BRONCHOSPASMS Not recommended for asthma ppx Po forms include IR and ER tabs and an oral solution Oral forms= LONGER ONSET OF ACTION; not appropriate for tx or acute asthma attacks Proper use of inhaler = effectiveness of drug Duration: 2-6 hrs for INHALATION ; 8-12 HR for ORAL (longer duration for oral ) S/E: uncommon some pts get palpitations, HA, throat irritation , tremors, nervousness, restlessness, and tachy (adrenergic s/e) less common → insomnia, dry mouth (cholinergic) uncommon s/e → chest pain, paradoxical bronchospasms , allergic reactions caution when giving to pts w hx of cardiac disease, CAD or HTN – b/c of possible cardiovascular effects use w beta blockers will inhibit bronchodilation a Avoid MAOIs w/in 14 days of starting med Can cause HYPOKALEMIA at high doses (Remember : can cause cardiovascular effects) Caffeine > nervousness, tremor, palpitations – AVOID IT Tx of overdose: overdose results in exaggerated SNS activation → causing dysrhythmias, hypokalemia, hyperglycemia. Admin of cardioselective beta adrenergic antagonists may be needed. _______________ TX chronic asthma w anticholinergics (aka cholinergic blockers) Alternative bronchodilators Block PNS → increasing SNS effects → bronchodilation → better breathing Ipatropium is oldest and most frequent anticholinergic prescribed ; has SLOWER onset of action ; produces LESS INTENSE bronchodilation ; BUT when combined w a beta agonist is produces greater effect > EX: Combivent Respimat; mix of both
Tiotropium- has LONGER duration of action than Ipatropium; inhaled form txt’s COPD and asthma maintenance Stiolto Respimat (tiotropium w LABA olodaterol) – used for maintenance tx of COPD. Inhaled anticholinergics are safe meds , systemic s/e not common S/E : usually are dry mouth, HA, cough, GI distress, anxiety IPRATROPIUM (Atrovent) → think iprATropium (AT= ANTICHOLINERGIC) Bronchodilator/ anticholinergic Anticholinergic drug that is admin via INHALATION and INTRANASAL routes Inhalation- relieves and prevents bronchospasms of COPD Ipratropium combined w albuterol (Combivent Respimat) – first line drug for tx bronchospasms for COPD, bronchitis, and emphysema Off label tx for asthma exacerbation Combined w beta agonists/corticosteroids → BRONCHODILATION Nasal spray – approved for s/s relief of runny nose r/t common cold/allergic rhinitis Inhibits nasal secretions but has NO DECONGESTANT action TX LIMITED TO 3 WEEKS ** Wait 2-3 mins between doses Avoid eye contact → blurred vision Few systemic effects s/e irritation of URT , cough, dry nasal mucosa, hoarseness , bitter taste ( RINSE MOUTH after admin ), IN admin can cause epistaxis and excessive drying don’t give to pts allergic to soya lecithin Use w atropine → additive anticholinergic effects Use with antidiabetic drug pramlintide → both slow peristalsis and can cause life threatening GI s/s TX OF CHRONIC ASTHMA WITH METHYLXANTHINES Used to be preferred drugs for asthma Not anymore – only used for asthma not responsive to beta agonists or inhaled corticosteroids
Theophylline and aminophylline – bronchodilators r/t caffeine Have narrow safety margin- especially w prolonged use s/e : insomnia, nervousness (like caffeine) admin PO and IV rather than INHALATION PPX OF ASTHMA W CORTICOSTEROIDS -TX INFLAMMATION !! ** ICS ( inhaled corticosteroids) are used for the LT PREVENTION of asthmatic attacks Oral corticosteroids are used for SHORT TERM management of ACUTE SEVERE ASTHMA Dampen the activation of inflammatory cells and increase production of anti-inflammatory mediators Mucus production is < which < edema which < airway obstruction They sensitize bronchial smooth muscle to be more responsive to beta agonist stimulation < bronchial hyperresponsiveness to allergens that trigger asthma attacks Can be admin systematically or INHALATION INHALED CORTICOSTEROIDS- preferred tx for PREVENTING ASTHMA attacks; need to be taken daily; suppress inflammation without major a/e . – DON’T TX ACUTE EPISODES – long onset s/s will improve in 1-2 weeks but meds may need to be taken up to 4-8 wks for max effect LABA may be px for pts w persistent asthma → for additive effect ORAL PREDNISONE- given if pt unresponsive to other tx Oral admin limited to 5-7 days → pt then switched to inhaler for LT management INHALED corticosteroids are inhaled so slowly → equal no systemic s/e ; local s/e → hoarseness, oropharyngeal candidiasis. If taken longer than 10 days – can produce >BS, PU, adrenal gland atrophy PO/INHALED taken longer than 10 days → can affect BONE physiology in adults/kids Adults at risk for osteoporosis should receive periodic bone mineral density tests Taken longer than 14 days → taper off BECLOMETHASONE (Qvar) Anti-imflammatory drug for asthma and allergic rhinitis/ INHALED CORTICOSTEROID Avail through aerosol inhalation or nasal spray for allergic rhinitis
First line drugs for LT management of asthma in kids/adults 3-4 wks for max effect Reduces inflammation → < freq of asthma attacks Does NOT work/tx ACUTE ASTHMA ATTACKS- it is NOT a bronchodilator IN- effective at <s/s allergic rhinitis a/e : inhaled- few systemic s/e small amts swallowed w each dose- observe for corticosteroid TOXICITY local s/e – hoarseness, dry mouth, changes in taste development of cataracts in adults Corticosteroids → Cataracts LT Intranasal or inhaled- cause growth inhibition in kids (monitor growth in kids) Contraindicated if infection is present bc it can mask s/s infection Oropharyngeal candidiasis d/t constant deposits of drug in oral cavity PPX of asthma w Leukotriene modifiers Second line meds to reduce inflammation and ease bronchoconstriction Used as alt drugs in management of asthma s/s Mediators of the immune response involved in allergic and asthmatic reactions . Synthesized by mast cells , neutrophils, basophils, and eosinophils When released in the airway → cause edema, inflammation, and bronchoconstrict 3 drugs modify these reactions ^^ Zileuton (Zyflo) – blocks LIPOXYGENASE , enzyme used to synthesize leukotrienes Zafirlukast (accolate) And montelukast (singulair) block leukotriene receptors ^^ ALL 3 REDUCE INFLAMMATION^^ Not considered bronchodilators Approved for ppx of asthma , taken PO Zileuton has slower onset (2hrs) → not used for acute asthma attacks s/e : HA, cough, nasal congestion, GI upset may occur older than 65 - > r/o infections
don’t take or give to pts w SIGNIFICANT HEPATIC DYSFUNCTION or in chronic alcohol users bc these drugs are metabolized mainly by the liver. ** MONTELUKAST (Singulair) Anti-inflammatory drug for asthma ppx / leukotriene modifier Used for ppx of persistent, chronic asthma ,exercise induced bronchospasms(take 2 hrs before activity) ; and allergic rhinitis Prevents airway edema and inflammation Blocks leukotriene receptors in airways Given PO RAPID onset of action – but STILL NOT used for acute bronchospasm attacks Only drug approved for peds Avail in chewable tabs and as granules to mix w applesauce, mashed carrots or ice cream s/e: HA (most common) , N/D, some pts have serious neuropsychiatric events → suicidal ideation , hallucinations, aggressiveness, depression careful use in pts w preexisting hepatic impairment may increase ALT levels – check LIVER TESTS !!! (Remember its metabolized by the liver)