Pharmacology Flashcards
Advantages of treatment of the respiratory tract with inhaled aerosols?
- Aerosol doses are usually smaller than doses for system administration
- Onset of drug action is rapid
- Delivery is targeted to the organ requiring treatment
- Less systemic side effects, or less often or less severe
Primary focus of respiratory care pharmacology…
The delivery of bronchoactive inhaled aerosols to the respiratory tract for the diagnosis and treatment of pulmonary diseases.
Pharmacokinetic phase of drug action
The time course and disposition of a drug in the body based on its absorption, distribution mechanism, and elimination.
Fully ionized vs. nonionized drugs
Fully ionized- not absorbed across a lipid membrane, effects are largely local. (Ipratropium)
Nonionized- lipid-soluble and diffuses across a cell membrane into the bloodstream, effects can be systemic. (Atropine)
Pharmacodynamic phase of drug action
the mechanisms of drug action by which a drug molecule causes its effects on the body
Types of receptors in the lungs
Sympathetic (adrenergic)
Parasympathetic (cholinergic)
Neurotransmitters of the sympathetic and parasympathetic systems
Sympathetic- Norepinephrine (adrenergic)
(similar to epinephrine or adrenaline)
Parasympathetic- Acetylcholine (cholinergic)
Adrenergic
-Drug that stimulates a receptor responding to norepinephrine or epinephrine
Antiadrenergic
Drug that blocks a receptor for norep. or epinephrine
Cholinergic
Drug that stimulates a receptor for acetylcholine (mimics acetylcholine)
Anticholinergic
drug that blocks a receptor for acetylcholine
Muscarinic
Drug that stimulates acetylcholine receptors specifically at parasympathetic nerve ending sites
Receptors in the heart and effects
Beta-1 adrenergic (increases rate and force)
M2-cholinergic (decreases rate)
Receptors in bronchiole smooth muscle
Beta-2 adrenergic (bronchodilation)
M3-cholinergic (bronchoconstriction)
Receptors in pulmonary blood vessels
Alpha-1 adrenergic (vasoconstriction)
Beta-2 adrenergic (vasodilation)
M3-cholinergic (vasodilation)
Receptors in bronchial blood vessels
Alpha-1 adrenergic (vasoconstriction)
Beta-2 adrenergic (vasodilation)
Receptors at submucosal glands
Alpha-1-adrenergic (increased fluid, mucin)
Beta-2-adrenergic (increased fluid, mucin)
M3-cholinergic (Exocytosis, secretion)
Most common use for adrenergic bronchodilators?
-to improve flow rates in asthma (including exercise induced asthma), acute and chronic bronchitis, emphysema, bronchiectasis, cystic fibrosis, and other OBSTRUCTIVE airway states.
Indications for short-acting bronchodilators… (beta-2 agonists like albuterol and levalbuterol)
-indicated for relief of acute reversible airflow obstruction in asthma or other obstructive airway diseases (termed “rescue agents”)
Indications for long-acting bronchodilators… (salmeterol, formoterol, and arformoterol)
-indicated for maintenance bronchodilation and control of bronchospasm and nocturnal symptoms of asthma or other obstuctive diseases, such as COPD.
Indication for racemic epinephrine
Often used by inhaled aerosol or by direct lung instillation for its strong beta-adrenergic vasoconstricting effect to reduce airway swelling after extubation or during epiglottitis, croup, or bronchiolitis or to control airway bleeding during endoscopy.
Bronchodilator effects
Alpha stimulation, beta-1, and beta-2 stimulation
Alpha-1 receptor stimulation- vasoconstriction and a vasopressor effect (increased BP)
Beta-1 receptor stimulation- causes increased HR and myocardial contractility
Beta- 2 receptor stimulation- relaxes bronchial smooth muscle, stimulates mucociliary activity, inhibitory action on inflammatory mediator release
Ultra-short-acting adrenergic bronchodilators (catecholamines)
Epinephrine (Adrenaline Chloride) (Alpha, beta)
-Onset 3-5 minutes, Duration 1-3 hours, peak 5-20 mins
-SVN, 1% solution, 0.25-0.5 ml 4 times daily
Racemic epinephrine (microNefrin) (Alpha, beta)
-Onset 3-5 mins, Duration 0.5-2 hrs, peak 5-20 mins
-SVN, 2.25% solution, 0.25-0.5ml 4 times daily
Short-acting adrenergic bronchodilator agents (noncatecholamine)
Albuterol (Proventil HFA, Ventolin HFA) (beta-2)
-Onset 15 min, Duration 5-8 hours, peak 30-60 mins
-SVN- 0.5% solution, 0.5 ml (2.5mg), MDI: 200ug/puff, 2 puffs every 4-6hrs
Levalbuterol (Xopenex) (beta-2)
-Onset 15 min, Duration 5-8 hours, peak 30-60 mins
-SVN 0.31, 0.63, or 1.25 mg/3ml, 3 times daily
Long-acting adrenergic bronchodilators
-Salmeterol (Servant Diskus) (beta-2 agonist)
Onset 20 mins, Duration is 12 hours, peak 3-5, DPI: 50ug/blister, twice daily.
Adverse effects of adrenergic bronchodilator agents
-Dizziness, Hypokalemia, Loss of bronchoprotection (loss of ability of beta-2 agonists to prevent bronchoconstriction from a stimuli), Nausea, tolerance (tachyphylaxis-decrease in response to drug), Worsening ventilation/perfusion (V/Q) ratio (decrease in PaO2/SpO2).
Assessment of bronchodilator therapy
- Monitor flow rates and lab reports of PFT’s before and after
- Access ABG’s or pulse ox. saturation
- Note effect of beta agonist on blood glucose (increase) and K+ (decrease) lab values
- Emphasize patient education that beta agonists do not treat underlying inflammation and don’t prevent progression of asthma
- Instruct and then verify correct use of aerosol delivery device
- Instruct patients on assembly and cleaning of inhalation devices
- Long-acting beta agonist (assess ongoing lung function such as FEV1 and peak expiratory flows, assess amount of rescue beta agonist use, assess number of exacerbations, hospitalizations, days absent from school/work, and ability to reduce dose on concomitant corticosteroids
Anticholinergic bronchodilators
as opposed to adrenergic
Produce airway relaxation by blocking cholinergic receptors that induce bronchoconstriction.
- *Effective only if bronchoconstriction is secondary to cholinergic activity
- Adrenergic actively stimulates and anticholinergic passively blocks
Indications for use of anticholinergic bronchodilators
Indicated as bronchodilators for maintenance treatment in COPD, including chronic bronchitis and emphysema.
Indications for both Adrenergic and Anticholinergic bronchodilators
For use in patients with COPD receiving regular treatment who require additional bronchodilation for relief of airflow obstruction.
Example: Ipratropium bromide and albuterol (Combivent; DuoNeb)
Mode of action of Anticholinergic bronchodilators
Ipratropium bromide and tiotropium act as competitive antagonists for acetylcholine at M3 muscarinic receptors on airway smooth muscle
Adverse effects of Anticholinergic bronchodilators
Ipratropium and tiotropium bromide have little side effects because they are fully ionized. Eyes should be protected during nebulization.
Atropine sulfate is nonionized and does cause a number of systemic side effects such as; dry mouth, pupillary dilation, lens paralysis, increases intraocular pressure, increases HR, urinary retention, and altered mental state. Not recommended by nebulization.
Mucous-controlling agents
N-acetyl-cysteine (10 or 20%) (NAC) (Mucomyst) (*always given with bronchodilator)
-SVN (3-5ml) used for bronchitis (efficacy not proven)
Dornase alfa (Pulmozyme)
-SVN (2.5mg/ampule, x’s 1 a day) Cystic fibrosis
Side effects of Mucus-controlling agents
NAC-
-Irritation of the airway and cause of bronchospasm, especially in subjects with hyperactive airways. Pretreatment with adgrenergic bronchodilator can reduce airway resistance with NAC.
-Airway obstruction secondary to rapid liquefaction of secretions
-Disagreeable odor secondary to hydrogen sulfide
-Incompatibility with certain antibiotics if mixed in solution
-increased concentration and toxicity towards end of nebulizer treatment
-Nausea, rhinorrhea
-Stomatitis
-Reactivity with rubber, copper, iron, cork
Dornase alfa
-Pharyngitis, laryngitis, voice alteration, chest pain, conjunctivitis,
Mode of action of NAC and Dornase alfa
NAC- breaks disulfide bonds
Dornase alfa- proteolytic enzyme that breaks down DNA material from neutrophils found in purulent secretions
Inhaled Corticosteroids
-Endogenous hormones produced in the adrenal cortex, regulate basic metabolic functions in the body and exert an antiinflammatory effect. Those used to treat Asthma and COPD are glucocorticoids.
Indications for use of corticosteroids
For antiinflammatory maintenance therapy of persistent asthma and severe COPD.
Mode of action of corticosteroids
Glucocorticoids are lipid-soluble drugs that act on intracellular receptors. Do not provide immediate relief as mechanism of action takes hours or days to have full effect.
Types of inhaled corticosteroids available
Beclomethasone dipropionate HFA (QVAR)
-Dosage: MDI 40 and 80 ug/puff, adults and children >12, twice daily
Flunisolide hemihydrate HFA (AeroSpan)
-Dosage: MDI 80 ug/puff, adults and children>12, twice daily
Budesonide (Pulmicort Flexhaler or Respules)
-Dosage: Flexhaler (DPI, 90ug/actuation and 180ug/act. >12 yrs
Respules (SVN, 0.25mg, 0.5mg or 1mg/2ml, children 1-8yrs
Fluticasone propionate/salmeterol (Advair Diskus and HFA)
-Dosage: Diskus (DPI, 100ug, 250ug or 500ug fluticasone/50 ug salmeterol
HFA (100 ug/50ug, 1 inhalation twice daily, ~12hrs apart
Symbicort
-Dosage: MDI, 80ug or 1600ug budesonide/4.5 ug formoterol, >12 yrs take 320ug or 160ug/9ug twice daily.
Dulera
-Dosage: MDI, 100ug or 200ug mometasone/5ug formoterol, >12 yrs previously medium dose (400ug/20ug daily) previously high dose (800ug/20ug daily)
Adverse effects of corticosteroids
Much less systemic effects than other classes of inhaled aerosolized drugs.
Systemic- adrenal insufficiency, extra-pulmonary allergy, acute asthma, HPA supression, Growth retardation (controversial), Osteoporosis (controversial)
Local- Oropharyngeal infections (most common side effect), dysphonia, cough, bronchoconstriction, incorrect use of MDI
Nonsteroidal antiasthma drugs
Cromolyn sodium (NasalCrom)
-Dosage: Spray, 40mg/ml, 1 spray each nostril, 3-6x’s/ 4-6 hrs)
Montelukast (Singulair)
-Dosage: Tablets, 10, 5, or 4mg, >15yrs one10mg tablet daily, children 6-14yrs (one 5mg chewable daily, 2-5yrs (One 4mg chewable daily)
Omalizumab (Xolair)
-Dosage: >12yrs, one subcutaneous injection every 4wks
monoclonal antibodies or anti-IgE agents
Indications for use of antiasthma drugs
Prophylactic management of persistent asthma (step 2 or greater)
Cromolyn sodium and antileukotrienes recommended as alternatives to inhaled corticosteroids in step 2 and step 3 asthma
Cromlyn sodium and montelukast are often used in infants as alternatives to steroids in step 2 asthma
Antileukotrienes can be useful in combination with corticosteroids to reduce the dose of the streroid in step 2 through step 4 asthma
Monoclonal antibodies considered in appropriate populations.
Mode of action of antiasthma drugs (4 drugs)
- Cromlyn sodium- degranulates mast cells in response to allergic and nonallergic stimuli preventing release of histamine, etc.
- Zafirlukast and montelukast act as leukotriene receptor antagonists and are selective competitive antagonists of leukotriene receptors LTD4 and LTE4 (prevents bronchoconstriction)
- Zileuton inhibits the 5-lipoxygenase enzyme that catalyzes the formation of leukotrienes form arachonidonic acid
- Omalizumab inhibits attachment of IgE to mast cells, reducing inflammatory mediator response.
Adverse effects of antiasthma drugs
Inappropriate use, controllers rather than relievers and so people tend to overuse them thinking they aren’t working.
-Headaches, liver enzyme changes, abdominal pain, dyspepsia
Aerosolized antiinfective agents
Pentamidine isethionate (NebuPent)
-Dosage: 300mg powder in 6ml water, 300mg every 4 wks in treatment of PCP prophylaxis
Ribavirin (Virazole)
-Dosage: 6 g powder in 300ml water, given every 12-18 hours/day for 3-7 days by SPAG nebulizer for treatment of RSV
Tobramycin (TOBI)
-Dosage: 300mg/5ml ampule, >6yrs, 300mg 28 days on, 28 days off to treat P. aeruginosa infection in CF
Adverse effects of antiinfective agents
Pentamidine- cough, bronchial irritation, bronchospasm, wheezing, fatigue, metallic taste in mouth, conjunctivitis, rash and chest pain, decreases appetite, nausea, night sweats, chills, pancreatitis, hypoglycemia, spontaneous pneumothoraces, neutropenia
Ribavirin- skin rash, eyelid erythema, and conjunctivitis
Tobramycin- possible auditory and vestibular damage with potential for deafness and nephrotoxicity, dysphonia, tinnitus
