Pharmacology Asthma/COPD/Mucus/TB Flashcards
Non-specific adrengergic agonists
Bronchodilators; Epinephrine, Ephedrine, Isoproterenol
B2 Specific agonists with quick onset and short duration
Bronchodilators; Albuterol, Terbutaline
B2 specific agonists with slow onset and long duration
Bronchodilators; Salmeterol, Formoterol (used with steroids)
Cholinergic antagonists
Bronchodilators; Atropine, Ipratropium
Methylxanthines
Bronchodilators and anti-inflammatory; aminophylline, theophylline
Cromolyns
Anti-inflammatory; cromolyn sodium
Corticosteroids
Anti-inflammatory; budesonide, fluticasone, fluticasone (w/ Salmeterol), budesonide (w/ formoterol), Mometasone, Beclomethasone, Ciclesonide, Prednisone (oral), Prednisolone, Methylprednisolone, Dexamethasone (oral or IV)
Leukotriene Receptor Blockers
Anti-inflammatory; Monteleukast, Zafirlukast
Leukotriene Synthesis Inhibitors
Anti-inflammatory; Zileuton
Anti IgE Antibody
Omalizumab
Sympathomimetics MOA
increase levels of cAMP; some inhibition on the release of mediators from mast cells; some inhibition on microvascular permeability; promote to a small degree mucocilliary transport
Sympathomimetics Adverse Effects
N/V, HA, fall in BP, increase Heart Rate, Cardiac Arrhythmias, PaO2 decrease, CNS toxic effects (agitation, convulsions, coma, respiratory and vasomotor collapse)
AntiMuscarinics MOA
Competitive Ach-muscarinic blockade, reduce airway smooth muscle constriction, enhance B2 mediated bronchodilation
AntiMuscarinics Adverse Effects
Pupillary dilation and cycloplegia
Ipratropium
A antimuscarinic that is poorly absorbed with no significant systemic effects
Combivent
Combined anti-cholinergic and B2 agonist that is more effective at producing improved lung function than either alone; it is indicated for COPD
Methylxanthines Effects
increase cAMP, block muscular adenosine receptors, decrease release of mediators; bronchodilation, anti-inflammatory effect, positive isotropic and chronotropic effects, increased CNS activity, increased gastric acid secretion, weak diuretic effect, increased skeletal muscle strength (diaphragm)
Methylxanthines Adverse Reactions
N/V, nervousness, HA, insomnia, hypokalemia, hyperglycemia, tachycardia, cardiac arrhythmias, tremor, neuromuscular irritability and seizures
Cromolyn Sodium Effects
alters the activity of chloride channels, inhibits degranulation of mast cells in the lung, inhibit the inflammatory response by acting on eosinophils, inhibits cough by action on airway nerves, reduces bronchial hyperactivity associated with exercise and antigen inhaled asthma
Cromolyns Adverse Effects
No systemic toxicity; unpleasant taste, irritation of trachea leading to cough and bronchospasm
Rare: chest pain, restlessness, hypotension, arrhythmias, nausea, vomiting, CNS depression, seizures, anorexia
Glucocorticoid Effects
decreases production of inflammatory cytokines, reduces mucus secretions, reduces bronchial hyperactivity, enhance the effect of B2 agonists
Glucocorticoid MOA
binds to glucocorticoid receptor cause decreased mRNA stability through effect on tristetraprolin leading to decreased TNF, IL6, GM-CSF, COX2; decreases inflammatory genes; increases anti-inflammatory genes (SLPI, MKP-1, GILZ); decreases TH2 by blocking GATA3
Inhaled Glucocorticoid Adverse Effects
oropharyngeal candidiasis, hoarseness, dry mouth; decreased bone mineral density in premensopausal women; decrease growth rate of children
Oral glucocorticoids Adverse Effects (prolonged use)
Cushing syndrome, glucose intolerance, increased blood pressure and weight, bone demineralization, cataracts, immunosupression, retarded growth in children
Cushing Syndrome
Caused by glucocorticoids - weight gain in abdomen, face (moon face), neck, buffalo hump; thin skin with easy bruising stretch marks; increased acne, facial hair; scalp hair loss; ruddy complexion of face and neck; acanthuses (neck darkening); child obesity and poor growth in height; high BP
Steroids primary target
Phospholipase A2 (stops conversion of Membrane phospholipids to Arachidonic Acid)
Nedocromil primary target
COX1/2 (stops conversion of Arachidonic Acid to PGG2)
Zileuton primary target
5-LO (stops conversion of arachidonic acid to LTA4)
Zafirlukast primary target
Block Leukotriene receptor
Seatrodast primary target
blocks thromboxane A2 receptor
LTB4 role
Neutrophil chemoattractant
LTC4 and LTD4 role
mimic many symptoms of asthma - bronchial hyper reactivity, bronchoconstriction, mucosal edema, increased mucus secretion
Zafirlukast and Monteleukast Role
Block LTD4 receptors, decrease bronchial reactivity and bronchoconstriction, decrease mucosal hyper secretion and mucosal edema, decrease airway inflammation
Zafirlukast Adverse Effects
G.I.T. disturbances, mild HA and elevation of liver enzymes in some patients; high doses in rodents have caused hepatic and bladder cancer and histolytic carcinoma
Monteleukast Adverse Effects
G.I.T. disorders, laryngitis, pharyngitis, nausea, otitis, sinusitis, viral infections; suicidal ideation possible
Zileuton Affects
inhibits leukotriene formation - decreases smooth muscle contraction and blood vessel permeability and reduces leukocyte movement to damaged area
Zileuton Adverse Effects
Causes hepatic enzyme elevation - LFTs required; other effects mild and self limited
Zileuton Interactions
CYP1A2 substrate and inhibitor - interaction with theophylline and others
Omalizumab Effects
binds to IgE, preventing IgE release of inflammatory mediators, leading to decreased allergic response; it reduces severity/frequency of asthma attacks, requires inhaled steroid with it; improves long term asthma control
Omalizumab Adverse Effects
anaphylaxis, redness, bruising, warmth, buring, pain, inflammation at injections site, sore throat, cold symptoms, increase in CV complications, no known drug interactions
COPD Treatment Options
Smoking cessation with nicotine replacement or Bupropion; bronchodilator SABA or LABA; Antmuscarinics; Theophylline and derivatives; combo therapy; steroids, guafensesin, N-acetylcystine; supplemental O2; surgery, lung volume reduction, transplants
Contraindicated drugs in airway disease
sedatives, beta blockers, aspirin and other COX inhibitors, ACE inhibitors, Local anesthetics containing epinephrine
Doxapram
Respirayoty stimulant used for drug induced respiratory depression, acute hypercapnia in COPD; has narrow margin of safety; short acting and given by infusion
Doxapram MOA
activates peripheral carotid receptors
Locations of Cough Receptors and Nerves Involved
airway bifurcations, distal esophagus - link to cough centers via vagus and superior laryngeal nerves
Location of cough control
Medulla
Acute cough
a cough lasting less than three weeks
Subacute cough
cough lasting three to eight weeks
Chronic cough
cough lasting greater than eight weeks
Cough with clear secretions
bronchitis
Cough with purulent secretions
bronchial infections
cough with yellow secretions
inflammatory disorders
cough with malodorous secretions
anaerobic infection
Non productive cough
viral illness, bronchospasm, allergies, airway obstruction, GERD
Complications of cough
Exhaustion, urinary incontinence, pain, insomnia, syncope, stroke, rib fractures
Nonpharmacological treatment for cough
Elimate irritants, hard candies, lozenges, humidifiers, vaporizers, hydration
Dextromethorphan (DM Drugs) Effects
antitussive; suppresses the cough reflex by direct action on the cough center; nonopiod but equal potency to codeine; quick onset with 3-6hr duration; wide margin of safety
Dextromethorphan metabolism
metabolized by CYP2D6 to active metabolite dextrorphan
Dextromethorphan Side Effects
Dizziness, drowsiness, N/V, diarrhea, irritability, excitability, light headedness, trouble sleeping
Dextromethorphan Contra
Concurrent use of MAOI antidepressants; advanced respiratory insufficiency; hepatic disease; hypersensitivity to any ingredients
Diphenhydramine (benadryl) effects
antihistamine - H1 receptor antagonist; suppresses cough reflex by direct effect on cough center; 15 min onset; 4-6hr duration; indicated for nonproductive cough caused by irritation
Diphenhydramine Adverse Effects
Drowsiness, respiratory depression, blurred vision, dry mouth, urinary retention, constipation
Diphenhydramine Contra
Prostate hypertrophy, urinary obstruction, asthma, COPD, peptic ulcer, individuals on MAOIs
Codeine effects
opioid analgesic that acts on mu receptors but has lower affinity than morphine; depresses cough reflex by direct effects on cough control center; 10-30 min onset; 4-6hr duration
Codeine Adverse Effects
Constipation, sedation, histamine release, vasodilation, orthostatic hypotension, dizziness
Codeine Contras
Hypersensitivity, labor of premature birth, preganany, prostatic hypertrophy, individs on sedatives, patients with acute respiratory depression, asthma, COPD
Topical cough relievers
Camphor and menthol and eucalyptus
Guaifenesin effects
symptomatic relief of ineffective productive cough w/ chest congestion; not for chronic cough; loosens and thins lower respiratory tract secretions by increasing the volume and reducing the viscosity of secretions
Guaifenesin Adverse effects
Dizziness, dry mouth, rash, diarrhea, drowsiness, N/V, stomach pain, diarrhea, uric acid nephrolithiasis (large doses)
Nasal decongestants MOA
Alpha adrenergic agonist (sympathomimetic) causing constriction of blood vessels throughout the body, reducing blood supply to nose, decreasing amount of blood in sinusoid vessels, decreasing mucosal edema.
Nasal Decongestant Drugs
Pseudoephedrine (oral, systemic) - releases norepi from adrenergic nerves, phenylephrine (oral, systemic) - directly stimulates adrenergic receptors on postsynaptic sites; both have short half life
Pseudoephedrine metabolism
metabolized to only a minor extant by N-demthylation to norpseudoephedrine
Phenylephrine metabolism
rapid metabolism by MOA and COMT in GI mucosa, liver and other tissues
Systemic Decongestants Adverse Effects
CV stimulation, CNS stimulation - more likely with children/elderly; causes rebound congestion due to ischemia
Systemic decongestant Contras
hyperthyroidism, bradycardia, partial heart block, uncontrolled HTN, V Tach
Oxymetazoline
Afrin; topical nasal spray; do not use for more than 3-5 days; preferred topical agent in pregnancy
Levamfetamine
Inhaled decongestant - does not cause nasal rebound for 7 days
Propylhexadrine
inhaled decongestant that is often abused via cotton plug ingestion or injection
Mucolytics MOA
promote breakdown of mucus by breaking physical bonds within mucus
Mucolytic uses
diseases with excessive production of mucus; cystic fibrosis, COPD, Bronchiectasis, Respiratory infections (TB)
Facilitation of Mucus Clearance
Provide adequate hydration, remove causative factors, optimize tracheobronchial clearance, reduce inflammation
Bromohexine
Secretolytic, increases the production of serous mucus in the respiratory tract and decreases the viscosity of phlegum
Mucolytics - N-Acetyl Cysteine, Acetadote, Erdosteine, Carbocysteine MOA
break the bonds by substituting sulfhydryl radical thus breaking disulfide bonds within mucus; given by aerosol into ET tube; can be given orally to reduce liver injury due to Tylenol overdose
Mucolytic Adverse Effects
Bronchospasm, increased mucus production, incompatible with antibiotics in nebulizer, N/V, bad odor due to hydrogen sulfide, must be used within 96 hrs.
Sodium Bicarbonate
Used to increase the pH of mucus by weakening carbohydrate side chains, thus weaking polysaccharide chains; can be injected directly into the trachea
Dornase Alfa (Pulmozyme)
clone of the natural human pancreatic DNase enzyme which digests extracellular DNA; it reduces the viscosity of secretions during an infection.
Dornase Alfa Indications
Cystic fibrosis, chronic bronchitis, bronchiectasis - has no effect on non-infected sputum
Dornase Alfa (pulmozyme) adverse effects
voice alteration, pharyngitis/laryngitis, rash, chest pain, conjuctivitis
Pulmozyme Contras
patients hypersensitive to Chinese Hamster Ovary cell products
Amiloride
diuretic that can be given by aerosol for pts with CF; Na channel blocker, preventing dehydration of the mucus
Denufosol Tetrasodium
Enhances mucosal hydration and mucus clearance by activating Cl- secretion and inhibition ENa transport via activation of P2Y2 receptors; Fast track treatment for CF
Barriers to TB treatment
slow growth, intracellular location, development of resistance, noncompliance, drug toxicity and interactions
TB first line therapy
Isoniazide + Rifampin + Pyrazinamide + Ethambutol/Streptomycin
M. Avium first line therapy
Clarithromycin + Ethambutol or Clofazimine or Ciprofloxacin or Amikacin
Latent TB treatment schedule
Isoniazid for 9 months; Isoniazid for 6 months; Isoniazid and Rifapentine for 3 months once weekly (highest compliance); Rifampin daily for 4 months
Patients who can’t have Isoniazid and Rifapentine
kids under 2; HIV infected pts because of drug interaction possibility; pregnant women; patients with presumed resistance to either drug
Initial phase Active TB treatment
isoniazid, rifampin, pyrazinamide, and ethambutol for 8wks
Continuation phase Active TB treatment
Daily or twice weekly isoniazid and Rifampin for 18 weeks; can drop Ethambutol once susceptibility to primary drugs is known
Isoniazid MOA
inhibits cell wall synthesis by interfering with mycolic acid synthesis; tidal to rapidly dividing bacilli; static for slowing growing; penetrates host cells
Ethambutol MOA
Disrupts cell wall synthesis by inhibiting arabinosyl transferase, disrupting arabinogalactan synthesis, leading to increased cell wall permeability; static effect, must have actively dividing bacilli, slow development of resistance, no cross resistance
Pyrazinamide MOA
exact target unknown but disrupts plasma membrane and disrupts energy metabolism; converted to active agent by bacilli; decrease pH below threshold for bacterial growth; tidal/static concentration dependent; active against TB in acid environment of lysosome and macrophage
Rifampin MOA
inhibits RNA synthesis by binding beta subunit of RNA polymerase; bacerticidal for intra or extra cellular mycobateria
Isoniazid resistance
inability to take up the drug; alteration in target enzyme; overproduction of target enzyme; emerges rapidly when used alone so never use alone
Isoniazid absorption,
rapidly absorbed from GI tract with oral dose; can also be given IM; half life of 1-4hrs
Isoniazid distribution
all tissues and fluid; with inflamed meninges get therapeutic levels in CSF; crosses placenta and breast milk
Isoniazid Metabolism
acetylated via N-acetyl transferase - fast/slow acetylators affect therapy; chronic liver disease will decrease metabolism; excreted in urine as drug and inactive metabolites
Isoniazid Adverse Effects
Peripheral neuropathy (correct with Vit B6 supplement), Hepatotoxicity (dose related)
Isoniazid Drug interactions
Antacids with Al3+ salts decrease absorption (split dosing), corticosteroids decrease efficacy, inhibits P450 isozyme that metabolizes phenytoin, diazepam, fluoxetine, nelfinavir, etc.
Rifampin Resistance
lack of binding due to beta subunit alteration; never given alone due to rapid resistance
Rifampin absorption
Well absorbed orally; impaired by food or para-aminosalicyclic acid
Rifampin distribution
penetrates all tissues including CSF; 75-85% protein bound
Rifampin Metabolism
Deacetylated in liver; excreted mainly in bile, small amount in renal tubules - no adjustment with renal insufficiency
Rifampin Adverse Effects
Discolors body fluid (turns tears orange-red), GI disturbances and nervous system complaints, fever, chills, aches; Hepatotoxicity (jaundice with liver disease, especially slow acetylators)
Rifampin Interactions
Induction of CYP450 - reduces half life of drugs metabolized by this system (prednisone, Propanodol, sulfamides, dapsone, ketoconazole, HIV protease inhibitors, NNRTIS, etc); makes anticoagulants and oral contraceptives less effective; Probenecid increases serum levels of Rifampin when taken concurrently
Rifampin Uses
first line TB treatment; MRSA w/ Vancomycin; prophylaxis for people exposed meningococci or H flu.; most active antileprosy drug
Ethambutol Absorption and Distribution
Absorbed orally; distributed widely with concentrated areas in kidneys, lungs, saliva; therapeutic levels in CSF, crosses placenta, distribute in breast milk;
Ethambutol Elimination
Partially metabolized in liver; excreted in urine; half like of 3.5hr that extends up to 15hr with renal disease so reduce dose if renal dysfunction
Ethambutol Adverse Effects
Optic neuritis (decreased visual acuity and color discrimination, constriction of visual fields) - dose related and reversible, allergic reactions, increase in serum irate (hyperuricemia - may be increased by INH and Pyridoxine)
Ethambutol Interactions
Al3+ containing antacids reduce absorption (split dose timing)
Pyrazinamide Distribution and Metabolism
Absorbed rapidly from GI tract; distributed widely including CSF and breast milk (undocumented about placenta); eliminated after being hydrolyzed by liver active metabolite
Pyrazinamide Adverse Effects
Dose related hepatoxicity; mild non gout related arthralgias; hyperuricemia due to inhibition of irate excretion - usually asymptomatic
Multidrug resistant TB (MDR TB)
TB that is resistant to Isoniazid and Rifampin
Cycloserine
used for MDR TB for active TB, Mycobacterium avium, and UTIs
Cycloserine MOA
blocks cell wall synthesis, structural analog to D-alanine so blocks enzymes required for D alanine incorporation into pentapeptide of peptidoglycan strands; cidal/static conc dependent; effective in resistant organisms; shows no cross resistance
Cycloserine Absorption, Distribution and Excretion
Absorbed orally; distributed widely not protein bound to lung, pleural/synovial fluids, CSF, placenta, breast milk; excreted unchanged renal mech - requires dose adjustment with renal issues
Cycloserine Adverse Effects
CNS issues that are reversible with discontinuation of medication; HA, tremor, vertigo, confusion, psychosis with suicidal ideation, paranoia, seizures (increase with alcohol use)
Cycloserine Contras
History of epilepsy
Ethionamide
inhibits peptide synthesis (similar to Isoniazid with different MOA), oral drug, widely distributed, hepatic metabolism, conc dependent static/cidal, last line therapy due to GI, neuro, Hepto toxicity; resistance develops when used alone; Pyridoxine relieves neuro issues
Extensive Drug Resistant TB (XDRTB)
does not respond to INH, RIF, and the second line drugs; requires 2 years of extensive drug treatment
Capreomycin
unknown MOA, bacteriostatic, IM administration; nephrotoxic (proteinuria, cylinduria, nitrogen retention), ototoxic (hearing loss, tinnitus, vestibular disturbances); resistance when used alone; effective in MDRTB; last resort drug
