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What is the therapeutic purpose of alpha/beta adrenergic agents?
Beta-Adrenergic: Relaxation of bronchial smooth muscle and bronchodilation, to reduce Raw and to improve ventilatory flow rates in airway obstruction resulting from COPD,astma,CF,acute bronchitis.
Alpha-Adrenergic: Topical vasoconstriction and decongestation used to treat upper airway swelling.
What is the therapeutic purpose of anticholinergic agents?
Relaxation of cholinergically induced bronchoconstriction to improve ventilatory flow rates in COPD and asthma.
What is the therapeutic purpose of mucoactive agents?
Modification of properties of respiratory tract mucus; current agents reduce viscosity and promote clearance of secretions.
What is the therapeutic purpose of corticosteroids?
Reduction and control of airway inflammatory response usually associated with asthma (lower respiratory tract) or with seasonal or chronic rhinitis (upper respiratory tract).
What is the therapeutic purpose of antiasthmatic agents?
Prevention of onset and development of the asthmatic response, through inhibition of chemical mediators of inflammation.
What is the therapeutic purpose of antiinfective agents?
Inhibition or eradication of specific infective agents, such as Pneumocystis carinii (jiroveci)(pentamidine),RSV(ribavirin),Pseudomonas aeruginosa in CF or Influenza A and B.
What is the therapeutic purpose of exogenous surfactants?
Approved clinical use is by direct intratracheal instillation, for the purpose of restoring more normal lung compliance in respiratory distress syndrome of newborns.
What is the therapeutic purpose of prostacyclin analogues?
Clinically indicated to treat pulmonary hypertension for the purpose of decreasing shortness of breath and increasing walking distance.
What are some of the adrenergic agents?
Albuterol, Arfomoterol, Formoterol, Levalbuterol, Metaproterenol, Pirbuterol, Salmeterol, Indacaterol, Racemic epinephrine
What are some of the anticholinergic agents?
Ipratropium bromide, tiotripium bromide
What are some of the mucoactive agents?
Acetylcysteine, Dornase alfa
What are some of the coriticosteroids?
Beclomethasone dipropionate, Budesonide, Ciclesonide, Flunisolide, Fluticasone propionate, Mometasone furoate
What are some of the antiasthmatic agents?
Cromolyn sodium, Montelukast, Omalizumab, Zafirlukast, Zileuton
What are some of the antiinfective agents?
Aztreonam, Pentamidine, Ribavirin, Tobramycin, Zanamivir
What are some exogenous surfactants?
Beractant, Calfactant, Lucinactant, Poractant alfa
What are some prostacyclin analogues?
What is the first pass effect? What are other ways to bypass the first pass effect?
- Initial metabolism of a drug taken orally and traveling the portal vein to the liver before the drug reaches the systemic circulation.
- Injection, buccal/sublingual, transdermal, rectal, inhalation
Describe the basic mechanism of drug receptors and the four mechanisms for transmembrane signaling which are well understood.
Most drug receptors are proteins,or polypeptides, whose shape and electric charge provide a match to a drug's corresponding chemical shape or charge. Drug receptor proteins include receptors on cell surfaces and within the cell.
Lipid-soluble drugs cross the cell membrane and act on intracellular receptors, to initiate the drug response. Ex-Corticosteroids,vitamin D, thyroid hormone
Intracellular Receptor Activation -The drug attaches to the extracellular portion of a protein receptor, which projects into the cell cytoplasm (transmembrane protein) and activates an enzyme system, such as tyrosine kinase, in the intracellular portion to initiate and effect. Ex- Insulin, platelet-derived growth factor PDGF
Drug-regulated Ion channels-The drug attaches to a surface receptor, which regulates the opening of an ion channel. Ex-Acetylcholine receptors on skeletal muscle, y-aminobutyric acid GABA
Receptors linked to G proteins-The drug attaches to a transmembrane receptor that is coupled to an intracellular enzyme by a G protein (guanine nucleotide-regulating protein). Ex- B-adrenergic agents, acetylcholine at paracsympathetic nerve endings
Describe dose-response relationship.
The response to a drug is proportional to the drug concentration. As drug concentration increases, and the drug effect also increases up to a maximal point ;this is graphed as a dose-response/concentration-effect curve. Increasing amounts of the drug increase the response in a fairly direct fashion; however, the rate of response usually diminishes as the dose increase, until a plateau of maximal effect is reached. In particular, the dose at which 50% of the response to the drug occurs is referred to as the ED50/EC50, the dose of the drug that produces 50% of the maximal effect.
Define agonist and differentiate full/partial.
A drug or chemical that binds to a corresponding receptor (affinity) and intitiates a cellular effect or response (efficacy).
Full agonist is a drug that gives a higher maximal response than a partial agonist.
A drug or chemical that is able to bind to a receptor (affinity) but causes no response (zero efficacy).
Define chemical, functional, and competitive antagonism.
Chemical antagonism- Direct chemical interaction between drug and biologic mediator, which inactivates the drug. An example is chelation of toxic metals by a chelating agent.
Functional antagonism- Can occur when two drugs each produce and effect, and the two effects cancel each other. For example, methacholine can stimulate parasympathetic(muscarinic) receptors in the airways, causing bronchoconstriction; epinephrine can stimulate B2 receptors in the airways, causing bronchodilation.
Competitive antagonism- Occurs when a drug has affinity for a receptor but no efficacy and at the same time blocks the active agonist from binding to and stimulating the receptor. For example, fexofenadine is a competitive antagonist to histamine on specific receptors (H1) on bronchial smooth muscle and the nasopharynx and is used to treat allergies to pollens.
Define synergism, additivity, and potentiation.
Synergism- Occurs when two drugs act on a target organ by different mechanisms of action, and the effect of the drug pair is greater than the sum of the separate effects of the drugs.
Additivity-Occurs when two drugs act on the same receptors, and the combined effect is the simple linear sum of the effects of the two drugs, up to a maximal effect.
Potentiation-A special case of synergism in which one drug has no effect but can increase the activity of the other drug.
Define idiosyncratic effect, hypersensitivity, tolerance, tachyphylaxis.
Idiosyncratic effect- Effect that is the opposite of, or unusual, or an absence of effect, compared with the predicted usual effect in an individual.
Hypersensitivity- Allergic or immune-mediated reaction to a drug, which can be serious, requiring airway maintenance or ventilatory assistance.
Tolerance- Decreasing intensity of response to a drug over time.
Tachyphylaxis- Rapid decrease in responsiveness to a drug.
What are the common devices for delivery of inhaled aerosol drugs?
Small volume nebulizers (SVN)- Jet(pneumatic) nebulizer, Mesh nebulizer, Ultrasonic nebulizer
Pressurized metered dose inhalers (pMDI)-Conventional metered dose inhaler, breath-actuated metered dose inhaler, (breath-actuated pressurized metered dose inhaler accessory devices)
Dry powder inhalers (DPI)- Unit-dose dry powder inhalers, multiple unit-dose dry powder inhalers, multiple-dose dry powder inhalers