CH.6 Pharmacology Flashcards
Adrenergic (Sympathomimetic)
–Cardiopulmonary system
—increase in HR, BP, and RR
—Bronchodilation
–Eye
—Mydriasis (dilation)
–GI Tract
—Decreased motility
–Insulin secretion
—decreased
Sympathetic Nervous System
–When stimulated:
—relaxes the bronchial smooth muscle
—dilate the airways
—lowers airway resistance
– 3 Types of Receptors
—Alpha, beta 1 in heart, and beta 2 in the lungs
Airway Anatomy
-Thress layers of the airway
–Mucosa: innermost layer
—has goblet cells that produce sticky mucus to catch and debris
—ciliated cells
–Submucosa
—Bronchial glands
—smooth muscle
—capillary network
—elastic tissue
–Adventitia
—Support of airways
Bronchoconstriction
–reduction of the inner diameter of airway
–Bronchospasm: contraction of smooth muscle. Airway diameter is reduced, caused reduction in airflow
–Inflammation (Airway Edema): injury to mucous membranes causes dilation of the blood vessels, Swollen tissue reduces the diameter of the lumen of the airway.
–Secretions: impairment of the normal mucociliary clearance mechanism of the lungs. Secretions in the airway reduce the airway diameter.
Development of Beta Agonists: Catecholamines
–catechol nucleus and an amine side chain
–Not very Beta 2 specific
–Degraded by enzymes COMT and MAO, not given orally
–All sympathomimetic bronchodilators are either catecholamines or derivatives of catecholamines
Development of Beta Agonists: Resorcinols
–short duration of action
–resistant to breakdown by enzymes
–can be given orally
–derive from the catecholamines
Development of Beta Agonists: Saligenins
–most widely prescribed
–Most Beta 2 specific
–Rapid onset
—-derive from the catecholamines
Adrenergic Bronchodilators as Stereoisomers
–catecholamines and derivatives
– similar physical and chemical properties
–different physiological effects
–example: Levalbuterol
Nonsuperimposable Molecular Mirror images
–(R)-Isomer (right isomer) (levo), active on airway beta receptors producing bronchodilation
–(S)-Isomer (left isomer) (dextro), not active on adrenergic receptors
–Natural epinephrine from the adrenal gland occurs only in the R-isomer
–Racemic mixture have an S and R isomer
–example: Levalbuterol
Clinical Indications for Adrenergic Bronchodilators
–Relaxation of smooth airway muscle in the presence of reversible obstruction
–Can be short-acting or long-acting
–Asthma: acute, chronic, exercise-induced
–Bronchitis
–Emphysema
–Bronchiectasis
–Other obstructive airway disease
Indication for Short-Acting Agents
–Acute reversible airflow obstruction
–“rescue” agents or “ relievers”
–Albuterol
–Levalbuterol
–Metaproterenol
Indication for Long-Acting Agents
–maintenance bronchodilation, control of bronchospasm, and control of nocturnal symptoms
–“controllers”
–Salmeterol
–Formoterol
–Arformoterol
–Indacaterol
–Olodaterol
–Vilanterol
Bronchodilators’ Classification
–Ultrashort acting: duration less than 3 hours
—example: racemic epinephrine
–Short acting: duration of 4 to 6 hours
—examples: albuterol, levalbuterol, metaproterenol
–Long acting: duration of 12 to 24 hours
—examples: salmeterol, formoterol, arformoterol, indacaterol, olodaterol, vilanterol
Catecholamine
–Racemic Epinephrine: nebulized
–Control airway bleeding during endoscopy
–Reduce upper airway swelling: Postextubation stridor, Epiglottis, Croup, Bronchiolitis
–Allergic Reactions
–Decongestant
–Alpha-adrenergic vasoconstricting effect
Catecholamine: Racemic Epinephrine (Racemic Epi)
–Ultra-short acting
–Trade name: Asthmanefrin
–Mode of action: a and B receptors
–Method of administration: SVN 2.25%, 0.25-0.5 mL QID
–Onset: 3-5 mins
–Peak: 5-20 mins
–Duration: 0.5-2 hrs
Catecholamine: Epinephrine
–Potent catecholamine bronchodilator
–Stimulates both a- and B- receptors
–High prevalence of side effects: tachycardia, increased BP, Tremor, Headache, Insomnia
Metabolism of Catecholamines
–Rapidly inactivated by COMT
–Duration of action is limited
–1.5 to 3 hrs
–Unsuitable for oral administration: inactivated in gut and liver
–Also inactivated by: heat, light, air
Resorcinol Agents
–Better for maintenance therapy
–Significantly longer duration of action: 4-6hr
-Slower peak effect: 30-60 minutes
–Examples: Terbutaline (IV), Metaproterenol
Resorcinols: Metaproterenol
–PO-tablet or syrup
–More Beta- 2 specific than catecholamines
–Treats bronchospasm, has many cardiac effects
–Onset: 1-5 min
–Peak: 60 minutes
–Duration: 2-6 hrs
Resorcinols: Terbutaline (IV)
–parenteral
–treats bronchospasm and stops premature labor by relaxing smooth muscle
Saligenin Agents
– B2 Preference
–Effective by mouth
–Peak effect in 30-60 minutes
–Duration: 4-6 hrs
–Examples: albuterol, levalbuterol
Albuterol
– Tade Names: Proventil HFA, Ventolin HFA, ProAir HFA, AccuNeb
–Available as:
—MDI: 2 puffs, tid, qid
–Nebulizers: 0.5% (5mg/ml), 0.5ml, tid, qid
–Syrup: 2mg/5ml, 1-2 tsp tid, qid
–Extended release oral tablets: 2,4, and 8mg, bid, tid, qid
–given continuously for severe asthma
–Short acting
–Onset: 15 min
–Peak: 30-60 min
–Duration: 5- 12 hrs
–for lower airways
Levalbuterol (Xopenex): The (R)- Isomer of Albuterol
–released in 1999 as the first synthetic inhaled solution available as a pure (R)-isomer of racemic albuterol
–Trade name: Xopenex
–Available as HFA MDI and nebulizer
–Available in four nebulizer does:
—0.31mg/ 3mL
—0.63mg/3 mL
–1.25mg/3 mL
–1.25mg/05 mL concentrated
Single (R)- Isomer Formulation of Albuterol
–side effects of tremor and heart rate changes were less
–more potent that Albuterol with less side effects
–1.25 mg Levalbuterol dose showed higher peak effect on FEV1, than racemic albuterol
Nebulization of Albuterol
–used for management of severe asthma
–reduces need for frequent therapist attendance
–generally, 10 to 15 mg/hour for adult
–or 2.5mg to 5 mg, Q20 minutes, three times
–If MD orders 10mg/hour of ).5% Albuterol, how many mls should be given 2 hours
Nebulization of Albuterol
–Delivery Methods:
—refilling SVN
—Volumetric infusion pump
—Large-volume nebulizer
–Toxicity and monitoring:
—Potential complications: cardiac arrhythmias, hypokalemia, hyperglycemia, tremor
Long-Acting B-Adrenergic Agents
–offer less frequent dosing and nocturnal
–Extended-release albuterol
–Salmeterol
–Formoterol
–Arformoterol
–Indacaterol
–Olodaterol
–Vilanterol
Extended-Release Albuterol
–Available as Vospire ER
–4-mg or 8-mg oral tablet
–Activity time, 8-12 hrs
Salmeterol (Serevent Diskus)
–Available as DPI
–Bronchodilator effect:
–Onset: 20 min
–Peak 3-5 hrs
–Duration: 12 hrs
–Long-acting
– take BID
Formoterol (Performist, Foradil)
–B2- Selective agonist
–Onset: 15 min
–Peak: 30-60 min
–Duration: 12 hrs
–Available as an SVN and a DPI
Used for:
—Maintenance of asthma
—Asthma (5 year+)
—Exercise-induced bronchospasm (5+ years)
—COPD
–Long-acting
–Use BID
Arformoterol (Brovana)
–B2- Selective agonist
–Single isomer of formoterol
–Onset: 15 min
–Peak: 30-60 min
–Duration: 12 hrs
–Available as nebulizer solution
Approved for:
–Maintenance treatment of COPD
–Maintenance therapy of asthma not controlled by inhaled corticosteroids
–Pt uses MDI
Indacaterol (Arcapta Neohaler
–B2- Selective agonist
–Available as a DPI
–Onset: 5 min
–Peak: 30 min
–Duration: 24 hrs
–Ultra-long lasting
-Approved for
–Maintenance treatment of COPD
Olodaterol (Striverdi Respimat)
–B2-Selective agonist
–Ultra-long lasting
–Onset: 5 min
–Peak: 30-60 min
–Duration: 24 hrs
-Approved for:
–maintenance treatment of COPD
Vilanterol
–Not available as monotherapy
–B2- selective agonist approved in fixed combination agents will:
—Fluticasone (Breo Ellipta)
—Umeclidinuim (Anoro Ellipta)
–Ultra-long lasting
Safety Concerns with Long-Acting B2 Agonists (LABAs)
-Not to used:
–without a controller medication
–by patients who are controlled on low-dose or medium-dose inhaled Corticosteroids (ICS)
–by patients on beta blocker drugs (for SABAs)
-Should be used:
–Only if patients are not controlled with ICS
–For short term only
–Children must use in conjunction with a corticosteroid
Mechanism of Action: a-Receptor stimulation
–vasoconstriction effect
–Examples: phenylephrine, epinephrine
Mechanism of Action: B1- receptor stimulation
–increased HR and contractile force
Mechanism of Action: B2-Receptor Stimulation
–relaxation of bronchial smooth muscle
