Term
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Definition
Epinephrine: 0.5 mL of 1:100 soln; 0.5 mL of 11.25 mg soln in 2.25% saline (13.5 mg of Racepinephrine HCl USP)
Brand Name: Adrenalin; Primatene Mist or Epinephrine CFC inhaler; cannot be made or sold after December 31, 2011; Asthmanefrin an alternative to Primatene (OTC); Epipen
Actions: Alpha, Beta 1 & Beta 2 Receptors
Indications: Asthma and reversible bronchospasm in allergic reactions
Dosing : 320 mcg per puff; 60-90 minute duration;
Contraindications: Should be used with caution in cardiac patients or tachycardias; patients on MAOIs and tricyclic antidepressants
Precautions: Protect from light
Side Effects: Palpitations, anxiety,
tremors, nausea and vomiting |
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Term
| Med Chemistry: Epinephrine |
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Definition
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Term
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Definition
Ephedrine: 50 mg in water for injection; FDA banned in US in 2004
Brand Name: Claritin-D, Sudafed
Actions: Alpha, Beta 1 & Beta 2 Receptors
Indications: Asthma and reversible bronchospasm in allergic reactions. Also used for appetite suppressant and stimulant
Dosing : Similar to Epinephrine but weaker; 50mg/mL , IM, SC and IV with a longer duration > 90 min
Contraindications: Should be used with caution in cardiac
patients or tachycardias and not taken with
certain antidepressants, namely SNRIs (serotonin-
norepinephrine re-uptake inhibitors)
Precautions: Protect from light
Side Effects: Palpitations, anxiety,
tremors, nausea and vomiting |
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Term
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Definition
phenethylamine alkaloid. Alkaloid
The CIP system or the R-S system was devised by three European chemists: R.S. Cahn, C.K. Ingold and V. Prelog to designate the configuration of chiral center of enantiomers |
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Term
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Definition
Isoproterenol: 80-120 mcg via microaserosol, inhaled pressure canister(rarely used for asthma)
Brand name: Isuprel HCl, Medihaler-Iso
Actions: 60-90 min duration of action on Beta 1 & 2 Receptors
Indications: Rarely used for Asthma due to its increased asthma mortality rate in the UK (mid-1960’s). Today use to manage bronchospasm during anesthesia and adjunctive treatment for shock
Dosing: Maximal bronchodilation within 5 minutes; has a 60 to
90 minute duration of action
Contraindications: Cardiac arrhythmias associated
with tachycardia
Precautions: IV infusions have caused clinical
deterioration and death
Side Effects: Dizziness, BP changes,
headaches, pulmonary edema,
tremors, nausea and vomiting |
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Term
| Med Chemistry: Isoproterenol |
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Definition
The β activity of isoproterenol is more enhanced over norepinephrine and epinephrine
activity at the alpha (α) receptors decreases and activity at the beta (β) receptors increases
Due to CH2CH3 on R1 |
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Term
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Definition
Albuterol (Short Acting)
Terbutaline (Short Acting)
Metaproterenol(Short Acting)
Pirbuterol( Short Acting)
Salmeterol(Long Acting; partial agonist)
Formoterol (Long Acting; full agonist)
Indacaterol (Ultra-long acting; Approved in Europe only) |
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Term
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Definition
World Health Organization recommended name: Salbutamol
Albuterol sulfate: Inhalation aerosol at 80 and 200 inhalation; inhalation soln at 0.63, 1.25 and 2.5 mg/3mL, also 5mg/mL; Syrup: 2 mg/5mL; Tablets at 2,4 and 8 mg
Brand Name: Proventil, Proventil-HFA, Ventolin, Volmax, Vospire, and ProAir
Actions: Short acting (onset 5-15 min; duration 3-5 hr) at the Beta 2 Receptors
Indications: Asthma or exercise-induced asthma can
also be
used to treat patients with emphysema or chronic
bronchitis
Dosing: 1-2 inhalations q 4-6 h by aerosol; exercise-induced bronchospasm is 2 inhalation 15 min prior exercise. Nebulizer dose
is 0.63 mg, 1.25 mg or 2.5 mg 3-4 times a day.
Tablet dose or syrup is 2 or 4 mg given tid or
qid
Peak Plasma Time: Inhalation: 2-5 hr.; oral: 2-2.5 hr.
Distribution: protein bound 10%
Metabolism: Liver
Elimination: t1/2: 3-4 hr.; excretion: urine
Contraindications: Should be used with caution in cardiac
patients or tachycardias and not taken with
certain antidepressants, namely SNRIs (serotonin-
norepinephrine re-uptake inhibitors) MAOIs; beta-blocker i.e.,
propranolol
Precautions: Causes hypokalemia (low potassium)
so combining with a loop diuretics i.e, furosomide
(Lasix) may increase hypokalemia
Side Effects: Palpitations, headaches |
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Term
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Definition
short-acting Beta 2 adrenergic agonist
tertiary butyl group in salbutamol (or albuterol) makes it more selective for β2-receptors
The drug is sold as a racemic mixture mainly because the (S)-enantiomer blocks metabolism pathways while the (R)-enantiomer shows activity. |
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Term
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Definition
Terbutaline is listed by the World Anti-Doping Agency (WADA) as a prohibited drug for Olympic athletes
Terbutaline sulfate: Tablets: 2.5 and 5 mg. Injection: 1 mg/ml. Inhaler: 0.2 mg/puff. Nubulizer: 1 mg/ml.
Brand name: Brethine, Bricanyl, Brethaire (All are no longer available in US)
Actions: Short acting on Beta 2 Receptors; inhalation:5 min; oral: 30 min
Indications: is used to relieve and prevent bronchospasms caused by asthma, emphysema or bronchitis. It also is used for preventing preterm labor, a tocolytic agent
Dosing: 2.5-5 mg 3 to 4 times daily approximately 6 hours apart
while awake; subcutaneous, 0.2 mg q 15-30 minutes for two
dose; inhaler, 2 puffs q 4-6 h; preterm labor, 2.5 to
10 mcg/min via iv infusion. Typical effective dose is
17.5-30 mcg/min and treatment should not exceed
72 hours
Peak Plasma Time: Inhalation: 2-5 hr.; oral: 2-2.5 hr.
Distribution: protein bound 10%
Metabolism: Liver
Elimination: Half-life (T1/2) – 3-4 hr.; excretion: urine
Contraindications: Should be used with caution in cardiac
patients or tachycardias and not taken with
certain antidepressants, namely SNRIs (serotonin-
norepinephrine re-uptake inhibitors) MAOIs; beta-blocker i.e.,
propranolol
Precautions: Causes hypokalemia (low potassium)
so combining with a loop diuretics i.e, furosomide
(Lasix) may increase hypokalemia
Side Effects: Palpitations, headaches |
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Term
| Med Chemistry: Terbutaline |
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Definition
short-acting β2 adrenergic agonist
The tertiary butyl group in terbutaline makes it more selective for β2-receptors
Since there is no hydroxy group on the 4 position of the benzene ring - the molecule is less susceptible to metabolism by Catechol-O-methyltransferase (COMT) enzyme |
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Term
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Definition
metaproterenol sulfate: Inhalation aerosol (100-200 puffs) at 0.65 mg/puff; inhalation soln at 0.4-0.6 % soln in 2.5 ml (contents contain 10-15 mg) also in 5% soln; Syrup: 10 mg/5mL; Tablets at 10 and 20 mg
Brand Name: Alupent, Metaprel
Actions: Moderate selectivity at the Beta 2 Receptors and has significant Beta 1 Receptor activity (onset 5 min via inhalation; duration 2-6 hr)
Indications: Bronchodilator for treatment of asthma and COPD (emphysema and bronchitis)
Dosing: 2-3 inhalations q 3-4 h by aerosol (no more thatn 12 puff/day); Nebulizer dose: 0.01 mL/kg up to 0.3 mL 5% solution nebulized q 4-6hr; Tablet dose is
20 mg given tid or qid; Syrup 10mg/5mL tid or
qid
Peak Plasma Time: 60 min
Absorption: inhaled (3%)
Metabolism: metabolized in liver and GI, major metobolite, metaproterenol-O-sulfate is produced in the GI; Orciprenaline is not metabolized by catechol-0-methyltransferase nor have glucuronide conjugates been isolated to date.
Excretion: Half-life (T1/2) 6 hr; urine (40%)
Contraindications: Should not taken with beta-blockers
ie., propranolol;Theophylline may increase (toxicity);
antidepressants (TCAs and MAOIs)
Precautions: Causes hypokalemia
Side Effects: Palpitations, headaches,
arrhythmias |
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Term
| Med Chemistry: Metaproterenol |
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Definition
Metaproterenol or oriprenaline is a direct acting resorcinol analog of isoproterenol
The N-Isopropyl is Beta directing and the combination of the resorcinol ring system enhances the β2 selectivity
short-acting β2 adrenergic agonist with some β1 activity
It is the least potent of the β2, and this is most likely due of the poor β2 selectivity of isopropyl group |
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Term
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Definition
Pirbuterol inhalers will not be made, dispensed, or sold in the United States in their current form after December 31, 2013. The U.S. Food and Drug Administration (FDA) has set this final date for the medication in order to comply with the Montreal Protocol on Substances That Deplete the Ozone Layer. These inhalers contain chlorofluorocarbons (CFCs),chemicals that deplete the ozone layer
Pirbuterol acetate: (aerosol, metered, inhalation); Each 14.g canister provides 400 puffs and each 2.8 g canister provides 80 puffs; Each actuation delivers 253 mcg of pirbuterol (as pirbuterol acetate) from the valve and 200 mcg of pirbuterol (as pirbuterol acetate) from the mouthpiece.
Brand Name: Maxiar (autohaler; breath-activated metered-dose inhaler)
Actions: Short acting (onset < 5 min; duration 5 hr) at the Beta 2
Receptors
Indications: Acute asthma and COPD and maintenance
Dosing: 1-2 actuations q 4-6hr PRN, no more than 12
actuations/day
Peak Plasma Time: Unknown; systemic blood levels of pirbuterol are below the limit of assay sensitive (2-5 ng/ml) following inhalation of doses up to 800 mcg (twice the maximum recommended dose)
Absorption: Rapidly absorbed following aerosol administration
Metabolism: unknown; not metabolized by catechol-O-methyltransferase.
Excretion:Half-life (T1/2) 2 hr; urine (50%; pirbuterol + sulfate conjugate)
Contraindications: Similar to albuterol; should not taken with beta-blockers ie., propranolol; antidepressants (TCAs and MAOIs)
Precautions: Causes hypokalemia
Side Effects: Palpitations, headaches,
arrhythmias |
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Term
| Med Chemistry: Pirbuterol |
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Definition
an interesting analog of albuterol in which the benzene ring has been replaced by a pyridine ring
Similar to albuterol, pirbuterol is a selective β2 agonist available only for inhalation administration |
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Term
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Definition
(partial agonist)
Salmeterol (xinafoate): It is a long-acting beta-adrenoceptor agonist (LABA); micronized powder formulation administered via a breath-activated multidose powder inhaler (Diskus); double-foil blister strip of a powder formulation of salmeterol xinafoate for oral inhalation only. Each blister on the double-foil strip within the device contains 50 mcg of salmeterol; usually administered concomitantly with inhaled corticosteroids,i.e., Fluticasone/salmeterol (Advair) or beclomethasone
Brand Name: Serevent Diskus
Actions: long acting (5 min; duration 12 hr) at the Beta 2 Receptors due to its lipid solubility
Indications: COPD and exercise-induced bronchospasm, caution with patient with asthma (managed). Should not used for acute asthma
or COPD have warning to caused
asthma-related death
Dosing: one inhalation twice daily with 12 hr between doses
Peak Plasma Time: Does not predict therapeutic effects; Tmax= 20 min; mean Cmax = 167 pg/mL
Absorption/Distribution: Rapidly absorbed following aerosol administration; 96 % protein bound
Metabolism: Extensively metabolized by hydroxylation; Hepatic CYP3A4
Excretion: Eliminated in feces (60%) and urine (25%); Half-life (T1/2) 5.5 days; Xinafoate moiety half-life is 11 days
Contraindications: Use without a concomitant long-term asthma control medication (i.e.,, inhaled corticosteroid) for the treatment of asthma; hypersensitivity to salmeterol or product components; Similar to albuterol; should not taken with beta-blockers ie., propranolol; antidepressants (TCAs and MAOIs);
Precautions: Causes hypokalemia
Side Effects: Palpitations, headaches, hypertension
arrhythmias |
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Term
| Med Chemistry: Salmeterol |
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Definition
Salmeterol has the same phenyl ring substituition R3 as albuterol but also an unusually long and lipophilic group R1
The octanol-water partition coefficient, log P for salmeterol is 3.88, compared with 0.66 for albuterol
Salmeterol is approximately 50-fold more selective than albuterol for β2 receptor
The long duration of action results from the specific binding interaction (‘anchoring”) of the phenyl group at the end of the extended lipophilic side chain |
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Term
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Definition
(Full agonist)
Formoterol : It is a long-acting beta-adrenoceptor agonist (LABA); marketed in four forms: a dry-powder inhaler (DPI), a metered-dose inhaler (MDI), an oral tablet, and an inhalation solution; formoterol are used as "symptom controllers" to supplement prophylactic orticosteroid therapy (i.e., fluticasone). A "reliever" short-acting β2 agonist (i.e., salbutamol) is still required
Brand Name: Under various trade names including Foradil/Foradile, Oxeze/Oxis, Atock, Atimos (Modulite), and Perforomist
Actions: long acting (5 min; duration 12 hr) at the Beta 2 Receptors due to its lipid solubility
Indications: COPD and exercise-induced bronchospasm, caution with patient with asthma (managed). Should not used for acute asthma
or COPD have warning to caused
asthma-related death
Dosing: one inhalation (12 mcg inhalation capsule) twice daily with 12 hr between doses; one 20 mcg/2mL via nebulizer every 12 hr
Peak Plasma Time: 92 pg/ml within 5 min of administration
Absorption/Distribution: Rapidly absorbed following aerosol administration; 61-64% protein bound; Serum albumin binding was 31% to 38% over a range of 5 to 500 ng/mL
Metabolism: Extensively metabolized by hepatic demethylation and glucuronidation; Hepatic CYP2D6, CYP2C19, CYP2C9 and CYP2A6 are involved
Excretion: Eliminated via renal and fecal; Half-life (T1/2) 10 hours; Contraindications: Use without a concomitant long-term asthma control medication (i.e.,, inhaled corticosteroid) for the treatment of asthma; hypersensitivity to salmeterol or product components; Similar to albuterol; should not taken with beta-blockers ie., propranolol; antidepressants (TCAs and MAOIs);
Precautions: Causes hypokalemia
Side Effects: Palpitations, headaches, hypertension
arrhythmias |
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Term
| Med Chemistry: Formoterol |
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Definition
Formoterol has 3’-formylamino and 4’-hydroxy ring R3 substituion pattern and an alkoxyphenylethyl lipophilic group R1 on the nitrogen
Formoterol is less lipophilic ( og P = 1.6) than salmeterol, it has a 12 hour duration of action similar to salmeterol
It is unstable to heat and moisture therefore it is administered as an inhaled dry powder.
It is a mixture of (R,R)-(-)- and (S,S)-(+)- stereoisomers with the (R, R)-isomer having 1000-fold more affinity for the β2 receptor than the (S,S)-isomer |
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Term
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Definition
Theophylline is used to treat asthma (acute and chronic)
Theophylline preparation commonly used is aminophylline, a theophylline-ethylenedimine complex |
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Term
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Definition
Theobromine is 3.7-dimethyl
xanthine |
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Term
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Definition
Major source is beverages i.e., tea cocoa
and coffee, respectively
Caffiene is 3.7- tri-
methylxanthine |
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Term
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Definition
Methylxanthine have effects on the CNS, kidney, cardiac, skeletal muscle and smooth muscle
Theophylline is most selective in its smooth muscle effects
Caffeine has a marked CNS effects
In CNS: mild cortical arousal with increased alertness and deferral of fatigue, larger dose act as effective bronchodilator causing nervousness and tremor
In Cardiovascular: has positive chronotropic and inotropics effect; low concentration inhibits adenosine receptor in sympathetic nerves, increase cardiac output, decrease blood viscosity
In Gastrointestinal Tract: secretion of both gastric acid and digestive enzyme
In Smooth Muscle: bronchodilation as the major therapeutic action in
asthma; in sufficient concentration inhibits antigen-induced release
of histamine |
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Term
| Med Chemistry: Methylxanthine |
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Definition
methylxanthine differ by the position and number of methyl on their xanthine ring system
Theophylline is 1.3-dimethylxanthine; adenosine antagonist; acts as an acid pka=8.6; metabolized by combination of C-8 oxidation and N-demethylation in liver; urinary metabolite, 1,3 dimethyl uric acid(product of the action xanthine oxidase) |
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Term
| Clinical Uses Anti-Muscarinic Agents |
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Definition
Inhalation of the modified prototypical antimuscranic, atropine which is a selective quaternary ammonium derivative, ipratropium bromide (Atrovent) are effective in bronchodilation and partial inhibition of provoked bronchospasm
The modified atropine, Ipratropium bromide delivered in high dose is poorly absorbed into circulation and does not enter CNS and the degree of PNS varies among patients
Effective in patients with COPD resulting in a partial reversibility rather than patient with asthma
A longer acting, selective antimuscarinc agent, tiotropium (Spriva or Cipla), is approved for Tx of COPD
It binds to M1, M2 and M3 receptor with equal affinity; taken via inhalation at a single dose of 18 mcg with 24 hour duration; reduce COPD exacerbation and has been approved by FDA as a treatment for COPD
It has not been approved for Tx of asthma but has been shown to be as
effective as the addition of long-acting Beta-agonist insufficiently
controlled by inhaled corticosteroid therapy alone |
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Term
| Clinical Uses Corticosteroids Agents |
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Definition
MOA: Anti-inflammatory properties; they do not relax airway smooth muscle but reduce reactivity and reduce their frequency of asthma exacerbation; inhibition of inflitrates by lymphocytes, eosinophils and mast cells in asthmatic airway
Clinical use to improve all indices of asthma control, severity of symptoms and bronchial reactivity, exacerbations and quality of life
Aerosol Tx is the most effective way to avoid systemic adverse effects
Beclomethasone, budesonide, ciclesonide, flnisolide, flticasone, mometasone and triamcinolne deliver to airway with minimum systemic absorption
Side effect of inhaled topical corticosteroid is oropharyngeal candidiasis
Ciclesonide is a prodrug, and becomes activated by cleavage
By esterase in bronchial cells. When absorbed the active product is
tightly serum bound minimizing risk of toxicity
Inhaled corticosteroid are properly labeled as “controller,”
they are effective as long as taken |
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Term
| Clinical Uses Cromolyn and Nedocromil Agents |
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Definition
MOA: Cromolyn and nedrocromil alter the function of delayed chloride channels in the cell membranes, inhibiting cell acivation
Cromolyn sodium (disodium cromoglycate) and nedrocromil widely used Tx for asthma management and have low solubility, poor absorption from the GI tract
Nedocromil has low bioavailability and is only available in meter-dose aerosol
Inhalation of microfine powder or microfine suspension; effectively inhibits both antigen and exercise-induced asthma and chronic use (four times daily)
Have no effects on airway smooth muscle tone and are ineffective in reversing asthmatic bronchospasm. Only valuable when taken prophylactically |
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Term
| Clinical Uses Leukotriene Pathway Inhibitors Agents |
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Definition
MOA: Interrupint the leukotriene pathway by inhibiting 5-lipoxygenase and inhibiting binding of LTD4 to its receptor target tissue
Efficacy in blocking airway responses to exercise and to antigen challenge has been observed in both categories zileuton, a 5-lipoxygenase inhibitor, and zafirlukast and montelukast, LTD4-recptor antagonists
All improve asthma control and reduce the frequency of asthma exacerbations
Advantage is that they can be taken orally especially when complying to inhaled therepies is poor
Zileuton is least prescribed because of reported liver toxicity and montelukast most prescribed due to its once-daily treatment and can be taken without meals. |
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Term
| Anti-IgE Monoclonal Antibodies |
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Definition
Anti-IgE Monoclonal Antibodies: monoclonal antibody targeted against the portionof IgE that binds to its receptor (FCε-RI and FCε-R2 receptors) on mast cells and other inflammatory cells
Omalizumab, inhibits the binding of IgE on mast cells but does not activate IgE already bound to these cells thus not allowing mast cell degranulation
Administration of Omalizumab reduces IgE levels and lessens asthma severity and reduces corticosteroid requirement
Reduce the frequency and severity of asthma exacerbations |
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Term
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Definition
Smoke Cessation Studies (colloquially quitting smoking) the process of
discontinuing the practice of inhaling a smoked substance
Cigarette smoke is the major risk factor for COPD and chronic lower respiratory
diseases like asthma, bronchitis and emphysema.
Nicotine is a drug in tobacco that is addictive. It is rapidly absorbed in the airway epithelium and 1mg of nicotine is absorbed from each cigarette
Methods that have been found to be effective include interventions
directed at or via health care providers and health care systems;
medications including nicotine replacement therapy (NRT) and
varenicline (nicotine partial agonist); bupropion
(nicotine antagonist) individual and group counseling;
and Web-based programs. |
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