Adrenergics I & Ii

Front 1

15. Epinephrine

Back 1

•Endogenous ligand produced by adrenal medulla (80% epi; 20% norepi)
•Activates α1, α2 (Epi≥NE); β1 (Epi = NE); β2 (Epi>>>NE) to ↑SNS
•↑HR (β1), ↓TPR (β2), no change BP (systolic ↑ b/c ↑ contraction, diastolic ↓ b/c ↓ TPR), ↑CO (↑HR x ↑SV)
•low dose: primarily β2 effects (vasodilation)
•high dose: β1 and α effects (vasoconstriction)
•Indication: asthma (Primatine mist) or anaphylaxis
•MOA: β2 receptor agonist: ↑cAMP → (1) relaxation of bronchial smooth m. (2)inhibition of release mediators from inflammatory cells. •Side Effects: non-specific → stimulates all α & β receptors → has CV effects
•Action: fast onset (15 min), but short acting (lasts 60-90 minutes) b/c broken down by COMT in tissues.
•Admin: can be administered subcutaneously.

Front 2

41. Carvedilol

Back 2

•Β & α1 agonist
•Indication: hypertension; heart failure. Has been shown to decrease mortality in patients with moderate heart rate.
•MOA:
Blocks β receptors → ↓CO;
Blocks α receptors→vasodilation (↓TPR;
Baroreceptor reflex is blocked because there are no receptors available to compensate

Front 3

42. Labetalol

Back 3

•Β & α1 agonist
•Indication: hypertension; heart failure.
•MOA:
Blocks β receptors → ↓CO;
Blocks α receptors → vasodilation (↓TPR;
Baroreceptor reflex is blocked because there are no receptors available to compensate

Front 4

47. Salmeterol

Back 4

•β2 specific agonist
•Example: Serevent: dry powder inhaler
•Indication: asthma. Can be used for chronic therapy. Also available in corticosteroid combination.
•MOA: β2 receptor agonist: potent & highly selective.
•Dose/Admin:
Slower onset (15-20 min), peak effect (>45 min). Not Rescue medication.
Long acting (12 hr) due to high lipid solubility = depot effect (drug sits in fat)
Depot effect provides the advantage (over albuterol) that nighttime symptoms can be controlled.
Do NOT use >2x/day b/c drug accumulates in blood.
Available in combination w/ corticosteroid fluticasone (Advair) →easier for those who require β agonist + steroid treatment.

Front 5

50. Fluticasone

Back 5

•Corticosteroid—Anti-inflammatory
•Indication: Asthma (first line treatment for persistent, chronic asthma.) Steroids are not effective in COPD, which involves an immediate TH1 mediated response.
•MOA: inhibit the inflammatory response by: (1) preventing the production & release of inflammatory mediators and (2) inducing apoptosis in eosinophils & TH2 lymphocytes. Overall effect is suppression of the inflammatory response and a reduction in airway hyperresponsiveness, but not a cure of the underlying disease. Lung damage from airway remodeling is not reversed by steroid use.
•Dosing/Admin: low (2 puffs 2x/day), medium (2 puffs 4x/day), high (4puffs 4x/day).
Use the lowest dose that will control symptoms. High doses increase the risk of systemic absorption.
Because this is steroidal, it will take days to become fully effective. Not for immediate relief.
•Side Effects: thrush (oropharyngeal yeast infection), dysphonia (hoarseness). Incidence of side effects is reduced by using a spacer & by rinsing mouth after taking drug.

Front 6

51. Methylpredisolone (Solu-Medrol)

Back 6

•Corticosteroid: Oral or parenteral steroid
•Example: Solu-Medrol
•Indication: some cases of severe persistent asthma; can consider for short term use (5-10 days) during exacerbations in all patients—fewer side effects w/ short term use.
•MOA:
Dosing: effects occur in 6-12 h.
•Admin precautions: long term use can cause adrenal suppression, so do not stop treatment suddenly. Patient must be weaned slowly.
•Side Effects: ↑BP, ↑ diabetes, ↑risk of infections, weight gain, osteoporosis, cataracts, facial swelling, Cushingoid habitus.

Front 7

52. Zafirlukast/Montelukast

Back 7

•Leukotriene Receptor Antagonist
•Example: Zafirlukast (Accolate) (2x/day)
Montelukast (Singulaire) (1x/day)
•Indication: chronic use in mild to moderate asthma usually in combination with inhaled steroid; addition of a leukotriene modifer may allow for a reduction in the dose of inhaled steroid.
•MOA: blocks leukotriene receptors preventing all deleterious effects mediated by leukotrienes (bronchoconstriction, chemotaxis of inflammatory cells, mucous production, increased vascular permeability). Receptors are on smooth muscle.
•Dose/Admin: available for oral use only.

Front 8

53. Cromolyns (as a class)

Back 8

•Mast cell stabilizers
•Example: Chromolyn Sodium (Intal); Nedocromil (Tilade)
•Indication: chronic treatment of mild to moderate asthma (more effective in children & young adults); to prevent exercise induced asthma
•MOA: prevents release of mediators from mast cells—especially upon antigen challenge and in response to exercise; decrease vagal reflex
•Dosing: 4x/day MDI or via nebulization
•Side Effects: not significant, very safe (often used in kids)

Front 9

54. Omalizumab

Back 9

•IgG Monoclonal Antibody= Anti-IgE antibody.
•Example: Xolair
•Indication: patients with allergen induced, moderate to severe asthma whose symptoms are inadequately controlled by inhaled corticosteroids
•MOA: IgG monoclonal antibody that binds IgE and prevents its binding to mast cells
•Dose/Admin: Administered subcutaneously every 2-4 weeks over months. Causes dramatic lowering of IgE levels but not a dramatic decrease in symptoms
•Side Effects: worrisome (↑ risk of infections)
•Note: Very Expensive

Front 10

33. Albuterol

Back 10

•β2 receptor Agonist
•Example: Proventil, Ventolin, Generic Albuterol
▪Indication: Asthma; bronchospasm. For quick relief in all stages of asthma & to prevent exercise induced asthma. Not indicated for chronic or repeated use.
•MOA: β2 receptor agonist. When inhaled, albuterol stimulates β2 receptors on the respiratory smooth muscle→bronchodilation. Delivery to site of action by inhalation reduces systemic side effects.
•Side Effects: less cardiac stimulation than nonselective agents because of delivery by inhalation.
•Dose/Admin: rapid onset (1/in 5 min), peak effect (15-30 min), short acting (3-4 hr). Available MDI (metered dose inhaler), for nebulization, oral. Inhalation by MDI is the preferred delivery method.

Front 11

39. Metoprolol

Back 11

•selective β1 receptor agonist
•Indication: Hypertension (especially in patients w/ lung disease, COPD, asthma)
•MOA: Blocks β1 receptor → ↓ contractility & rate of contraction →↓CO.
Allows ↑ exercise tolerance because β2 receptors are still intact, so vasodilation of skeletal muscle can occur during exercise to allow for increased O2 consumption.
•Side Effects: Even though metoprolol is selective for β1, cross reactivity can occur w/ β2, so it is not 100% safe for asthmatics.

Front 12

40. Pindolol

Back 12

•Β1 antagonist w/ intrinsic sympathomimetic activity (ISA) = PARTIAL AGONIST
•Indication: hypertension in patients with bradycardia (low HR)
•MOA: β1 and β2 receptors are partially activated, but unable to respond to more potent catecholamines.
•Side Effects: Because of ISA, it is less likely to cause bradycardia in patients with hypertension & low HR (athletes). It doesn’t always slow the HR @ rest as much as other β blockers, but it still blocks an increase in HR & CO produced by the SNS.

Front 13

38. Propranolol

Back 13

•NON SELECTIVE β BLOCKER (β1 & β2 antagonist)
•Indication: treatment of cardiovascular disorders: hypertension, angina, post MI, cardiac arrhythmias, heart failures, glaucoma.
•MOA:
Blocks β1→ ↓CO (→↓BP→reflex peripheral vasoconstriction)
Blocks β2 →bronchoconstriction, reflex peripheral vasoconstriction, increase Na+ retention.
•Dose/Admin:
high 1st pass effect (variability in concentration in plasma is high)
T1/2 = 3.5-6h, but sustained release preparation is available.
•Side Effects: Local anesthetic properties & CNS effects