Beta Agonists and PDE inhibitors

Isoproterenol (Isoprenaline)

non selective beta 1&2 agonist

↓ peripheral vascular resistance
(TPR), dilates skeletal muscle vessels.
 ↑ CO by positive inotropic (contractility) and
chronotropic (HR) effects.
 Uses: bradycardia, heart block, and
certain arrhythmias.
 ADRs: include tachycardia,
palpitations, arrhythmias, headache.
 DDIs: β-blockers and MAOIs (NE/EPI —> /TCAs (Anticholinergic (Ach decreases HR —> additive effect to increased HR)

Dobutamine

beta 1 selective agonist
 Structurally related to dopamine with mixed α and β activity.
 Stimulates β1 receptors enhancing cardiac contractility and rate.
 Used for short-term cardiac decompensation post-surgery or acute
heart failure.
 Rapid onset with short half-life (~2 min).
 Common ADRs: increased blood pressure, heart rate, arrhythmias,
possible myocardial ischemia

beta 2 selective agonists

 MOA: Relax bronchial smooth muscle and reduce
airway resistance.
 Therapeutic use: Acute bronchospasm relief in
asthma and COPD.
 ADRs: Tremor, mild tachycardia,
restlessness, hypokalemia (activation of Na/K pump, Gs, inc cAMP), hyperglycemia (increase PKA due to inc cAMP, liver —> enzymes for gluconeogenesis/glycogenolysis, muscle —> inhibit GLUT4, adipose tissue —> more FFA and
headache.
 DDIs: β-blockers, MAOIs/TCAs, Loop/Thiazide
diuretics, and Digoxin
 Inhalation reduces systemic adverse effects
compared to oral/parenteral

Albuterol, levabuterol (L isomer, may have fewer cardiac effects)
Metaproterenol, Terbutaline (prevent preterm labor), Pirbuterol

beta 2 agonist, SABA
clinical use: Acute asthma, COPD rescue
adverse effects: Tremor, tachycardia, hypokalemia
DDIs: β-blockers ↓ effectiveness;
MAOIs/TCAs ↑ cardiovascular
effects; Loop/Thiazide diuretics ↑
hypokalemia; Digoxin ↓ serum
digoxin concentration
Rescue inhaler. Use >2 days/week
(excluding exercise) suggests poor
asthma control.

salmeterol, formoterol, arformoterol(Nebulized COPD maintenance) LABAs

b2 agonist, side effects: tremor, palpitations

DDI same as albuterol, never use alone, use with ICS—> budesonide,

Indacaterol,
Olodaterol, Vilanterol (VLABAs)

 Indicated mainly for COPD
maintenance therapy.
 QD dosing with rapid onset and
sustained action.
 Often used in combination with
muscarinic antagonists or
corticosteroids.
 Not recommended for
asthma treatment.

mirabegron, vibegron

b3 selective agonist

 Expressed in bladder smooth muscle,
adipose tissues, and myocardium.
 MOA: Promote detrusor muscle
relaxation to increase bladder
capacity.
 Therapeutic use: Overactive bladder
syndrome (e.g., Mirabegron,
Vibegron).
 ADRs: Increased blood pressure,
urinary tract infections, headache.
 Mirabegron is a moderate CYP2D6
inhibitor; watch drug interactions

epinephrine

 Nonselective agonist at α1, α2, β1 and β2
receptors; the net effect shifts with dose.
 Low dose: β effects dominate
vasodilation with ↑ HR and contractility.
 High dose: α1 vasoconstriction
dominates ↑ BP.
 Systolic BP ↑ due to ↑ HR and
contractility
 Diastolic BP ↑ due to ↑
vasoconstriction
 First line in anaphylaxis and in cardiac arrest
 Also used to prolong local anesthetics
 ADRs: tachycardia, arrhythmias,
hypertension, tremor, and anxiety.

dopamine

D₁ → β₁ → α₁ (Dose dependent)

Shock, hypotension
Tachy-arrhythmias

MAOIs markedly potentiate
dopamine; Phenytoin may cause
hypotension/bradycardia; β-
blockers reduce cardiac effects

Theophylline (Theo-24, elixophylline)

non selective PDEi
Asthma (rare), COPD (rare)
 Methylxanthines: theophylline,
aminophylline, caffeine, pentoxifylline.
 MOA: nonselective PDE inhibition plus
adenosine-receptor antagonism
 Effects: bronchodilation with CNS and
cardiac stimulation.
 Uses: adjunct in refractory asthma and
COPD; caffeine citrate for apnea of
prematurity; pentoxifylline for claudication

Metabolized by CYP1A2: levels
rise with cimetidine, macrolides
and fluoroquinolones, and fall
with smoking.

aminphylline

Acute severe asthma (rare), severe
COPD exacerbations
ADR: same as theophylline
DDI: same as theophylline
IV salt of theophylline. Converted to
theophylline in vivo; 80% theophylline

Milrinone

Primacor
PDE3i

short-term support in acute
decompensated heart failure, useful when beta
blockade is on board because it acts distal to
the receptor.
 20 to 30 times more potent than inamrinone
 Less risk of thrombocytopenia than
anamrinone
ADR: Hypotension, ventricular
arrhythmias, headache
DDI: Additive hypotension with vasodilators
and other inotropes

Inodilator: Increases cardiac contractility
while causing vasodilation. IV only. Not
recommended for chronic heart failure
due to increased mortality

Roflumilast

Daliresp, PDE4i
Severe COPD with chronic bronchitis and frequent exacerbations
ADR: Weight loss, diarrhea, nausea, insomnia, anxiety, depression
DDI: Strong CYP3A4 inducers (rifampin, carbamazepine, phenytoin, phenobarbital) ↓ effectiveness
Not a bronchodilator. Reduces COPD
exacerbations by decreasing airway
inflammation. Monitor weight and mood