Adrenergic Agonists

Oyarce Pharmacology

Effector organs?

1. Eyes- a1, B2

2. Blood vessels- a1, a2, B2

3. Heart- B1

4. Lungs- B2

5. Stomach-

6. Intestine-

7. Kidneys- a1, a2, B1, B2

8. Bladder- a1, B2

Adrenergic receptors in eyes?

a1- Dilator muscle contraction, only sympathetic innervation

B2- Ciliary muscle relaxation, sympathetic and parasympathetic innervation

Adrenergic effects in respiratory tract?

B2- Bronchial smooth muscle relaxation (bronchodilation), decreased airway resistance, decreased mucus secretion

Preferred mode of delivery for respiratory drugs?

Inhalation

Short Acting Beta Agonists (SABA)?

Albuterol, Levalbuterol

Systemic Short Acting Beta Agonists?

Terbutaline, Epinephrine

Long Acting Beta Agonists (LABA)

Formoterol, Salmeterol

Ultra Long Acting Beta Agonists?

Indacaterol, Arformoterol, Olodaterol, Vilanterol

Oral and IV drug respiratory drug?

Albuterol

Oral, SubQ, and Inhalation respiratory drug?

Terbutaline

Formoterol qualities?

• LABA, not for acute use

• Onset: 5 min

• DOA: Over 12 hrs

• Metabolism: MAO and COMT

• Lipophilic

• Fecal elimination

Salmeterol qualities

• LABA, not for acute use

• Onset: 19 min

• DOA: Over 12 hours

• Metabolism: COMT and MAO

• Lipophilic

• Fecal elimination

Smooth muscle contraction?

1. Intracellular Ca2+ concentrations increase when Ca2+ enters cell and is released from sarcoplasmic reticulum

2. Ca2+ binds to calmodulin (CaM)

3. Ca2+-calmodulin activates myosin light chain kinase (MLCK)

4. MLCK phosphorylates light chains in myosin heads and increases myosin ATPase activity

5. Active myosin crossbridges slide along actin and create muscle tension

Smooth muscle relaxation

1. Decrease Ca2+ levels needed for muscle contraction

2. Activate Ca2+ pump, Na+/Ca2+ exchanger, and decrease phosphatidylinositol hydrolysis

3. Decrease myosin-actin interactions , which inhibits MLCK and activates MLC phosphatase—> inhibits phosphorylation of myosin

4. Phosphorylation of K+ channel

Combination inhalers?

Long acting B2 agonist + corticosteroid

Advair made of?

Salmeterol and fluticasone

Symbicort made of?

Formoterol and budesonide

Dulera made of?

Formoterol and mometasone

Breo Ellipta made of?

Vilanterol and fluticasone

Side effects of B2 agonists?

• Muscle tremors

• Tachycardia

• Hypokalemia

• Tolerance

Adrenergic effects in the heart?

• Increased heart rate- SA node (chronotropy)

• Increased rate of conduction- AV node (dromotropy)

• Increased force of contraction (inotropy)

Adrenergic receptors in cardiomyocytes?

Mostly B1, some a1 and B2

Adrenergic effect in cardiomyocytes?

Increased contraction

Cardiac beta agonist drugs?

• Epinephrine- B1 and B2 for cardiac arrest

• Dobutamine- B1 for increased contractility, short term treatment for heart failure, cardiac surgery, and MI

Adverse effects of cardiac beta agonists?

• Significant increase in heart rate and blood pressure

• Risky for patients with hypertension, atrial fibrillation, and MI

Sympathetic effects on vascular smooth muscle?

Vasoconstriction (a1, a2) or vasodilation (B2)

Selective a1 andrenergic agonists?

Metaraminol, Midodrine (orthoststic hypotension)

Side effects of Midodrine?

Urine retention, goose bumps, Bradycardia

Presynaptic a2A adrenergic agonist?

Clonidine

Postsynaptic a2 adrenergic agonist?

Brimonidine

Clonidine?

• ROA: Oral, transdermal patch, IV

• Absorption: Good

• Bioavailability: 85%

• DOA: 6-10 hours

• Half life: 12-16 hours

• Metabolism: Hepatic

• Excretion: Urine

• Side effects: Hypotension (main), activation of CNS a2 presynaptic receptors

• Uses: Systemic hypertension, Tachycardia, Pheochromocytoma

Brimonidine?

• Treats glaucoma, eye redness

• Decreases fluid production in eye, vasoconstriction

• Side effects: Drowsiness, Conjunctivitis, eye itching, dry mouth

Adrenergic agonist effects in glands?

• Mainly a2, some a1

• Decreased mucus secretion, decreased salivation

Sympathetic effects in urinary tract?

• a1, B3, some B2

• Promotes urinary retention

Adrenergic effects in GI tract?

• Decreased movement through GI tract

• B2 in smooth muscle, a1 in sphincter

Adrenergic effects on uterine contractions?

• Non-pregnancy: Uterine relaxation (B2)

• Pregnancy: Uterine contraction (a1), uterine relaxation (B2)

• Terbutaline

• Side effect: Increased HR

Anaphylaxis?

Allergens in blood activate mast cells, releasing histamine

Shock?

Life threatening condition that occurs when blood flow is insufficient

Indirect adrenergic agonists?

Increase E or NE to stimulate adrenergic receptors

Decrease E and NE re-uptake?

Cocaine and desipramine

Increase E and NE release

Amphetamine, Ephedrine, Tyamine

Amphetamine effects?

• Potent CNS stimulant

• Increase BP

• Increase HR

Ephedrine effects?

• Stimulates HR and cardiac output

• CNS stimulant

• a and B

Tyramine effects?

• Indirect sympathomimetic action due to release of CAs

• Increases NE release

Cocaine effects?

• Tachycardia

• Increase BP

• EuphoriDea, excitement

Desipramine effects?

• Tricyclic antidepressant

Atomoxetine effects?

Clonidine-like effect in CNS