Pharm - Lecture 8 - Adrenergic agonists Flashcards
What drugs are Direct-acting Adrenergic agonists - Catecholamines? (6)
1) Norepinephrine
2) Epinephrine
3) Isoproterenol
4) Dopamine
5) Dobutamine
6) Methyldopa
What is the receptor selectivity for Norepinephrine?
a1, a2, B1
What are the cardiovascular effects of Norepinephrine? (3)
1) Peripheral vasoconstriction
- increased peripheral vascular resistence (a1)
2) Increased blood pressure (a1)
3) can cause reflex bradycardia (vagally mediated)
What are the therapeutc uses of Norepinephrine? (2)
1) used as a vasoconstrictor under certain intensive care situations (i.e. shock) (a1)
2) elevate blood pressure during reduced sympathetic tone (neurological injury or during use of spinal anesthesia) (a1)
What is the receptor selectivity of Epinephrine?
a1, a2, B1, B2
What are the cardiovascular effects of Epinephrine? (3)
1) Increased heart rate, contractile force, cardiac output (B1)
2) Increased systolic, decreased diastolic blood pressure (a1)
3) Constriction of most vascular beds but dilation of skeletal muscle blood vessels - net effect is to decrease peripheral vascular resistence (B2)
What are the respiratory effects of Epinephrine?
Bronchodilation (B2)
What are the metabolic effects of Epinephrine?
1) Hyperglycemia (stimulates gluconeogensis and glycogenolysis; inhibits insulin release) (B2)
2) Lipolysis - increase free fatty acids (B2)
What are the therapeutic uses of Epinephrine?
1) rapid relief of hypersensitivity reactions to drugs and other allergens
2) Co-administered with local anesthetics to increase duration of action (a1)
3) Bradyarrhythmias - restore rhythm in patients with cardiac arrest (B1)
4) opthalmic uses - mydriatic, decrease hemorrhage, conjunctival decongestion (a1)
What is the receptor selectivity for Isoproterenol?
B1, B2
What is the cardiovascular effects of Isoproterenol? (3)
1) Decrease peripheral resistance (B2)
2) Increase heart rate, contractile force, cardiac output (B1)
3) Decrease mean blood pressure (B2)
What are the respiratory effects of Isoproterenol?
Bronchodilation (B2)
What are the therapeutic uses of Isoproterenol?
In emergencies to stimulate heart rate during bradycardia or heart block (B1)
What is the receptor selectivity for Dopamine?
DA1, B1, a1
What are the cardiovascular effects of dopamine?
Low Dose?
Medium dose?
High dose?
Low dose: vasodilation of renal and mesenteric arteries - decreased peripheral resistance (DA1 receptor)
Medium dose: Increase heart rate, contractile force, cardiac output (B1 receptor)
High dose: vasoconstriction and increase peripheral resistance (a1)
What are the therapeutic uses of Dopamine?
severe decompensated heart failure, shock (cardiogenic; septic)
What is the receptor selectivity for Dobutamine?
racemic mixture: overall effect as B1 agonist
What are the cardiovascular effects of Dobutamine?
1) Increased cardiac rate, contractility and output (B1)
2) Minimal change in peripheral resistence and blood pressure
What are the therapeutic uses for Dobutamine?
1) short term treatment of cardiac decompensation (surgery, CHF, MI) (B1)
2) cardiac stress testing (B1)
How is Methyldopa metabolized in the body?
Methyldopa is an orally active pro-drug: it is meabolized in adrenergic nerve terminals in CNS to a-methyldopamine and a-methylnorepinephrine - these are stored in nerve terminals and released upon stimulation
What is the receptor specificty for a-methyldopamine and a-methylnorepinephrine?
1) potent a2 receptor agonist
Stimulation reduces sympathetic outflow
What is the therapeutic use of Methyldopa?
anti-hypertensive (a2)
What are the side effects of Methyldopa? (4)
Sedation
dry mouth
edema
rebound hypertension with sudden discontinuation
(all a2 - CNS)
What drugs are direct acting Adrenergic agonists that are non-catecholamines? (4)
1) Phenylephrine
2) Clonidine
3) Albuterol
4) Salmeterol
What is the receptor specificty of Phenylephrine?
acts only on a1 adrenergic receptors
What are the effects of Phenylephrine?
Increased systolic and diastolic blood pressure (a1)
Decrease Heart rate (reflex)
Decrease blood flow to most vascular beds (a1 - cause of higher resistence)
What are the therapeutic uses of Phenylephrine? (4)
1) opthalmic: mydriatic, decrease hemorrhage, conjuctival decongestion (a1)
2) nasal decongestant: oral or nasal spray (a1)
3) used with local anesthetics to increase duration of action (a1)
4) treatment of hypotension (orthostatic hypotension, shock) i.v. administration (a1)
What is the receptor specificty of Clonidine?
orally active a2 selectve agonist
What is the major therapeutic use of Clonidine?
Anti-hypertensive (a2 - CNS)
What does Clonidine cause?
1) Prolonged blood pressure lowering (a2 - CNS)
2) Decreased peripheral resistance, heart rate and cardiac output (a2 - CNS)
What are the adverse effects of Clonidine? (3)
1) dry mouth and sedation (50% of patients)
2) edema
3) rebound hypertension with sudden discontinuation
(all a2 CNS issues)
What is the receptor specificty for Salmeterol?
B2 adrenergic receptor agonist
How is Salmeterol administered?
available only for inhalation
What is the duration of action for Salmeterol?
over 12 hours
What is the mechanism of action for indirect acting adrenergic agonists?
They release endogenous norepinephrine from nerve terminals
What are the Indirect acting adrenergic agonist only drugs?
1) Tyramine
What is the mechanism of Tyramine?
Releases norepinephrine from sympathetic nerves causing sympathomimetic actions
Where is Tyramine found?
Found at high levels in certain foods (fermented foods such as wines, beer, certain cheeses and sausages)
How is Tyramine metabolized and why is this significant?
Tyramine is metabolized by MAO to an inactive product. Patients taking MAO inhibitors can experience hypertensive crisis if they ingest foods with high Tyramine
What is the mechanism for mixed acting adrenergic agonist drugs?
Increases norepinephrine release AND stimulates adrenergic receptors
What are the Mixed acting adrenergic agonist drugs? (3)
1) Amphetamine
2) Ephedrine
3) Pseudoephedrine
What is the effect of Amphetamine?
Powerful CNS stimulant
Releases NE from adrenergic neurons
Is a weak direct alpha and beta agonist itself
Depresses appetitie
What is the therapeutic use of Amphetamine? (2)
1) Narcolepsy
2) attention deficit disorder
What are the actions of Ephedrine?
1) Direct agonist of alpha and beta receptors
2) Releases NE that activates adrenergic receptors
How is Ephedrine administerd?
orally
What is the effect of Ephedrine?
CNS stimulation
Where can ephedrine be found?
Some herbal suppliments contain ephedrine, leading to an inadvertant consumption of high doses. The FDA bannd the sale of supplements containing ephedra
What is the specific receptor action of Pseudoephedrine?
Direct a1 agonist (little B2 activity)
How is Pseudoephedrine administered?
Orally
What is the effect of Pseudoephedrine?
CNS stimulation, but less than Ephedrine
What is the therapeutic use of Ephedrine?
nasal decongestant (a1)
Illigally: used as a precurser to synthesize methamphetamine
What are the side effects of adrenergic alpha receptor agonists? (3)
1) Throbbing headache due to potent vasoconstriction
2) Cerebral hemmorrhage - due to increase in system blood pressure
3) restlessness, anxiety
What are the side effects of adrenergic Beta receptor agonists? (4)
1) Increased heart rate (palpitations)
2) Pericardial pain (angina) usually due to increased heart rate
3) Cardiac rrhythmias
4) Restlessness, anxiety
