Cardiovascular-Renal 1: Exam 2 Adrenergic Agonists (Dr. Pulgar)

Choose the α1-selective agonists

phenylephrine

ephedrine

pseudoephedrine

Choose the α2-selective agonists

clonidine

brimonidine

tizanidine

Choose nonselective α agonists

oxymetazoline

tetrahydrozoline

naphazoline

Choose the nonselective β agonist

isoproterenol

Choose the β1-selective agonist

dobutamine

Choose the β2-selective agonist

albuterol

Choose the sympathomimetic amines

Amphetamine, dextroamphetamine (Adderall-XR)

Methylphenidate (Concerta)

Dexmethylphenidate (Focalin)

Lisdexamfetamine (Vyvanase)

What is the therapeutic use for intranasal Phenylephrine?

treatment of cold symptoms and allergic rhinitis

What are the effects of phenylephrine of the nasal mucosa?

Vasoconstriction via selective activation of a1-adrenoceptor, decreases nasal blood flow and mucous secretion

T/F: 10 mg oral formulations of phenylephrine (Sudafed-PE) are as effective as pseudophedrine

False

Why is phenylephrine used as a pressor agent for maintaining blood pressure during surgery or spinal anesthesia?

resistant to COMT

How do oral preparations of Ephedrine and Pseudoephedrine treat allergic and cold symptoms?

causing selective a1-adrenoceptor activation and release of endogenous catecholamines; vasoconstriction

Why do Ephedrine and Pseudoephedrine have greater drug bioavailability?

resistant to COMT because they lack catechol group

What are the local effects of clonidine?

vasoconstriction

What are the central effects of clonidine?

vasodilation (sympatholysis)

T/F: Clonidine is both a sedative and antihypertensive

True

T/F: Certain formulation of _ can be used to treat ADHD and cancer pain

clonidine

What are the effects of clonidine?

lowers BP and causes sedation

What is a therapeutic use for brimonidine?

open-angle glaucoma

What is the therapeutic use of tizanidine?

muscle relaxant

T/F: Oxymetazoline is an intranasal direct active α agonist that at low doses activate central α-adrenoreceptors

false: high doses

What side effect may occur due to prolong use of oxymetazoline?

rebound congestion or drug induced rhinitis

What drugs are in the same family as oxymetazoline?

tetrahydrozoline & naphazoline

What are the therapeutic uses of dobutamine?

Short-term use in pts with decreased contractility due to HF or cardiac surgical procedures leading to cardiac decompensation

What are the ADEs of dobutamine?

increases in SBP and HR

↑ ventricular response in pts with preexisting AFib.

What are the therapeutic uses for mirabegron?

Relaxes the bladder muscles to prevent uncontrolled urination

What are the ADEs for mirabegron?

Headache, dizziness, dry mouth, constipation, back pain, joint pain, difficulty emptying the bladder

What are the effects of isoproterenol?

Decrease BP (vasodilation), increase HR (via reflex effect)

What is the MOA of amphetamine, dextroamphetamine, methylphenidate, lisdexamfetamine, & dexmethylphenidate?

Enhance the release of catecholamines (not agonists)

Inhibits monoamine oxidase (MAO)

What is the MOA of cocaine?

blocks monoamine transporters used in amphetamine MOA, inhibiting its effects

What are the therapeutic uses of sympathomimetic amines?

ADHD, appetite suppressant, & narcolepsy

Which enzymes metabolize Epi, NE, & dopamine?

COMT & MAO

How is NE released from sympathetic nerve endings?

Ca2+ in the cytosol causes fusion of NE-containing vesicle with the synapse terminal

Rank the sympathetic agonists active on α receptors from strongest to weakest: NE, isoproterenol & epi

Epinephrine > NE >> isoproterenol

Rank the sympathetic agonists active on β receptors from strongest to weakest: NE, isoproterenol & epi

Isoproterenol > epinephrine > norepinephrine

How do β agonists cause biological effects?

increasing cAMP

How do α1 agonists cause biological effects?

activates PKA

Which G receptor do α1 agonists interact with?

Gq

Which G receptor do α2 agonists interact with?

Gi

Which G receptor do β agonists interact with?

Gs

When α1 activates Gq receptor which second messenger is activated?

IP3

When α2 activates Gi receptor which second messenger is deactivated?

cAMP deactivated

When β activates Gs receptor which second messenger is activated/increased?

cAMP increased

How does the activation of β adrenoreceptor promote cardiac inotropy

PKA phosphorylates LTCC and sarcoplasmic calcium-ATPase

How does the activation of β adrenoreceptor promote cardiac chronotropy

cAMP activates

Hyperpolarization Cyclic Nucleotide-dependent channels (HCN)

What are Hyperpolarization Cyclic Nucleotide-dependent channels (HCN)?

funny channels (If) in SAN cells

How does the activation of β adrenoreceptor promote smooth muscle relaxation?

increase cAMP decreases MLCK (relaxation)

How does the activation of α1 adrenoreceptor promote smooth muscle contraction?

activation of IP3 increases MLCK

What is MLCK?

Myosin Light Chain Kinase

How does the activation α2 of adrenoreceptor promote smooth muscle contraction?

deactivation of cAMP causes MLCK to be unihibited

Which kinase and second messenger do β agonists activate to relax blood vessels?

PKA & cAMP

How does the activation α1 of adrenoreceptor affect BP & HR?

increases BP (vasoconstriction)

decreases HR (reflex)