Adrenergic Agonists 2 Flashcards by DJ Reloj

Norepinephrine inactivation by

neuronal uptake of COMT and MAO (uptake 1)

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PK of NE:

POLAR, found in urine, poorly absorbed in gut

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Receptor selectivity of NE

a1=a2; B1&raquo_space; B2

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Receptor selectivity of E

a1=a2; B1 = B2

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Receptor selectivity of Phenylephrine, Methoxamine

a1>a2&raquo_space;» B (alpha agonists)

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Receptor selectivity of Clonidine, Methyldopa

a2>a1&raquo_space;» B (alpha agonists)

alpha 2 agonists decrease sympathetic outflow –> decreased TPR and HR

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Receptor selectivity of Dobutamine

B1&raquo_space; B2&raquo_space;» a (beta agonist)

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Receptor selectivity of Isoproterenol

B&raquo_space;» a (strong beta agonist)

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Receptor selectivity of Terbutaline, Albuterol

B2&raquo_space; B1&raquo_space;» a (beta agonists)

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Receptor selectivity of Dopamine

D1=D2&raquo_space; B&raquo_space; a

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Receptor selectivity of Fenoldopam

D1&raquo_space; D2

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Norepinephrine CVS effects?

Increased PVR –> Increased SP/DP
Increased SV
CO variable

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Which has the greater effect on BP? NE or E? Why?

Norepinephrine because of increase in PVR (predominant alpha receptor activation–NE does not at on B2 which is responsible for vasodilation)

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Why does NE result in reflex bradycardia but not E?

Epi will not cause a tremendous increase in BP because it acts on B2 receptors responsible for vasodilation. Norepi will act on alpha 1 receptors (blood vessels) and beta 1 (heart) but not beta 2. The increase in blood pressure evokes a baroreceptor vagal reflex in bradycardia.

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How can NE cause tissue necrosis and sloughing when extravasated through IV?

Vasoconstriction

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Impaired circulation due to NE can be relieved by what?

phentolamine (alpha receptor antagonist)

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What is the metabolic precursor of NE and E?

Dopamine

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What are the effects of low doses of Dopamine on CVS?

Vasodilation (D1 receptors at renal, mesenteric, and coronary beds)

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Cardiogenic shock is treated with?

DA > isoproterenol

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What are the effects of moderately high doses of Dopamine on CVS?

Beta 1 receptor activation (heart) –> +inotropy with MINIMAL TACHYCARDIA

Alpha 1 activation (vascular) –> vasoconstriction

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What can dopamine cause the release of at nerve terminals?

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What are the effects of low doses of Dopamine on renal system?

D1 stim –> natriuresis –> diuresis

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This is a benzazepine derivative and agonist for peripheral D1 receptors with moderate affinity for a2 receptors.

Fenoldopam

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Which drug has dopamine receptor affinity and is used as a vasodilator in severe HTN?

Fenoldopam

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Synthetic analog of dopamine:

Dopexamine

This has D1 and D2 affinity and inhibits catecholamines uptake.

Dopexamine (also B2 activity)

Therapeutic uses of Dopexamine:

severe CHF, cardiogenic and septic shock (similar to dopamine)

Powerful beta receptor agonist. Acts on all beta receptors.

Isoproterenol

Administration of isoproterenol?

Parenteral or aerosol

Metabolism of isoproterenol?

In liver by COMT. POOR substrate for MAO

What are the effects of isoproterenol on the CVS?

Decrease DP --> Decrease BP (SP varies) +inotropic/chronotropic effects (B1) --> increase CO Vasodilation (B2) --> decreased PVR

What are the effects of isoproterenol on smooth muscles?

Bronchodilation (B2) | Vasodilation in skeletal muscles (B2)

B2 agonists are effective in asthmatics because of two reasons. What are they?

1) bronchodilation | 2) inhibition of antigen-induced release of histamine and other inflammatory mediators

Therapeutic uses of isoproterenol:

1) Emergency bradycardia or heart block, in anticipation of cardiac pacemaker insertion or in patients with ventricular arrythmias 2) Replaced in treatment of asthma, COPD, and shock

Beta agonist used clinically as a racemate preparation

Dobutamine

Which Dobutamine isomer is a more potent beta agonist?

(+) isomer

Which Dobutamine isomer is a potent alpha 1 agonist?

(-) isomer

Which Dobutamine isomer is an alpha 1 antagonist?

(+) isomer

Dobutamine selective for beta 1 or beta 2?

Selective beta 1

Effects of dobutamine is similar to _____ but with less ____

dopamine; tachycardia

Dopamine at high doses = vaso____? Dopamine at low doses = vaso____?

high dose --> vasoconstriction (A1 r) low dose --> vasodilation (D1 r)

Which CVS effect of dobutamine is more prominent? Inotropic or Chronotropic

Inotropic (alpha 1 r)

Therapeutic uses for Dobutamine:

SHORT TERM: cardiac compensation in post-cardiac surgery or CHF or acute MI

Contraindications for Dobutamind

idopathic hypertrophic subaortic stenosis

What beta 2 selective agonist is used for SHORT-TERM prevention of pre-term labor as well as a bronchodilator?

Terbutaline

Aside from short-term prevention of pre-term labor what else can Terbutaline be used for?

As a bronchodilator

Differences between Albuterol/Salbutamol and Salmeterol?

Salbutamol/Albuterol: Short-acting, fast onset Salmeterol: Prolonged action, SLOW onset (not suitable for status asthmaticus). Lipophilic. HIGHLY selective for Beta 2.

Drug of choice for Nocturnal asthma:

Salmeterol + Formoterol

What long-acting B2 agonist with fast onset is used for nocturnal asthma?

Formoterol

Long-acting beta 2 agonist that may cause death or near death experience from increased CVS activity

Arformoterol

Which beta 2 agonist is used ONLY as a uterine relaxant to arrest premature labor and prolong pregnancy

Ritodrine

ULTRA LONG ACTING Beta 2 agonist with fast onset of action used ONLY for COPD

Indacaterol

Which class or subclass of drugs mainly causes vasoconstriction --> increased PVR and BP, causes pupillary dilator contraction, intestinal and bladder sphincter contraction

alpha 1 agonists

Selective alpha agonist used as Nasal decongestant. Which alpha type?

Phenylephrine, alpha 1

Why is Phenylephrine not a catecholamine?

Lacks a -OH group at position 4. Catecholamines have -OH groups at 3 and 4.

Why does Phenylephrine have a longer duration of action than catecholamines?

It is not inactivated by COMT

Therapeutic uses of Phenylephrine aside from nasal decongestion?

Mydratic agent. Hemostatic agent. Vasopressor (increase in BP results in reflex bradycardia)

What drug is used to treat paroxysmal supraventricular tachycardia?

Phenylephrine (lowers HR)

Repeated use of topical nasal decongestants ultimately results in what?

Rebound congestion: intense vasocostriction --> tissue hypoxia --> local mediator release --> vasodilation --> hyperemia --> congestion OR receptor desensitization --> beta response predominates over alpha

Long acting topical nasal decongestants:

Oxymetazoline (important), Xylometazoline

Short acting topical nasal decongestants

Tetrahydrozoline, Nephazoline

Which oral nasal decongestant can cause hemorrhagic strokes at high doses?

Phenylpropanolamine

Which oral nasal decongestant is highly regulated for its role in shabu/methampetamine manufacturing?

Pseudoephedrine

Active metabolite of midodrine?

desglymidodrine

Primary indication is treatment of patients with autonomic insufficiency & orthostatic hypotension

Midodrine

Frequent complication of midodrine?

supine hypertension

Mixed-acting sympathomimetics:

epinephrine (direct) | ephedrine (direct on both, with additional indirect on alpha)

Which mixed-acting sympathomimetic is resistant to enzyme?

ephedrine | epinephrine is sensitive

Which mixed-acting sympathomimetic is polar?

epinephrine

Which mixed-acting sympathomimetic crosses BBB?

ephedrine

Which mixed-acting sympathomimetic has longer duration?

ephedrine

Which mixed-acting sympathomimetic is more efficacious?

epinephrine

In case of ephedrine toxicity, what should be done?

Since ephedrine is a weak base, the urine should be acidified with ascorbic acid or ammonium chloride to render it more ionized.

MoA of indirect-acting sympathomimetics?

1) enter SNS nerve endings and displace stored catecholamines or DA 2) inhibit catecholamine reuptake

Its D-isomer is more potent than its L-isomer.

Amphetamine

Used for narcolepsy, ADHD, and to suppress appetite. Dependence forming.

Amphetamine

Contraindication of methylphenidate

acute angle glaucoma (promotes NE release, aggravating glaucoma)

Tyramine's MoA?

Indirect sympathomimetic action. Promotes release of stored catecholamines.

This class of drugs prevent uptake 1.

Catecholamine reuptake inhibitors.

Atomoxetine: class? Moa? Therapeutic use?

Catecholamine reuptake inhibitor. Increases available NE in noradrenergic synapses. ADHD.

This drug is similar to atomoxetine

Reboxitine

Only local anaesthetic agent with sympathomimetic effects

Cocaine

Which serotonin and NE reuptake inhibitors are used for Tx of obesity?

Sibutramine

Which serotonin and NE reuptake inhibitors are used for Tx of fibromyalgia?

Milnacipran

Which serotonin and NE reuptake inhibitors are used for Tx of depression? Which is only depression.

Duloxetine for depression only. Milacipran can be used as an antidepressant as well as for fibromyalgia.

alpha 2 agonist used in opiate withdrawal

clonidine

alpha 2 agonist used in pregnancy hypertension

methyldopa