[PCOL] 2.3 Sympathetic Nervous System (Sympathomimetics)

Drugs that increase the concentration of catecholamines in the cleft by increasing exocytosis or inhibiting reuptake of NE are classified as what type of Adrenergic Agents?

A. Direct Acting

B. Indirect Acting

C. Mixed Acting

D. Centrally Acting

B. Indirect Acting

Explanation: Indirect Acting drugs elicit their effect by increasing the concentration of endogenous catecholamines in the synaptic cleft, either by increasing release or inhibiting reuptake.

The Natural Catecholamines (NE, Epi, Dopa) are classified as Direct Acting Non-Selective agents because they:

A. Stimulate only one receptor type.

B. Act primarily in the CNS.

C. Stimulate more than one type of receptor (alpha, beta, Dopa).

D. Inhibit the reuptake of NE.

C. Stimulate more than one type of receptor (alpha, beta, Dopa).

Explanation: These Natural Catecholamines are non-selective because they stimulate a variety of Adrenergic receptors (alpha, beta, Dopa), although their affinity varies.

In terms of receptor affinity, the Natural Catecholamines generally show a Higher affinity at which type of receptor at low doses?

A. alpha receptors

B. Dopa receptors

C. beta receptors

D. M (Muscarinic) receptors

C. beta receptors

Explanation: The Pharmacodynamics section states a Higher affinity at beta receptors than alpha. Therefore, low doses primarily elicit the beta effect, while higher doses are needed for the alpha effect to manifest.

What is the Receptor Selectivity hierarchy for Epinephrine / Adrenaline?

A. beta1>alpha1

B. D1>beta1>alpha1

C. beta2=beta1>alpha1

D. alpha1>beta2

C. beta2=beta1>alpha1

Explanation: Epinephrine acts as a potent agonist at both beta1 and beta2 receptors equally, with lower affinity at alpha1. This balanced beta effect makes it the drug of choice for anaphylaxis (beta1 cardiac stimulation + beta2 bronchodilation).

What is the Receptor Selectivity hierarchy for Norepinephrine / Levarterenol?

A. beta2>beta1>alpha1

B. D1>beta1>alpha1

C. alpha1=beta1

D. beta1>alpha1

D. beta1>alpha1

Explanation: Norepinephrine is listed as beta1>alpha1. It has very little affinity for beta2 receptors. Its potency at alpha1 makes it a good vasoconstrictor, which is why it's the 1st line inotropic agent for septic shock (to raise BP).

Natural Catecholamines are typically administered via IV, SQ, or inhalation routes, but not orally (PO). This is due to which Pharmacokinetic characteristic?

A. Acid Stability

B. Ease of Absorption

C. Extensive first pass effect (acid labile, unstable in gastric acid)

D. Low molecular weight

C. Extensive first pass effect (acid labile, unstable in gastric acid)

Explanation: They are Acid labile (Unstable in gastric acid) and undergo extensive first pass metabolism, leading to Decreased oral BA (Bioavailability).

Epinephrine and Norepinephrine are metabolized by MAO and COMT into which major urinary metabolite that can be used to diagnose pheochromocytoma?

A. Homovanillic acid

B. Vanillyl mandelic acid (VMA)

C. Dipivefrin

D. Serotonin

B. Vanillyl mandelic acid (VMA)

Explanation: The final metabolic product of both Epinephrine and Norepinephrine is VMA (3-methoxy-4-hydroxy mandelic acid). Elevated VMA levels in the urine can indicate pheochromocytoma (CA of adrenal medulla), which overproduces these Catecholamines.

What is the 1st line clinical use for Epinephrine/ Adrenaline?

A. Management of septic shock

B. Treatment of oliguria

C. Anaphylaxis and anaphylactic shock

D. Local anesthesia

C. Anaphylaxis and anaphylactic shock

Explanation: Epinephrine is the DOC (Drug of Choice) for anaphylaxis due to its swift and potent effects on beta1 (cardiac stimulant) and beta2 (bronchodilation) receptors, as well as alpha1 (vasoconstriction) to raise BP.

Which drug is the pivalic ester prodrug of Epinephrine used in the management of glaucoma?

A. Norepinephrine

B. Dipivefrin

C. Dopamine

D. Phentolamine

B. Dipivefrin

Explanation: Dipivefrin is a prodrug used for glaucoma to help reduce IOP (intraocular pressure).

Norepinephrine / Levarterenol (Levophed) is the 1st line inotropic agent used to manage which type of hypotension?

A. Cardiogenic shock

B. Septic shock / distributive shock

C. Hypovolemic shock

D. Neurogenic shock

B. Septic shock / distributive shock

Explanation: Norepinephrine is the DOC for Septic shock (type of distributive shock) because its potent alpha1 activity is essential for reversing the systemic vasodilation characteristic of this condition.

What is the effect of Dopamine when given at a low dose (1-3 ug/kg/min), and which receptor mediates this effect?

A. Vasoconstriction (alpha1)

B. Increased heart rate (beta1)

C. Renal vasodilation (D1 activation)

D. Uterine relaxation (beta2)

C. Renal vasodilation (D1 activation)

Explanation: Dopamine exhibits a dose-dependent response. At the lowest doses, it selectively stimulates the D1 receptor, causing Renal vasodilation (increase GFR) and is used to treat oliguria (urine output <500 mL/day).

What is the major adverse effect of Dopamine overstimulation at alpha1 receptors and its antidote?

A. Tachyarrhythmias; Beta-blockers

B. Hypotension; NE

C. Peripheral vasoconstriction → digital necrosis; Phentolamine

D. Bronchospasm; Epinephrine

C. Peripheral vasoconstriction → digital necrosis; Phentolamine

Explanation: Dopamine at high doses (>5 ug/kg/min) stimulates alpha1 receptors, causing severe vasoconstriction that can lead to digital necrosis (loss of blood flow to fingers/toes). The antidote for this alpha1 effect is the alpha blocker Phentolamine.

Direct-acting selective agonists are characterized by stimulating only one type of receptor. Which receptor type is stimulated by the drugs Phenylephrine, Oxymetazoline, and Methoxamine?

A. beta1

B. beta2

C. D1

D. alpha1

D. alpha1

Explanation: The drugs listed (e.g., Phenylephrine, Oxymetazoline, Methoxamine) are specifically classified as selective alpha1 agonists.

What is the primary effect of alpha1 agonist stimulation on smooth muscle, leading to an increase in systemic vascular resistance (SVR)?

A. Vasodilation

B. Bronchodilation

C. Contraction and Vasoconstriction

D. Relaxation

C. Contraction and Vasoconstriction

Explanation: alpha1 receptor activation causes smooth muscle contraction, primarily leading to vasoconstriction in blood vessels, which increases SVR and thus BP.

What is the Drug of Choice (DOC) among the alpha1 agonists for managing nasal congestion (decongestant effect), often sold under the brand name Drixine?

A. Phenylephrine

B. Methoxamine

C. Oxymetazoline

D. Tetrahydrozoline

C. Oxymetazoline

Explanation: Oxymetazoline is listed as a selective alpha1 agonist used for the Mgt of nasal congestion (Drixine), making it a DOC for this local use.

Which alpha1 agonist is administered intravenously (IV) for the management or as an adjunct for acute hypotension?

A. Midodrine

B. Oxymetazoline

C. Propylhexidine

D. Phenylephrine

D. Phenylephrine

Explanation: IV Phenylephrine is specifically mentioned as a clinical use for the management of acute hypotension.

Which selective alpha1 agonist is used to manage arrhythmia because its strong vasoconstriction effect causes a reflex bradycardia?

A. Phenylephrine

B. Midodrine

C. Methoxamine

D. Xylometazoline

C. Methoxamine

Explanation: Methoxamine is listed for the Mgt of arrhythmia due to its alpha1-mediated vasoconstriction causing reflex bradycardia.

When alpha1 agonists are used locally (intranasal/ocular) for more than 3 to 5 days, what common local adverse effect occurs, leading to worsening congestion?

A. Systemic hypertension

B. Urinary retention

C. Digital necrosis

D. Rebound hyperemia or rhinitis medicamentosa

D. Rebound hyperemia or rhinitis medicamentosa

Explanation: Local alpha1 agonists (nasal decongestants) should be used for Not More Than (NMT) 3 days to prevent the side effect of Rebound hyperemia or rhinitis medicamentosa (Systemic tolerance).

What systemic side effect of alpha1 agonists is a concern for patients with Benign Prostatic Hyperplasia (BPH)?

A. Hypertension exacerbation

B. Rebound hyperemia

C. Precipitation of urinary retention

D. Reflex bradycardia

C. Precipitation of urinary retention

Explanation: alpha1 stimulation contracts the bladder sphincter and prostatic smooth muscles, leading to the Precipitation of urinary retention in patients with BPH.

Which alpha1 agonist is used as a local vasoconstrictor in eye drops (e.g., EyeMo Red) to relieve redness?

A. Oxymetazoline

B. Propylhexidine

C. Tetrahydrozoline

D. Phenylephrine

C. Tetrahydrozoline

Explanation: Tetrahydrozoline is listed as a selective alpha1 agonist used as a Local vasoconstrictor (EyeMo Red) to treat conjunctival redness.

What is the primary function of selective alpha2 agonists on intraocular pressure (IOP)?

A. Increases production of aqueous humor

B. Increases outflow of aqueous humor

C. Inhibits synthesis of aqueous humor

D. Causes ciliary muscle contraction

C. Inhibits synthesis of aqueous humor

Explanation: Selective alpha2 agonists, such as Apraclonidine and Brimonidine, are used as anti-glaucoma drugs because their effect on the ciliary body is to decrease the synthesis of aqueous humor, thus lowering IOP.

Which drug, classified as a selective alpha2 agonist, is the Drug of Choice (DOC) for managing hypertension in pregnant patients?

A. Clonidine

B. Guanfacine

C. Methyldopa

D. Hydralazine

C. Methyldopa

Explanation: Methyldopa (Aldomet) is specifically indicated for the management of hypertension in pregnant patients (e.g., chronic hypertension or preeclampsia).

Clonidine is the Drug of Choice (DOC) for managing hypertension in patients with what co-morbid condition?

A. Congestive heart failure

B. Undergoing hemodialysis

C. Benign prostatic hyperplasia (BPH)

D. Bronchial asthma

B. Undergoing hemodialysis

Explanation: Clonidine is listed as an alternative for hypertension and the DOC for hypertension in patients undergoing hemodialysis.

Which of the following is the final, desired therapeutic effect of Clonidine, mediated by pre-synaptic alpha2 activation?

A. Vasoconstriction and transient increase in BP

B. Vasodilation and lasting decrease in BP

C. Post-synaptic alpha1 receptor activation

D. Inhibition of Dopa decarboxylase

B. Vasodilation and lasting decrease in BP

Explanation: The final and lasting therapeutic effect of Clonidine is vasodilation, resulting in decreased BP. This occurs due to the activation of pre-synaptic alpha2 receptors, which inhibits NE release and enhances NE reuptake.

What is the initial, transient effect of Clonidine, caused by its weak post-synaptic alpha2 receptor activation?

A. Vasodilation

B. Reflex tachycardia

C. Vasoconstriction

D. Increased NE release

C. Vasoconstriction

Explanation: Clonidine's initial effect is a transient increase in BP due to vasoconstriction, caused by its activation of post-synaptic alpha2 receptors before its central effect takes over.

Methyldopa is a prodrug that is converted into its active form, alpha-methyl NE. This active metabolite binds to alpha2 receptors but specifically does not bind to which type of adrenergic receptor?

A. alpha1 receptors

B. alpha2 receptors

C. beta receptors

D. D1 receptors

C. beta receptors

Explanation: The active form of Methyldopa, alpha-methyl NE (a pseudo-NT), is described as acting like NE but not binding to beta receptors, mediating its central antihypertensive effect solely through alpha2 receptors.

Which of the following is the most common side effect of Methyldopa?

A. Hepatotoxicity

B. Positive Coombs Test

C. Sedation

D. Rebound hypertension

C. Sedation

Explanation: Sedation and depression are common side effects of Methyldopa, as it is a centrally acting agent that can cross the Blood Brain Barrier (BBB).

Clonidine withdrawal-induced hypertension (rebound hypertension) can be managed by which of the following interventions?

A. Administration of a pure alpha1 agonist like Phenylephrine

B. Reinstate Clonidine or administer Labetalol or Nitroprusside

C. Administration of a DOPA decarboxylase inhibitor like Carbidopa

D. Administration of a peripheral vasodilator like Hydralazine only

B. Reinstate Clonidine or administer Labetalol or Nitroprusside

Explanation: Rebound hypertension upon abrupt Clonidine withdrawal is an emergency managed by either restoring Clonidine dosing or using powerful parenteral antihypertensive agents like Labetalol, Nitroprusside, or Nicardipine.

Which side effect of Methyldopa is associated with doses greater than 2 grams per day and suggests a toxic effect on the liver?

A. Hemolytic anemia

B. Hepatotoxicity

C. Severe depression

D. Peripheral neuropathy

B. Hepatotoxicity

Explanation: Hepatotoxicity is listed as an adverse effect of Methyldopa, particularly with doses exceeding 2 g/day, consistent with a dose-dependent toxicity of the prodrug.

What is the significance of a False Positive Coombs Test result, which is a known side effect of Methyldopa?

A. It is a diagnostic marker for hepatic cirrhosis.

B. It is used in hemolytic anemia.

C. It indicates an increased risk of peripheral neuropathy.

D. It confirms acute renal failure.

B. It is used in hemolytic anemia.

Explanation: The positive Coombs Test result is associated with the development or risk of hemolytic anemia in patients taking Methyldopa.

The mechanism of action for the antihypertensive effect of selective alpha2 agonists is best described as:

A. Direct inhibition of the sympathetic nervous system at the effector organ.

B. Activation of autoregulation by binding to pre-synaptic alpha2 receptors.

C. Increased synthesis of Norepinephrine (NE) in the synaptic cleft.

D. Blockade of post-synaptic alpha1 receptors in the CNS.

B. Activation of autoregulation by binding to pre-synaptic alpha2 receptors.

Explanation: These drugs lower blood pressure primarily by binding to pre-synaptic alpha2 receptors, which is an autoregulatory mechanism that reduces central sympathetic outflow by inhibiting NE release.

Which two selective alpha2 agonists are most preferred for the management of glaucoma?

A. Clonidine and Methyldopa

B. Guanabenz and Guanfacine

C. Apraclonidine and Brimonidine

D. Phenylephrine and Oxymetazoline

C. Apraclonidine and Brimonidine

Explanation: Apraclonidine and Brimonidine are specifically mentioned as the selective alpha2 agonists used for glaucoma, with Brimonidine being more preferred.

Which synthetic catecholamine acts non-selectively on beta1 and beta2 receptors (beta1=beta2), making it an alternative inotropic agent for heart failure?

A. Dobutamine

B. Epinephrine

C. Isoproterenol

D. Norepinephrine

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C. Isoproterenol

Explanation: Isoproterenol (Isoprenaline) is a non-selective beta agonist with equal affinity for beta1 and beta2 receptors, used as an alternative intravenous infusion for inotropic support in heart failure and shock states.

Which selective beta1 agonist is considered the first line agent for managing cardiogenic shock?

A. Isoproterenol

B. Dopamine

C. Dobutamine

D. Epinephrine

C. Dobutamine

Explanation: Dobutamine is a cardioselective (beta1 selective) agonist that is the first line agent for cardiogenic shock and management of acute heart failure (AHF) due to its strong positive inotropic effect.

Dobutamine is used as a diagnostic agent in what specific procedure?

A. Angiography

B. Dobutamine Stress Test

C. Pulmonary function testing

D. Echocardiogram

B. Dobutamine Stress Test

Explanation: Dobutamine is used as a pharmacologic agent for the Dobutamine Stress Test (along with Dipyridamole and Adenosine) to evaluate cardiac function when the patient cannot perform physical exercise.

Which class of selective beta2 agonists is designated as the Drug of Choice (DOC) for the acute exacerbations of bronchial asthma (relievers)?

A. Long Acting Beta Agonists (LABA)

B. Short Acting Beta Agonists (SABA)

C. Non-selective beta agonists

D. Alpha1 agonists

B. Short Acting Beta Agonists (SABA)

Explanation: SABAs like Salbutamol (Albuterol) and Terbutaline are the first line relievers for bronchial asthma acute exacerbations due to their fast onset of action.

Long Acting Beta Agonists (LABA) like Salmeterol and Formoterol are designated as the Drug of Choice (DOC) for what role in bronchial asthma and COPD?

A. Relievers for acute exacerbations

B. Controllers

C. Tocolytics

D. Management of hyperkalemia

B. Controllers

Explanation: LABAs are the DOC for bronchial asthma "controllers" and are used as controllers for COPD, typically in combination with inhaled corticosteroids (e.g., Salmeflo is Salmeterol + Fluticasone).

Which side effect is noted to be increased in mortality risk when using Long Acting Beta Agonists (LABA) for bronchial asthma, leading to a contraindication in children?

A. Hypokalemia

B. Tremors

C. Cardiovascular (CV) failure and tachyarrhythmia

D. Urinary retention

C. Cardiovascular (CV) failure and tachyarrhythmia

Explanation: The notes specifically warn that LABAs increase the risk of mortality from cardiovascular failure with bronchial asthma and are contraindicated in children, likely due to beta1-mediated tachyarrhythmia.

Selective beta2 agonists are clinically used for the management of bronchial asthma, pre-term labor, and as adjuncts in the management of which electrolyte imbalance due to their hypokalemic effects?

A. Hyponatremia

B. Hypercalcemia

C. Hyperkalemia

D. Hypomagnesemia

C. Hyperkalemia

Explanation: Beta2 agonists promote the uptake of potassium into cells, causing a hypokalemic effect, which makes them useful adjuncts in the management of hyperkalemia.

Tocolytics are agents that induce uterine relaxation to prevent premature labor. Which beta2 agonist is used off-label as a tocolytic and is known to have more beta1 effects than other tocolytic drugs?

A. Isoxsuprine (Duvadilan)

B. Ritodrine

C. Salbutamol

D. Terbutaline

D. Terbutaline

Explanation: Terbutaline (often given subcutaneously) is listed as an off-label tocolytic and is noted to have more beta1 effects compared to the other tocolytics.

Which selective D1 agonist is administered intravenously (IV) for the management of hypertensive crisis?

A. Dopamine

B. Norepinephrine

C. Fenoldopam

D. Epinephrine

C. Fenoldopam

Explanation: Fenoldopam is a selective D1 agonist (causing renal vasodilation and diuresis) used intravenously to rapidly lower blood pressure in a hypertensive crisis.

What is a listed side effect of beta2 agonists that can be a limiting factor in their use?

A. Urinary retention

B. Hypokalemia

C. Sedation

D. Hypotension

B. Hypokalemia

Explanation: While hyperkalemia is an indication for their use, the hypokalemic effect itself is a noted side effect. Other side effects include Tachycardia, Palpitations, and Tremors.

Why is the selective D1 agonist Fenoldopam contraindicated in patients with glaucoma?

A. It causes systemic hypertension.

B. It exacerbates hyperkalemia.

C. It increases intraocular pressure (IOP).

D. It causes severe sedation.

C. It increases intraocular pressure (IOP).

Explanation: Fenoldopam is listed with a contraindication for glaucoma because it increases intraocular pressure (IOP).

Which Long Acting Beta Agonist (LABA) is explicitly mentioned to have a slow onset of action?

A. Formoterol

B. Bambuterol

C. Indacaterol

D. Salmeterol

D. Salmeterol

Explanation: Salmeterol is noted to have a slow onset of action, differentiating it from Formoterol, which has a fast onset of action.

The classification "Mixed Acting" for adrenergic agonists implies that the drug has what two types of mechanisms?

A. Stimulates alpha and beta receptors

B. Inhibits reuptake and metabolism

C. Direct receptor activation and Indirect release/inhibition

D. Acts on the CNS and periphery

C. Direct receptor activation and Indirect release/inhibition

Explanation: Mixed-acting agents are defined as having both a Direct Acting component (binding to adrenergic receptors) and an Indirect Acting component (increasing NE concentration through release or reuptake inhibition). Ephedrine is the classic example of this dual mechanism.

Which drug, belonging to the Mixed Acting and Centrally Acting categories, is the Drug of Choice (DOC) for the management of Attention-Deficit Hyperactivity Disorder (ADHD)?

A. Amphetamine

B. Phentermine

C. Methylphenidate (Ritalin)

D. Modafinil

C. Methylphenidate (Ritalin)

Explanation: Methylphenidate is listed as the first line treatment (DOC) for the management of ADHD. Amphetamine is listed as an alternative treatment.

Which mixed/centrally acting adrenergic agonist carries a significant risk of causing hemorrhagic strokes, particularly in young women?

A. Methamphetamine

B. Phentermine

C. Phenylpropanolamine (PPA)

D. Methylphenidate

C. Phenylpropanolamine (PPA)

Explanation: Phenylpropanolamine (PPA) is specifically noted for the risk of hemorrhagic strokes, especially in young women, and it was historically used as a nasal decongestant and anorexiant.

Which of the following is listed as an alternative treatment for Attention-Deficit Hyperactivity Disorder (ADHD)?

A. Modafinil

B. Phenmetrazine

C. Amphetamine

D. Phenylpropanolamine

C. Amphetamine

Explanation: While Methylphenidate is the first line treatment, Amphetamine is listed as an alternative for the management of ADHD.

What is the primary clinical use for the Centrally Acting adrenergic agonists Phentermine and Phenmetrazine?

A. Management of narcolepsy

B. Treatment of hemorrhagic stroke

C. Appetite suppressant (anorexiant)

D. Management of hypotension

C. Appetite suppressant (anorexiant)

Explanation: Phentermine, Phenmetrazine, and Phenylpropanolamine are listed under Centrally Acting Agonists for their use as appetite suppressants or anorexiants.

The anorexiants Phentermine and Phenmetrazine can cause which severe adverse effect that requires symptomatic treatment with drugs like Sildenafil Citrate or Epoprostenol?

A. Tachyarrhythmia

B. Hemorrhagic stroke

C. Pulmonary Hypertension (HTN)

D. Physical addiction

C. Pulmonary Hypertension (HTN)

Explanation: The notes explicitly list pulmonary HTN as a severe adverse effect of Phentermine and Phenmetrazine, requiring symptomatic treatment with vasodilators/antagonists like Sildenafil Citrate (Revatio), Epoprostenol (PGI2), or Bosentan (Endothelin-1 antagonist).

Which of the following side effects is a major concern for all Centrally Acting Adrenergic Agonists, with Amphetamine being noted as the most addicting?

A. Risk of pulmonary HTN

B. Tachyarrhythmia

C. Increased risk of addiction (physical and psychological dependence)

D. Agitation and confusion

C. Increased risk of addiction (physical and psychological dependence)

Explanation: Increased risk of addiction is a generalized side effect of Centrally Acting Adrenergic Agonists (PPPAM), with Amphetamine noted as the most addicting.

Which drug, known to be a Mixed Acting Adrenergic Agonist, is used for the management of hypotension along with Metaraminol?

A. Amphetamine

B. Mephentermine

C. Phenmetrazine

D. Phenylpropanolamine

B. Mephentermine

Explanation: Mephentermine is listed with Metaraminol for the management of hypotension. Both are mixed-acting agents.

Which drug, a derivative of amphetamine, is specifically named as Shabu and is classified as a Drug of Abuse?

A. Methylphenidate

B. Ecstasy (MDMA)

C. Phentermine

D. Methamphetamine

D. Methamphetamine

Explanation: Methamphetamine is specifically identified as "Shabu" and listed as a Drug of Abuse under the Amphetamine category.

The group of Centrally Acting Adrenergic Agonists can be summarized by the mnemonic PPPAM. What does the "P" in PPPAM represent?

A. Phenylpropanolamine, Phentermine, Phenmetrazine

B. Phenylpropanolamine, Phenmetrazine, Procaine

C. Phentermine, Phentolamine, Phenylpropanolamine

D. Pindolol, Prazosin, Phenmetrazine

A. Phenylpropanolamine, Phentermine, Phenmetrazine

Explanation: The Centrally Acting drugs are summarized by PPPAM: Phenylpropanolamine, Phentermine, Phenmetrazine, Amphetamine, and Methylphenidate.