Cardiology > Adrenergics > Flashcards

Adrenergics Flashcards

(19 cards)

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1
Q

Sympathomimetics

  • Definition
  • Catecholamines
  • Non-catecholamines
  • Direct-acting sympathomimetics
  • Indirect-acting sympathomimetics
  • Mixed-acting sympathomimetics
A
  • Definition
    • Drugs that produce effects similar to the SNS
    • Potentiate noradrenergic neruotransmission or stimulate adrenergic receptors at effector organs
  • Catecholamines
    • Contain a catechol nucleus (benzene ring w/ 2 hydroxyl groups) & an amine-containing sidechain (Epi, NE, & DA isoproterenol)
    • Potent agonists
    • Susceptible to oxidation/autoxidation
    • If given orally, almost completely metabolized before reaching systemic circulation
  • Non-catecholamines
    • Stable
    • Given orally
    • Not metabolized
  • Direct-acting sympathomimetics
    • Adrenergic agonists acting on alpha, beta, or both adrenergic receptors
  • Indirect-acting sympathomimetics
    • Act pre-synaptically
    • Increase catecholamine availability by…
      • Releasing/displacing NE from sympathetic nerve varicosities
      • Blocking the transport of NE into sympathetic neurons (e.g., cocaine)
      • Blocking metabolizing enzymes (MAO, COMT)
  • Mixed-acting sympathomimetics
    • Release NE & act directly on adrenergic receptors (e.g., ephedrine, dopamine)
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2
Q

Sympathomimetic drugs

  • Direct-acting
    • Non-selective (4)
    • Selective (4)
  • Indirect-acting (4)
  • Mixed-acting (2)
A
  • Direct-acting
    • Non-selective
      • Epinephrine (alpha1, alpha2, beta1, beta2)
      • Norepinephrine (alpha1, alpha2, beta1, beta2)
      • Oxymetazoline (alpha1, alpha2)
      • Isoproterenol (beta1, beta2)
    • Selective
      • Phenylephrine (alpha1)
      • Clonidine (alpha2)
      • Dobutamine (beta1)
      • Trebutaline (beta2)
  • Indirect-acting
    • Releasing agent (amphetamine, tyramine)
    • Uptake inhibitor (cocaine, SNRI)
    • MAOIs (TCA)
    • COMT inhibitors (entacapone)
  • Mixed-acting
    • Ephedrine (alpha1, alpha2, beta1, beta2, releasing agent)
    • Dopamine (DA, beta, high dose alpha, releasing agent)
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3
Q

Catecholamines

A
  • Catechol + amine group
    • Catechol group: high potency
    • Amino group: activity
  • Acute inotropes / vasopressors
  • Rapid inactivation
    • Metabolism or reuptake
    • Short half-life
  • Poor penetration into the CNS
    • May have some CNS effects
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4
Q

Epinephrine (Epi, adrenaline)

  • Drug
  • Receptors
  • Pharmacological dose
  • Use
  • Pharmacological response depends on…
A
  • Drug
    • Direct-acting, non-selective
  • Receptors
    • beta2 >= beta1 > alpha1 >= alpha2
    • Low dose: beta effects only
      • Increases contractility & heart rate
      • Induces bronchodilation
      • Minor effects on mean BP
    • High dose: alpha effects
      • For cardiac arrest
  • Pharmacological dose
    • Increases systemic vascular resistance & diastolic BP
    • Critical for perfusion of organs during CPR
    • Decreases non-vital organ perfusion (splanchnic, intestinal, renal & skin)
  • Use
    • Initial CPR (bolus) & post-CPR stabilization (infusion)
    • Anaphylactic shock
    • Acute severe asthma
    • Glaucoma
    • Mixed w/ local anesthetics to prolong their effects
  • Pharmacological response depends on…
    • Ratio & sensitivity of receptors
    • Penetration of circulating Epi into target organ
    • Concentration fo Epi at site of action
    • Level of activation at ANS
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5
Q

Norepinephrine (NE, noradrenaline)

  • Drug
  • Receptors
  • Effects
  • Use
  • Administration
A
  • Drug
    • Direct-acting, non-selective
  • Receptors
    • beta1 > alpha1 > alpha2
  • Effects
    • Arterial & venous vasoconstrictor
    • Reduces renal, cutaneous, & muscle blood flow
    • Little to no effect on splanchnic blood flow
  • Use
    • Restoration of BP in severe, acute hypotension
      • Post pheocrhomocytomectomy, sympathectomy, or spinal anesthesia
      • Septic shock
    • Adjunctive treatment in cardiac arrest
  • Administration
    • Only via central venous catheter b/c extravasation causes severe local tissue damage
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6
Q

Dopamine (DA)

  • Drug
  • Receptors
  • Use
  • Selective agonist
A
  • Drug
    • Mixed-acting
    • Precursor of NE + releaser of NE from nerve endings
  • Receptors
    • DA > beta1 >> alpha1
    • Low dose: D1
      • Increase splanchnic, cerebral, coronary, & renal blood flow
      • Inhibit NE release
    • Mid dose: beta1
      • Increase cardiac contractility
      • Little/no effect on BP or HR
    • High dose: alpha1
      • Increase BP & HR (marked tachycardia)
      • Vasoconstriction
      • Decrease renal & splanchnic blood flow
  • Use
    • Shock syndrome
    • Chronic heart heart failure w/ oliguria & low/normal vascular resistance
  • Selective agonist
    • Fenoldopam
    • Antihypertensive agent used in hypertensive crisis
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7
Q

Isoproterenol (Iso)

  • Drug
  • Receptors
  • Effects
  • Use
A
  • Drug
    • Direct-acting, non-selective
  • Receptors
    • beta1 > beta2
  • Effects
    • Increases myocardial oxygen demand
      • Unfavorable balance for O2 supply vs. demand
      • Since also vasodilates & decreases diastolic pressure, may decrease coronary perfusion & provoke myocardial ischemia
    • Bronchodilator
    • Chronotropic: increases HR, potentiates AV conduction
    • Inotropic: increases contractility & cardiac output
  • Use
    • Beta blocker overdose
    • After cardiac surgery in patients w/ prior beta-blockade
      • Low contractility, low HR, high peripheral resistance
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8
Q

Dobutamine

  • Drug
  • Receptors
  • Effects
  • Use
A
  • Drug
    • Direct-acting, selective
  • Receptors
    • beta1 > beta2 >> alpha1
  • Effects
    • Hemodynamic: increase contractility, HR, & vasodilation
    • More prominent inotropic than chronotropic effects (than Iso)
    • minimal effects on myocardial oxygen demand
      • Favorable balance for O2 supply vs. demand
    • No direct effects on renal or splanchnic blood flow
  • Use
    • Inotropic support in short-term treatment of cardiac decompensation
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9
Q

Bronchodilators

  • Drug
  • Receptors
  • Short-acting
  • Long-acting
  • Use
A
  • Drug
    • Selective beta2 adrenergic receptor agonists
  • Receptors
    • beta2
  • Short-acting
    • Terbutaline & albuterol
    • Given via inhalation “as needed”
  • Long-acting
    • Salmeterol, formoterol, arfomoterol
    • Given via adjunctive therapy twice a day
  • Use
    • COPD
    • Asthma
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10
Q

Tocolytic agents

  • Drug
  • Receptors
  • Examples
  • Use
  • Side effects
A
  • Drug
    • Selective beta2 adrenergic receptor agonists
  • Receptors
    • beta2
  • Examples
    • Ritodrine
      • Activates adenylyl cyclase –> increases cAMP production –> enhances Ca2+ efflux from vascular smooth muscle cells
      • Decreases intensity & frequency of uterine contractions
    • Terbutaline
  • Use
    • Delay / control premature labor
    • Allow maternal transport/adminsitered steroids to work
    • Don’t prevent pre-term labor
  • Side effects
    • Maternal & fetal tachycardia
    • Palpitations
    • Hypokalemia
    • Hyperglycemia
    • Cardiac ischemia
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11
Q

Phenylephrine

  • Drug
  • Receptors
  • Effects
  • Use
  • Administration
  • Side effects
A
  • Drug
    • Direct-acting, selective
    • alpha1 adrenergic agonist
  • Receptors
    • alpha1
  • Effects
    • Arterial vasoconstriction
    • Vasopressor
  • Use
    • Nasal, mydriatic, & ophthalmic decongestant
  • Administration
    • IV
  • Side effects
    • Hemorrhoid discomfort
    • Hypertension
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12
Q

Clonidine

  • Drug
  • Receptors
  • Effects
  • Use
A
  • Drug
    • Direct-acting, selective
    • Selective central alpha2 adrenergic agonist
  • Receptors
    • alpha2
  • Effects
    • Acts in vasomotor center (rostral ventrolateral medulla, RVLM) to regulate/inhibit SNS
    • Sympathoinhibitory effects: reduce central sympathetic outflow & vasomotor tone
    • Decreases NE releaes by activating alpha2 receptors
  • Use
    • Hypertension
    • Hypertensive urgency
    • Severe pain
    • Opioid or nicotine withdrawal
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13
Q

Indirectly Acting Sympathomimetics

  • Mechanism
  • Effects in peripheral organs
  • Effects in CNS
  • Use
  • Releasing agents
  • Uptake inhibitor
  • MAOIs
  • COMT inhibitors
A
  • Mechanism
    • Enter presynaptic nerve terminal –> activate neurotransmitter release –> increase concentrations of catecholamines in synaptic clefts –> increased sympathetic response
    • May bind to an adrenergic receptor (direct agonistic activity)
  • Effects in peripheral organs
    • When drug doesn’t cross BBB
    • beta1: induce cardiac stimulation (beta1) w/ increased contractions, tachycardia, & palpitations
    • alpha1: induce vasoconstriction to increase peripheral resistance & BP, mydriasis, difficulty in micturition
    • beta2: bronchodilation
    • Effects develop more slowly, last longer, & attenuate w/ reptitive administrations (tachyphylaxis)
  • Effects in CNS
    • ​Increase NE –> antidepressant, vigilance, anorectic effect
    • Increase DA –> antiparkinson or antidepressant effects, induce addiction
  • Use
    • Vasoconstrictors
    • CNS stimulants
    • Appetite suppressants
    • Antidepressants
    • Antiparkinsonism
  • Releasing agents
    • Amphetamine, tyramine
  • Uptake inhibitor
    • Cocaine, SNRI
    • Drugs for ADHD
    • Tricyclic antidepressants (TCA)
  • MAOIs
    • Selegiline
  • COMT inhibitors
    • Entacapone
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14
Q

Drugs to Treat ADHD

  • Drugs
  • Adverse effects
A
  • Methylphenidate (Ritalin)
    • Blocks reuptake of NE & DA
    • Stimulates cerebral cortex
  • Dexamphetamine
    • Promotes release of catecholamines (NE & DA)
    • Inhibits catecholamine reuptake
  • Buproprion
    • Inhibits neuronal uptae of NE & DA
  • Atomoxetine
    • Inhibits NE reuptake
  • Adverse effects (cardiovascular)
    • HTN
    • Arrhythmias
    • QT interval prolongation
    • Sudden death
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15
Q

Adrenergic Crisis

  • Definition
  • Life-threatening because…
  • Most common cause
  • Other causes
  • Hyper-adrenergic state is caused by…
A
  • Definition
    • Sudden & marked increase in circulating & extracellular levels of catecholamines (EPI = NE > DA)
    • Main sources: adrenal gland & sympathetic nerve terminals
  • Life-threatening because…
    • Extreme tachycardia
    • Severe elevation in BP (hypertensive crisis
  • Most common cause
    • Cocaine overdose
  • Other causes
    • Intoxication w/ amphetamine & other central sympathetic stimulants
    • Pheochromocytoma (uncontrolled, paroxysmal hypertension)
    • Ingestion of tyramine while receiving MAOIs
    • Clonidine, beta blocker, opiate, & alcohol withdrawal
  • Hyper-adrenergic state is caused by…
    • Subarachnoid hemorrhages
    • Severe pain
    • Panic attack
    • Myocardial infarction
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16
Q

Adrenergic Syndrome vs. Anticholinergic Syndrome

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A
  • Both
    • Mydriasis
    • Tachycardia ( /HTN for adrenergic)
    • Hyperthermia
    • Disorientation ( / agitation for adrenergic)
    • Hallucinations
  • Adrenergic Syndrome
    • Diaphoresis (axillary sweating)
  • Anticholinergic Syndrome
    • Dry skin
17
Q

Selective alpha1 Adrenergic Antagonists

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A
  • Drugs
    • alpha1A = alpha1B = alpha1D
      • Prazosin
      • Doxazosin
      • Terazosin
    • alpha1A = alpha1D > alpha1B
      • Alfuzosin
      • Tamsulosin
      • Silodosin
  • Effects
    • Inhibit vasoconstriction induced by endogenous catecholamines & exogenous sympathomimetics
    • Vasodilates resistant arteriorlar vessels & veins
    • Decrease peripehral resistance –> decrease venous return –> decrease BP
    • Magnitude of effects depends on SNS activity: upright > supine
  • Use
    • Hypertension
    • Benign prostatic hyperplasia (BPH)
      • Prostate & lower urinary tract tissues have high density of alpha1A receptors
      • Blocking these receptors may alleviate symptoms of BPH
18
Q

Non-Selective alpha Adrenergic Antagonists

  • Drugs
  • Effects
  • Use
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A
  • Drugs
    • Phenoxibenzamine
      • Irreversible antagonist
    • Phentolamine
      • Competitive antagonist
  • Effects
    • Antihypertensive
    • Reflex cardiac stimulation
  • Use
    • Limited b/c of significant adverse effects
    • Preoperative treatment of pheochromocytoma & other adrenergic crises
    • Frost bite
    • Prevention of dermal necrosis after sympathomimetic extravasation
19
Q

Ergot Alkaloids

  • Drug
  • Effects
  • Examples
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A
  • Drug
    • Hard-to-classify group
    • alpha adrenergic receptor agonists or antagonists
    • Weak DA receptor agonists
    • 5-HT receptor antagonists / partial agonists
  • Effects
    • Active substances occur naturally in a fungus that infests cereal crops
    • Poisoning incidents
      • Mental disturbance
      • Severe & painful peripheral vasoconstriction
      • Gangrene
  • Examples
    • Ergotamine
      • Treats migraine
    • Ergonovin
      • Prevents postpartum hemorrhage
    • Bromocriptin
      • DA receptor agonist
      • Used in parkinsonism
      • Controls secretion of prolactin to prevent/suppress lactation & treat hyperprolactinemia
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