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    Topic 2 - Adrenergic Drugs

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    Angeli Gregorio
    This document discusses adrenergic drugs that act on the sympathetic nervous system. It begins by classifying adrenergic agonists based on their chemistry as either catecholamines or non-catecholamines, and based on their mechanism of action as endogenous catecholamines, direct-acting agonists, indirect-acting agonists, or mixed-acting agonists. It then describes the sites and mechanisms of these different classes of drugs. The document concludes by discussing the clinical uses of both adrenergic agonists and antagonists, as well as their common adverse effects.

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    Topic 2 - Adrenergic Drugs

    Uploaded by

    Angeli Gregorio
    241 views52 pages
    This document discusses adrenergic drugs that act on the sympathetic nervous system. It begins by classifying adrenergic agonists based on their chemistry as either catecholamines or non-catecholamines, and based on their mechanism of action as endogenous catecholamines, direct-acting agonists, indirect-acting agonists, or mixed-acting agonists. It then describes the sites and mechanisms of these different classes of drugs. The document concludes by discussing the clinical uses of both adrenergic agonists and antagonists, as well as their common adverse effects.

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    Drugs which acts on sympathetic ANS

    Original Title

    Adrenergic Drugs

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    This document discusses adrenergic drugs that act on the sympathetic nervous system. It begins by classifying adrenergic agonists based on their chemistry as either catecholamines or non-catecholamines, and based on their mechanism of action as endogenous catecholamines, direct-acting agonists, indirect-acting agonists, or mixed-acting agonists. It then describes the sites and mechanisms of these different classes of drugs. The document concludes by discussing the clinical uses of both adrenergic agonists and antagonists, as well as their common adverse effects.

    Copyright:

    © All Rights Reserved
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    241 views52 pages

    Topic 2 - Adrenergic Drugs

    Uploaded by

    Angeli Gregorio
    This document discusses adrenergic drugs that act on the sympathetic nervous system. It begins by classifying adrenergic agonists based on their chemistry as either catecholamines or non-catecholamines, and based on their mechanism of action as endogenous catecholamines, direct-acting agonists, indirect-acting agonists, or mixed-acting agonists. It then describes the sites and mechanisms of these different classes of drugs. The document concludes by discussing the clinical uses of both adrenergic agonists and antagonists, as well as their common adverse effects.

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    Topic 2 - Adrenergic Drugs

    Specific Objectives
    1. To classify and enumerate drugs acting on
    the sympathetic divisions of the autonomic
    nervous system
    2. To describe the sites and mechanisms of
    drugs acting on the sympathetic divisions
    of the autonomic nervous system
    3. Understand the effects of sympathetic
    agonists and antagonists
    SYMPATHOMIMETICS

    ADRENERGIC AGONISTS
    CLASSIFICATION OF SYMPATHOMIMETICS
    (ADRENERGIC AGONISTS)

    • BASED ON CHEMISTRY
    – Catecholamines
    – Noncatecholamines

    • BASED ON THEIR MECHANISMS OF ACTION


    – Endogeneous Catecholamines
    – Direct-acting adrenergic agonists
    – Indirect-acting adrenergic agonists
    – Mixed acting adrenergic agonists
    BASED ON CHEMISTRY
    DIFFERENCES BETWEEN CATECHOLAMINES
    FROM NONCATECHOLAMINES
    CATECHOLAMINES NONCATECHOLAMINES
     Contain the 3,4-  Not metabolized by MAO
    dihydroxybenzene groups and COMT (no catechol
     High potency in activating α hydroxyl groups)
    and β receptors
     Metabolized by MAO and
     Longer half-lives
    COMT  Administered orally
     Short duration of action
     Do not penetrate the CNS
    CLASSIFICATION OF SYMPATHOMIMETICS
    BASED ON CHEMISTRY
    CATECHOLAMINES
     Dopamine
     Epinephrine
     Isoproterenol
     Norepinephrine
     Dobutamine
    CLASSIFICATION OF SYMPATHOMIMETICS
    BASED ON CHEMISTRY
    NON-CATECHOLAMINES
     Phenylephrine
     Methoxamine
     Ephedrine
     Amphetamine
    BASED ON
    MECHANISMS OF
    ACTION
    Classification of Sympathomimetics based on
    Mechanism of action
    Endogeneous Direct-Acting Indirect-Acting Mixed-Acting
    Catecholamines
    Epinephrine α agonists Releasers Direct- and
    Norepinephrine β agonists Reuptake Inhibitors Indirect-acting
    Dopamine
    ENDOGENEOUS
    CATECHOLAMINES
     Major α and β direct-acting agonists
    Epinephrine (Adrenaline) – no effect at α2
    Norepinephrine (Noradrenaline,
    Levarterenol)– little effect on β2
    Dopamine – D1 = D2 > β1 > α1
    DIRECT-ACTING
    ADRENERGIC
    AGONISTS
    MOA OF ADRENERGIC AGONISTS (DIRECT-ACTING)

    α2 agonists

    α1 agonists

    β agonists (β1 β2 β3)


    Direct-acting Sympathomimetics

    • Binding to 1, 2,


    1, or 2 adrenergic
    receptors activates
    SECONDARY
    MESSENGERS.
    Properties of α-Adrenergic Receptors
    Type of Locations Effects
    Receptor
    α1 : Gq Radial muscle of the iris Pupillary dilation
    Arteriolar smooth muscle Incr PR and BP
    Phospho- GI and GU, trigone and Retention
    lipase C sphincters
    DAG, IP3 Pilomotor smooth muscle Piloerection
    Seminal vesicle smooth Ejaculation
    muscle
    Liver Glycogenolysis and gluconeogenesis
    α2 : Gi Presynaptic nerve terminals Inhibits release of NE (presynaptic
    inhibition)
    adenylyl Platelets Aggregation
    cyclase Pancreatic β cells Inhibits insulin release
    cAMP (hyperglycemia)
    Properties of β-Adrenergic Receptors

    TYPE OF LOCATIONS EFFECTS


    RECEPTOR

    β1 : Gs Heart Increase in heart rate, contractility


    and conduction
    Juxtaglomerular cells Incr in secretion of renin (incr BP)
    β2 : Gs Vascular smooth muscle Vasodilation (relaxation)
    Bronchiolar smooth muscle Bronchodilation (relaxation)
    adenylyl GI and urinary bladder Decr GI and GU motility
    Cyclase (detrusor-β) smooth (relaxation)
    cAMP muscle
    Uterine smooth muscle Decr uterine contraction
    (relaxation)
    Skeletal muscle Uptake of K+ in skeletal muscles
    Liver Glycogenolysis & gluconeogenesis
    β3 : Gs Adipose tissue Lipolysis
    -RECEPTOR AGONISTS
     α1-selective direct-acting agonists
     Phenylephrine
     Methoxamine
     Midodrine
     α2-selective direct-acting agonists (NOT
    SYMPATHOMIMETICS when orally administered)
     Clonidine
     Methyldopa
     Guanfacine
     Guanabenz
     Apraclonidine
     Brimonidine
    -RECEPTOR AGONISTS
    • β-nonselective direct-acting
    – Isoproterenol - aka Isoprenaline
    • β1-selective direct-acting
    – Dobutamine
    • β2-selective direct-acting
    – Albuterol – aka Salbutamol
    – Metaproterenol
    – Terbutaline
    – Pirbuterol
    – Salmeterol
    – Formoterol
    – Indacaterol
    Dopamine Receptors

    Types Location Effect


    D1 Smooth muscle Dilates renal blood
    AC vessels
    D2 Nerve endings Modulates
    AC transmitter release

    FENOLDOPAM – D1 AGONIST
    INDIRECT-ACTING
    ADRENERGIC AGONISTS
    A. Release neurotransmitters from presynaptic nerve
    terminals to produce a sympathomimetic effect
    (RELEASERS)
    • Amphetamine
    • Methamphetamine
    • Tyramine
    • Phenmetrazine
    • Methylphenidate
    • Modafinil
    INDIRECT-ACTING
    ADRENERGIC AGONISTS
    B. Catecholamine Reuptake inhibitors
    • Cocaine
    • Atomoxetine
    • Reboxetine
    • Sibutramine
    MIXED-ACTING ADRENERGIC
    AGONISTS
    Drugs act both directly and indirectly.
    DIRECT: Receptor Activation
    INDIRECT: Releaser/Reuptake Inhibition
    EXAMPLES: Ephedrine
    Pseudoephedrine
    Mephentermine
    Phenylpropanolamine
    CLINICAL USES OF ADRENERGIC
    DRUGS
    Endogeneous Catecholamines
    I. EPINEPHRINE- first line cardiac stimulant,
    first line agent for anaphylactic shock;
    local vasoconstrictor, glaucoma
    II. NOREPINEPHRINE – first line agent for septic
    shock
    III. DOPAMINE – management of cardiogenic
    shock, CHF
    Direct-acting Sympathomimetics
    • PHENYLEPHRINE & METHOXAMINE
    – Marketed as nasal and ophthalmic decongestants
    • CLONIDINE, METHYLDOPA, GUANFACINE,
    GUANABENZ, APRACLONIDINE, BRIMONIDINE
    – Hypertension
    • ISOPROTERENOL
    – Bronchodilator, AV Block
    • DOBUTAMINE
    – First line agent for cardiogenic shock, acute HF
    Direct-acting Sympathomimetics
    • METAPROTERENOL, ALBUTEROL, TERBUTALINE,
    PIRBUTEROL, SALMETEROL, FORMOTEROL,
    INDACATEROL
    – Bronchodilators
    • RITODRINE, TERBUTALINE, ISOXSUPRINE
    – Uterine relaxant
    Indirect-acting
    Sympathomimetics

    –RELEASERS
    • Amphetamine
    • Methamphetamine
    –Useful in narcolepsy,
    hyperkinetic
    syndrome of children,
    attention deficit
    hyperactivity disorder
    (ADHD)
    Indirect-acting
    Sympathomimetics
    –RELEASERS
    • Phenmetrazine - anorexiant and a popular
    drug of abuse
    • Methylphenidate – ADHD
    • Modafinil – narcolepsy
    Indirect-acting
    Sympathomimetics
    • REUPTAKE INHIBITORS
    – COCAINE
    • Local anesthetic
    – ATOMOXETINE
    • Treatment of ADHD
    – SIBUTRAMINE
    • Treatment of obesity
    Mixed Sympathomimetics

    – Ephedrine – clinically used to treat narcolepsy


    – Mephentermine & Metaraminol – Treatment
    of hypotension
    – Phenylpropanolamine – Decongestant in oral
    OTC drugs
    Common Adverse Effects of
    Adrenergic Agonists
    • Catecholamines –extensions
    of alpha- or beta- actions
    • CNS disturbances –
    nervousness, anorexia,
    insomnia, anxiety,
    aggressiveness, paranoid
    behavior, convulsions

    nausea
    Common Adverse Effects of
    Adrenergic Agonists
    • Alpha-1 agonist –
    hypertension
    • Beta-1 agonist – sinus
    tachycardia, arrhythmias
    • Beta-2 agonist – skeletal
    muscle tremor
    • Cocaine – drug abuse,
    cardiac arrhythmias or
    infarction, convulsions
    ADRENERGIC ANTAGONISTS
    SYMPATHOLYTICS
    Classification of Sympatholytics
    (Adrenergic Antagonists)

    • Based on Mechanism of Action


    – Direct acting Sympatholytics (direct acting alpha and
    beta blockers)
    – Centrally-acting Sympatholytics (alpha2-adrenergic
    agonists)
    – Peripherally-acting Sympatholytics (adrenergic
    neuronal blockers)
    Classification of Sympatholytics: Direct-acting:
    α-blockers

    • α1 – adrenergic selective, • α1,α2 – nonselective,


    reversible irreversible
    – Prazosin – Phenoxybenzamine
    – Doxazosin • α1,α2 – nonselective,
    – Terazosin reversible
    – Tamsulosin – Phentolamine
    – Alfuzosin • α2 – selective, reversible
    – Yohimbine
    Classification of Sympatholytics: Direct-acting:
    β-blockers
    • β1-selective blockers
    – Bisoprolol, Betaxolol
    – Esmolol
    – Atenolol, Acebutolol
    – Metoprolol
    • Non-selective β-adrenergic antagonists
    – Nadolol
    – Sotalol
    – Timolol
    – Propranolol
    Classification of Sympatholytics: Direct-acting:
    β-blockers
    • β-blockers with Intrinsic Sympathomimetic Activity (ISA)
    – Acebutolol
    – Pindolol
    • β-blockers with α-blocking capacity
    – Labetalol
    – Carvedilol
    • β2-selective blocker
    – Butoxamine
    Centrally & Peripherally Acting Sympatholytics

    • Centrally Acting • Peripherally Acting


    Sympatholytics Sympatholytics
    (α2-agonists) (Adrenergic Neuronal
    – Clonidine Blockers)
    – Methyldopa – Reserpine
    – Guanfacine – Guanethidine
    – Guanabenz – Guanadrel
    – Bretylium
    Peripherally-acting
    Sympatholytics

    Centrally-acting
    sympatholytics

    α2 antagonists

    β antagonists α1 antagonists
    CLINICAL USES OF ADRENERGIC
    BLOCKERS
    SELECTIVE ALPHA1-ANTAGONISTS
    • Prazosin and Prazosin analogs (terazosin,
    doxazosin, trimazosin, tamsulosin)
    HYPERTENSION
    Selective alpha1 blocker
    • Management of urinary
    BENIGN PROSTATIC hesitancy
    HYPERPLASIA
    • Prevention of urinary
    retention in men with BPH
    Clinical Uses of Nonselective Alpha blockers
    – Presurgical management of
    pheochromocytoma
    – Phenoxybenzamine
    ▫ Carcinoid tumor
    ▫ Mastocytosis
    • Phentolamine
    ▫ Tissue damage – accidental local infiltration of
    potent alpha agonists
    ▫ Rebound hypertension /Hypertension –
    overdose of drugs
    ▫ Erectile dysfunction
    β1-selective antagonists
    ▫ HYPERTENSION
    ▫ ANGINA
    ▫ MI
    ▫ THYROID
    STORM
    Non-selective β-blockers

    ▫ ARRHYTHMIA
    ▫ ACUTE PANIC SYNDROME
    ▫ MIGRAINE HEADACHE
    β-blockers with α blocking
    capacity

    CHRONIC CHF
    ADVERSE EFFECTS OF ADRENERGICS
    ANTAGONISTS
    α-Blockers
    • Orthostatic hypotension
    • Reflex tachycardia
    (Nonselective alpha
    blockers)
    • Syncope (Selective alpha1
    blocker)
    • exaggerated orthostatic
    hypotensive response to
    the first dose
    • Nausea and vomiting
    • Sexual Dysfunction
    β-Blockers
    • Bradycardia
    • AV blockade
    • Heart failure
    • Asthma -
    bronchoconstriction
    • Augmentation of
    hypoglycemia
    • Lipidemia
    • Sedation, fatigue & sleep
    alterations
    • Dizziness
    • Orthostatic hypotension
    Common Adverse Effects of
    Adrenergic Neuronal Blockers

    • Reserpine
    – CNS depression
    – Bradycardia
    – GI disturbances
    – Extrapyramidal effects
    Adverse Effects of Drugs that Interfere with
    Central Sympathetic Outflow (α2-agonist)

    • Methyldopa (α2-agonist)
    – Edema
    – Sedation (drowsiness)
    – Dry mouth & nasal mucosa
    – Headache
    – Reduced libido (impotence)
    – (+) Coomb’s test (hemolytic
    anemia)
    – Hepatotoxicity
    – Lactation (incr prolactin
    secretion)
    Adverse Effects of Drugs that Interfere with
    Central Sympathetic Outflow (α2-agonist)

    • Clonidine
    – Sedation (dizziness)
    – Rebound hypertension
    – Dry mouth
    – Itching & redness of skin
    (patch)
    – Mild orthostatic
    hypotension
    – Endocrine problems

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