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Andrenoceptor Activating Drugs

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Adrenoceptor Agonists and Sympathomimetic Drugs | Pharmacology Aleyssa | Jeng DIVISIONS OF HUMAN NERVOUS SYSTEM NERVOUS SYSTEM The SNS is an important regulator of virtually ALL organs Mediated by norepinephrine release ! activates adrenoceptors on postsynaptic sites Epinephrine is released from the adrenal medulla in response to stress ! Norepinephrine acts as a neurotransmitter ! Epinephrine acts as a hormone SYMPATOMIMETIC DRUG CLASSIFICATION: 1. Direct Agonists – directly interact with and activate adrenoceptors Pharmacologic effects depend on: route of administration, relative affinity for adrenoceptor subtypes, and relative expression of receptor subtypes in target tissues 2. Indirect Agonists – actions depend on its ability to enhance the actions of endogenous catecholamines Displace stored catecholamines, or decrease clearance of released NE Inhibit reuptake Prevent metabolism (MAO, COMT) Greater effects under conditions of increased sympathetic outflow 3. Mixed-Acting – leads to some or all of the characteristic effects of endogenous catecholamines SYMPATHETIC NERVOUS SYSTEM FIGHT OR FLIGHT RESPONSE RESULTS IN: 1. Increased BP 2. Increased blood flow to brain, heart and skeletal muscles 3. Increased muscle glycogen for energy 4. Increased rate of coagulation 5. Pupil dilation Human Nervous System Central Nervous System Peripheral Nervous System Autonomic Nervous System With Neurotransmitter NOREPI & ACETYLCHOLINE Either "FIGHT & FLIGHT" or "REST & DIGEST" Includes NEURONS & GANGLIA outside of the brain & spinal cord Peripheral NS Autonomic NS (Involuntary) Sympathetic NS (Adrenergic) Para sympathetic NS (Cholinergic) Somatic NS (Voluntary) Sympathomimetic Direct Agonist (Epi/NE) Indirect Agonist
Transcript
  • Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!

    !Aleyssa |"Jeng

    DIVISIONS OF HUMAN NERVOUS SYSTEM

    NERVOUS SYSTEM

    The SNS is an important regulator of virtually ALL organs Mediated by norepinephrine release !

    activates adrenoceptors on postsynaptic sites Epinephrine is released from the adrenal

    medulla in response to stress ! Norepinephrine acts as a neurotransmitter ! Epinephrine acts as a hormone

    SYMPATOMIMETIC DRUG CLASSIFICATION:

    1. Direct Agonists directly interact with and activate adrenoceptors Pharmacologic effects depend on: route

    of administration, relative affinity for adrenoceptor subtypes, and relative expression of receptor subtypes in target tissues

    2. Indirect Agonists actions depend on its ability to enhance the actions of endogenous catecholamines Displace stored catecholamines, or

    decrease clearance of released NE Inhibit reuptake Prevent metabolism (MAO, COMT) Greater effects under conditions of

    increased sympathetic outflow

    3. Mixed-Acting leads to some or all of the characteristic effects of endogenous catecholamines

    SYMPATHETIC NERVOUS SYSTEM FIGHT OR FLIGHT RESPONSE RESULTS IN:

    1. Increased BP 2. Increased blood flow to brain, heart and

    skeletal muscles 3. Increased muscle glycogen for energy 4. Increased rate of coagulation 5. Pupil dilation

    Human!Nervous!System!Central!Nervous!System!

    Peripheral!Nervous!System! Autonomic!Nervous!System!

    With!Neurotransmitter!NOREPI!&!ACETYLCHOLINE!

    Either!"FIGHT!&!FLIGHT"!or!"REST!&!DIGEST"!!

    Includes!NEURONS!&!GANGLIA!outside!of!the!brain!&!spinal!cord! Peripheral!NS!Autonomic!NS!(Involuntary)!

    Sympathetic!NS!(Adrenergic)! Para!sympathetic!NS!(Cholinergic)!

    Somatic!NS!(Voluntary)!

    Sympathomimetic!Direct!Agonist!(Epi/NE)!

    Indirect!Agonist!

  • PRECURSOR Tyrosine: Amino acid found in many foods including cheese and dairy products BIOSYNTHESIS

    Rate Limiting (TH): Controls production, found in axons L-DOPA: L-3-4-dihydroxyphenylalanine NOREPINEPHRINE SYNTHESIS

    Tyrosine transported into Noradrenergic ending

    by a Na-dependent carrier

    Tyrosine converted to Dopamine and transported into the vesicle by VMAT (which can be blocked by reserpine)

    Dopamine is converted to NE in the vesicle by Dopamine-B-hydroxylase

    Physiologic release of transmitter occurs when an action potential opens voltage-sensitive calcium channels and increases intracellular calcium.

    Fusion of vesicles results in expulsion of NE, cotransmitters, and dopamine-B-hydroxylase (blocked by guanethidine and bretylium)

    After release NE diffuses out or is transported into the cytoplasm by NET (can be blocked by cocaine and TCA)

    Regulatory receptors are present on the presynaptic terminal. SNAPs, synaptosome-associated proteins; VAMPs, vesicle-associated membrane proteins

    REGULATION The actions of catecholamine are terminated by: (1) Reuptake into nerve terminals by NET (2) Dilution by diffusion out of the junctional cleft and uptake at extraneuronal sites by ENT, OCT1, and OCT2 (3) Metabolic transformation (1) Reuptake into nerve terminals by NET Once released, NE will interact with the

    receptors. If there is excess NE, the body will balance &

    regulate it release by NET (norepinephrine transporter) & alpha-2

    NET (NE transporter) is a Na-dependent transporter, which needs high Na+ concentration entering the presynaptic fiber. NET has higher affinity to NE but highest with DOPAMINE & low affinity to EPI. (D>NE>Epi)

    NET primarily responsible in terminating the activity of NE because it removes 90% of NE in synaptic cleft area. Thus, increasing the re-uptake of NE.

    NET can be inhibited by tricyclic antidepressants & cocaine. Thus, NE is still high in the synaptic cleft.

    There are certain substances that can be taken up by NET (not only NE, Dopa, Epi) like mixed sympathomimetic agents (ex. Amphetamine, Ephidrine & Tyramine). Once they are taken, it will enter the presynaptic fiber. As it enters, it will be transported by VMAT going inside the storage vesicle. If the mixed sympathomimetic drug is inside the vesicle, it will NOT allow the NE to go inside the vesicle causing

  • Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!

    !Aleyssa |"Jeng

    displacement of NE in synaptic cleft. If the mixed sympathomimetic drug is given repeatedly at close interval. NE stores will be depleted causing lesser sympathetic effect.

    Alpha-2 is an autoreceptor, which prevents NE release. When there is excess NE in the synaptic cleft that occupies ALL the post-synaptic receptors. The excess NE will occupy the alpha-2 receptor. Hence, preventing the release of NE.

    Summary: (responsible in regulation the AMOUNT of NE) o NET increase re-uptake of

    neurotransmitters. It is the major pathway in terminating the activity of NE (90%)

    o Alpha-2 decrease/prevent the release of neurotransmitters

    Other mechanisms in regulation of NE release:

    1] Up & down regulation The receptors are the one being regulated. If up-regulated the response of the

    receptor of the agonist will be greater. Thus, effects are increase.

    If down-regulated the response of the receptor of the agonist will be diminished. o Most of the time, down-regulation is a

    result of loss of receptors (ex. If all the receptors are occupied & thus, there will be NO available receptors for the next batch of the transmitters)

    2] Post-synaptic excitatory potential (NOT sympathetic in nature) This is inhibited by GABA

    (3) Metabolic transformation - Metabolism, thru enzymes MAO & COMT Both MAO & COMT are distributed widely throughout the body, including the brain; the highest concentrations of each are in the liver and the kidney.

    DESENSITIZATION Occurs after exposure to almost all

    sympathomimetics Tolerance, refractoriness, and tachyphylaxis

    Covalent bond in receptor irreversible

    HOMOLOGOUS when the receptor is repeatedly activated by the same agent that activates it

    HETEROLOGOUS - when there is diminished in the response of the receptors by other agonist

    CHEMICAL STRUCTURE

    Substitution on the Benzene Ring

    Hydroxyl group at the 3rd and 4th position will tell whether the agent has a good alpha or beta activity

    o Absence of hydroxyl group = will reduce the drug effect

    2 functions of hydroxyl group: o Maximal alpha & beta activity o Recognition of COMT

    Hydroxyl group at phenyl ring will be the one that will be recognized by COMT. If absence or lack 1 of hydroxyl group, COMT will NOT degrade the agent. Causing inc./greater the bioavailability. ! Phenylephrine has greater bioavailability than Epinephrine

    Phenylephrine o Lack the hydroxyl group at both

    positions o Has lesser potency than EPI in terms of

    alpha activity & negligible beta activity o Lesser effect BUT delay degradation by

    COMT ! stays in the system longer

    Adrenergic!Receptors!Alpha!1,2!

    Beta!1,2,3! Dopamine!1S5!

  • Epinephrine

    o Has a complete hydroxyl group at 3rd & 4th position ! greater effets, shorter action

    Alkyl substituents in Amino Group

    A drug that has an alkyl substituent in amino group has increased BETA-receptor activity

    The bulkier the alkyl substituent the greater effect of BETA activity

    EPI has better BETA activity than NE (none)

    ISOPROTERENOL has the greatest B-activity because it has bulkier/larger group of substituents ! weak at alpha-receptors

    Substitution on the A-carbon Substitution at alpha carbon will delay

    oxidation by MAO Phenylephrine will be degraded easily by

    MAO d/t absence of substitution at alpha carbon

    Alpha-methyl compounds ! phenylisopropylamine ! some have enhanced ability to displace catecholamines from their storage sites in noradrenergic nerves. This means that a portion of their activity is dependent on the presence of normal NE stores (indirect sympathomimetics)

    Substitution on the B-carbon

    If there is hydroxyl group at B-carbon, it implies that the agent can directly act on the receptors.

    ADRENERGIC RECEPTORS AFFINITY FOR ALPHA RECEPTORS: Epinephrine > Norepinephrine >> Isoproterenol FOR BETA RECEPTORS: Isoproterenol > Epinephrine > Norepinephrine 1 receptors have equal affinity for epinephrine

    and norepinephrine 2 receptors have a higher affinity for

    epinephrine than for norepinephrine

    ADRENOCEPTOR TYPES & SUBTYPES

    Rec

    epto

    r

    Ago

    nist

    Ana

    goni

    st

    Effects

    Gen

    e on

    C

    hrom

    osom

    e

    1 Type

    Penyl ephrine

    Prazosin

    IP3, DAG common to all

    1A C5 1B C8 1D C20

    2 Type

    Clonidine

    Yohimbine

    cAMP common to all

    2A Oxymeta zoline

    C10

    2B Prazosin C2 2C Prazosin C4 Type

    Isopro terenol

    Propra nolol

    cAMP common to all

    1 Dobu tamine

    Betaxolol C10

    2 Albuterol Butox amine

    C5

    3 C8

  • Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!

    !Aleyssa |"Jeng

    ORGAN SYSTEM EFFECTS TYPE TISSUES ACTION - 1

    Most vascular smooth muscles (innervated)

    Contraction

    Pupillary dilator muscle

    Dilates Pupil

    Pilomotor smooth muscle

    Erects Hair

    Prostate Contraction Heart

    Increase Force of Contraction

    - 2

    Postynaptic CNS adrenoceptor

    Mutliple

    Platelets Aggregation Adrenergic/Cholinergic nerve terminals

    Inhibition of release of transmitter

    Some vascular muscles

    Contraction

    Fat cells Inhibition of Lypolysis

    - 1

    Heart Increase force & rate of contraction

    Juxtaglomerular cells Increase Renin release

    - 2

    Respiratory Uterine Vascular smooth muscles

    Relaxation

    Skeletal muscles Promotes Potassium Uptake

    Human Liver Glycogenolysis - 3 Fat cells Activates

    Lipolysis D 1 Smooth muscles Dilates vessels

    (Renal) D 2

    Nerve endings

    Modulates Transmitter Release

    CARDIOVASCULAR SYSTEM ALPHA RECEPTORS Increase arterial resistance Alpha, agonists decrease blood pressure by

    actions in the CNS, through their direct effect on a blood vessel may be constriction

    Alpha, agonists are useful in the treatment of hypertension

    BETA RECEPTORS Beta-1 has direct effect on the heart more than

    Beta-2 1 selective agonists do not induce

    vasodilatation, so they increase cardiac output with less reflex tachycardia

    Beta-2 decreases arterial resistance CATECHOLAMINES Cathecol + amine (NH2) Members:

    o Dopamine o Norepinephrine (Noradrenaline) o Epinephrine (Npepinephrine)

    STRUCTURE ACTIVITY RELATIONSHIP OF SYMPHATOMIMETIC DRUGS

  • Maximal alpha & beta activity -OH group at 3,4 position on benzene ring Absence OH at C-3 reduce potency

    : Blocks oxidation by MAO prolonged action : -OH facilitates activation of receptor important

    for storage in neutral vesicles SPECIFIC DRUGS CATHECHOLAMINES & SYMPHATOMIMETIC

    DRUGS

    DIRECT ACTING SYMPATHOMIMETICS ALPHA-1 SELECTIVE

    o Phenylephrine o Midodrine o Methoxamine

    ALHA-2 SELECTIVE o Clonidine o Methyldopa o Guanfacine o Guanabenz o Dexmedetomidine o Xylometazoline & Oxymetazoline

    BETA-1 SELECTIVE o Dobutamine o Prenalterol

    ENDOGENOUS CATECHOLAMINES EPINEPHRINE

    o Primary hormones secreted by the adrenal medulla in mammals

    NOREPINEPHRINE o Major neurotransmitter in the peripheral

    sympathetic nervous system (postganglionic adrenergic erves)

    DOPAMINE o Found predominantly in the basal ganglia of

    the CNS EPINEPHRINE POTENT STIMULANT: BOTH

    o Effects on target organ-complex POWERFUL CARDIAC STIMULANT

    o Predominantly on -1 receptors of the myocardium

    o Cells of pacemaker IT AFFECTS RESPIRATION

    o Primarily by relaxing bronchial muscle DIRECT RESPONSES

    o in contractile force o Accelerated rate of rise of isometric tension o Enhanced rate of relaxation o time to peak tension o excitability o Acceleration of the rate of spontaneous

    beating o Induction of automaticity in specialized

    regions of the heart o GIT smooth muscle is relaxed due to

    activation of both & adrenergic receptors

    o Intestinal tone and the frequency and amplitude of spontaneous contractions are reduced

    o Stomach is relaxed o Pyloric and ileocecal sphincters are

    contracted o Response of uterine muscles vary with

    species, phase of sexual cycle, state of gestation and dose given

    o Inhibits uterine tone & contractions during the last trimester

    Endogenous!Cathecolamines!Epinephrine!

    Norepinephrine!Dopamine!

    Direct!Acting!Sympathomimetics!AlphaS2!Selective!BetaS1!Selective!BetaS2!Selective!

  • Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!

    !Aleyssa |"Jeng

    METABOLIC EFFECTS o Insulin secretion is inhibited through an

    interaction with 2 receptors and enhanced by activation of 2 receptors

    o Glucagon secretion is enhanced by an action on the receptors of the cells of pancreatic islets

    o Decreases the uptake of glucose by peripheral tissues

    UNTOWARD EFFECTS o May cause restlessness, apprehension,

    headache, and tremor which may be secondary to the effects on the CV system, skeletal muscles & intermediary metabolism

    INJECTIONS o 1:1000 o 1:10,000 o 1:100,000

    DOSE o Usual SC adult: 0.3-0.5 mg o IV (cardiac arrest): 0.25 mg o INH 1:100 1% formulation

    NOREPINEPHRINE LACK THE METHYL SUBSTITUTION IN THE AMINO

    GROUP o 10% - 20% of the catecholamine content of

    human adrenal medulla A POTENT AGONIST AT RECEPTOR

    o Less potent than epinephrine on the receptors of most organs

    INCREASE IN CORONARY BF o Indirectly induced coronary dilation and to

    elevated BP DOPAMINE CENTRAL NEUROTRANSMITTER

    o D1 receptors in vascular beds which leads to vasodilation

    o Also activates 1 receptors in the heart o Low doses peripheral resist. o At higher doses activates receptors

    leading to vasoconstriction o High rates of infusion of dopamine mimics

    actions of epinephrine DOPAMINE RELATED DRUGS

    o Fenoldopam " D1-receptor-selective agonists " Lowers BP in severe hypertension

    o Dopexamine " Synthetic analog related to dopamine

    with intrinsic activity at dopamine receptors as well as at the 2-adrenergic receptors

    " Used in pts with severe CHF, sepsis, & shock

    EPI Nor

    EPI DOPA

    Bronchospasm

    Shock

    CHF w/ oliguria & low or normal peripheral resist

    Hypersensitivity Low BP

    Cardiogenic & septic shock

    Cardiac Arrest Post-intubation Infectious Croup ADRENERGIC AGONIST

    2-SELECTIVE

    O Metaproterenol O Albuterol O Pirbuterol O Fenoterol O Procaterol O Ritodine O Terbutaline O Isoetharine O Bitolterol O Formoterol O Salmeterol

    !Adrenergics!Agonists!1!Selective!!

    Isoproterenol! Dobutamine!Penalterol!2!Selective!Metaproterenol!Albuterol!Pirbuterol!

  • MIXED ACTING Ephedrine Pseudoephedrine Phenylpropanolamine

    INDIRECT ACTING ANDRENERGIC AGONIST RELEASING AGENTS

    o Amphetamine " CNS stimulants & readily enters CNS " Peripheral actions mediated through

    catecholamine release " Moderate doses: restlessness, insomnia

    anxiety " High dose: paranoid state " Alerting, sleep deferming acion, improve

    attention " Loss of apetite weight loss but long

    term cannot achieve the goal " Therapeutic application: NARCOLEPSY " MODAFINIL

    Amphetamine substitute used for narcolepsy

    " METHAMPHETAMINE Higher ratio of CNS to peripheral

    actions than amphetamine " PHENMETRAZINE

    Amphetamine like effect used as ANOREXIANT

    " METHYLPHENIDATE (RITALIN) Amphetamine variants used in

    children with ADHD o Tyramine

    " By product in the body metabolized by MAO.

    " It is found in high concetrations in fermented foods such as cheese

    " It releases stored catecholamines and has a noradrenaline like effect

    " In patients treated with MAO inhibitors effect of Tyramine may be greatly intensified

    " In patient taking an irreversible MAO inhibitor drug, 20-50 mg of Tyramine increases the BP significantly

    " Cheese, sausage, pickled fish, & yeast supplements contain sufficient Tyramine to be dangerous

    FOODS REPUTED TO HAVE A HIGH CONTENT OF TYRAMINE & OTHER SYMPATHOMIMETIC AGENTS

    FOOD TYRAMINE CONTENT (Average Serving) Beer No data Broad beans, Fava Negligible (but contains

    beans dopamine) Cheese, natural or aged Nil to 130 mg Chicken Liver Nil to 9 mg Chocolate

    Negligible (but contains Phenylethylamine)

    Sausage, fermented (salami, pepperoni, summer sausage)

    Nil to 74 mg

    Smoked/pickled fish Nil to 198 mg Snails No data Wine (Red) Nil to 3 mg Yeast (dietary brewers yeast supplements)

    2-68 mg

    UPTAKE INHIBITOR

    o Cocaine " Local anesthetic that also inhibits

    norepinephrine reuptake " It produces an AMPHETAMINE-LIKE

    EFFECT that is shorter lasting and more intense

    " The major action of cocaine in the CNS is to inhibit dopamine reuptake into the neurons in the pleasure centers of the brain

    " Cocaine may precipitate convulsions, cerebral hemorhhage, arrythmias or myocardial infarction

    MAO/COMT INHIBITORS o Pargyline o Entacapone

    SHOCK Although sympathomimetic drugs have been

    used in the treatment of virtually all forms of shock, their efficacy is unclear

    In most forms of shock, vasoconstriction mediated by the sympathetic NS is already intense

    Indeed, efforts aimed at reducing rather than increasing peripheral resistance may be more fruitful

    A decision to use vasoconstrictors or vasodilators is best made on the basis of information about the underlying cause

    HYPOTENSIVE SHOCK If cerebral, renal, cardiac perfusion is

    maintained, hypotension itself does not usually require vigorous direct treatment

    The use of sympathomimetic drugs merely to elevate a BP that is not an immediate threat to the patient may increase morbidity

  • Adrenoceptor*Agonists*and*Sympathomimetic*Drugs*|*Pharmacology*!

    !Aleyssa |"Jeng

    Direct-acting agonists such as norepinephrine, phenylephrine, methoxamine have been utilized in this setting

    For the treatment of chronic orthostatic hypotension, oral ephedrine has been the traditional therapy

    ANAPHYLACTIC SHOCK EPINEPHRINE, 0.3-0.5 mg (0.3-0.5 mL of 1:1000

    epinephrine solution) is the drug of choice Intramuscular injection may be preferred In patients with impaired cardiovascular

    function, intravenous injection of epinephrine is required

    Glucocorticoids and antihistamines (bot H1 & H2 antagonists) may be useful as secondary therapy.

    CARDIOGENIC SHOCK Positive inotropic agents such as dopamine or

    dobutamine may have a role in this situation In low doses, these drugs may increase cardiac

    output & cause little peripheral vasoconstriction The goal of therapy in shock should be to

    optimize tissue perfusion, not BP OTHER CARDIAC PROBLEMS Epinephrine may be useful in cardiac arrest by

    redistributing blood flow to coronaries and to the brain

    Heart failure may respond to the positive inotropic effects of drugs such as dobutamine

    Development of tolerance is a major limitation to the use of catecholamines in heart failure

    EYE Alpha adrenergic drugs (phenylephrine) cause

    mydriasis antagonists decrease the production of

    aqueous humor Glaucoma responds to a variety of

    sympathomimetic & sympathoplegic drugs Apraclonidine & brimonidine are 2 selective

    agonists used in glaucoma

    GENITOURINARY TRACT 1A receptor mediated constriction of the

    bladder base & prostate The 2 receptors of the bladder wall mediate

    relaxation Ejaculation depends on normal receptor (and

    purinergic receptor) The detumescence of erectile tissue is brought

    about by norepinephrine (and neuropeptide Y) released from sympathetic nerves

    MISCELLANEOUS The sweat glands, located on the palms of the

    hands increase sweat production These are glands associated with psychologic

    stress Renin secreton is stimulated by 1 and inhibited

    by 2 receptors In high concentrations, epinephrine and related

    agents cause leukocytosis TOXICITY Marked elevations in BP Cardiac ischemia & failure Sinus tachycardia & even serious ventricular

    arrythmias Myocardial damage, particularly after prolonged

    infusion If an adverse sympathomimetic effect requires

    urgent reversal, a specific adrenoceptor antagonist can be used

    You$are$going$to$want$to$give$up.$Dont.$

  • EGBautistaII 4

    . Dru

    gs

    CLASS

    DRUGS

    PHARMACOLOGICAL

    ACTIONS

    THERAPEUTIC APPLICATIONS

    UNTOW

    ARD EFFECTS

    COMM

    ENTS

    DIR

    EC

    T-A

    CT

    ING

    (SE

    LE

    CT

    IVE

    )

    A1-selective

    Phenylephrine M

    idodrine M

    ethoxamine

    Xylom

    etazoline O

    xymetazoline has alpha2 also

    Mephenterm

    ine M

    etaraminol

    Vasoconstriction

    Nasal congestion (used topically)

    coz vessels are dilated

    Pupillary dilation Postural hypotension (m

    idodrine)

    Hypertension

    Reflex bradycardia

    Dry m

    outh, sedation, rebound hypertension upon abrupt w

    ithdrawal

    Mephenterm

    ine and m

    etaraminol also act indirectly

    to release NE

    Midodrine is a prodrug

    converted in vivo to an active com

    pound

    A2-selective

    Clonidine

    Methylnorepinephrine

    Guanfacine

    Guanabenz

    Methyldopa

    Decrease sym

    pathetic outflow from

    brain to periphery resulting in decreased PV

    R and blood pressure

    Decrease nerve-evoked release of

    sympathetic transm

    itters D

    ecrease production of aqueous hum

    or

    Adjunctive therapy in shock

    Hypertension

    To reduce sympathetic response

    to withdraw

    al from narcotics,

    alcohol, and tobacco G

    laucoma

    Apraclonidine and brim

    onidine used topically for glaucom

    a and ocular hypertension M

    ethyldopa is converted in CN

    S to a-m

    ethyl NE, an

    effective a2 agonist

    B1-selective

    Dobutam

    ine Increase in contractility Som

    e increase in heart rate Increase in A

    V conduction

    Short-term

    treatment of cardiac

    decompensation after surgery, or

    patients with C

    HF or M

    I

    Increase in blood pressure and heart rate.

    Use w

    ith caution in patients w

    ith hypertension or cardiac arrhythm

    ias U

    sed only IV

    B2-selective

    Albuterol

    Bitolterol

    Fenoterol Procaterol M

    etaproterenol Terbutaline Ritodrine

    Isoetharine

    Relaxation of bronchial sm

    ooth m

    uscle Relaxation of uterine sm

    ooth m

    uscle Activation of other B

    2 receptors after system

    ic administration

    Bronchodilators for treatm

    ent of asthm

    a and CO

    PD

    Short/interm

    ediate-acting drugs for acute bronchospasm

    Ritodrine, to stop prem

    ature labor

    Skeletal m

    uscle tremor

    Tachycardia and other cardiac effects seen after system

    ic adm

    inistration (much less w

    ith inhalational use)

    Use w

    ith caution in patients w

    ith CV

    disease (reduced by inhalational adm

    inistration) M

    inimal side effects

    Non-selective

    (B1+B

    2) Isoproterenol (B

    1=B2)

    Increase in contractility Som

    e increase in heart rate Increase in A

    V conduction

    Short-term

    treatment of cardiac

    decompensation after surgery, or

    patients with C

    HF or M

    I

    Increase in blood pressure and heart rate.

    Use w

    ith caution in patients w

    ith hypertension or cardiac arrhythm

    ias U

    sed only IV

    M

    ixed (alpha &

    beta) Epinephrine A

    1=A

    2; B1=

    B2

    Increase in heart rate Increase in blood pressure Increased contractility Slight decrease in PV

    R

    Increase in cardiac output Vasoconstriction (viscera)

    Open-angle glaucom

    a W

    ith local anesthetics to prolong action Anaphylactic shock

    Com

    plete heart block or cardiac arrest

    Palpitation Cardiac arrhythm

    ias Cerebral hem

    orrhage H

    eadache Trem

    or Restlessness

    Not given orally

    Life saving in anaphylaxis or cardiac arrest

  • EGBautistaII

    Vasodilation (skeletal m

    uscle) Increase in blood glucose and lactic acid

    Bronchodilator in asthm

    a

    N

    orepinephrine A

    1=A

    2; B1>

    >B

    2

    Increase in systolic and diastolic blood pressure Vasoconstriction

    Increase in PVR

    Direct increase in heart rate and

    contraction Reflex decrease in heart rate

    Hypotension

    Sim

    ilar to Epi H

    ypertension

    Not absorbed orally

    Dopam

    ine D

    opamine (D

    1=D

    2) Fenoldopam

    (D1>

    D2)

    Improve renal blood flow

    D

    ilates blood vessel, inhibits sym

    pathetic discharge

    It dilates renal vasculature U

    sed for malignant H

    PN

    (Fenoldopam)

    MIX

    ED

    AC

    TIN

    G

    Ephedrine

    Pseudoephedrine

    Appetite stim

    ulant

    Associated w

    / hemorrhagic

    strokes

    Phenylpropanolam

    ine

    IN

    DIR

    EC

    T A

    CT

    ING

    A

    mphetam

    ine-like d

    isplace

    rs

    Am

    phetamine

    Metham

    phetamine

    Phenmetrazine

    Methylphenidate

    Modafinil

    Tyramine

    promotes N

    E release; mostly

    used for weight reduction

    Modafinil inhibit both N

    E &

    dopamine transporter

    Tyramine displace N

    E from

    storage vesicle & prom

    ote NE

    release

    Catecholam

    ine R

    euptake Inhibitors in

    hibit N

    ET

    Satom

    oxetine Reboxetine

    Sibutram

    ine D

    uloxetine Cocaine

    Sibutram

    ine only appetite suppressant approved by FD

    A;

    also (-) reuptake of serotonin D

    uloxetine - antidepressant

    A/E: tachycardia

    for ADHD ( down regulation )

    for depression


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