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    6 Symaptholytic

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    Youeel Ibrahem
    This document discusses various classes of drugs that antagonize adrenergic receptors and their therapeutic uses. It describes alpha blockers such as prazosin and doxazosin that are used to treat hypertension and benign prostatic hyperplasia. It also discusses beta blockers such as propranolol, metoprolol, and atenolol that are used for cardiovascular conditions like hypertension, angina, heart failure, and myocardial infarction. Third generation beta blockers like carvedilol and nebivolol are highlighted for their additional mechanisms of action.

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    6 Symaptholytic

    Uploaded by

    Youeel Ibrahem
    25 views48 pages
    This document discusses various classes of drugs that antagonize adrenergic receptors and their therapeutic uses. It describes alpha blockers such as prazosin and doxazosin that are used to treat hypertension and benign prostatic hyperplasia. It also discusses beta blockers such as propranolol, metoprolol, and atenolol that are used for cardiovascular conditions like hypertension, angina, heart failure, and myocardial infarction. Third generation beta blockers like carvedilol and nebivolol are highlighted for their additional mechanisms of action.

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    6-symaptholytic

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    This document discusses various classes of drugs that antagonize adrenergic receptors and their therapeutic uses. It describes alpha blockers such as prazosin and doxazosin that are used to treat hypertension and benign prostatic hyperplasia. It also discusses beta blockers such as propranolol, metoprolol, and atenolol that are used for cardiovascular conditions like hypertension, angina, heart failure, and myocardial infarction. Third generation beta blockers like carvedilol and nebivolol are highlighted for their additional mechanisms of action.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    25 views48 pages

    6 Symaptholytic

    Uploaded by

    Youeel Ibrahem
    This document discusses various classes of drugs that antagonize adrenergic receptors and their therapeutic uses. It describes alpha blockers such as prazosin and doxazosin that are used to treat hypertension and benign prostatic hyperplasia. It also discusses beta blockers such as propranolol, metoprolol, and atenolol that are used for cardiovascular conditions like hypertension, angina, heart failure, and myocardial infarction. Third generation beta blockers like carvedilol and nebivolol are highlighted for their additional mechanisms of action.

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    © All Rights Reserved
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    of 48

    “Block or decrease the effects of sympathetic nerve

    stimulation, endogenous catecholamines and adrenergic


    drugs”

    Adrenergic receptor blockers antagonize receptor action


    of epinephrine & related drugs

    Adrenergic neurone blocking agents act by interfering


    with release of adrenergic transmitter

    Central sympatholytics

    Ganglion blockers

    Chemical sympathectomy
    Alpha Blockers
    Non-Selective α Adrenergic
    Antagonists:

    Phenoxybenzamine & Phentolamine


    Referred to as "classical" α blockers
    Postural hypotension is a prominent feature can
    precipitate cardiac arrhythmias
    Therapeutic Uses
    Pheochromocytoma
    Phenoxybenzamine is often used in preparing the
    patient for surgery
    Controls episodes of severe HTN and minimizes other
    ADRs of catecholamines
    Dose 40-120 mg given in two or three divided
    portions
    Useful for the treatment of hypertensive crises that
    follow withdrawal of clonidine or ingestion of
    tyramine-containing foods during the use of non-
    selective MAO inhibitors
    Toxicity and Adverse Effects
    Hypotension -major adverse effect
    Alarming tachycardia, cardiac arrhythmias, and
    ischemic cardiac events, including myocardial
    infarction
    Phentolamine should be used with caution in
    patients with a history of peptic ulcer
    Prazosin
    a relatively specific α1-adrenergic receptor antagonist.
    Well absorbed orally ; bioavailability is 50-70%
    Peak concentrations within 1-3 hours after oral dose
    Initial dose 1 mg, usually given at bedtime
    A maximal effect generally is observed with a total daily
    dose of 20 mg in patients with hypertension
    Uses- HTN, BPH, scorpion bite
    S/E- orthostatic hypotension, syncope, nasal congestion
    "first dose response"
    Terazosin
    Less potent than prazosin but retains high specificity
    for α1 receptors
    Bioavailability -high (>90%), t1/2 ~12 hours, duration of
    action extends beyond 18 hrs
    More effective for BPH
    Initial first dose of 1 mg is recommended
    Doses of 10 mg/day may be required for maximal
    effect in BPH
    Doxazosin
    Highly selective antagonist at α1 receptors
    T1/2 is 20 hours, duration of action may extend to 36
    hrs bioavailability & extent of metabolism is similar
    to prazosin
    Given initially as a 1mg dose for HTN & BPH
    Adverse effects
    Marked postural hypotension & syncope seen 30-90
    mins after an initial dose of prazosin & 2-6 hours after
    an initial dose of doxazosin

    Syncopal episodes also have occurred with a rapid ↑ in


    dosage or with the addition of a 2nd antihypertensive
    with prazosin

    Nonspecific ADRs- headache, dizziness & asthenia


    rarely limit treatment with prazosin
    Therapeutic Uses
    Hypertension
    Prazosin and its congeners -used successfully in the
    treatment of essential HTN

    These drugs improve rather than worsen lipid profiles


    and glucose-insulin metabolism who are at risk for
    atherosclerotic disease
    Congestive Heart Failure
    α receptor antagonists have been used in the treatment
    of CHF, as have other vasodilating drugs

    Due to dilation of both arteries & veins → reduction of


    preload & afterload, which ↑cardiac output &
    ↓pulmonary congestion
    Benign Prostatic Hyperplasia (BPH)
    Prazosin ↓ resistance in some patients with impaired
    bladder emptying caused by prostatic obstruction or spinal
    injury
    Other Disorders
    Variant angina (prinzmetal's angina)
    Vasospastic disorders
    ↓ Ventricular arrhythmias induced by coronary
    artery ligation or after reperfusion in animals
    α2 Receptor Antagonists
    Yohimbine
    Competitive antagonist
    May benefit some patients with psychogenic erectile
    dysfunction
    Useful for diabetic neuropathy and in the treatment of
    postural hypotension
    Additional α Adrenergic Receptor Antagonists
    Ergot Alkaloids
    Indoramin
    selective, competitive α1 receptor antagonist that is used
    for the treatment of hypertension, BPH, and in the
    prophylaxis of migraine
    ↓ BP with minimal tachycardia
    ↓ incidence of attacks of Raynaud's phenomenon
    (is excessively reduced blood flow in response to cold
    or emotional stress).
    lacks a well-defined place in current therapy
    Beta blockers
    β antagonists can be distinguished by the following
    properties:

    Relative affinity for β1 and β2 receptors

    Intrinsic sympathomimetic activity

    Differences in lipid solubility

    Capacity to induce vasodilation

    Pharmacokinetic parameters
    Classification
    MSA ISA Lipid Absorpn BA (%) T1/2 Protein
    Solub. (%) binding
    Therapeutic Uses
    Cardiovascular Diseases
    Hypertension??!!, Angina, Acute Coronary Syndromes
    & Congestive Heart Failure
    Myocardial Infarction

    Many trials- β receptor antagonists administered


    during the early phases of acute MI & continued long-
    term may ↓ mortality by ~25%

    Angina pectoris

    Act by ↓ cardiac work & O2 consumption


    Congestive Heart Failure

    A number RCTs shows certain β receptor antagonists are


    highly effective for pts with all grades of heart failure
    secondary to left ventricular systolic dysfunction
    Use of β Antagonists in Other Cardiovascular
    Diseases
    Propranolol- in hypertrophic obstructive
    cardiomyopathy and angina, palpitations, and
    syncope in patients with this disorder

    Pheochromocytoma – should only used after


    administering α blockers

    Acute dissecting aortic aneurysm


    Glaucoma
    Useful for open-angle glaucoma
    e.g.Carteolol, betaxolol, levobunolol, metipranolol
    timolol and levobetaxolol
    Have an onset in ~30 mins with a duration of 12-24 hrs
    systemic absorption can lead to adverse cardiovascular
    and pulmonary effects in susceptible patients
    Caution- pts at risk for adverse systemic effects of β
    receptor antagonists
    Betaxolol- most effective antiglaucoma drug at
    reducing Na+/Ca2+ influx
    Other Uses
    Propranolol, timolol, and metoprolol are effective for
    the prophylaxis of migraine
    Propranolol- effective in controlling acute panic
    symptoms in individuals who are required to perform
    in public or in other anxiety-provoking situations
    Propranolol also may be useful in the treatment of
    essential tremor
    Of some value in the treatment of patients
    undergoing withdrawal from alcohol or those with
    akathisia
    AKATHISIA. there is an urge to move about constantly.
    It is the most common motor adverse effect of
    treatment with antipsychotics

    Propranolol and nadolol are efficacious in the


    primary prevention of variceal bleeding in patients
    with portal hypertension
    Adverse Effects and Precautions
    On Cardiovascular System
    β receptor antagonists may induce congestive heart
    failure in susceptible patients
    Life-threatening bradyarrhythmias
    Symptoms of peripheral vascular disease may worsen
    Abrupt discontinuation of receptor antagonists after
    long-term treatment can exacerbate angina and may
    increase the risk of sudden death
    Pulmonary function
    May cause a life-threatening increase in airway
    resistance
    CNS
    Fatigue, sleep disturbances (including insomnia and
    nightmares),
    Metabolism
    Should be used with great caution in patients with
    diabetes who are prone to hypoglycemic reactions
    Miscellaneous
    Sexual dysfunction
    Drug Interactions
    Aluminum salts, cholestyramine, and colestipol may
    decrease the absorption of β blockers
    Phenytoin, rifampin, and phenobarbital, smoking-
    induce hepatic biotransformation enzymes - decrease
    plasma concentrations of receptor antagonists (e.g.,
    propranolol)
    Cimetidine and hydralazine may increase the
    bioavailability of agents such as propranolol and
    metoprolol by affecting hepatic blood flow
    Overdosage
    Hypotension, bradycardia, prolonged AV conduction
    times, and widened QRS complexes are common
    manifestations of overdosage
    Non-Selective β Adrenergic Receptor
    Antagonists
    Propranolol
    For HTN & angina, initial oral dose 40-80 mg/day
    Uses - supraventricular arrhythmias, ventricular
    arrhythmias, PVCs, digitalis-induced
    tachyarrhythmia's, MI, pheochromocytoma,
    essential tremor & prophylaxis of migraine
    Nadolol
    Long-acting antagonist with equal affinity for 1 and
    2 receptors
    Distinguishing characteristic of nadolol is its
    relatively long t1/2
    Timolol
    A potent, non-selective β receptor antagonist
    Interestingly, the ocular formulation of timolol used
    for the treatment of glaucoma, may be extensively
    absorbed systemically
    Adverse effects can occur in susceptible patients,
    such as those with asthma or congestive heart
    failure
    Pindolol
    with intrinsic sympathomimetic activity
    Used to treat angina
    β1 selective adrenergic receptor antagonists
    Metoprolol
    Significant first-pass metabolism
    Uses: essential HTN, Angina, tachycardia, CHF,
    Adjunct to treat hyperthyroidism
    Atenolol
    Very hydrophilic
    Also used in graves disease
    Initial dose is 50 mg/day OD may be ↑100 mg
    Less CNS s/e than other β blockers and less
    bronchoconstriction
    Esmolol
    Rapid onset ,short duration
    Also class 2 anti arrhythmic
    Slow iv injection
    Used during surgeries to prevent or treat
    tachycardia
    And SVT
    Useful in severe post op HTN
    THIRD GENERATION β BLOCKERS

    NITRIC OXIDE ALPHA2 ALPHA1 Ca2+ ENTRY K+ CHANNEL ANTIOXIDANT


    PRODUCTION RECEPTOR RECEPTOR BLOCKADE OPENING ACTIVITY
    AGONISM ANTAGONISM

    Celiprolola Celiprolola Carvedilol Carvedilol Tilisolola Carvedilol

    Nebivolol Carteolol Bucindolola Betaxolol

    Carteolol Bopindolola Bevantolola Bevantolola

    Bopindolola Nipradilola

    Nipradilola Labetalol
    Labetalol
    Selective Alpha1 and Nonselective Beta Blocker
    ↓ BP by ↓ SVR (alpha1)
    Vasodilation via α1 blockade & partial beta2 agonist
    activity
    ↓ HR by attenuating reflex tachy via β Blockade
    Unchanged C.O.
    S/e – postural hypotension
    Carvidilol
    Has antioxidant and anti inflammatory property
    Produces vasodilation
    FDA approved for HTN, CHF,LV dysfunction following MI
    Improves ventricular function and ↓ mortality and
    morbidity in mild to severe CHF
    Nebivolol
    Highly selective
    NO donor→vasodialation, potential to improve
    endothelial fuction, no deleterious effect on lipid profile
    & carbohydrate metabolism
    Use: HTN, CHF
    Neuron blocking drugs
    Guanethidine
    Act mainly by preventing release of NE at nerve endings
    Pharmacological sympathectomy
    Uses- HTN, glaucoma, neuropathic pain,& given IM for
    htnsive crises, severe pre eclampsia
    ADRs- severe postural hypotension, diarrheoa, renal
    impairment
    Bretylium
    Causes initial release of NE→ blocks adrenergic
    transmission by preventing NE release from adrenergic
    nerve endings
    Blocks K+ channels- class III antiarrhythmic activity
    Guanadrel
    False neurotransmitter- accumulated, stored & released
    like NE but is inactive at adrenergic receptors
    M/A- Replacement of NE with inactive transmitter
    ADRs- hypotension, fatigue ,lassitude, Sexual
    dysfunction, Diarrhoea
    Reserpine
    Inhibit vesicular catecholamine transporter
    Sedation, inability to concentrate- MC ADRs occasionally
    psychotic depression→suicide
    Recent interest -at low doses, in combination with
    diuretics, for hypertension
    Metyrosine
    Inhibits tyrosine hydroxylase
    Adjuvant to phenoxybenzamine & other α adrenergic
    blockers for pheochromocytoma & in preoperative
    preparation for resection of pheochromocytoma
    ADR- crystalluria
    Central sympatholytics
    α Methyldopa
    MOA: Converted to α methyl NE which acts on α2
    receptors in brain & causes inhibition of adrenergic
    discharge in medulla – ↓PVR & ↓BP
    Various adverse effects – cognitive impairment, postural
    hypotension, positive coomb`s test etc – Not used
    therapeutically now except in Hypertension during
    pregnancy (category B drugs)
    Clonidine
    Imidazoline derivative, partial agonist of central α2
    receptor
    Not frequently used now because of tolerance and
    withdrawal hypertension
    Conclusion

    Thank you

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