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K16 Farmakologi Obat Simpatis
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SIMPATOMIMETIKASIMPATOLITIKJazanul Anwar_Hasanul ArifinDepartemen Farmakologi & Terapeutik Fakultas Kedokteran USU2009
SIMPATOMIMETIKA
syaraf pasca ganglionneurotransmitersintesapenimbunanpenglepasanperombakanreseptorperangsanganperangsanganSimpatomimetikaperangsangan
TYROSINE _METYLDOPA_> NA ___ NAAdrenalin COMTMAO
Adrenergik dan Penghambat AdrenergikNENENEDDDDDreseptorSimpatomimetik yang bekerja langsung/NENENENENEDDreseptorNENENEDNEDDreseptorABCSimpatomimetik yang bekerja tidak langsungSimpatomimetik yang bekerja campuranD : obat simpatomimetikE/NEamfetamine
Simpatomimetika langsungSimpatomimetika tak langsung
SIMPATOMIMETIKA (KIMIAWI)Endogen:adrenalinnoradrenalindopaminNonendogen:
1-adrenergik : phenylephrine, methoxamin 2-adrenergik : clonidine, oxymetazoline-adrenergik : adrenalin -adrenergik : isoprenaline1-adrenergik : dobutamine2-adrenergik : terbutaline, procaterolDopamin (D) : dopaminD1 : fenoldopamD2 : bromocriptinCATECHOLAMINENONCATECHOLAMINE : amfetamin, metamfetamin
1 Agonists
MethoxaminePenylpropranolaminePhenylephrineMephentermineMetaraminolMitodrine
1 Agonists Response utama & kegunaan klinikMethoxamine: i.v. hipotensi es paroxysmal takhikardiPhenylephrine: | vasokonstriksi nasal decongestantPhenylpropranolamine: vasokonstriksi nasaldecongestantMephentermine: direk & indirek, i.m. MetaraminolMitodrineResistens vaskuler perifer naik
1 AgonistsKontraindikasiHypertension Ischemic organ diseasesPembesaran Prostrat Pemberian bersama dg obat-obat jg menambah kadar NAMAO inhibitorssympathomimetika tak langsung
2 AgonistsPrototypeClonidineBrimonidine
2 Agonists Response utama & tempat kerjaResponseVasodilatasiProduksi cairan mata berkurangTempat kerjaPeripheralPrejunctional: mengurangi penglepasan NASome postjunctional sites (eye, pancreas, platelets)
SSP: mengurangi sympathetic outflow
2 Agonists Kegunaan klinikAntihypertensives
Menurunkan tekanan intraocular glaucoma sudut terbuka
2 AgonistsCara pemberianOral
Transdermal
Topical (to eye)
2 AgonistsEfek sampingBradycardia(kelambatan denyut jantung)SSP (50% of population) sedasi mulut keringDisfungsi Sexual
1 AgonistsPrototype Dobutamine
Response utama - KardiostimulasiKegunaan klinikGagal jantungShock CardiogenicEfek tak diinginkanArrythmias(variasi irama normal denyut jantung, meliputi kelainan frekuensi,regularitas,lokasi asal impuls)
2 AgonistsPrototypesAlbuterolSalbutamolSalmeterolRitodrine
2 Agonists ResponsesBronchodilationAlbuterolSalbutamolSalmeterol Terbutalin
Uterine dilationRitodrine
2 AgonistsClinical usesBronchodilatasiAsthmaCOPD
Tocolytic agents Late term gestation
2 AgonistsEfek tak diinginkanSymptoms stimulasi 1 TachycardiaWidening pulse pressure (systolic pressure rise)Symptoms of 2 stimulationWidening pulse pressure (diastolic pressure drop)Drop in serum K+ (skeletal muscle uptake)Skeletal muscle tremor
2 AgonistsAdverse Effects (Cont.)CNSAnxietyRestlessnessApprehension
Tolerance to bronchodilationWithout tolerance to adverse effect such as tachycardia.
2 AgonistsContraindicationsCardiac diseaseCoronary artery diseaseArrhythmiasDiabetesHyperthyroidismCo-administration MAO inhibitorsIndirect-acting sympathomimetics
Obat-obat adrenergik /simpatomimetik
AdrenergikReseptorPemakaian dalam klinikEpinefrin (Adrenalin)1, 1, 2Anafilaktik syok, asma akut, henti jantungEfedrin1, 1, 2Hipotensi, bronkospasme, kongesti hidungNE 1, 1Syok vasokonstriktor kuatPseudoefedrin1, 1DekongestanFenilefrin1DekongestanFenilpropanolamin (PPA)1, 1DekongestanDopamin1HipotensiIsoproterenol1, 2Payah jantung kongestif aliran darah miokardium dan curah jantungMetaproterenol1, 2Bronkospasme, blok jantung akutAlbuterol2BronkospasmeTerbutalin2Relaksasi uterus
SIMPATOLITIKA
syaraf pasca ganglionneurotransmitersintesapenimbunanpenglepasanperombakanreseptorperangsanganpenghambatan perangsanganpenghambatanSimpatomimetikaSimpatolitikaperangsanganpenghambatanpenghambatan penghambatanpenghambatan
PENGHAMBAT SINTESABlokade penimbunanBLOKADE PENGLEPASANBLOKADE RESEPTOR
NT inhibition On presynaptic endingDrug affecting NT synthesisDrug affecting NT storageDrug affecting NT release
On postsynaptic endingDrug affecting parasympathetic receptorsDrug affecting sympathetic receptors
SIMPATOLITIKAPRASINAPSPASCASINAPSPENGHAMBAT SINTESA-METHYL DOPABLOKADE PENIMBUNANRESERPINEPENGHAMBAT PENGLEPASAN NAGUANETHIDINEBLOKADE RESEPTOR BLOKADE RESEPTOR
BLOKADE PENYIMPANAN NA RESERPINE (RAUWOLFIA SERPENTINE)KEGUNAAN KLINIK: HIPERTENSIEFEK SAMPING: ssp- DEPRESI SEDASI PERIFERI NASAL CONGESTIPENGHAMBAT PENGLEPASAN NAGUANETHIDINE
Selectivity of AntagonistsSelective antagonistsNonselective (1/2) antagonistsSelective 1 antagonistsUroselective 1A antagonistsSelective antagonistsNonselective (2) antagonistsSelective 1 antagonists
Nonselective adrenergic ( antagonists
Nonselective AntagonistsClinical Uses: LimitedPheochromocytomaBenign prostatic obstruction(Phenoxybenzamine)Autonomic hyperreflexiaAdverse EffectsMigraine headache(Ergot alkaloids)CardiovascularTachycardia (reflex)Orthostatic hypotentionNasal congestionNon cardiovascularGI (Phentolamine)Impotence (Phenoxybenzamine)Potential mutagen (Phenoxybenzamine)
Selective 1 AntagonistsAdvantage over non-selective agentslack 2 componentless prejunctional control (less reflex tachycardia)
less CNS component of actionUses HypertensionCongestive heart failureBenign prostatic hyperplasiaPrazosin (BID dosage)Doxazosin &Terazosin (QD dosage)Pheochromocytoma
Selective 1 AntagonistsAdverse EffectsOrthostatic hypotensionUsually becomes toleratedGive first dose at nightNasal congestion
Uroselective 1A AntagonistTamsulosinQD dosageClinical UseBenign Prostatic HyperplasiaAdverse EffectsRetrograde ejaculationNOTE: Avoids orthostatic hypotension in most
Selective 2 AntagonistsYohimbineApparent Mechanism of Actionmajor mechanism of action appears to be increasing sympathetic outflow from CNSClinical Uses - (limited):ImpotencyDiabetic neuropathy painOrthostatic hypotension
AntagonistsIn hypertensive (hyperkinetic heart-induced)Decrease blood pressureIn heart failureDecrease heart work & protect against arrythmiasAsthma or other bronchospasmcause bronchoconstrictionDiabetesmask symptoms of insulin-induced hypoglycemiaaugment insulin-induced hypoglycemia
AntagonistsPrototype - PropranololPure antagonist, no Intrinsic Sympathomimetic Activity(ISA) (i.e. not a partial agonist)
Nonselective to subtypes
High lipid solubility - Enters gut & CNS
High first pass metabolism - causing low bioavailability
Has membrane-stabilizing activityQuinidine-like effects, Na+ channel blockade, (local anesthetic)
AntagonistsNonselectivePropranolol
Nadolol: long half-life
Timolol: use in glaucoma
Pindolol: ISA
Selective1 Metoprolol
Atenolol: limited entry
Esmolol: short half-life
Acebutolol: ISA
Bisoprolol
Uses of AntagonistsCardiovascularHypertensionAnginaArrhythmiasMyocardial infarctionHeart failureCV Symptoms ofHyperthyroidism PheochromocytomaAortic aneurysmMigraine headacheNon-cardiovascularGlaucoma
Somatic symptoms of anxiety (e.g. stage fright)
Fine muscle tremors
Nonselective Adrenergic AntagonistsLabetalol: and 1 antagonist Partial 2 agonistCarvedilol and 1 antagonistAntioxidantAnti-ischemic agentRecent report supports it improves cardiac performance > than metoprolol in chronic heart failure
AntagonistsAdverse EffectsCardiovascularInduce CHF or bradycardial arrhythmiaSudden withdrawal - in anginal patients may cause sudden death (due to receptor supersensitivity)
Bronchospasm
CNS - sleep disturbance, depression
Lacking recognition of hypoglycemia
Penghambat Adrenergik / Simpatolitik
Penghambat AdrenergikReseptorPemakaian dalam klinikTolazolinHipertensiFentolaminHipertensiPrazosinHipertensiPropanolol 1, 2Hipertensi, aritmia, angina pectoris, pasca infark miokardiumNadolol1, 2Hipertensi, anginaPindolol1, 2 HipertensiTimolol1, 2 Hipertensi, pasca infark miokardiumMetoprolol1Hipertensi, angina, pasca infark miokardiumAtenolol 1Hipertensi, anginaAsebutolol1Hipertensi, aritmia ventrikel
Thank you
Benign prostatic hyperplasia (BHP)Incidence 50% of age >60 90% of age >85Definition: Nonmalignant enlargement of prostate due to growth of Epithelia/glandular (mechanical obstruction)Smooth muscle (dynamic obstruction - urethra)Symptoms: hesitancy, urgency, frequency, dysuria, nocturia, straining, dribbling, etc.
AntagonistsMechanism & Sites of ActionsCardiovascular - vascular smooth musclecontractionReversal adrenalinePrejunctional 2 negative feedback on NE releaseNon-cardiovascular sitesBladder
AntagonistsNonselectivePhentolamine (reversible, competitive)Phenoxybenzamine (irreversible, noncompetitive)Ergot alkaloids (dirty drugs with multiple sites of action)Selective 1 antagonists Prazosin Uroselective 1A antagonistsTamsulosin
AntagonistsResponse in normal person during stressShort-term effectBlock heart sympathetic response rate and contraction - decrease CO block of sympathetic control of rhythm & automaticityIncrease TPR (block vascular 2 & increased reflex sympathetic tone)Long term effectCO remains downTPR returns to normal
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