3 ADRENERGICS STIMULANTS [AGONISTS] Direct SympathomimeticsIndirect SympathomimeticsDual Sympathomimetics
4 ADRENERGIC STIMULANTS According to mode of action;Direct; Stimulate adrenergic receptors directly.e.g. adrenaline, noraderanaline, dopamine, isoprenaline, phenylephrine, clonidine, dobutamine, salbutamol….etcIndirect;Release of NE from presynaptic stores at adrenergic terminals. e.g. amphetamineInhibit uptake its availability in synapse. e.g. CocaineDual; Direct and indirect stimulation of adrenergic receptorse.g. ephedrine, pseudoephedrine
5 ADRENERGIC STIMULANTS According to spectrum of action;Non-Selective;norepinephrine, epinephrine, dopamine, isoprenaline, ephedrine,…etcSelective;a1; Phenylephrinea2; Clonidineb1; Dobutamineb2; Salbutamol
6 Direct Sympathomimetics ADRENERGICS AGONISTSDirect Sympathomimetics
7 ADRENERGIC STIMULANTS DIRECT Acting SympathomimeticsADRENALINENaturally released from adrenal medulla 2ndry to stress, hunger, fearInactivated by intestinal enzymes, so given parentral & by inhalationActs on all ADR; b =/> a .Pharmacological actions see physiological actions of the SNSHeart stimulate properties of heart (b1) (increase heart rate and contractilityBP (b1) & (a1) / (b2)Vascular SMC; constrict skin + peripheral (a1) / dilate coronary+skeletal (b2)Non vascular SMC;Lung bronchiodilatation (b2)GIT motility (b2) / contract sphincter (a1)Bladder detrusor m. (b2) / contract trigone & sphincter (a1)Pregnant uterus tocolytic (b2)Eye mydriasis (a1) / no effect on accommodation or intraocular PMetabolism insulin (a2) , glucagon (b2), liver glycogenolysis + sk m. glycolysis (b2) / adipose lipolysis (b3 /b2)CNS little, headache, tremors & restlessness
8 Used locally; as haemostatic (in epistaxsisالرعاف ) ADRENALINEIndicationsUsed locally; as haemostatic (in epistaxsisالرعاف )with local anesthetics its absorption toxicity & prolong action bleeding from incisionUsed systemically for treatment ofAllergic reactions drug of choice in anaphylactic shock, angioneurotic edema as it is the physiological antagonist of histaminei.e. BP & cause vasoconstrictionIn status asthmatics given parentally bronchodilatation (2) + mucosal edema (a1)N.B. Selective b2 are better by inhalationIn cardiac arrest directbut now through central lineN.B. Selective b1 are better
9 Tachycardia, palpitation, arrhythmias, angina pains ADRENALINEADRsTachycardia, palpitation, arrhythmias, angina painsHeadache, weakness, tremors anxiety and restlessness.Hypertension cerebral hemorrhage and pulmonary edema.Coldness of extremitiesTissue necrosis and gangrene if extravasationNasal stuffiness rebound congestionContraindicationsCongestive heart failure CHD, hypertension, peripheral arterial disease.Hyperthyroidism.
10 ADRENERGIC STIMULANTS Direct Acting SympathomimeticsNOREPINEPHRINE = NORADRENALINENaturally released from postganglionic adrenergic fibresNot much used severe vasoconstrictionActs on a > b1 > > > b2Only administered IV - Not IM or Subcutaneous necrosisIt BP [ systolic & diastolic] reflex bradycardia (vagal stimulation)IndicationsUsed systemically; hypotensive states (in spinal anesthesia, in septic shock, if fluid replacement and inotropics fail) !!!Used topically; as a local haemostaticwith local anesthetic !!!???ISOPRENALINESynthetic; show no presynaptic uptake norbreakdown by MOA longer action. Acts on b > > a10 times > broncho-dilatation Was used by inhalation in acute asthmaUsed in cardiac arrest but contraindicated in hyperthyroidism & congestive heart failure [CHD]
11 ADRENERGIC STIMULANTS Direct Acting SympathomimeticsDOPAMINEVessels a1 vasoconstrictionKidney D1 vasodilatationHeart b1 force + diuresisNatural CNS transmitter.Released from postganglionicadrenergic fibres (> renal vessels)Releases NE from postganglionic adrenergic fibresActs on D1 > b1 > a1On heart InotropicOn BP According to dose;first D1then due to b1followed by a1 effect
12 ADRENERGIC STIMULANTS Direct Acting SympathomimeticsDOPAMINEGiven parentrally by infusionIndicationsIt is the drug of choice in treatment of SHOCK septic, hypovolaemic (after fluid replacement), cardiogenicIt BP & CO (b1), without causing renal impairment (D1)Can be given in acute heart failure (HF) but better dobutamine
13 ADRENERGIC STIMULANTS Direct Acting SympathomimeticsDOBUTAMINESynthetic. Given IV.Acts on b1 > b2 > > > a1On heart Inotropic with little chronotropic effectOn BP Hardly any effect; b1 & b2 counterbalance + no a1IndicationsGiven parentrally by infusion for short term management of cardiac decompensation after cardiac surgery, in acute heart failure [AHF].It does not oxygen demand
14 ADRENERGIC STIMULANTS Direct Acting SympathomimeticsPHENYLPHERINESyntheticGiven orally & has prolonged duration of action.Acts as selective a1MIDODRINEPeaks in 20 min.t½ 30 min.On heart reflex bradycardia How?On BP due to vasoconstriction (a1 )In HypotensionIndicationsSystemically; Pressor agent in hypotensive states. InfusionTerminate atrial tachycardia (through reflex bradycardia)Nasal decongestant. OralTopically; Local Haemostatic, with Local anesthesiaDecongestant (nasal & ocular)
15 ADRENERGIC STIMULANTS Direct Acting SympathomimeticsPseudoephedrineNasal & Ocular DecongestantsPhenylephrineMethoxamineNaphazolineOxymetazoline HCI (Afrin)Xylometazoline HCI (Otrivine)Used for treatment of nasal stuffinessBut can cause Rebound nasal stuffinessCLONIDINESynthetic, Given orally or as patch.Selective on presynaptic a2 BP (at nucleus tractus solitarius to sympathetic outflow) Antihypertensive agent ???N.B. Brimonidine a2 agonist used in glucoma
16 ADRENERGIC STIMULANTS Direct Acting SympathomimeticsSALBUTAMOLSynthetic. Given orally, by inhalation or parentral.Selective on b2 on bronchi.Bronchodilater asthma & chronic obstructive airway disease (COPD)N.B. Salmeterol & Formoterol are longer acting preparationsOther selective b2 agonists :Terbutaline; Bronchodilator & TocolyticRitodrine; Tocolytic postpone premature labour(labour that begins before the 37th week of gestation).
17 ADRENERGICS STIMULANTS [AGONISTS] Indirect SympathomimeticsAMPHETAMINEIt acts indirectly;Release NE from adrenergic nerve endingsBecause it depletes vesicles of stored NE tachyphylaxsisActs on a& b + CNS stimulant effects; euphoria causes its abuse….. Weight appetite increase energy expenditureNo more used induces psychic & physical dependence
18 ADRENERGICS STIMULANTS [AGONISTS] Dual SympathomimeticsEPHEDRINEMixed sympathomimetic;Prolonged direct action on receptors receptor down regulationRelease NE from adrenergic nerve endings depletes stores tachyphylaxsisAbsorbed orally, not destroyed by MAO or COMT prolonged actionActs on a& b+ > facilitate neuromuscular transmission & retention of urine+ has CNS stimulant effects less than amphetamineAbused by athletes and prohibited during games.
19 Agents specifically indicated for hypotension Midodrine, Phenylephrine, Norepinephrine, PhenylpropanolamineAgents specifically indicated for cardiogenic shockAHFDobutamine, Dopamine, EpinephrineAgents specifically indicated for shockDopamine, NorepinephrineAgents specifically indicated for cardiac arrest Dobutamine, Epinephrine, NorepinephrineAgents specifically indicated for bronchial asthmaSalbutamol, Salmeterol, Formoterol, Terbutaline, IsoprenalineAgents specifically indicated for premature labourRitodrine, TerbutalineAgents specifically indicated for nasal decongestionPseudoephedrine, Naphazoline, Oxymetazoline, Phenylephrine, XylometazolineAgents specifically abused in sports Ephedrine, Amphetamine