Download - Adrenergic System - Drdhriti
-
7/31/2019 Adrenergic System - Drdhriti
1/73
Adrenergic System
Department of Pharmacology
NEIGRIHMS, Shillong
-
7/31/2019 Adrenergic System - Drdhriti
2/73
Neurotransmission in ANS
-
7/31/2019 Adrenergic System - Drdhriti
3/73
Noradrenergic transmission
Nor-adrenaline is the majorneurotransmitter of theSympathetic system
Noradrenergic neurons are
postganglionic sympatheticneurons with cell bodies inthe sympathetic ganglia
They have long axonswhich end in varicosities
where NA is synthesizedand stored
-
7/31/2019 Adrenergic System - Drdhriti
4/73
Adrenergic transmission
Catecholamines:
Natural: Adrenaline, Noradrenaline, Dopamine
Synthetic: Isoprenaline, Dobutamine
Non-Catecholamines:
Ephedrine, Amphetamines, Phenylepherine, Methoxamine,Mephentermine
Also called sympathomimetic aminesas most of themcontain an intact or partiallysubstituted amino (NH2)group
-
7/31/2019 Adrenergic System - Drdhriti
5/73
Catecholamines:Compounds containinga catechol nucleus(Benzene ring with 2
adjacent OH groups)and an aminecontaining side chainNon-catecholamineslack hydroxyl (OH)
group
-
7/31/2019 Adrenergic System - Drdhriti
6/73
Biosynthesis ofCatecholamines
Phenylalanine
PH
Rate limiting Enzyme
5-HT, alpha Methyldopa
Alpha-methyl-p-
tyrosine
-
7/31/2019 Adrenergic System - Drdhriti
7/73
Storage of Noradrenaline
-
7/31/2019 Adrenergic System - Drdhriti
8/73
Release of NA Feedback Control
-
7/31/2019 Adrenergic System - Drdhriti
9/73
Regulators of NA release
-
7/31/2019 Adrenergic System - Drdhriti
10/73
Uptake of Catecholamines
-
7/31/2019 Adrenergic System - Drdhriti
11/73
Reuptake
Sympathetic nerves take up amines and releasethem as neurotransmitters
Uptake I is a high efficiency system more specific
for NA Located in neuronal membrane
Inhibited by Cocaine, TCAD, Amphetamines
Uptake 2 is less specific for NA Located in smooth muscle/ cardiac muscle
Inhibited by steroids/ phenoxybenzamine
No Physiological or Pharmacological importance
-
7/31/2019 Adrenergic System - Drdhriti
12/73
Metabolism of CAs
Mono Amine Oxidase (MAO) Intracellular bound to mitochondrial membrane
Present in NA terminals and liver/ intestine
MAO inhibitors are used as antidepressants
Catechol-o-methyl-transferase (COMT) Neuronal and non-neuronal tissue
Acts on catecholamines and byproducts VMA levels are diagnostic for tumours
-
7/31/2019 Adrenergic System - Drdhriti
13/73
Metabolism of CAs
(Homovanillic acid) (Vanillylmandelic acid)
-
7/31/2019 Adrenergic System - Drdhriti
14/73
Adrenergic neurotransmission
-
7/31/2019 Adrenergic System - Drdhriti
15/73
-
7/31/2019 Adrenergic System - Drdhriti
16/73
-
7/31/2019 Adrenergic System - Drdhriti
17/73
How Many of them ????
Alpha () Beta ()
Adenoreceptors
1 3 21 2
2B 2C 2A
1A 1B 1D
-
7/31/2019 Adrenergic System - Drdhriti
18/73
-
7/31/2019 Adrenergic System - Drdhriti
19/73
Potency of catecholamines onAdrenergic Receptors
Adr NA
Iso
Iso Adr
NA
Log Concentration
Aortic strip contraction Bronchial relaxation
-
7/31/2019 Adrenergic System - Drdhriti
20/73
Molecular Effector Differences- Vs
Receptors: IP3/DAG
cAMP
K+ channel opening
Receptors: cAMP
Ca+ channel opening
-
7/31/2019 Adrenergic System - Drdhriti
21/73
Recall: Adenylyl cyclase: cAMPpathway
PKA Phospholamban
Increased
Interaction with
Ca++
Faster relaxation
Troponin
Cardiac
contractility
Other
Functional
proteins
PKA alters the functions of manyEnzymes, ion channels,transportersand structural proteins.
Faster sequestration ofCa++ in SR
-
7/31/2019 Adrenergic System - Drdhriti
22/73
PKc
Also Recall: Phospholipase C:IP3-DAG pathway
-
7/31/2019 Adrenergic System - Drdhriti
23/73
Beta receptors
All receptors activate adenylate cyclase, raising the intracellularcAMP concentration
Type 1: These are present in heart tissue, and cause an increased heart rate by
acting on the cardiac pacemaker cells
Type 2: These are in the vessels of skeletal muscle, and cause vasodilatation, whichallows more blood to flow to the muscles, and reduce total peripheralresistance
Beta-2 receptors are also present in bronchial smooth muscle, and causebronchodilatation when activated
Stimulated by adrenaline, but not noradrenaline
Bronchodilator salbutamol work by binding to and stimulating the 2receptors
Type 3: Beta-3 receptors are present in adipose tissue and are thought to have a
role in the regulation of lipid metabolism
-
7/31/2019 Adrenergic System - Drdhriti
24/73
Differences between 1, 2 and 3
Beta-1 Beta-2 Beta-3
Location Heart and JG cells Bronchi, uterus,Blood vessels,
liver, urinary tract,eye
Adiposetissue
Agonist Dobutamine Salbutamol -
Antagonist Metoprolol, Atenolol Alpha-methylpropranolol
-
Action onNA
Moderate Weak Strong
-
7/31/2019 Adrenergic System - Drdhriti
25/73
Clinical Effects of -receptorstimulation 1: Adrenaline, NA and Isoprenaline:
Tachycardia
Increased myocardial contractility
Increased Lipolysis
Increased Renin Release
2: Adrenaline and Isoprenaline (not NA)
Bronchi Relaxation
SM of Arterioles (skeletal Muscle) Dilatation
Uterus Relaxation
Skeletal Muscle Tremor
Hypokalaemia
Hepatic Glycogenolysis and hyperlactiacidemia
3: Increased Plasma free fatty acid increased O2 consumption -increased heat production
-
7/31/2019 Adrenergic System - Drdhriti
26/73
Adrenergic receptors - alpha
Type 1 Blood vessels with alpha-1 receptors are present in the
skin and the genitourinary system, and during the fight-or-flight response there is decreased blood flow to theseorgans
Acts by phospholipase C activation, which forms IP3 andDAG
In blood vessels these cause vasoconstriction
Type 2
These are found on pre-synaptic nerve terminals Acts by inactivation of adenylate cyclase, cyclic AMP levels
within the cell decrease (cAMP)
-
7/31/2019 Adrenergic System - Drdhriti
27/73
Differences between 1 and 2
Alpha-1 Alpha-2Location Post junctional blood vessels
of skin and mucousmembrane, Pilomotor muscle
& sweat gland, radial musclesof Iris
Prejunctional
Function Stimulatory GU,Vasoconstriction, glandsecretion, Gut relaxation,
Glycogenolysis
Inhibition of transmitterrelease, vasoconstriction,decreased central symp.
Outflow, plateletaggregation
Agonist Phenylephrine, Methoxamine Clonidine
Antagonist Prazosin Yohimbine
-
7/31/2019 Adrenergic System - Drdhriti
28/73
1 adrenoceptorsClinical effects
Eye -- Mydriasis
Arterioles Constriction (rise in BP)
Uterus -- Contraction
Skin -- Sweat Platelet - Aggregation
Male ejaculation
Hyperkalaemia
Bladder Contraction 2 adrenoceptors on nerve endings mediate negative
feedback which inhibits noradrenaline release
-
7/31/2019 Adrenergic System - Drdhriti
29/73
Molecular Basis of AdrenergicReceptors
Also glycogenolysisin liver
Inhibition ofInsulinrelease andPlateletaggregationGluconeogenesis
-
7/31/2019 Adrenergic System - Drdhriti
30/73
Dopamine receptors
D1-receptors are post synaptic receptorslocated in blood vessels and CNS
D2-receptors are presynaptic present in CNS,ganglia, renal cortex
-
7/31/2019 Adrenergic System - Drdhriti
31/73
Summary of agents modifyingadrenergic transmission
Step Actions DrugSynthesis of NA Inhibition - methyl-p-tyrosine
Axonal uptake Block Cocaine, guanethidine,ephedrine
Vesicular uptake Block Reserpine
Vesicular NA Displacement Guanethidine
Membrane NA pool Exchange diffusion Tyramine, Ephedrine
Metabolism MAO-A inhibitionMAO-B inhibitionCOMT inhibition
MoclobemideSelegilineTolcapone
Receptors 1 21 + 21
PrazosinYohimbinePropranololMetoprolol
-
7/31/2019 Adrenergic System - Drdhriti
32/73
-
7/31/2019 Adrenergic System - Drdhriti
33/73
Adrenaline as prototype
Potent stimulant of alpha and beta receptors
Complex actions on target organs
-
7/31/2019 Adrenergic System - Drdhriti
34/73
Heart
Beta-1 mediated action - Powerful Cardiac stimulant - +vechronotropic, +ve inotropic
Acts on beta-1 receptors in myocardium, pacemaker cells andconducting tissue
Heart rate increases by increasing slow diastolic depolarization of cellsin SAN
High doses cause marked rise in heart rate and BP causing reflexdepression of SAN unmasking of latent pacemaker cells in AVN andPF arrhythmia (sensitization of arrhythmogenic effects by Halothane)
Cardiac systole is shorter and more powerful
Cardiac output is enhanced and Oxygen consumption is increased
Cardiac efficiency is markedly decreased
Conduction velocity in AVN, atrial muscle fibre, ventricular fibre andBundle of His increased benefit in partial AV block Reduced refractory period in all cardiac cells
-
7/31/2019 Adrenergic System - Drdhriti
35/73
Blood Vessels
Seen mainly in the smaller vesselsarteriolesVasoconstriction (alpha) andvasodilatation (beta)depends on the drug
Decreased blood flow to skin and mucusmembranes and renal bedsalpha effect (1and 2) -
Increased blood flow to skeletal muscles,coronary and liver vessels - (Beta-2 effect)counterbalanced by a vasoconstrictor effectof alpha receptors
-
7/31/2019 Adrenergic System - Drdhriti
36/73
Blood Pressure
Depends on the Catecholamine involved
NA causes rise in Systolic, diastolic and meanBP (no beta-2 action) unopposed alpha action
Isoprenaline causes rise in systolic but fall indiastolic BP mean BP falls (beta-1 and beta-2)
Adr causes rise in systolic BP, but fall in diastolic
BP mean BP generally rises (slow injection) Decreased peripheral resistance at low conc. Beta
receptors are more sensitive to Adr than alphareceptors
-
7/31/2019 Adrenergic System - Drdhriti
37/73
Blood Pressure contd.
Rapid IV injection of Adrenaline marked rise inSystolic and diastolic BP
Large concentration alpha action predominates
vasoconstriction even in skeletal muscle But BP returns to normal in few minutes
A secondary fall in mean BP occurs
Mechanism rapid uptake and dissipation ofAdr at low conc. Alpha action lost but betaaction predominatesDale`s Vasomotorreversal phenomenon
-
7/31/2019 Adrenergic System - Drdhriti
38/73
Dale`s Vasomotor ReversalPhenomenon
-
7/31/2019 Adrenergic System - Drdhriti
39/73
Actions of Adrenaline
Respiratory: Powerful bronchodilator Relaxes bronchial smooth muscle (not NA)
Beta-2 mediated effect
Physiological antagonist to mediators ofbronchoconstriction e.g. Histamine GIT : Relaxation of gut muscles (alpha and beta) and constricted
sphincters reduced peristalsis not clinical importance
Bladder: relaxed detrusor muscle (beta) muscle but constriction of
Trigone both are anti-voiding effect
Uterus: Adr contracts and relaxes Uterus (alpha and beta action)but net effect depends on status of uterus and species pregnantrelaxes but non-pregnant - contracts
-
7/31/2019 Adrenergic System - Drdhriti
40/73
Actions of Adrenaline contd.
Skeletal Muscle: Facilitation of Ach release in NM junction (alpha -1)
Beta-2 acts directly on Muscle fibres
Abbreviated active state and less tension in slowconducting fibres and enhanced muscle spindle firing tremor
CNS: No visible clinical effect in normal doses as low
penetration except restlessness, apprehension andtremor
Activation of alpha-2 in CNS decreases sympathetic outflow andreduction in BP and bradycardia - clonidine
-
7/31/2019 Adrenergic System - Drdhriti
41/73
Metabolic effects
Increases concentration of glucose and lacticacid
Calorigenesis (-2 and-3)
Inhibits insulin secretion (-2)
Decreases uptake of glucose by peripheraltissue
Simulates glycogenolysis - Beta effect Increases free fatty acid concentration in blood
Hypokalaemia initial hyperkalaemia
-
7/31/2019 Adrenergic System - Drdhriti
42/73
ADME
All Catecholamines are ineffective orally
Absorbed slowly from subcutaneous tissue
Faster from IM site Inhalation is locally effective
Not usually given IV
Rapidly inactivated in Liver by MAO andCOMT
-
7/31/2019 Adrenergic System - Drdhriti
43/73
Clinical Question!
Question: A Nurse was injecting a dose of penicillinto a patient in Medicine ward without prior skin testand patient suddenly developed immediate
hypersensitivity reactions. What would you do? Answer: As the patient has developed Anaphylactic
reaction, the only way to resuscitate the patient isinjection of Adrenaline
0.5 mg (0.5 ml of 1:10000) IM and repeat after 5-10minutes
Antihistaminics: Chlorpheniramine 10 20 mg IM or IV
Hydrocortisone 100 200 mg
-
7/31/2019 Adrenergic System - Drdhriti
44/73
Adrenaline Clinical uses
Injectable preparations are available in dilutions1:1000, 1:10000 and 1:100000
Usual dose is 0.3-0.5 mg sc of 1: 10000 solution
Used in: Anaphylactic shock
Prolong action of local anaesthetics
Cardiac arrest
Topically, to stop bleeding
Hyperkinetic children ADHD, minimal brain dysfunction
Anorectic
-
7/31/2019 Adrenergic System - Drdhriti
45/73
-
7/31/2019 Adrenergic System - Drdhriti
46/73
ADRs
Restlessness, Throbbing headache, Tremor,Palpitations
Cerebral hemorrhage, cardiac arrhythmias
Contraindicated in hypertensives,hyperthyroid and angina poctoris
Halothane and beta-blockers not indicated
-
7/31/2019 Adrenergic System - Drdhriti
47/73
Other Adrenergic Drugs
-
7/31/2019 Adrenergic System - Drdhriti
48/73
Noradrenaline
Neurotransmitter released frompostganglionic adrenergic nerve endings(80%)
Orally ineffective and poor SC absorption
IV administered
Metabolized by MAO, COMT
Short duration of action
-
7/31/2019 Adrenergic System - Drdhriti
49/73
Actions and uses
Agonist at 1(predominant), 2 and 1 Adrenergic receptors Equipotent with Adr on 1, but No effect on 2
Increases systolic, diastolic B.P, mean pressure, pulse pressureand stroke volume Total peripheral resistance (TPR) increases due to vasoconstriction -
Pressor agent Increases coronary blood flow Decreases blood flow to kidney, liver and skeletal muscles Uses: Injection Noradrenal bitartrate slow IV infusion at the rate
of 2-4mg/ minute used as a vasopressor agent in treatment ofhypovolemic shock and other hypotensive states in order to raise
B.P Problems: Down regulation of receptors, Renal Vasoconstriction Septic and neurogenic shock (?)
-
7/31/2019 Adrenergic System - Drdhriti
50/73
Noradrenaline - ADRs
Anxiety, palpitation, respiratory difficulty
Acute Rise of BP, headache
Extravasations causes necrosis, gangrene Contracts gravid uterus
Severe hypertension, violent headache,photophobia, anginal pain, pallor andsweating in hyperthyroid and hypertensivepatients
-
7/31/2019 Adrenergic System - Drdhriti
51/73
Isoprenaline
Catecholamine acting on beta-1 and beta-2 receptors negligibleaction on alpha receptor
Therefore main action on Heart and musclevasculature
Main Actions: Fall in Diastolic pressure, Bronchodilatation andrelaxation of Gut
ADME: Not effective orally, sublingual and inhalation (10mg tab. SL)
Overall effect is Cardiac stimulant (beta-1)
Increase in SBP but decrease in DBP (beta-2) Decrease in mean BP
Used as Bronchodilator and for treatment of AV block, Stokes-AdamSyndrome etc.but not preferred anymore
Adrenaline NA and
-
7/31/2019 Adrenergic System - Drdhriti
52/73
Adrenaline, NA andIsoprenaline - Summary
-
7/31/2019 Adrenergic System - Drdhriti
53/73
Dopamine
Immediate metabolic precursor ofNoradrenalin
High concentration in CNS - basal ganglia,limbic system and hypothalamus and also inAdrenal medulla
Central neurotransmitter, regulates body
movements ineffective orally, IV use only, Short T 1/2 (3-5minutes)
-
7/31/2019 Adrenergic System - Drdhriti
54/73
Dopamine
MECHANISM:
Agonists at dopaminergic D1, D2 receptors
Agonist at adrenergic 1 and 1
-
7/31/2019 Adrenergic System - Drdhriti
55/73
Dopamine
In small doses 2-5 g/kg/minute, it stimulates D1-receptors in renal, mesenteric and coronary vesselsleading to vasodilatation (Increase in cAMP)
Recall: Renal vasoconstriction occurs in CVS shock due tosympathetic over activity
Increases renal blood flow, GFR an causes natriuresis
Interaction with D2 receptors (present in presynaptic adrenergicneurones)suppression of NA release (no alpha effect)
-
7/31/2019 Adrenergic System - Drdhriti
56/73
Dopamine cond.
Moderate dose (5-10 g/kg/minute), stimulates 1-receptors in heart producing positive inotropic andchronotropic actions actions
Releases Noradrenaline from nerves by 1-stimulation
Does not change TPR and HR Great Clinical benefit in CVS shock and CCF
High dose (10-30 g/kg/minute), stimulates vascularadrenergic 1-receptors (NA release)vasoconstriction and decreased renal blood flow
-
7/31/2019 Adrenergic System - Drdhriti
57/73
Why renal and mesentericvasodilatation is useful in Shock?
Increases renal blood flow, GFR ancauses natriuresis
In CVS shock
excessive sympatheticactivity leading to ischemia of gut,sloughening and entry of Bacteria tosystemic circulation - septicemia
-
7/31/2019 Adrenergic System - Drdhriti
58/73
-
7/31/2019 Adrenergic System - Drdhriti
59/73
Adrenergic agonists
Selective Alpha-1 Agonists: Phenylepherine, Ephederine, Methoxamine,
Metaraminol, Mephentermine
Selective Alpha-2 Agonists: Clonidine, -methyldopa, Guanfacine and
Guanabenz
-2 Adrenergic agonists:
Salbutamol, Terbutaline, Salmeterol,Reproterol, Oxiprenaline, Fenoterol,Isoxsuprine, Rimiterol, Ritodrine, Bitolterol andIsoetharine
Adrenergic Drugs
-
7/31/2019 Adrenergic System - Drdhriti
60/73
Adrenergic DrugsTherapeutic Classification
Pressor agents: NA, Phenylephrine, ephedrine, Methoxamine, Dopamine
Cardiac Stimulants: Adr, Dobutamine and Isoprenaline, Dopexamine
Nasal Decongestants:
Phenylepherine, Xylometazoline, Oxymetazoline, Naphazoline andTetrahydrazoline and Phenylpropanolamine and Pseudoephidrine
Bronchodilators: Isoprenaline, Salbutamol, Salmeterol, Terbutaline, Formeterol
Uterine Relaxants: Ritodrine, Salbutamol, Isoxsuprine
Anorectics Fenfluramine, Dexfenfluramine and Sibutramine
CNS Stimulants: Amphetamine, Methamphetamine
-
7/31/2019 Adrenergic System - Drdhriti
61/73
Ph l h i S l i
-
7/31/2019 Adrenergic System - Drdhriti
62/73
Phenylepherine - Selective,synthetic and direct 1 agonist
Actions qualitatively similar to noradrenaline Long duration of action
Resistant to MAO and COMT Does not cross BBB, so no CNS effects
Peripheral vasoconstriction leads to rise in BP but Reflexbradycardia
Produces mydriasis and nasal decongestion
Use: hypovolaemic shock as pressor agent
Sinusitis & Rhinitis as nasal decongestant (common in oral preparations) Mydriatic in the form of eye drops and lowers intraocular pressure
ADRs: Photosensitivity, conjunctival hyperemia and hypersensitivity Administered parenteraly & topically (eye, nose)
What are Mucosal
-
7/31/2019 Adrenergic System - Drdhriti
63/73
What are MucosalDecongestants?
Nasal and bronchial decongestants are the drugs usedin allergic rhinitis, colds, coughs and sinusitis as nasaldrops - Sympathomimetic vasoconstrictors with -effects are used
Drugs: Phenylepherine, xylometazoline, Oxymetazoline,PPA, Pseudoephidrine etc.
Drawbacks: Rebound congestion due to overuse
However, mucosal ischaemic damage occurs if used excessively(more often than 3 hrly) or for prolonged periods (>3weeks)
CNS Toxicity Failure of antihypertensive therapy Fatal hypertensive crisis in patients on MAOIs
Use only a few days since longer application reduces ciliary action
-
7/31/2019 Adrenergic System - Drdhriti
64/73
Nasal Decongestants
Pseudoephedrine to Ephedrinebut less CNS and Cardiaceffects Poor Bronchodilator
Given in combination with antihistaminics, antitussives and NSAIDsin common cold and, allergic rhinitis, blocked Eustachian tube etc.
Rise in BP inhypertensives
Phenylpropanolamine (PPA)is similar to ephedrine and usedas decongestants in many cold and cough preparations
Also as weight loosing agent
Xylometazoline, Oxymetazoline etc.
-
7/31/2019 Adrenergic System - Drdhriti
65/73
Amphetamine Synthetic compound similar to Ephedrine Pharmacologically
Known because of its CNS stimulant action psychoactive drug andalso performance enhancing drug
Actions:
alertness, euphoria, talkativeness and increased work capacity fatigue
is allayed (acts on DA and NA neurotransmitters etc.reward pathway) increased physical performance without fatigue short lasting (Banned
drug and included in the list of drugs of Dope Test) deteriorationoccurs
RAS Stimulation wakefulness, sleep deprivation (then physicaldisability)
However, anxiety, restlessness, tremor and dysphoria occurs
Other actions: Stimulation of respiratory centre, Hungersuppression, also anticonvulsant, analgesic and antiemeticactions
-
7/31/2019 Adrenergic System - Drdhriti
66/73
Amphetamine contd.
Drug of abuse marked psychological effect but littlephysical dependence
Generally, Teenage abusers - thrill or kick
High Dose Euphoria, excitement and may progress todelirium, hallucination and acute psychotic state
Also peripheral effects like arrhythmia, palpitation, vascularcollapse etc.
Repeated Dose Long term behavioural abnormalities
Starvation acidic urine
Uses: Hyperkinetic Children (ADHD), Narcolepsy,Epilepsy and Parkinsonism
-
7/31/2019 Adrenergic System - Drdhriti
67/73
Anorectics
Drugs used for suppression of appetite
MOA: Inhibition of NA/DA or 5-HT uptakeenhancement of monoaminergic transmission
NA agents affect the appetite centre andSerotonergics act on satiety centre
Fenfluramine, dexfenfluramine andsibutramineALL ARE BANNED NOW
Reasons: Heart valve defects, fibrosis andpulmonary hypertension etc.
-
7/31/2019 Adrenergic System - Drdhriti
68/73
Clonidine
Centrally acting:Agonist to postsynaptic 2Aadrenoceptors in brain vasomotor centre inbrainstem (presynaptic Ca++ level increased NArelease) Decrease in BP and cardiac output
Peripherally action: High dose activates peripheralpresynaptic autoreceptors on adrenergic nerveending mediating negative feedback suppression of
noradrenaline release Overdose stimulates peripheral postsynaptic 1
adrenoceptors & cause hypertension byvasoconstriction
-
7/31/2019 Adrenergic System - Drdhriti
69/73
Clonidine contd.
Uses: ADHD in children, opioid withdrawal (restless legs, jitters andhypertension), alcohol withdrawal (0.3 to 0.6 mg)
Abrupt or gradual withdrawal causes rebound hypertension
Onset may be rapid (a few hours) or delayed for as long as 2 days andsubsides over 2-3 days
Never use beta-blockers to treat Available as tablets, injections and patches
Sedation, dry mouth, dizziness and constipation etc.
TCAs antagonize antihypertensive action & increase reboundhypertension of abrupt withdrawal
Low dose Clonidine (50-100g/dl) is used in migraine prophylaxis,menopausal flushing and chorea
Moxonidine, Rilmenidine Newer Imidazolines
2 Adrenergic Agonists
-
7/31/2019 Adrenergic System - Drdhriti
70/73
2 Adrenergic Agonists discussed elsewhere!
Short acting : Salbutamol, Metaproterenol, Terbutaline,pirbuterol
Selective for 2 receptor subtype
Used for acute inhalational treatment of bronchospasm.
Onset of action within 1 to 5 minutes
Bronchodilatation lasts for 2 to 6 hours
Duration of action longer on oral administration
Directly relax airway smooth muscle
Relieve dyspnoea of asthmatic bronchoconstriction
Long acting: Salmeterol, Bitolterol, colterol
Uterine Relaxants - discussed
-
7/31/2019 Adrenergic System - Drdhriti
71/73
Uterine Relaxants discussedelsewhere!
Antioxytocics or tocolytic agents
2 agonists relax uterus Used by i.v. infusion to inhibit premature labour Isoxsuprine, Terbutaline, Ritodrine, Salbutamol Tachycardia & hypotension occur Use minimum fluid volume using 5% dextrose as
diluents Ritodrine:50 g/min, increase by 50 g/min every
10 minutes until contractions stop or maternal heartrate is 140 beats/minute. Continue for 12-48 hoursafter contractions stop
-
7/31/2019 Adrenergic System - Drdhriti
72/73
Remember ?
Steps of Biosynthesis of Catecholamine
Distribution of adrenergic receptors
Individual Functions of Adrenergic receptors
All aspects of adrenaline Dale`sPhenomenon
Dopamine/Dobutamine actions
Nasal decongestants - Phenylephrine
Amphetamine and Clonidine - Desirable
-
7/31/2019 Adrenergic System - Drdhriti
73/73