A power point presentation on Adrenergic system and Adrenergic Drugs suitable for Undergraduate MBBS level students

1. Adrenergic System
Dr. D. K. Brahma
Department of Pharmacology
NEIGRIHMS, Shillong, Meghalaya

2. Neurotransmission in ANS

3. Noradrenergic transmission
 Nor-adrenaline is the major
neurotransmitter of the
Sympathetic system
 Noradrenergic neurons are
postganglionic sympathetic
neurons with cell bodies in
the sympathetic ganglia
 They have long axons
which end in varicosities
where NA is synthesized
and stored

4. Adrenergic transmission
Catecholamines:
 Natural: Adrenaline, Noradrenaline, Dopamine
 Synthetic: Isoprenaline, Dobutamine
Non-Catecholamines:
 Ephedrine, Amphetamines, Phenylepherine, Methoxamine,
Mephentermine
Also called sympathomimetic amines as most of them
contain an intact or partially substituted amino (NH2)
group

5. • Catecholamines:
Compounds containing
a catechol nucleus
(Benzene ring with 2
adjacent OH groups)
and an amine
containing side chain
• Non-catecholamines
lack hydroxyl (OH)
group

6. Biosynthesis of
Catecholamines
Phenylalanine
PH
Rate limiting Enzyme
5-HT, alpha Methyldopa
Alpha-methyl-p-tyrosine

7. Storage of Noradrenaline

8. Release of NA – Feedback Control

9. Regulators of NA release

10. Uptake of Catecholamines

11. Reuptake
 Sympathetic nerves take up amines and release
them 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

12. 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

13. Metabolism of CAs
(Homovanillic acid) (Vanillylmandelic acid)

14. Adrenergic neurotransmission

15. Adrenergic Receptors

16. Adrenergic Receptors
 Adrenergic receptors (or adrenoceptors) are a class of G-protein
coupled receptors that are the target of catecholamines
 Adrenergic receptors specifically bind their endogenous ligands –
catecholamines (adrenaline and noradrenline)
 Increase or decrease of 2nd messengers cAMP or IP3/DAG
 Many cells possess these receptors, and the binding of an
agonist will generally cause the cell to respond in a flight-fight
manner.
 For instance, the heart will start beating quicker and the pupils
will dilate

17. How Many of them ????
Adenoreceptors
Alpha (α) Beta (β)
α 1 α 2 β1 β 2 β3
α 2A α 2B α 2C
α 1A α 1B α 1D

18. Differences - Adrenergic
Receptors (α and β) !
 Alpha (α) and Beta (β)
 Agonist affinity of alpha (α):
 adrenaline > noradrenaline > isoprenaline
 Antagonist: Phenoxybenzamine
 IP3/DAG, cAMP and K+ channel opening
 Agonist affinity of beta (β):
 isoprenaline > adrenaline > noradrenaline
 Propranolol
 cAMP and Ca+ channel opening

19. Potency of catecholamines on
Adrenergic Receptors
Aortic strip contraction Bronchial relaxation
Adr NA
α β
Iso
Iso Adr
NA
Log Concentration

20. Molecular Effector Differences
- α Vs β
α Receptors:
 IP3/DAG
 cAMP
 K+ channel opening
β Receptors:
 cAMP
 Ca+ channel opening

21. Recall: Adenylyl cyclase: cAMP
pathway
PKA alters the functions of many
Enzymes, ion channels,
transporters
and structural proteins.
PKA Phospholamban
Increased
Interaction with
Ca++
Faster relaxation
Troponin
Cardiac
contractility
Other
Functional
proteins
Faster sequestration of
Ca++ in SR

22. Also Recall: Phospholipase C:
IP3-DAG pathway
PKc

23. Beta receptors
 All β receptors activate adenylate cyclase, raising the intracellular cAMP
concentration
 Type β1:
 These are present in heart tissue, and cause an increased heart rate by
acting on the cardiac pacemaker cells
 Type β2:
 These are in the vessels of skeletal muscle, and cause vasodilatation, which
allows more blood to flow to the muscles, and reduce total peripheral
resistance
 Beta-2 receptors are also present in bronchial smooth muscle, and cause
bronchodilatation when activated
 Stimulated by adrenaline, but not noradrenaline
 Bronchodilator salbutamol work by binding to and stimulating the β2
receptors
 Type β3:
 Beta-3 receptors are present in adipose tissue and are thought to have a
role in the regulation of lipid metabolism

24. Differences between β1, β2 and β3
Beta-1 Beta-2 Beta-3
Location Heart and JG cells Bronchi, uterus,
Blood vessels,
liver, urinary tract,
eye
Adipose
tissue
Agonist Dobutamine Salbutamol -
Antagonist Metoprolol, Atenolol Alpha-methyl
propranolol
-
Action on
NA
Moderate Weak Strong

25. Clinical Effects of β-receptor
stimulation
 β1: Adrenaline, NA and Isoprenaline:
 Tachycardia
 Increased myocardial contractility
 Increased Lipolysis
 Increased Renin Release
 β2: Adrenaline and Isoprenaline (not NA)
 Bronchi – Relaxation
 SM of Arterioles (skeletal Muscle) – Dilatation
 Uterus – Relaxation
 Skeletal Muscle – Tremor
 Hypokalaemia
 Hepatic Glycogenolysis and hyperlactiacidemia
 β3: Increased Plasma free fatty acid – increased O2 consumption -
increased heat production

26. Adrenergic receptors - alpha
 Type α1
 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 these
organs
 Acts by phospholipase C activation, which forms IP3 and
DAG
 In blood vessels these cause vasoconstriction
 Type α2
 These are found on pre-synaptic nerve terminals
 Acts by inactivation of adenylate cyclase, cyclic AMP levels
within the cell decrease (cAMP)

27. Differences between α1 and α2
Alpha-1 Alpha-2
Location Post junctional – blood vessels
of skin and mucous
membrane, Pilomotor muscle
& sweat gland, radial muscles
of Iris
Prejunctional
Function Stimulatory – GU,
Vasoconstriction, gland
secretion, Gut relaxation,
Glycogenolysis
Inhibition of transmitter
release, vasoconstriction,
decreased central symp.
Outflow, platelet
aggregation
Agonist Phenylephrine, Methoxamine Clonidine
Antagonist Prazosin Yohimbine

28. α1 adrenoceptors
Clinical effects
 Eye -- Mydriasis
 Arterioles – Constriction (rise in BP)
 Uterus -- Contraction
 Skin -- Sweat
 Platelet - Aggregation
 Male ejaculation
 Hyperkalaemia
 Bladder Contraction
 α2 adrenoceptors on nerve endings mediate negative
feedback which inhibits noradrenaline release

29. Molecular Basis of Adrenergic
Receptors
Also glycogenolysis
in liver
Inhibition of
Insulin
release and
Platelet
aggregation
Gluconeogen
esis

30. Dopamine receptors
 D1-receptors are post synaptic receptors
located in blood vessels and CNS
 D2-receptors are presynaptic present in CNS,
ganglia, renal cortex

31. Summary of agents modifying
adrenergic transmission
Step Actions Drug
Synthesis of NA Inhibition α - 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 inhibition
MAO-B inhibition
COMT inhibition
Moclobemide
Selegiline
Tolcapone
Receptors α 1
α 2
β1 + β2
β1
Prazosin
Yohimbine
Propranolol
Metoprolol

33. Adrenaline as prototype
 Potent stimulant of alpha and beta receptors
 Complex actions on target organs

34. Heart
 Beta-1 mediated action - Powerful Cardiac stimulant - +ve
chronotropic, +ve inotropic
 Acts on beta-1 receptors in myocardium, pacemaker cells and
conducting tissue
 Heart rate increases by increasing slow diastolic depolarization of cells
in SAN
 High doses cause marked rise in heart rate and BP causing reflex
depression of SAN – unmasking of latent pacemaker cells in AVN and
PF – 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 and
Bundle of His increased – benefit in partial AV block
 Reduced refractory period in all cardiac cells

35. Blood Vessels
 Seen mainly in the smaller vessels –
arterioles – Vasoconstriction (alpha) and
vasodilatation (beta) – depends on the drug
 Decreased blood flow to skin and mucus
membranes and renal beds – alpha effect (1
and 2) -
 Increased blood flow to skeletal muscles,
coronary and liver vessels - (Beta-2 effect)
counterbalanced by a vasoconstrictor effect
of alpha receptors

36. Blood Pressure
 Depends on the Catecholamine involved
 NA causes rise in Systolic, diastolic and mean
BP (no beta-2 action) – unopposed alpha action
 Isoprenaline causes rise in systolic but fall in
diastolic 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 alpha
receptors

37. Blood Pressure – contd.
 Rapid IV injection of Adrenaline marked rise in
Systolic 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 of
Adr – at low conc. Alpha action lost but beta
action predominates – Dale`s Vasomotor
reversal phenomenon

38. Dale`s Vasomotor Reversal
Phenomenon

39. Actions of Adrenaline
 Respiratory:
 Powerful bronchodilator
 Relaxes bronchial smooth muscle (not NA)
 Beta-2 mediated effect
 Physiological antagonist to mediators of
bronchoconstriction 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 – pregnant
relaxes but non-pregnant - contracts

40. 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 slow
conducting fibres and enhanced muscle spindle firing
– tremor
 CNS: No visible clinical effect in normal doses – as low
penetration except restlessness, apprehension and
tremor
 Activation of alpha-2 in CNS decreases sympathetic outflow and
reduction in BP and bradycardia - clonidine

41. Metabolic effects
 Increases concentration of glucose and lactic
acid
 Calorigenesis (β-2 and β-3)
 Inhibits insulin secretion (α-2)
 Decreases uptake of glucose by peripheral
tissue
 Simulates glycogenolysis - Beta effect
 Increases free fatty acid concentration in blood
 Hypokalaemia – initial hyperkalaemia

42. 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 and
COMT

43. Clinical Question!
 Question: A Nurse was injecting a dose of penicillin
to a patient in Medicine ward without prior skin test
and 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 is
injection of Adrenaline
 0.5 mg (0.5 ml of 1:10000) IM and repeat after 5-10
minutes
 Antihistaminics: Chlorpheniramine 10 – 20 mg IM or IV
 Hydrocortisone 100 – 200 mg

44. Adrenaline – Clinical uses
 Injectable preparations are available in dilutions
1:1000, 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

45. CPR - Image

46. ADRs
 Restlessness, Throbbing headache, Tremor,
Palpitations
 Cerebral hemorrhage, cardiac arrhythmias
 Contraindicated in hypertensives,
hyperthyroid and angina poctoris
 Halothane and beta-blockers – not indicated

47. Other Adrenergic Drugs

48. Noradrenaline
 Neurotransmitter released from
postganglionic adrenergic nerve endings
(80%)
 Orally ineffective and poor SC absorption
 IV administered
Metabolized by MAO, COMT
 Short duration of action

49. Actions and uses
 Agonist at α1(predominant), α2 and β1 Adrenergic receptors
 Equipotent with Adr on β1, but No effect on β2
 Increases systolic, diastolic B.P, mean pressure, pulse pressure
and 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 of
hypovolemic shock and other hypotensive states in order to raise
B.P
 Problems: Down regulation of receptors, Renal Vasoconstriction
 Septic and neurogenic shock (?)

50. 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 and
sweating in hyperthyroid and hypertensive
patients

51. Isoprenaline
 Catecholamine acting on beta-1 and beta-2 receptors – negligible
action on alpha receptor
 Therefore main action on Heart and muscle
vasculature
 Main Actions: Fall in Diastolic pressure, Bronchodilatation and
relaxation 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-Adam
Syndrome etc. – but not preferred anymore

52. Adrenaline, NA and
Isoprenaline - Summary

53. Dopamine
 Immediate metabolic precursor of
Noradrenalin
 High concentration in CNS - basal ganglia,
limbic system and hypothalamus and also in
Adrenal medulla
 Central neurotransmitter, regulates body
movements ineffective orally, IV use only,
 Short T 1/2 (3-5minutes)

54. Dopamine
MECHANISM:
 Agonists at dopaminergic D1, D2 receptors
 Agonist at adrenergic α1 and β1

55. Dopamine
 In small doses 2-5 μg/kg/minute, it stimulates D1-
receptors in renal, mesenteric and coronary vessels
leading to vasodilatation (Increase in cAMP)
 Recall: Renal vasoconstriction occurs in CVS shock due to
sympathetic over activity
 Increases renal blood flow, GFR an causes natriuresis
 Interaction with D2 receptors (present in presynaptic adrenergic
neurones) – suppression of NA release (no alpha effect)

56. Dopamine – cond.
 Moderate dose (5-10 μg/kg/minute), stimulates β1-
receptors in heart producing positive inotropic and
chronotropic actions actions
 Releases Noradrenaline from nerves by β1-
stimulation
 Does not change TPR and HR
 Great Clinical benefit in CVS shock and CCF
 High dose (10-30 μg/kg/minute), stimulates vascular
adrenergic α1-receptors (NA release) –
vasoconstriction and decreased renal blood flow

57. Why renal and mesenteric
vasodilatation is useful in Shock?
Increases renal blood flow, GFR an
causes natriuresis
In CVS shock – excessive sympathetic
activity leading to ischemia of gut,
sloughening and entry of Bacteria to
systemic circulation - septicemia

58. Dobutamine - Derivative of
Dopamine
 MOA:
 Acts on both alpha and beta receptors but more prominently in beta-1
receptor – increase in contractility and CO
 Does not act on D1 or D2 receptors – No release of NA and thereby
hypertension
 Predominantly a beta-1 agonist with weak beta-2 and selective alpha-1
activity
 Racemic mixture consisting of both (+) and (−) isomers - the (+) isomer
is a potent β1 agonist and α1 antagonist, while the (−) isomer is an α1
agonist
 Overall beta-1 activity and weak beta-2 activity
 Increase in force of contraction and cardiac output but no change in
heart rate
 Uses: Clinically give in dose of 2-8 mcg/kg/min IV infusion in Heart
failure in cardiac surgery, Septic and cardiogenic shock, Congestive Heart
failure
 ADRs: Tachycardia, hyperension, angina and fatal arrhythmia

59. Adrenergic agonists
Selective Alpha-1 Agonists:
 Phenylepherine, Ephederine, Methoxamine,
Metaraminol, Mephentermine
Selective Alpha-2 Agonists:
 Clonidine, α-methyldopa, Guanfacine and
Guanabenz
Β-2 Adrenergic agonists:
 Salbutamol, Terbutaline, Salmeterol,
Reproterol, Oxiprenaline, Fenoterol,
Isoxsuprine, Rimiterol, Ritodrine, Bitolterol and
Isoetharine

60. Adrenergic Drugs –
Therapeutic Classification
 Pressor agents:
 NA, Phenylephrine, ephedrine, Methoxamine, Dopamine
 Cardiac Stimulants:
 Adr, Dobutamine and Isoprenaline, Dopexamine
 Nasal Decongestants:
 Phenylepherine, Xylometazoline, Oxymetazoline, Naphazoline and
Tetrahydrazoline and Phenylpropanolamine and Pseudoephidrine
 Bronchodilators:
 Isoprenaline, Salbutamol, Salmeterol, Terbutaline, Formeterol
 Uterine Relaxants:
 Ritodrine, Salbutamol, Isoxsuprine
 Anorectics
 Fenfluramine, Dexfenfluramine and Sibutramine
 CNS Stimulants:
 Amphetamine, Methamphetamine

61. Ephedrine
 Plant alkaloid obtained from Ephedra vulgaris – Mixed acting drug
(also metaraminol) – effective orally
 Crosses BBB and Centrally – Increased alertness, anxiety,
insomnia, tremor and nausea in adults. Sleepiness in children
 Effects appear slowly but lasts longer (t1/2-4h) – 100 times less
potent
 Tachyphylaxis on repeated dosing (low neuronal pool)
 Used as bronchodilator, mydriatic, in heart block, mucosal
vasoconstriction & in myasthenia gravis
 Not used commonly due to non-specific action
 Uses: Mild Bronchial asthma, hypotension due to spinal anaesthesia
 Available as tablets, nasal drop and injection

62. Phenylepherine - Selective,
synthetic and direct α1 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 Reflex
bradycardia
 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)

63. What are Mucosal Decongestants?
 Nasal and bronchial decongestants are the drugs used
in allergic rhinitis, colds, coughs and sinusitis as nasal
drops - Sympathomimetic vasoconstrictors with α-
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

64. Nasal Decongestants
 Pseudoephedrine to Ephedrine but less CNS and Cardiac
effects
 Poor Bronchodilator
 Given in combination with antihistaminics, antitussives and NSAIDs
in common cold and, allergic rhinitis, blocked Eustachian tube etc.
 Rise in BP inhypertensives
 Phenylpropanolamine (PPA) is similar to ephedrine and used
as decongestants in many cold and cough preparations
 Also as weight loosing agent
 Xylometazoline, Oxymetazoline etc.

65. Amphetamine
 Synthetic compound similar to Ephedrine Pharmacologically
 Known because of its CNS stimulant action – psychoactive drug and
also 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)” – deterioration
occurs
 RAS Stimulation – wakefulness, sleep deprivation (then physical
disability)
 However, anxiety, restlessness, tremor and dysphoria occurs
 Other actions: Stimulation of respiratory centre, Hunger
suppression, also anticonvulsant, analgesic and antiemetic
actions

66. Amphetamine – contd.
 Drug of abuse – marked psychological effect but little
physical dependence
 Generally, Teenage abusers - thrill or kick
 High Dose – Euphoria, excitement and may progress to
delirium, hallucination and acute psychotic state
 Also peripheral effects like arrhythmia, palpitation, vascular
collapse etc.
 Repeated Dose – Long term behavioural abnormalities
 Starvation – acidic urine
 Uses: Hyperkinetic Children (ADHD), Narcolepsy,
Epilepsy and Parkinsonism

67. Anorectics
 Drugs used for suppression of appetite
MOA: Inhibition of NA/DA or 5-HT uptake –
enhancement of monoaminergic transmission
 NA agents affect the appetite centre and
Serotonergics act on satiety centre
 Fenfluramine, dexfenfluramine and
sibutramine – ALL ARE BANNED NOW
 Reasons: Heart valve defects, fibrosis and
pulmonary hypertension etc.

68. Clonidine
 Centrally acting: Agonist to postsynaptic α2A
adrenoceptors in brain – vasomotor centre in
brainstem (presynaptic Ca++ level – increased NA
release)
 Decrease in BP and cardiac output
 Peripherally action: High dose activates peripheral
presynaptic autoreceptors on adrenergic nerve
ending mediating negative feedback suppression of
noradrenaline release
 Overdose stimulates peripheral postsynaptic α1
adrenoceptors & cause hypertension by
vasoconstriction

69. Clonidine – contd.
 Uses: ADHD in children, opioid withdrawal (restless legs, jitters and
hypertension), 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 and
subsides 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 rebound
hypertension of abrupt withdrawal
 Low dose Clonidine (50-100μg/dl) is used in migraine prophylaxis,
menopausal flushing and chorea
 Moxonidine, Rilmenidine – Newer Imidazolines

70. β2 Adrenergic Agonists –
discussed elsewhere!
 Short acting : Salbutamol, Metaproterenol, Terbutaline,
pirbuterol
 Selective for β2 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

71. Uterine Relaxants - discussed
elsewhere!
 Antioxytocics or tocolytic agents
 β2 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 μg/min, increase by 50 μg/min every
10 minutes until contractions stop or maternal heart
rate is 140 beats/minute. Continue for 12-48 hours
after contractions stop

72. Remember ?
 Steps of Biosynthesis of Catecholamine
 Distribution of adrenergic receptors
 Individual Functions of Adrenergic receptors
 All aspects of adrenaline – Dale`s
Phenomenon
 Dopamine/Dobutamine actions
 Nasal decongestants - Phenylephrine
 Amphetamine and Clonidine - Desirable

73. ध न य व ा द /Khuble
i