Noradrenaline is a neurotransmitter that acts on α1, α2, and β1 receptors. It increases blood pressure through vasoconstriction and is used as a vasopressor agent. Isoprenaline acts mainly on β1 and β2 receptors and is used as a bronchodilator. Dopamine acts on D1, D2, α1, and β1 receptors. Low doses cause renal and mesenteric vasodilation while moderate doses have positive inotropic effects. Dobutamine is a derivative that predominantly acts on β1 receptors to increase contractility without affecting heart rate. Ephedrine, phenylephrine, and other sympathomimetic drugs have various adrenergic

1. Other
Adrenergic Drugs
BY: Joseph Anthony G. Martinez

2. 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

3. 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

4. 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

5. 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

6. Adrenaline, NA and
Isoprenaline - Summary

7. 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)

8. Dopamine
• MECHANISM:
– Agonists at dopaminergic D1, D2 receptors
– Agonist at adrenergic α1 and β1

9. 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)

10. 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

11. 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

12. 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

13. 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

14. 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

15. 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

16. 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)

17. 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
• 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

18. 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.

19. 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

20. Amphetamine
• 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

21. 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.

22. 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

23. Clonidine
• 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

24. 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

25. Uterine Relaxants
• 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

26. THANK YOU!!