Adrenergic drugs

1. Adrenergic drugs
S. Parasuraman, M.Pharm., Ph.D.,
Senior Lecturer, Faculty of Pharmacy,
AIMST University.

2. Overall actions of Adrenaline and
Noradrenaline
• The actions of a sympathomimetic amine depend on its
relative activity at different types of adrenergic receptors.
• Heart:
– Adrenaline (Adr) increases heart rate by increasing the
slope of slow diastolic depolarization of cells in the SA
node.
– Adr also increase the force of contraction and reduce
refractory period (RP) of all types of cardiac cells
acting through β1 receptor.
– In higher dose Adr produce arrhythmias and increases
blood pressure (BP).

3. Overall actions of Adrenaline and
Noradrenaline
• Blood vessels:
– Adrenergic drug produces both vasoconstriction
(mediated through α) and, vasodilatation
(mediated through β2) and these effect depends
on drug and its dose.
– The direct effect of Adr/ NA on cerebral vessels is
not prominent.

4. Overall actions of Adrenaline and
Noradrenaline
• Blood pressure:
– The effect is depends on the amine, its dose and
rate of administration.
– NA causes rise in systolic, diastolic and mean
blood pressure and it dose not cause vasodilation.
• NA: more specific to alpha ARs than beta ARs
• Adr: alpha ARs and beta ARs equal action
• Isoprenaline: More specific to beta ARs than
alpha ARs

5. Overall actions of Adrenaline and
Noradrenaline
• Blood pressure:
Norepinephrine • Heart Rate - Decreases due to reflex increase in vagal
tone on SA and AV nodes.
• Contractile Force - Increases due to effects on beta1-ARs
on myocardial cells.
• Total Peripheral Vascular Resistance - Increases due to
activation of alpha1-ARs on vascular smooth muscle cells.
• Blood Pressure - Increases due to effects on total
peripheral vascular resistance
Isoproterenol • Heart rate - increases due to activation of beta1 receptors
in SA and AV nodes.
• Contractile force - increases due to activation of beta 1
receptors on myocardial cells.
• Total peripheral vascular resistance - decreases due to
activation of beta 2 receptors.
• Blood pressure = cardiac output x total peripheral vascular
resistance

6. Overall actions of Adrenaline and
Noradrenaline
• Blood pressure:
Low dose of
Epinephrine
• Heart Rate - Increases due to beta1-ARs on SA and AV
nodal tissues
• Contractile Force - Increases due to activation of beta1-
ARs on myocardial cells
• Total Peripheral Vascular Resistance - Decreases due to
preferential activation of beta2-ARs, at these doses there
would be little activation of alpha1-ARs
• Blood Pressure - Similar to isoproterenol
High dose of
Epinephrine
• Heart Rate - Similar to the effects of norepinepherine
• Contractile Force - Increases due to beta1-ARs on
myocardial cells
• Total Peripheral Vascular Resistance - Increases due to
activation of alpha1-ARs on vascular smooth muscle cells.
• Blood Pressure - Increases due to activation of alpha1-
ARs on vascular smooth muscle cells

7. Overall actions of Adrenaline and
Noradrenaline
• Respiration:
– Adr and isoprenaline are potent bronchodilators
(β2) but not NA.
– In therapeutic dose Adr can directly stimulate
respiratory centre (RC) and in toxic dose it causes
pulmonary edema by shifting blood from systemic
to pulmonary circuit.

8. Overall actions of Adrenaline and
Noradrenaline
• Eye:
– Mydriasis occurs due to contraction of radial
muscles of iris (α1). Adr has complex effects on
aqueous humor dynamics.
Adrenaline Aqueous secretion
↓
Trabecular outflow
↑
Uveoscleral outflow
↑

9. Overall actions of Adrenaline and
Noradrenaline
• Gastrointestinal tract:
– Muscle relaxation occurs through both α and β
receptors.
• Bladder:
– Detrusor is relaxed (β) and trigone is constricted (α):
both actions tend to hinder
• Uterus:
– Adr can contract and relax uterine muscle through
both α and β receptors.
– Human uterus is relaxed by Adr at term of pregnancy,
but at other times, its concentrations are enhanced.

10. Overall actions of Adrenaline and
Noradrenaline
• Splenic capsule:
– No evident on human systemic effect.
• Skeletal muscle:
– Neuromuscular transmission is facilitated.
– Action on autonomic nerve endings, is mediated
through α (α1 subtype) receptor activation on
motor nerve endings augments ACh release.
– The direct effect on muscle fibres is exerted
through β2 receptors.

11. Overall actions of Adrenaline and
Noradrenaline
• Central nervous system:
– Activation of α2 receptors in the brainstem (by
selective α2 agonists) results in decreased
sympathetic outflow → fall in BP and bradycardia.
– Clinically does not produce any marked CNS
effects because of poor penetration in brain, but
restlessness, apprehension and tremor may occur.

12. Overall actions of Adrenaline and
Noradrenaline
• Metabolic effects:
• Adr causes
– glycogenolysis → hyperglycaemia,
hyperlactacidaemia (β2)
– Lipolysis → rise in plasma free fatty acid (FFA) and
calorigenesis (β2 + β3).

13. Therapeutic classification of adrenergic drugs
Pressor agents Noradrenaline, Ephedrine, Dopamine,
Phenylephrine, Methoxamine
Cardiac stimulants Adrenaline, Dobutamine, Isoprenaline
Bronchodilators Isoprenaline, Salbutamol (Albuterol) ,
Salmeterol, Formoterol, Bambuterol,
Terbutaline
Nasal decongestants Phenylephrine, Pseudoephedrine, Phenyl
propanolamine
CNS stimulants Amphetamine, Methamphetamine,
Dexamphetamine
Anorectics (is a dietary
supplement or drug which
reduces appetite)
Fenfluramine, Sibutramine, Dexfenfluramine
Uterine relaxant and
vasodilators
Ritodrine, Isoxsuprine, Salbutamol,
Terbutaline

14. Therapeutic uses
• Vascular uses:
– Hypotensive states: Adrenergic drugs are one of the pressor
agents used along with volume replacement for neurogenic and
haemorrhagic shock.
– It is used in in the management of cardiogenic shock to raise BP
may also increase cardiac work. Slow i.v. infusion of
dopamine/dobutamine is more appropriate in this situation.
Dopamine increases cardiac contactility without causing
significant tachycardia. Dobutamine has relatively more
selective inotropic effect. Use of NA is practically outdated.

15. Therapeutic uses
• Vascular uses:
– Along with local anaesthetics: Adr may be
enhancing spinal anaesthesia by reducing spinal
cord blood flow or by its own analgesic effect
exerted through spinal α2 adrenoceptors.
– Duration of anaesthesia is prolonged and systemic
toxicity of local anaesthetic is reduced (addition of
adrenaline may increase safe limit by upto 40%).

16. Therapeutic uses
• Vascular uses:
– Control of local bleeding
– Nasal decongestant: α-agonists are used as nasal
decongestant. Nasal decongestants should be
used very cautiously in hypertensive patients and
in elderly males.

17. Therapeutic uses
• Vascular uses:
– Control of local bleeding
– Nasal decongestant: α-agonists are used as nasal
decongestant. Nasal decongestants should be
used very cautiously in hypertensive patients and
in elderly males.

18. Therapeutic uses
• Vascular uses:
– Peripheral vascular diseases: Isoxsuprine (a β2
adrenoreceptor agonist that causes direct relaxation
of uterine and vascular smooth muscle) is used in the
management of Buerger’s disease, Raynaud’s
phenomena, diabetic vascular insufficiency,
gangrene, frost bite, ischaemic ulcers, night leg
cramps and cerebral vascular inadequacy.

19. Therapeutic uses
• Cardiac uses:
– Cardiac arrest: Adr may be used to stimulate the heart.
– Partial or complete A-V block: Isoprenaline may be used
as temporary measure to maintain sufficient ventricular
rate.
– Congestive heart failure (CHF): Adrenergic inotropic drugs
are not useful in the routine treatment of CHF. Controlled
short term i.v. infusion of DA/dobutamine used in acute
cardiac decompensation during myocardial infarction,
cardiac surgery and in resistant CHF.

20. Therapeutic uses
• Bronchial asthma and COPD:
β2 stimulants are the primary drugs for treatment
of reversible airway obstruction.
• Allergic disorders:
Adr is a physiological antagonist of histamine which
is an important mediator of many acute
hypersensitivity reactions.

21. Therapeutic uses
• Mydriatic:
Phenylephrine is used to facilitate fundus
examination. It tends to reduce intraocular tension
in wide angle glaucoma.

22. Therapeutic uses
• Central uses:
– Attention deficit hyperkinetic disorder (ADHD):
Amphetamines have an apparently paradoxical effect
to calm down hyperkinetic children.
– Narcolepsy: Narcolepsy is sleep occurring in fits and is
adequately controlled by amphetamines.
– Epilepsy: Amphetamines are occasionally used as
adjuvants and to counteract sedation caused by
antiepileptics.

23. Therapeutic uses
• Central uses:
– Parkinsonism: Amphetamines improve mood and
reduce rigidity (slightly) but do not benefit tremor.
They are occasionally used as adjuvants in
parkinsonism.
– Obesity: The anorectic drugs can help the obese
to tolerate a reducing diet for short periods, but
do not improve the long-term outlook.

24. Therapeutic uses
• Uterine relaxant :
– Isoxsuprine, β2 adrenoreceptor agonist has been
used in threatened abortion and dysmenorrhoea.