Adrenegic drugs

1. ADRENERGIC DRUG
By
Prof. Saba Shaikh

2. ADRENERGIC SYSTEM
• The prime function of the adrenergic or sympathetic nervous system is to help
the human being to adjust to stress and prepare the body for fight or flight
reactions.
• When exposed to stress, the heart rate and stroke volume increase with the
resultant increase in cardiac output. The blood is shifted from the skin, gut,
kidney and glands to the heart, skeletal muscles, brain and lungs, as these organs
need more blood during stress. Pupils and bronchi are dilated and sweating is
increased.
• Blood glucose increases by glycogenolysis

3. Neurotransmitters
• Neurotransmitters of the sympathetic system are noradrenaline (NA,
norepinephrine) and dopamine (DA). Adrenaline (epinephrine) is the
major hormone secreted by the adrenal medulla.

4. Synthesis of catecholamines

5. Synthesis, storage, release and metabolism of
noradrenaline

7. α1 and α2 receptor stimulation: NA binds to α1 receptors and stimulates it to
produce response like vasoconstriction. Presynaptic α2 receptor stimulation inhibits
the further release of NA from the storage vesicles.

8. ADRENERGIC DRUG
OR
SYMPATHOMIMETICS

9. Sympathomimetics
• Sympathomimetics are drugs whose actions mimic that of
sympathetic stimulation. Catecholamines and sympathomimetics or
adrenergic drugs may be classified in various ways depending on the
presence/absence of catechol nucleus

11. Pharmacological Action:
• Cardiovascular System: increases the heart rate, force of contraction, cardiac output.
• Blood vessels and BP :Blood vessels of the skin and mucous membrane are
constricted (α1 ) and that of the skeletal muscles are dilated (β2 ) by adrenaline.
• Smooth Muscles:
Bronchi :Adrenaline is a powerful bronchodilator.
Uterus Nonpregnant uterus—contracts, Last month of pregnancy—relaxes.
Gut Smooth muscle is relaxed.
 Splenic capsule contracts resulting in the release of RBCs into the circulation

12. • Eye: Adrenaline causes mydriasis due to contraction of the radial muscles
of the iris (α1); it also reduces intraocular pressure.
• Metabolic Effects: Adrenaline increases the blood sugar level by enhancing
hepatic glycogenolysis. It also inhibits insulin release. By enhancing
breakdown of triglycerides in the adipose tissue, more free fatty acids are
made available in the plasma by action on β3 receptors in adipocytes.
• Skeletal Muscles: Catecholamines facilitate neuromuscular transmission by
action on both α and β receptors—they enhance the amount of ACh
released.

13. • Pharmacokinetics: As catecholamines are rapidly inactivated in the gut and
the liver they are not given orally. Adrenaline and NA are metabolised by
COMT and MAO.
• Adverse reactions: Anxiety, palpitation, weakness, tremors, pallor,
dizziness, restlessness and throbbing headache may follow adrenaline/NA
administration. In patients with ischaemic heart disease, both adrenaline
and NA can precipitate anginal pain. Rapid IV injection can cause sudden
sharp rise in BP which may precipitate arrhythmias, subarachnoid
haemorrhage or hemiplegia.

14. Uses of Adrenaline
• Anaphylactic shock
• Cardiac arrest
• Control of haemorrhage
• With local anaesthetics
• Acute bronchial asthma
• Glaucoma

15. Contraindication of Adrenaline
• Adrenaline is contraindicated in patients with angina pectoris,
hypertension and in patients on β blockers.

16. • Noradrenaline can be used in shock to increase BP—but it is very rarely used.
• Isoprenaline (Isoproterenol, Isopropyl arterenol) is a synthetic
catecholamine with predominantly β receptor stimulant action and
negligible α actions. It has cardiac stimulant and smooth muscle relaxant
properties. Due to vasodilation BP falls; it is a potent bronchodilator. Adverse
effects include palpitation, angina, headache and flushing.
• Isoprenaline is used in heart block and shock for its cardiac stimulant actions.
It can be used in bronchial asthma.

17. • Dopamine is the precursor of NA. It acts on dopaminergic and adrenergic receptors. It is a central
neurotransmitter.
• Low doses stimulate vascular D1 receptors in renal, mesenteric and coronary beds causing
vasodilatation in these vessels. Hence renal blood flow and GFR increase.
• Higher doses cause cardiac stimulation through β1 receptors and in high doses α1 receptors are
activated resulting in vasoconstriction and increased BP. Dopamine does not cross the BBB -
hence it has no CNS effects.
• It is given IV (2-5 μg/ Kg/min). It is short acting and the infusion rate can be adjusted to get the
appropriate effect by monitoring BP.
• Dopamine is metabolised by COMT and MAO. Epinine (Ibopamine) is an ester of methyldopamine
which acts like dopamine.

18. Uses of Dopamine
• Dopamine is used in the treatment of shock—cardiogenic, hypovolaemic and
septic shock for the following reasons:
Dopamine increases renal blood flow and thereby GFR.
DA stimulates the heart-increases force of contraction, cardiac output and B.P.
Hence it is of special value when shock is associated with renal dysfunction and
low cardiac output.
Because DA is short acting, the response can be easily controlled by modifying
the infusion rate.

19. • Dopexamine is a synthetic analog of dopamine acting on D1 D2 and
β2 receptors. It is found to have beneficial effects in CCF.
• Dobutamine a derivative of dopamine, is a relatively selective β1
agonist. Though it also activates α1 receptors, in therapeutic doses
the only dominant action is an increase in the force of contraction of
the heart without a significant increase in the heart rate.

20. NONCATECHOLAMINES
• Ephedrine is an alkaloid obtained from the plants of the genus Ephedra.
Ephedrine acts by direct stimulation of α and β receptors and indirectly through
release of NA. Repeated administration at short intervals result in tachyphylaxis.
Ephedrine raises BP by peripheral vasoconstriction and by increasing the cardiac
output. Like adrenaline it relaxes smooth muscles; it is a CNS stimulant and
produces insomnia, restlessness, anxiety, tremors and increased mental activity.
• Adverse effects include gastric upset, insomnia, tremors and difficulty in
micturition.

21. Uses
• Bronchial asthma
• Nasal decongestion
• Mydriasis
• Hypotension
• Narcolepsy
• Nocturnal enuresis (Bed wetting)
• Stokes Adam's syndrome

22. Amphetamine
• Amphetamine is a synthetic compound with actions similar to ephedrine;
tachyphylaxis can occur on repeated use. Amphetamine is a potent CNS
stimulant; it produces increased mental and physical activity, alertness, increased
concentration and attention span, elation, euphoria and increased capacity to
work. It also increases initiative and self confidence, postpones fatigue and
improves physical performance (temporarily) as seen in athletes. All these
properties make amphetamine a drug of dependence and abuse. Higher doses
produce confusion, delirium and hallucinations

23. Uses of Amphetamine
• Attention deficit hyperactivity disorder
• Narcolepsy
• Obesity
• Epilepsy

24. VASOPRESSORS
• These are α1 agonists and include metaraminol, mephenteramine, phenylephrine and
methoxamine. They increase the BP by increasing total peripheral resistance (TPR) or cardiac
output (CO) or both. They are given parenterally with constant monitoring of BP. Tachyphylaxis
may develop. Uses Vasopressors are used to raise the BP in hypotension as seen in cardiogenic or
neurogenic shock and during spinal anaesthesia. Metaraminol is an alpha stimulant and also acts
indirectly by NA release. CO is increased. It is also a nasal decongestant. Mephenteramine acts on
both α and β receptors to increase TPR and CO and thereby raises BP. It is orally effective. Pressor
effect is accompanied by bradycardia. Phenylephrine is a selective α1 stimulant; it is also a nasal
decongestant. Reflex bradycardia is prominent. It produces mydriasis without cycloplegia.
Methoxamine has actions similar to phenylephrine.

25. NASAL DECONGESTANTS
• Nasal decongestants are α1 agonists. They bring about vasoconstriction of
the nasal mucosa, resulting in its shrinkage and they decrease the volume
of the mucosa. Thus they relieve nasal congestion and decrease resistance
to airflow through the nose.They also reduce nasal secretion. The nasal
decongestants thus provide symptomatic relief in rhinitis due to allergy and
upper respiratory infections. Mechanism of action - Nasal decongestants
act by stimulating the α1 receptors present in the blood vessels of the
nasal mucosa.

26. • They bring about vasoconstriction of the nasal mucosa resulting in its
shrinkage. Thus they relieve nasal congestion.
• They may be used:
1. Orally Ephedrine Pseudoephedrine
2. Topically (as nasal drops) Oxymetazoline, Xylometazoline Naphazoline,
Phenylephrine Mephenteramine Metaraminol
Adverse effects When used orally ephedrine and pseudoephedrine can cause
insomnia, tremors and irritability. On topical use, nasal irritation can occur.

27. SELECTIVE β2 STIMULANTS
• Selective β2 stimulants include orciprenaline, salbutamol, terbutaline and the newer
ones include salmeterol, perbuterol, bitolterol, fenoterol and formoterol. These are
smooth muscle relaxants which produce bronchodilatation, vasodilation and uterine
relaxation without significant cardiac stimulation. Salbutamol and other β2 stimulants
can be given by inhalation. Side effects include muscle tremors, palpitation and
arrhythmias.
• Uses
• Bronchial asthma
• As uterine relaxants to delay premature labour

28. ANORECTIC AGENTS (ANOREXIANTS)
• Though amphetamine suppresses appetite, it is not recommended for the treatment of
obesity due to its central stimulant effects. Many amphetamine like drugs which suppress
appetite but lack significant CNS stimulant effects are now available. They are
fenfluramine, dexfenfluramine, mazindol, phenylpropanolamine (now banned),
penmetrazine and others. Adverse effects include risk of abuse, drowsiness and
depression because of which they are only used for short periods as adjuncts to other
measures. Sibutramine suppresses appetite and has been tried in obesity. It inhibits the
uptake of NA and 5-HT but causes many serious adverse effects including insomnia,
anxiety, mood changes, hypertension and cardiovascular deaths.