This document discusses sympathomimetic drugs and adrenergic agonists. It describes how sympathomimetics mimic the effects of sympathetic nerve stimulation by acting on adrenergic receptors. It classifies adrenergic agonists as catecholamines or non-catecholamines and discusses their differences. It also summarizes the endogenous catecholamines, their synthesis, storage, and release. Additionally, it provides details on adrenergic receptors and the therapeutic uses, pharmacological actions, and side effects of various adrenergic drugs including epinephrine, dopamine, isoproterenol, dobutamine, ephedrine, and mephenteramine.

1. SYMPATHETIC
NERVOUS SYSTEM
(ADRENERGICS)

2. SYMPATHOMIMETIC

Sympathomimetic drugs mimic the effects of
sympathetic nerve stimulation

Also adrenergic agonists

Adrenergic receptors

3. Adrenergic Agonists

Chemical classification
Catecholamines
 Non-catecholamines


4. Adrenergic Agonists
Differences
Catecholamine
 Cannot use orally
 Cannot cross BBB
Short-half
live
Examples:
Norepinephrine
Epinephrine
Isoproteronol
Dopamine
Dobutamine
Noncatecholamines
 Can use orally
 Can cross BBB
Longer half life
Examples:
Ephedrine
Phenylephrine
Terbutaline

5. ENDOGENOUS
CATECHOLAMINES
Naturally occurring in body:
 Norepinephrine -Sites: postganglionic sympathetic
sites (except sweat glands , erector pillorie, hair
follicles, )
 Epinephrine- Secreted by adrenal medulla
 Dopamine- Major transmitter in basal ganglia, CTZ,
limbic system, anterior pitutory.

6. SYNTHESIS

7. Catecholamine s
In dopaminergic
neurons, synthesis
stops here
Final step only in
adrenal medulla
and CNS neurons
Tyrosine
↓
Dopa
↓
Dopamine
↓
Norepinephrine
↓
Epinephrine
In noradrenergic
neurons,
synthesis stops
here

8. STORAGE, RELEASE, UPTAKE
L-Phenylalanine
Hepatic
hydroxylase

11. Adrenergic Receptors
These are mainly 2 types
(α) Alfa
(β) Beta
These are again subdivided into various types


12. ADRENERGIC RECEPTORS

13. ADRENERGIC DRUGS
Symphathomimetics

DIRECT SYMPHATHOMIMETICS








INDIRECT SYMPHATHOMIMETICS



Adrenaline
Noradrenaline
Isoprenaline
Phenylephrine
Methoxamine
Salbutamol
Xylometazoline
Tyramine
Amphetamine
MIXED SYMPHATHOMIMETICS



Ephedrine
Dopamine
Mephenteramine

14. THERAPEUTIC CLASSIFICATION OF
ADRENERGIC DRUGS
Pressor agents
Noradrenaline
Ephedrine
Dopamine
Phenylephrine
Methoxamine
Mephentermine
Cardiac stimulants
Adrenaline
Isoprenaline
Dobutamine
Bronchodilators
Adrenaline
Isoprenaline
Salbutamol
(Albuterol)
Terbutaline
Salmeterol
Formoterol
Bambuterol

15. Nasal decongestants
Phenylephrine
Xylometazoline
Oxymetazoline
Naphazoline
Pseudoephedrine
Phenyl propanolamine
CNS stimulants
Amphetamine Dexamphetamine Methamphetamine
Anorectics
Fenfluramine Dexfenfluramine Sibutramine
Uterine relaxant and vasodilators
Ritodrine
Isoxsuprine
Salbutamol
Terbutaline

16. PHARMACOLOGICAL ACTIONS
Cardiac effects

Positive chronotropic effect


Positive dromotropic effect


An action that increases heart rate
An action that speeds conduction of electrical
impulses (↑ conduction velocity through AV node)
Positive inotropic effect

An action that increases the force of contraction of
cardiac muscle

17. Cardiac effects of epinephrine
Cardiac output is determined by heart rate and
stroke volume
CO = HR x SV
Epi→ β1receptors at SA node→↑HR
Epi→ β1receptors on ventricular myocytes→
↑ force of contraction

18. vascular smooth muscle
α1


In blood vessels
supplying skin, mucous
membranes, viscera and
kidneys, vascular
smooth muscle has
almost exclusively
alpha1-adrenergic
receptors
Also biphasic response

19. Biphasic Response
α1+β1 effect
(A)
β2 effect (at low doses)
Mainly α -action
(B)
α Blocker E
β Blocker
β2 effect
E

20. vascular smooth muscle

In blood vessels supplying skeletal muscle, vascular
smooth muscle has both alpha1 and beta2 adrenergic
receptors
α1
α1 stimulation
β2
β2 stimulation

21. Effects of epinephrine on blood vessel caliber
α1


Blood vessels to
skin, mucous
membranes, viscera
and kidneys
Stimulation of α1adrenergic
receptors causes
constriction of
vascular smooth
muscle

22. Effects of epinephrine on blood vessel caliber:
skeletal muscle


At low plasma concentrations of Epi, β2 effect
predominates→ vasodilation
At high plasma concentrations of Epi, α1 effect
predominates→ vasoconstriction
α1
β2

23. Effects of Epi on arterial blood pressure
Arterial BP = CO x PVR
Epinephrine:
 ↑ CO
 Low doses ↓ PVR (arteriolar dilation in
skeletal muscle)
 High doses ↑PVR

24. Effects of epinephrine on airways

Epi→β2-adrenergic
receptors on airway
smooth muscle→
rapid, powerful
relaxation→
bronchodilation

25. Effects of epinephrine in the eye

α1
β2
Epi at α1adrenergic
receptors on
radial smooth
muscle →
contraction→
mydriasis

Epi at B2adrenergic
receptors→
relaxation of
ciliary muscle

26. OTHER SYSTEMS






GIT: Peristalsis is reduced, sphincters are contracted.
Bladder : Detrusors relaxed, trigone contracted
Splenic capsule : Contracts (alpha action), RBCs are
poured
Skeletal muscle : Neuromuscular transmission is
facilitated. (Tremors due to beta 2 actions)
CNS: Restlessness , tremors , fall in BP and bradycardia
Metabolic : Hyperglycemia, lipolysis

27. Mnemonic for therapeutic uses of
adrenaline ABCDEG
A- Anaphylactic shock
B- Bronchial asthma
C- Cardiac arrest
D- Delay absorption of local anesthetics
E- Epistaxis, Elevate BP
G- Glaucoma
Others : Reduce nasal congestion, Induces mydriasis

28. Epinephrine (contd..)
 Adverse effects of epinephrine
Hypertensive crisis
Dysrhythmias
Angina pectoris
Necrosis following extravasation
Hyperglycemia

29. Dopamine (DA)

Dopaminergic neurons in brain, enteric nervous
system and kidney

Dopaminergic receptors in brain, mesenteric and
renal vascular beds

30. Dopamine

Moderate doses DA:
 Stimulate DA receptors in mesenteric and
renal vascular beds → vasodilation
 Stimulate β receptors in heart → ↑HR and
1
↑force of contraction

High doses DA:
 Stimulate α
1
receptors → vasoconstriction

31. Therapeutic uses

Shock (moderate doses)
 ↑ blood flow to kidney and mesentery
 ↑ cardiac output

Refractory congestive heart failure
 Moderate doses ↑ cardiac output without
↑PVR

32. Synthetic Catecholamines: Isoproterenol

Very powerfully
stimulates β1- and β2adrenergic receptors

β1 SA nodal cells→↑HR
β1 AV nodal cells→↑
conduction velocity
No significant effect
at α1-adrenergic
receptors
β1 Ventricular muscle
cells→ ↑ force of
contraction

33. Synthetic Catecholamines: Isoproterenol

Very powerful β-adrenergic receptor agonist; no effect
at α-adrenergic receptors
α1
α1 stimulation
β2
β2 stimulation

34. Isoproterenol
↓arterial BP = ↑CO x ↓↓PVR
Decreased arterial blood pressure triggers
autonomic reflex arc

35. Autonomic reflex arc: baroreceptor reflex

36. Cardiovascular
control center in
medulla
Carotid and
↓BP
aortic
Carotid and
baroreceptors
aortic
↓BP
baroreceptors
Isoproterenol
↑ Sympathetic
outflow→↑NEpi
β1 ↑↑HR
↓ Parasympathetic
outflow→↓ACh
Reflex tachycardia
↑↑SV
+ dromotropic effect

37. Effects of isoproterenol on airways

Powerfully stimulates
β2-adrenergic
receptors on airway
smooth muscle→
rapid, powerful
relaxation→
bronchodilation

38. Therapeutic uses: isoproterenol


Bronchodilator
Complete AV block (3rd degree heart block)

39. Synthetic Catecholamines:
Dobutamine



It’s a derivative of DA but not a D1 or D2
receptor agonist
Stimulates β1- and β2-adrenergic receptors, but at
therapeutic doses, β1-effects predominate
Increases force of contraction more than
increases heart rate
↑CO = ↑HR x ↑ ↑ SV

40. Dobutamine: Therapeutic uses




Shock
MI
Cardiac surgery
Refractory congestive heart failure

41. Major toxic effects of catecholamines

All are potentially arrhythmogenic




Epi and isoproterenol more arrhythmogenic than
dopamine and dobutamine
Some can cause hypertension
Epinephrine, in particular, can cause CNS
effects – fear, anxiety, restlessness
Dobutamine can cause vomiting and seizures in
cats – must be used at very low doses

42. Adverse effects

CNS:
 Restlessness
 Palpitation
 Anxiety, tremors

CVS:
 Increase BP….cerebral haemmorrhage
 Ventricular tachycardia, fibrillation
 May precipitate angina or AMI

43. Non-catecholamine direct-acting
adrenergic agonists
Ephedrine
Stimulates α1-, β1 and β2-adrenergic receptors
and ↑ NE release from noradrenergic fibers
 Repeated injections produce tachyphylaxis
 It is resistant MAO, orally
 Longer acting (4-6), cross BBB


44.  Marketed as dietary supplement promoted to
aid weight loss, ↑ sports performance and ↑
energy. Ingredient in OTC nasal
decongestants and bronchodilators
Uses : Mild chronic Bronchial asthma,
hypotension during spinal anaesthesia
,occasionally for postural hypotension
 Sale prohibited by FDA in 2004 due to
risks of life-threatening cardiac
arrhythmias, stroke and death

45. Non-catecholamine direct-acting adrenergic
agonists: Phenylpropanolamine (PPA)




Actions much like ephedrine in the PNS
In veterinary medicine, used to treat urinary
incontinence in dogs
Available in OTC products for treatment of
nasal decongestion and as appetite suppressant
FDA has requested all companies
discontinue marketing products containing
PPA due to risk of hemorrhagic stroke

46. α1 –adrenergic
receptor
agonistcontraction
urethral smooth
muscle
β2 –adrenergic
receptor agonist
–relaxation
detrusor muscle

47. β2-selective adrenergic agonists
β2-adrenergic
receptors on bronchial
smooth muscle
Preferential affinity for β2adrenergic receptors, but at
sufficiently high doses, can
stimulate β1
terbutaline , albuterol
inhalation aerosol
Relax bronchial smooth
muscle→bronchodilation
Treatment of asthma,
chronic bronchitis

48. β2-selective adrenergic agonists

Due to selectivity for β2 receptors at
recommended doses, little-to-no direct
stimulation of β1 receptors in heart

Inhalant administration maximizes local effect
and minimizes systemic effects

49. Mephenteramine

It is mixed sympathomimetic

COP, BP, heart rate are increased

Active orally with longer DOA (2-6 hrs),can crosses BBB
Uses:


To treat hypotension due to spinal anesthesia and surgical
procedures
Shock in MI and other hypotensive states

51. USES
Vascular
Hypotensive states
 Shock: hemorrhagic/ hypovolemic, spinal,
neurogenic, cardiogenic, anaphylactic shock.
 Postural hypotension- in parkinsonism, diabetes
mallitus
 Along with local anaesthetics
 To control local bleeding
 Nasal decongestants
 Peripheral vascular diseases
Cardiac
 Cardiac arrest
 Partial AV block
 Congestive heart failure


52. Bronchial asthma
 Acute severe bronchial asthma
Allergic disorders
 Urticaria, angiodema, anaphylaxis
Mydriatics
 Fundus examination
 Wide angle glaucoma
CNS uses
 ADHD
 Narcolepsy
 Epilepsy
 Parkinsonism
 Obesity
Uterine relaxant

53. Adrenergic Agonists

Indirect:
Cause NE release only
 Example:

 Amphetamine
CNS stimulant
 Increases BP by alpha
effect on vasculature,
beta effect on heart
