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
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
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
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
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
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
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
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
50.
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
53. Adrenergic Agonists
Indirect:
Cause NE release only
Example:
Amphetamine
CNS stimulant
Increases BP by alpha
effect on vasculature,
beta effect on heart