2. Overview
The study of the sympathetic nervous system is
important from a clinical perspective. The SNS is
involved in controlling heart rate, contractility, blood
pressure, vasomotor tone, carbohydrate and fatty
acid metabolism etc. Stimulation of the SNS occurs in
response to physical activity, psychological stress,
allergies etc. Drugs influencing the SNS are used in
treatment of hypertension, shock, cardiac failure and
arrhythmias, asthma and emphysema, allergies and
anaphylaxis.
3. Sites of Drug Action – Modulation of
Neurotransmission
↓1
2. intake of
precursor
3. synthesis
4. storage
5. metabolism
7. reuptake 6. release 8. degradation
9. receptor
5. Sympathomimetics:
Drugs that mimic or facilitate the actions of the
sympatho-adrenal system.
a) Direct acting:
– Drugs that can act directly or specific adrenergic receptors
– Mimic the effects of NE and Epi
b) Indirect acting:
– Drugs that do not activate the adrenergic receptor directly
i. Facilitate release of NE
ii. Block neuronal uptake of NE
iii. Block metabolism of NE
9. Direct Acting Sympathomimetics:
Ahlquist designated the receptors as α or β based
on observations that catecholamines act on 2
principal receptors:
α1:
Epi ≥ NE >> INE
α2:
β1: INE > Epi = NE
β2: INE > Epi >> NE
14. adverse reactions
1.local ischemia and necrosis
2.acute renal failure
contraindications
HT
In pregnant females, NE should not be
used because it stimulates alpha 1
receptors in the uterus that cause
contraction
15.
16. Effect of NE to intact CVS
Mean arterial pressure
(MAP) = DBP + 1/3 of
(SBP-DBP)
α 1 ,α 2 ,β 1
17. metaraminol (aramine )
Mechanisms: 1.direct actions 2.indirect actions
Characteristics:
1.action is weaker and longer than NA
2.little adverse reactions: renal failure,
arrhythmias
3.stable, im.
4.tachyphylaxis
Uses: substitute for NA in treatment of shock
22. Epinephrine Reversal
(m m H g )
200
180
M e a n Arte ri a l Pre s s u re
160
phenoxybenzamine] 140
120 Epi PBZ
Epi
100
80
0 1 2 3 4 5 6 7 8 9 10
Tim e (re lative )
23. 5.BP
Low doses: β-adrenergic effects predominate
↑ HR, vasodilation of vascular smooth muscle
in skeletal muscle, other smooth muscle
effects
High doses: α-adrenergic effects predominate
Vasoconstriction of blood vessels in skin and
peritoneal cavity
↑ BP and reflex slowing of the heart
(baroreceptor reflex)
24. clinical uses
1. Relief of bronchospasm
2. Relief of hypersensitivity reactions and
anaphylaxis
3. To prolong the duration of action of local
anesthetics.
4. As a topical hemostatic to control superficial
bleeding from skin and mucosae
5. To restore cardiac rhythm in patients with
cardiac arrest.
25. Adverse effects:
Extensions of their effects in the CVS and the
CNS
Anxiety, tenseness, headache and paranoia
tachycardia, dysrhythmias
Large dose IV – cerebral hemorrhage,
pulmonary edema
Route of administration:
Inhalation
Injection (IM, SC, IV), not PO
Topical application
Rapidly degraded
27. Adrenergic Drugs cont’d:
Ephedrine
Acts directly and indirectly
Acts on α and β receptors and causes release of NE
Less potent and longer acting than epinephrine
Available OTC
Orally administered
Clinical use
Bronchodilation
Nasal decongestant
28. α, β,DA-R agonists
dopamine (DA)
Pharmacokinetics:
ivd, MAO/COMT; short t1/2, not across BBB
pharmacological actions
activate DA, α, β1-R
31. Effect of DA to intact CVS
DA1, Beta1
Moderate Dose
32. clinical uses
1.shock
2.chronic heart failure(CHF)
3.acute renal failure(ARF)
toxicity
high doses of DA is similar to that noted above
for NE. Since the drug has an extremely short
half life in plasma, DA toxicity usually disappear
quickly if the administration is terminated.
36. dobutamine
1.selective β1-R agonist
2.inotropic effect>chronotropic effect in
therapeutic dose
3.short-term treatment for CO↓
following cardiac surgery or CHF
caused by AMI
4.tachyphylaxis
37. Clinical Use of Adrenergic Agonists:
α – agonists:
Anaphylactic shock
Hypotension
Nasal congestion
Hemorrhage
Co-administration with local anesthetics
β – agonists:
Congestive heart failure – short term
Asthma – bronchial dilation
Tocolytic – stopping premature labour
39. Epinephrine Reversal
(m m H g )
200
180
M e a n Arte ri a l Pre s s u re
160
phenoxybenzamine] 140
120 Epi PBZ
Epi
100
80
0 1 2 3 4 5 6 7 8 9 10
Tim e (re lative )
40. phentolamine (regitine)
pharmacological actions
1.vessels : vessels dilate; BP ↓
“adrenaline reversal ”
2.heart: excited, CO ↑ HR ↑
a. vessel relaxation>BP ↓, baroreflex (+)
b. alpha2 blockade , NE release↑
3.other effects: cholinergic action
histamine-like action
41. Clinical uses
1.peripheral vasospasmatic disorders
2.local vasoconstrictor excess (eg, NA)
3.diagnosis and treatment of
pheochromocytoma
4.shock
5.CHF and AMI
6.others: male sexual dysfunction
43. tolazoline
The action of blocking α1-R is more
weakly than regitine.
While cholinergic action and histamine-
like action are stronger than regitine.
44. phenoxybenzamine
Pharmacokinetics: only iv, high liposolubility
pharmacological actions:
similar to phentolamine, but slow, strong and
long. it also can block the receptors of 5-HT
and HA.
45. Prazosin
the prototype of a family of potent and very selective
alpha 1 receptor antagonists. It has 1000X greater
affinity for alpha 1 vs alpha 2 receptors.
It blocks all alpha one receptor subtypes
equipotently. It is a short acting drug with a duration
of action of about 7 to 10 hours. Prazosin causes a
decrease in total peripheral resistance, but not an
increase in heart rate (since alpha 2 receptors are not
inhibited).
