1. The document discusses drugs that affect adrenergic synapses, specifically adrenopositive medications that facilitate nerve impulse transmission. 2. It describes different types of adrenergic receptors (α and β receptors) and their locations. Common adrenopositive medications like epinephrine, phenylephrine, isoprenaline are discussed along with their mechanisms and indications. 3. Side effects of these drugs include tachycardia, arrhythmias and increased oxygen demand of the heart. The document provides a detailed overview of adrenopositive medications and their effects on different adrenergic receptor subtypes.

1. DRUGS AFFECTING ADRENERGIC SYNAPSES:
ADRENOPOSITIVE MEDICATIONS

2. In the adrenergic synapses the transmission is
mediated by norepinephrine (NE).
The biosynthesis of NE from tyrosine occurs in the
adrenergic neurons with a number of enzymes being in-
volved.
Nerve impulses induce the release of NE into the
synaptic gap, followed by its interaction with the
adrenoceptors (ас) of the postsynaptic membrane.
Adrenoceptor is the biochemical system, sensitive to
NE.

3. Adrenoceptors (Ac) are divided into α- and β-ac.
α- ac are divided into α1- and α2 -ac.
β- ac are divided into β1-, β2 -and β3-ac.
α1- ac have postsynaptic localization and are located in the
vessels of the skin, mucous membranes, kidneys,
intestine and magistral vessels, sphincters and muscles of
the GIT and in splenic trabecules, in the iris radial muscle,
uterus, bladder, CNS.

4. α2 -ac are located presynaptically and beyond the
synapses. The physiologic role of the presynaptic a2-ac is
their involvement in the system of negative feedback,
controlling the release of NE. Stimulation of these
receptors by NE (or other drugs with a2-adrenomimetic
activity) inhibits NE release from the presynaptic
membrane in the synaptic gap, and vice versa block of
these receptors increases NE release from the
presynaptic membrane in the synaptic gap.

5. Among postsynaptic β-ac the
β1-ac are located in the heart,
β2-ac are located in the vessels of the heart, brain, liver,
lungs, skeletal muscles, and also in the bronchi, uterus,
muscles of the GIT,
β3-ac are located in the fatty tissue.
There are also presynaptic β-ac (β2-ac). They perform
positive reverse feedback, stimulating NE release.

6. Stimulation of α-ac leads to an increase in the
effectors function (except for the intestines, where
muscular tone subsides).
Stimulation of β-ac usually leads to a decrease in the
innervated organ function. However, stimulation of β-ac
of the heart is associated with an increase in the force and
rate of cardiac contractions, increases in automatism and
facilitation of atrioventricular conduction. Ac participate in
the control of carbohydrate and fat metabolism.

7. The action of NE on ac is short-term. It is mainly caused
by the swift uptake, up to 75—80%, of mediator present in
the synaptic gap by the terminals of the adrenergic fibres,
followed by its storage.
Catabolism of free NE is controlled by MAO and catechol
O-methyl- transferase enzyme.

8. Drugs that stimulate ac are called adrenomimetics (am),
while drugs that inhibit them are called adrenoblockers (ab).
Adrenopositive medications are drugs, which facilitate nerve
impulse pass in the synapse (am).
Classification of the adrenopositive medications
1. Adrenomimetics, stimulating α- and ß -ac
(α- and ß –adrenomimetics)
a) α,β-am of the direct action:
Epinephrine (Adrenalini hydrochloridum)
Norepinephrine

9. b) α,β-am of indirect action:
Tyramine
Ephedrine
2. Adrenomimetics, stimulating mostly α-ac
(α- adrenomimetics)
a) α1- am:
Phenylephrine (mezatonum)
b) α2- am:
Naphazoline (naphthizinum)
Xylometazoline (halazolinum)

10. 3. Adrenomimetics, stimulating mostly β-ac
(β- adrenomimetics)
a) β1- am:
Dobutamine
b) β2- am:
Salbutamol
Fenoterol
Terbutaline
c) β1, β2- am
Isoprenaline (Isadrine)

11. α- and ß –am
Epinephrine (adrenalini hydrochloridum) has a direct
stimulating effect on α- and ß –ac.
ß-ac more sensitive to epinephrine than α- ac.
ß–adrenomimetics effects of epinephrine are
1. Stimulation of the heart. By stimulating the β-ac of the
heart, epinephrine increases the force and rate of cardiac
contractions and this in turn causes the stroke and minute
volume of the heart to increase. Atrioventricular conduction
is improved. At the same time the consumption of oxygen
by myocardium is increased.

12. 2. Dilatation of the coronary, cerebral, hepatic,
pulmonary vessels and skeletal muscles vessels, which
is associated with the stimulation of β2-ac of these vessels.
It is manifested by a decrease of the diastolic pressure.
3. Bronchodilator effect. By stimulating β2-ac of the
bronchi, it relaxes their smooth muscles and eliminates
bronchospasm.
4. The tone of the uterus is reduced (because of the
stimulation of β2-ac)
5. The tone and motility of the GIT is reduced

13. 6. Stimulation of the metabolism. It stimulates
glycogenolysis (hyperglycaemia occurs) and lipolysis
(increase of blood plasma concentration of free fatty acids).
α–adrenomimetics effects of epinephrine are
1. Pupils dilatation. Epinephrine dilates the pupils (due to
the α–ac stimulation of the radial muscle of the iris and its
contraction), and decreases intraocular pressure
(production of the intraocular fluid is decreased).
2.Arterial pressure increases due to the α–ac stimulation
of the magistral vessels, vessels of the kidneys and others.
Hypertensiv reaction usually induces reflex bradycardia
from the mechanoceptors of the blood vessels.

14. 3. Contraction of the splenic capsule
4. Uterus tone increases
5. Sphincter tone increases, but the tone and motility of
the GIT reduce
Indications for use
1) It is effective as a bronchial spasmolytic for the
treatment of acute bronchial asthma attacks.
2) It is used for hypoglycaemic coma, caused by
antidiabetic drugs.
3) Epinephrine can be used to eliminate atrioventricular
block. In these cases it is used subcutaneously

15. 4. Epinephrine is added to lokal anesthetic solutions.
Vasoconstriction at the site of epinephrine injection intensifies
local anesthesia and reduces resorptive and, possibly, the
toxic effect of anesthetics.
5. It is used in ophthalmology to dilate the pupil and in the
open-angle glaucoma.
6. Epinephrine is administered for anaphylactic shock
(intramuscularly or intravenously).

16. Side effects
1. Tachycardia
2. Cardiac rhythm disorders
3. Consumption of oxygen by myocardium is increased
and may be a pain in the heart.

17. Ephedrine is indirect α,β-am. Ephedrine increases NE
concentration in synaptic gap due to the intensification of its
release from nervous fibers.
Ephedrine effects are the same as that Epinephrine.
α- am stimulate α–ac of the blood vessels and
increase their tone.
Phenylephrine (mezatonum) stimulates α1–ac of the
blood vessels and increases arterial pressure. Hypertensiv
reaction induces reflex bradycardia from the mechanoceptors
of the blood vessels (due to nerve vagus).
Mezatonum dilates the pupils (due to the α1–ac
stimulation of the radial muscle of the iris and its contraction)

18. Indications for use
Phenylephrine is used
 as a pressor drug at the acute vascular weakness (failure)
(intravenously dropwise),
 to enhance the effect of local anesthetics,
 for the treatment of open-angle glaucoma
Naphthizinum and Xylometazoline (α2- am) have
vasoconstrictive effect.
They are used locally in acute rhinitis.

19. Isoprenaline (isadrine) stimulates ß1-, ß2- ac.
By stimulating ß1-ac of the heart, isadrine increases the force
and rate of cardiac contractions. At the same time systolic
pressure increases. Isadrine facilitates atrioventricular
conduction and increases heart automatism.
Moreover, the drug also activate ß2-ac of the vessels
(especially the skeletal muscle vessels). This leads to a
decrease in diastolic pressure.
It effectively decreases the tone of the bronchi, muscles of the
GIT, as well as other smooth muscles, that have ß2-ac.

20. Indications for use
Isadrine is used
 to relieve bronchial spasm,
 for the treatment of atrioventricular block (sublingual
administration).
Adverse effects include
tachycardia,
cardiac arrhythmias,
headache

21. β2- am (Salbutamol, Fenoterol and etc.) selectively stimulate
β2- ac of the effector organs.
They are used as broncholytic drugs, as well as to reduce
contractile activity of the myometrium.
Dobutamine is β1- am. Its main effect is a marked positive
inotropic action. It is administered as a cardiotonic drug.