Drugs affecting adrenergic synapses

or norepinephrine (NE). The biosynthesis of NE from tyrosine occurs

in the adrenergic neurons (varicosities).
Formation of DOPA and dopamine takes place in the cytoplasm of neurons. Dopamine is converted to norepinephrine under the influence of dopamine hydroxylase in the vesicles.
Norepinephrine in the adrenal medulla turns into adrenaline under the influence of methyltransferase

endings noradrenaline is in a free state (mobile pool) and

in vesicles.
Inactivation of NE via monoamine oxidase (MAO) may regulate prejunctional levels of transmitter in the mobile pool.
Nerve impulses induce the release of NE into the synaptic gap. And NE interacts with its receptors.

mainly caused by the swift uptake (70-80%) by the terminals

of the anrenergic fibres. Small amounts of NE undergo extraneuronal uptake by the effector cells (smooth muscles).
Catabolism of NE is controlled by MAO and catechol O-methyltransferase.
Adrenoreceptors are divided into α- and β-subtypes.

localization and α2R are located presynaptically and beyond the synapses.

The main role of the presynaptic α2R is their involvement in the system of negative feedback, controlling the release of NE.
Stimulation of these receptors by NE or other drugs inhibits release of NE from the varicosities.

Presynaptic β2-R perform positive reverse feedback, stimulating NE release. So,

it can be confirmed that β-agonists facilitate the release of the NE and β-antagonists inhibit it.

adrenoreceptors
α1 - adrenoreceptors:
Constriction of vessels of the skin, kidneys, intestines;
Contraction

of the radial muscle of iris (mydriasis);
Contraction of myometrium;
Contraction of sphincters of the gastrointestinal tract;
Contraction in the capsule of the spleen;
Decrease of motility and tone of the intestine.

coronary;
Decrease in muscle tone of the bronchi;
Decrease in intestinal motility

and tone;
Decrease in the tone of myometrium;
Activation of glycogenolysis and lipolysis;
Increase in insulin secretion.

or sympathomimetics or adrenomimetics of indirect action: Ephedrine

Xylometazoline, Oxymetazoline;
β1, 2: Isoprenaline;
β1: Dobutamine;
Β2: Salbutamol, Salmeterol, Fenoterol,
Berodual (ipratropium bromide

+fenoterol).

and rate of cardiac contractions, increases the stroke and minute

volume of the heart, systolic blood pressure. The consumption of oxygen by myocardium is increased also. Hypertensive reaction usually induces reflex bradycardia from the mechanoreceptors of the blood vessels.
E. increases peripheral resistance of the blood vessels because it stimulates α AR, but dilates vessels via stimulation βAR.

the secretion of the bronchial glands, reduces the release of

inflammatory mediators (histamine) from mast cells.
E. reduces the tone and motility of gastrointestinal tract, but increases the tone of sphincters.
E. induces the contraction of the splenic capsule.
E. increases neuromuscular transmission.

and potassium increases) and
lipolysis (concentration of free fatty acids

increases).

of the radial muscles of the iris and decreases intraocular

pressure (production of the intraocular fluid is decreased).
Epinephrine causes spasm of blood vessels of the skin and mucous membranes, reduces exudation and inflammation.

up to 30 minutes.
Indications for use:
to prolong the effect

and reduce the toxicity of local anesthetics;
anaphylactic shock, allergic laryngeal edema;
relief of bronchospasm;
insulin overdose, hypoglycemia;
cardiac arrest, acute heart failure, hypotension.

β-AR.
It causes severe vasospasm and increases blood pressure (5-10

times stronger than epinephrine). Norepinephrine increases force of heart contractions, stroke volume of the heart, causes a reflex bradycardia (activation of the vagus nerve).
Norepinephrine is administered intravenously with vascular collapse during surgery, intoxication, injuries.

of necrosis.
It is contraindicated in hemorrhagic and cardiogenic shock

because it causes spasm of arterioles and increases the load on the heart.
Side effects: arrhythmias, headache, breathing disorders.

pressure and causes reflex bradycardia. But it does not affect

the heart.
It is more stable (duration of action after intravenous administration – 20 min; after subcutaneous – 40-50 min). It is effective after oral administration.

collapse,
to potentiate the action and reduce the toxicity of

local anesthetics,
open-angle glaucoma, conjunctivitis, rhinitis,
hemorrhoids (in suppositories).

mucosa, reduce inflammatory response, exudation.
They are used in rhinitis.

Side effects: irritant effect, atrophy of the nasal mucosa, tolerance.
Naphazoline has an inhibitory effect on the CNS.

the heart and increases the force and rate of cardiac

contractions; systolic pressure.
Isoprenaline activates β2-AR of the skeletal muscles vessels. This leads to a decrease in diastolic pressure. The mean arterial pressure is also decreased.

causes hyperglycaemia.
Indications for use: bronchial spasm, atrioventricular block.
Routes of

administration: sublingual, inhalation, intravenous, SC.
Adverse affects: tachycardia, cardiac arrhythmias, headache, tremor.

are used for the prevention and relief of bronchospasm.
They cause

relaxation of the uterus, prevent premature labor. They are used in threatened preterm labor.
They cause hyperglycemia, vasodilation, low blood pressure.

minute volume of the heart.
It improves atrioventricular conduction, increases myocardial

oxygen consumption.
It is used intravenously drip in acute heart failure.

Facilitates and increases the release of the mediator in the

synaptic gap
Increases the effect of sympathetic nerves on the organs

Ephedrine

broncholytic effect, inhibits intestinal peristalsis, dilates pupils.
It acts longer

and weaker than epinephrine.
It is absorbed from the gastrointestinal tract and penetrates through the BBB, resistant to MAO action.
Indication for the use: spasm of bronchi, to increase arterial pressure, atrioventricular block, rhinitis, narcolepsy.

in the varicosities),
tachycardia, increased blood pressure, hyperglycemia,
mental dependence

(causes euphoria), excitation, insomnia, tremor, doping effect.

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