Transcript Adrenoblockers - TMA Department Sites

“Adrenoblockers.
Simpatholitics "
Plan of lecture
1. Overview of the blockers,
2. Classification blockers.
3. Indications for use, side effects of blockers.
4. Pharmacodynamics, pharmacokinetics simpatholitics.
5. Application of the side effects simpatholitics
The aim of the lecture:
Generate knowledge about blockers and
sympatholytic.
Pedagogical objectives:
- Tell localization adrenergic structures;
- To introduce the general idea of the blockers and sympatholytic;
- Explain the indications for use of blockers and sympatholytic;
- Tell classification blockers;
- To reveal features of pharmacodynamics, pharmacokinetics and
simpatolitikov blockers.
- To talk about the use of blockers and sympatholytic in pediatrics
Drugs blocking adrenergic receptors
adrenoceptor blocking agents
Blocking α-adrenergic receptors
Tropafen (α1, α2) Phentolamine (α1, α2)
Dihydroergotoxin (α1, α2) Prazosin (α1)
Blocking the β-adrenergic receptors
Inderal (β1, β2) metoprolol, atenolol, talinolol (β1)
Blocking α- and β-adrenergic receptors
Labetalol (β1, β2, α1)
Means blocking adrenergic receptors (blockers)
Adrenergic blockers blocking, inhibiting action to them mediator
(norepinephrine), and adrenomimetic substances. The synthesis of
norepinephrine blockers do not affect.
Means blocking the α-adrenergic receptors
(α-blockers)
The presence of α-adrenoceptor blocking agents effect is easily detected
by their ability to reduce the pressor effect of epinephrine or "pervert"
him. Last seen in the fact that on the background of α-blockers
adrenaline does not increase blood pressure, and reduces it. This is due to
the fact that against the background of a block-adrenoceptor stimulating
effect is the effect of adrenaline on the β-adrenergic receptors vessels,
accompanied by their extension (reduced smooth muscle tone). Synthetic
drugs that block α1- and α2-adrenergic receptors, and phentolamine are
thropaphen.
Phentolamine (regitin) is a derivative of imidazoline.
Character-ized by severe, but short-lived α-adrenoceptor
blocking action (10-15 min after intravenous injection).
Furthermore, tachycardia (partly due to block presynaptic
α2-adrenoceptor), increases the motility of the
gastrointestinal tract, increased secretion of gastric glands
and miotropnoe exerts vasodilating action. Lowers blood
pressure phentolamine, due to its α-adrenergic blocking
miotropnym and antispasmodic action.
Phentolamine (regitin) is a derivative of imidazoline.
Character-ized by severe, but short-lived αadrenoceptor blocking action (10-15 min after
intravenous injection). Furthermore, tachycardia
(partly due to block presynaptic α2-adrenoceptor),
increases the motility of the gastrointestinal tract,
increased secretion of gastric glands and miotropnoe
exerts vasodilating action. Lowers blood pressure
phentolamine, due to its α-adrenergic blocking
miotropnym and antispasmodic action.
For a semi-synthetic drugs include di-ergot alkaloids dihydroergotoxin and dihydroergotamine.
Dihydrogenated ergot alkaloids are characterized by a more
pronounced natural α-adrenoceptor blocking effect, no
stimulating effect on the myometrium (pregnant uterus) less
vasoconstrictor activity and lower toxicity.
In medical practice, drugs that block the α1 and α2-adrenergic
receptors, use relatively rare. The most important effect of αblockers is to expand the peripheral vessels. Since it involves
the use of these drugs for various violations of the periperiph- eral circulation (endarteritis, Raynaud's disease, and
others.), Including the shock (hemorrhagic, cardiogenic), in
which the spasm of the arterioles - a fairly typical
phenomenon. Logical assignment α-blockers in
pheochromocytoma. Sometimes α-blockers are used in
hypertensive crises.
Considered drugs block as post-and presynaptic α-adrenergic receptors
(α1- and α2-). Keep in mind that block the presynaptic α2-adrenoceptor
violates physiological autoregulation products neurotransmitter
norepinephrine. As a result of violation of a negative feedback occurs
excessive release of norepinephrine, the recovery of the adrenergic
transmission. The latter explains the lack of resistance block postsynaptic
α1-adrenoceptor antagonists using indiscriminate effects (blockers α1- and
α2- adrenoreceptors). Marked tachycardia is also a result of increased
release of norepinephrine. From this point of view to practical medicine
more interesting blockers that block predominantly postsynaptic α1adrenergic receptors. Thanks functioning presynaptic α2-adrenoceptor
retained a negative feedback mechanism and, therefore, increased
noradrenaline release does not occur. Thus, the block of postsynaptic α1adrenoceptor sta¬novitsya more stable. Furthermore, there is no marked
tachycardia.
The drugs have an advantageous effect on the postsynaptic α1adrenergic receptors, is prazosin (pratsiol, minipress). By blocking
the activity of phentolamine exceed about 10 times. The main effect
of prazosin - lowering blood pressure. This effect is due to
decreased arterial tone and to a lesser extent of venous vessels,
venous return and decrease in heart function. Heart rate changes
little (may be a slight tachycardia). There are data on the inhibitory
effect of prazosin on phosphodiesterase.
The drug is effective when administered orally. Its action comes in
30-60 minutes and lasts for 6-8 hours.
Prazosin is used as an antihypertensive agent. Assign it usually on
the inside (possibly parenteral administration).
Means blocking the β-adrenergic receptors (β-blockers)
The most widely used β-blocker is a n a n Reelin (propranolol
hydrochloride, Inderal, obzidan, stobetin). It blocks β1 and β2-adrenergic
receptors (heart and blood vessels, bronchi, gastrointestinal tract, etc.).
Blocking β1-adrenergic receptors of the heart, propranolol causes
bradycardia and reduces the force of heart contractions, in connection with
which cardiac output is reduced. Depresses atrioventricular conduction
reduces automaticity.
Blood pressure is reduced upon administration of propranolol, particularly
during chronic administration. This is due to some extent to the decrease
in cardiac output. Total peripheral resistance generally tends first to
increase and then decrease. Against the background of the introduction of
propranolol pressor effect of adrenaline becomes similar to that of
norepinephrine, because it eliminates the final phase (lowering blood
pressure) associated with β2-adrenergic stimulation vessels. The
hypotensive effect of propranolol is also due to a decrease in production of
renin.
Inderal increases the tone of the bronchi and may provoke bronchospasm (the
result of β2-adrenergic receptors block the bronchi). An antagonist in relation to
its adrenalin hyperglycemic and lipolytic action.
Inderal is used in the treatment of angina pectoris (β1-adrenoceptor block leads to
a reduction of the heart, which reduces its oxygen demand), hypertension
(duration of treatment is accompanied by a gradual and sustained reduction in
blood pressure). Inderal is shown at supraventricular, such as atrial fibrillation (as
a result of the oppression of β1-adrenoceptor Inderal reduces the automatism and
increases the duration of the excitation from the atria to the ventricles). Inderal is
used to eliminate tachycardias different etiology (in mitral stenosis,
thyrotoxicosis), and arrhythmias induced by agonists or digitalis glycosides.
Using Inderal and glaucoma.
Possible side effects: heart failure, heart
unit, increased tone of peripheral vessels, bronchospasm. With PICs-vanced
prescribed Inderal diabetics, because it prolongs the drug hypoglycemia.
By blockers β1 and β2-adrenergic receptors is also oxprenolol (trazikor, koretal)
and a number of other drugs. Synthesized compounds blocking β1-adrenergic
receptors primarily heart. One of them - metoprolol (betalok, seloken). Β2adrenergic receptors on the bronchi, vessels had little effect. These drugs are
usually referred to as cardioselective (β1) blockers.
Metoprolol absorbed from the intestine well, but when passing through the liver, a
significant part of it is destroyed. The maximum effect is approximately 1½ hours
and lasts about 5-6 hours. Provided kidneys mainly as metabolites.
Metoprolol is used orally for hypertension. The side effects observed headache,
fatigue, sleep disturbance. In bronchial asthma may slightly increase the tone of the
bronchi.
Means blocking the α- and β-adrenergic receptors (α, β-blockers)
Drugs that block both types of adrenergic receptors is labetalol (trandat). He
also inhibits the neuronal uptake of noradrenaline reverse. β-Adrenoceptors
labetalol more sensitive than the α-adrenergic receptors. On ability to block βadrenergic receptors inferior anaprilinu and oppression by α-adrenergic
receptors - phentolamine. Reduces the total peripheral vascular resistance.
Labetalol is well absorbed when given enterally. Much of it is destroyed by the
first passage through the liver. Valid for 8- 10 hours. Provided kidneys (mainly
as metabolites). Labetalol is used as an antihypertensive agent.
TOOLS presynaptic active agent, inhibits the transfer of excitation to
adrenergic neurons (sympatholytic)
Simpatolitiki violate the transfer of excitation at the level of varicose nodules
adrenergic fibers, t. E. Pre-synaptic function. Adrenoretseptory not affect.
Against the background of these substances agonists direct effect not only
reduced, but even increased. Thus, sympatholytic and blockers have a
blocking effect on the different stages of the adrenergic nerve impulse
transmission.
By Simpatolitiki are oktadin, reserpine, ornid et al. Acting on varicose
thickening of adrenergic nerve fibers, these substances reduce the amount
of the neurotransmitter norepinephrine, released on nerve impulses.
Indirect action agonists (tyramine, ephedrine, amphetamine) in their
background are weaker than normal. Keep in mind that the mechanism of
action of different simpatolitikov varies. Among active simpatolitikov refers
guanidine derivatives - oktadin (guanethidine sulfate, ismelin, izobarin,
sanotenzin, abapressin). Its ability to inhibit the transmission of excitation
from adrenergic nerves in the effector for the following reasons.
Initially, when the content of norepinephrine in the varicose bulges are
not reduced, this can be attributed to the blocking effect of the drug on
presynaptic membrane and disrupting the release of neurotransmitter.
Gradually, under the influence of oktadin noradrenaline in varicose
thickening decreases. Attribute this to the fact that oktadin prevents
norepinephrine reuptake varicose bulges, as he undergoes oktadin
neuronal uptake due to the same transport systems, and norepinephrine.
In intraneyronalnyh depot oktadin also replaces norepinephrine. There
are also a depressing effect on the membrane vesicles oktadin and
violation of the deposit process norepinephrine. All this leads to the fact
that the located free in the cytoplasm norepinephrine largely inactivated
by monoamine oxidase (intraneyronalno) and partially released from
varicose thickenings unchanged.
As a result, on the background of accumulation in varicose thickening oktadin
content of norepinephrine significantly reduced. Therefore, in response to the
number of nerve impulses released neurotransmitter into the synaptic cleft
decreases, resulting in a reduction reaction of the effector. Noted umenshe¬nie
content of norepinephrine in the heart, blood vessels and other organs.
Oktadin little effect on the level of catecholamines in the central nervous system
(does not penetrate the blood-brain barrier) and the adrenal medulla.
The main effect is gradually developing oktadin (for several days) sustained
reduction in blood pressure. This is due to a decrease in cardiac output, the
occurrence of bradycardia, inhibition of pressor reflexes. With prolonged use
may decrease oktadin and total peripheral vascular resistance. Oktadin also
provides short-term ganglion-blocking action and a stimulating effect on β2adrenergic receptors vessels.
Hypotension can be preceded by a short (a few minutes to 1 hour or more)
increase in blood pressure caused by the release of norepinephrine from
adrenergic endings, which leads to an increase in cardiac output and
vasoconstriction. Oktadin affects the eyes. It appears a small contraction
of the pupil and the reduction of intraocular pressure. The latter is
obviously the result of improvement of outflow from the anterior chamber
of the eye and reduce production of intraocular fluid.
In connection with the blocking effect on adrenergic innervation oktadin
motility of the gastrointestinal tract increases. With the introduction of
oktadin been a slight depression of neuromuscular transmission.
Enter the oktadin inside. Thus 50% of absorbed substance. Through the
blood-brain barrier drug penetrates poorly. Biotrans-formation occurs in
the liver substance. Unchanged oktadin and its metabolites are excreted
primarily by the kidneys.
Expressed sympatholytic properties has rezerpin- alkaloid plants of the genus
Rauwolfia (Rauwolfia serpentina Benth. Et al.). Chemically an indole derivative.
Reserpine disrupts the deposit of norepinephrine in the vesicles, which leads to a
decrease in the content of norepinephrine in the varicose bulges. The main part of
accumulated within the cytoplasm of varicose thickenings free norepinephrine
deaminated as reserpine (as well as oktadin) does not inhibit monoamine oxidase.
A small portion of norepinephrine released from the endings unchanged. In reverse
the neuronal uptake of noradrenaline reserpine apparently not affected. Reserpine
reduces the amount of norepinephrine in the heart, blood vessels, adrenal medulla
and other organs. Reduced levels of catecholamines (and serotonin) also observed
in the central nervous system. As a result, the central nervous system reserpine has
a depressing effect. Reserpine has a calming (sedative) and weak antipsychotic
action, in connection with which it also refers to a group of neuroleptics. Promotes
sleep. Suppresses interoceptive reflexes. Enhances the effect of sleeping pills and
anesthetic drugs. Several depresses respiration, body temperature lowers.
As neuroleptic reserpine now rarely used. The greatest practical
importance is the hypotensive effect due to its peripheral (sympatholytic)
effects.
Arterial blood pressure when administered reserpine gradually decreases
(the maximum effect is observed in a few days). Hypotension during
chronic administration of reserpine associated with decreased cardiac
output and a decrease in total peripheral resistance and inhibition of the
pressor reflex. Ganglioblokiruyuschimi adrenoceptor blocking properties
and reserpine does not possess. Effect of reserpine on vasomotor centers
of most authors is denied, as in the experiment reserpine does not reduce
the efferent impulses in pregan-glionarnyh fibers adrenergic (sympathetic)
innervation.
Inhibition of reserpine adrenergic innervation leads to transformations
incense-cholinergic effects. This is manifested by bradycardia, increased
secretory and motor activity of the gastrointestinal tract, myositis.
It is also Simpatolitiki monochetvertichnoe ammonium
compound ornid (bretylium). It is different mechanism of
action from oktadin and reserpine. Basically blocks
presynaptic membrane, disrupting the release of
neurotransmitter. Ornid inhibits monoamine oxidase. In
addition, it inhibits the reuptake of norepinephrine. For
short application Ornid noradrenaline in varicose
thickening adrenergic fibers may not change, long-term use
is reduced. The duration of action is considerably less than
oktadin and reserpine (5-8 hr.).
Apply oktadin and reserpine mainly in the treatment of hyperpertonicheskoy disease. Oktadin as a hypotensive agent is
more effective than reserpine. Oktadin sometimes prescribed
for glaucoma. Getting used to oktadin and reserpine develops
very slowly, which is a great advantage of these drugs to
others, as they are usually used for a long time. Ornid as
antihypertensive agent is not used, because of the digestive
tract it is poorly absorbed and it quickly develops addictive.
In some cases ornid prescribed for heart arrhythmias.
Side effects when using oktadin and reserpine manifest
increase intestinal motility (relatively often diarrhea) and the
secretion of digestive glands (especially the stomach),
bradycardia; note the number of patients in pain parotid gland
swelling of the mucous membranes of the nasal cavity;
typically there is a delay in the body fluid. Orthostatic collapse
may occur when using oktadin (but much less frequently than
in the appointment ganglioblokatorov) and practically not
observed when using reserpine to treat hypertension
(sometimes arises in the treatment of mentally ill patients with
high doses of the drug).
In the application of reserpine possible side effects associated with the
influence of the drug on the central nervous system: drowsiness,
weakness. With prolonged use of the substance in large doses may
experience depression, rarely - extrapyramidal disorders. Increased
appetite also has central origin.
Increase on the background of simpatolitics secretion of digestive glands,
as well as bradycardia can eliminate drugs of atropine. Stimulating effect
on intestinal motility sometimes negate combination with
ganglioblokatorami that reduce the motor activity of the gastrointestinal
tract. Antagonists against reserpine its inhibitory effect on the central
nervous system are inhibitors of monoamine oxidase (nialamide),
restoring the balance of catecholamines and serotonin in the brain tissues.
When extrapyramidal disorders appoint agents, effective in the treatment
of Parkinson's disease (eg, tsiklodol).
Sympatholytics contraindicated in severe organic heart
disease, severe renal insufficiency, gastric ulcer and duodenal
ulcer. Oktadin not recommended to use in
pheochromocytoma.
The conclusion of the lecture.
In the appointment of drugs is necessary to consider the
individual characteristics of the organism and its status as
drug sensitivity varies depending on the age, sex, genetic
factors, the effect of drugs may also depend on the state of the
organism, in particular a pathology in which they are
assigned, is changed accordingly and the intended effect of
drugs.
Thus, a general practitioner in the appointment blockers and
sympatholytic necessary to analyze their pharmacokinetic and
pharmacodynamic characteristics and factors affecting them.
The conclusion of the lecture.
In the appointment of drugs is necessary to consider the
individual characteristics of the organism and its status as
drug sensitivity varies depending on the age, sex, genetic
factors, the effect of drugs may also depend on the state of the
organism, in particular a pathology in which they are
assigned, is changed accordingly and the intended effect of
drugs.
Thus, a general practitioner in the appointment blockers and
sympatholytic necessary to analyze their pharmacokinetic and
pharmacodynamic characteristics and factors affecting them.
Additional:
1. Mashkovskii MD Drugs. Directory. M .: Medicine, 2001, 2005.
2. Reference Vidal. M., 2010, 2011.
3. Fakhrutdinov SF Pharmacology. Textbook. Tashkent: Ibn Sina, 1995.
4. Makhsum MN, MM Malikov Pharmacology. Textbook. Tashkent: Ibn Sina, 1997.
5. Katsung BG Basic and Clinical Pharmacology. Monograph. St. Petersburg Moscow, 1998.
6. Khakimov ZZ, Asimov MM, Zaitseva OA, Radzhapova SZ Umum recipe.
Textbook. Tashkent, 2005.
7. Holmatov HH, Kharlamov, IA Major medicinal plants of Central Asia. Monograph.
Tashkent: Medicine, 1984.
8. General medical practice. Clinical guidelines and formulary. Under. Ed.
IN Denisova, JL Shevchenko, FG Nazyrova. - M .: GEOTAR-Media, 2005.
9.: //www.cibis.ru/catalogue/pharmacology_pharmacy_toxicology/a/sites/
52185.html; : //medvedev-ma.narod.ru/farmakologia/0.htm;
10.http: //max.1gb.ru/farm/;
11.: //nmu-student.narod.ru/farmacology;
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13.: //www.ronl.ru/formakologiya/; : //www.evrocet.ru/cshop/book-18921;
14.: //www.vsma.ac.ru/~pharm/; : //WWW.JEDI.RU/book-189216-115.html.