Transcript Antidepressants - TMA Department Sites

ANTIDEPRESSANTS.
In a significant degree ¬ tion is metabolized in the liver. One of its
metabolites - desmethyl-imipramine (desipramine) - has expressed
antidepressant activity and is used in medical practice. Excreted
as metabolites, conjugates and unchanged in the kidneys (40% on the 1st day), partly intestine. When using imipramine in
depression treatment effect occurs che ¬ cut 2-3 weeks. Side
effects most often associated with atropine their properties ¬
imipramine (dryness of the mouth, disturbance of accommodation,
tachycardia, constipation, difficulty in urination). Violations of the
law and of the ser ¬ dechno cardiovascular system. Imipramine in
therapeutic doses may reduce the ar ¬ ter pressure. So, against
his actions sometimes develop orthostatic hypotension. In high
doses can cause tachycardia, arrhythmias. Possible adverse
deviation on the part of mental activity. This is either excessive
sedation, or, on the contrary, the excitement, the Gallo ¬ tsinatsii,
and insomnia. When receiving imipramine may be headache,
tremor, allergic skin reactions, jaundice, leukopenia, and
agranulocytosis is rare. Pres ¬ Parat also contributes to weight
gain.
Imipramine is contraindicated in glaucoma, urinary abuse
associated with hypertrophy of the prostate. You can not combine
it with indiscriminate ¬ tive MAO inhibitors, as this toxic effects
occur ¬ you. If these two types of antidepressants prescribed
sequence, the interval after discontinuation of MAO inhibitors
should not be less than 1.5-2 weeks.
Similar to a drug imipramine clomipramine (Anafranil). Lee Bo ¬
expression affects the reuptake of serotonin.
Amitriptyline (triptizol) structurally similar to imipramine.
Pharmacodynamics and pharmacokinetics of amitriptyline and
imipramine are similar. In addition to the antidepressant activity of
amitriptyline are expressed in psychosedative properties. The
stimulatory effect of it available. In addition, it is superior to
imipramine for m-anticholinergic and antihistaminic action.
Amitriptyline is among the most active antidepressant ¬ by
intense media. The therapeutic effect it is revealed in 10-14 days.
It also includes tricyclic antidepressants azafen (pipofezinum). It
has a mild antidepressant activity and has a sedative effect.
Different in a positive way from those antidepressant lack of manticholinergic properties. Apply azafen with depression of mild to
moderate severity. The drug was well tolerated. Side effects are
observed only in certain cases, so azafen recom ¬ mended often
elderly patients. Assign it inside.
Reported drugs act indiscriminately on the neuronal uptake of
serotonin and norepinephrine. However, drugs and created a voter
¬ nym action. Thus, the synthesized compounds, especially
depressing neuronal uptake of serotonin. One such drug is
fluoxetine (Prozac frameks). According to the chemical structure, it
is derived phenoxypropylamino.
. It has high anti-depressant activity, ana ¬ logical that for tricyclic
antidepressants. The effect is at ¬ gradually (within 1-4 weeks).
From tricyclic antidepressants is different in that it has virtually no
sedation and is usually not detected ¬ inducing effect that no or
only very slightly m-anticholinergic action, not marked effect on
adrenergic receptors. Ge ¬ thermodynamics when fluoxetine is
stable. Body weight does not increase ¬ is. Furthermore, fluoxetine
has low toxicity. Well absorbed when administered inside.
Metabolized in the liver. One of its metabolites, norfluoxetine, has a
pronounced anti-depressant ac ¬ ciency. For fluoxetine, t 2 = 1-3
days (for norfluoxetine - 7-15 days). Stand metabolites and
unchanged drug by the kidneys. Of the side effects observed
violation of appetite, nausea, nervousness ¬ sion, headache,
insomnia, skin rashes.
You can not use fluoxetine with non-selective MAO inhibitors may
develop as a so-called "serotonin syndrome" associated with the
accumulation of excessive concentrations of serotonin. This may
be the muscular rigidity, hy ¬ pertermiey and cardiovascular
collapse, which is a danger to life. With that said between doses of
fluoxetine and non-selective MAO inhibitors should be an interval
of at least 2 weeks. Interactions with food ingredients for fluoxetine
were observed (as opposed to non-selective MAO inhibitors.)
Fluoxetine has been widely used in medical practice in the
treatment of depressive states ¬ chenii.
Selective inhibitors of neuronal uptake of serotonin for copper ¬
Qing practice offers a number of new drugs - setralin, paroxetine,
etc. The highest selectivity of action has paroxetine (Paxil).
). In vitro experiments have shown that paroxetine 320 times
stronger inhibits the reuptake of serotonin, norepinephrine than
(setralin - 190 times fluokse ¬ ting - 20 times). Paroxetine has high
anti-depressant and anxiolytic (anxiolytic) activity. Has little mholinob ¬ lokiruyuschee deystvie.Pri enterally absorbed
completely. 93-95% of the material ¬ Vaeth binding to plasma
proteins. Most of paroxetine metabolized in the liver of active
metabolites are formed. Metabolites are distinguished mainly by
the kidneys (~ 62%), the rest of the intestine is derived, t ~ 21 hours
time "semi ¬ life" of the drug increases with kidney failure and
cirrhosis of the liver.
1 introduced the drug once a day. The effect develops within 1-4
weeks. Pro ¬ duration of treatment is measured in months,
depending on the type of depression.
Paroxetine is well tolerated. Side effects are rare. Nausea,
headache, sometimes dryness in the mouth, drowsiness,
dizziness, etc.
Also synthesized drug that selectively blocks the neuronal
norepinephrine doses ¬ vat - maprotiline (ludiomil). According to
its pharmacological properties and ¬ to the application is similar
to imipramine. Absorbed from the digestive tract slow (9-16
hours). About 90% of the drug binds to plasma proteins, t, = 43-51
hours Undergoes bio ¬ transformation in the liver. Distinguished
maprotiline and its metabolites in the main ¬ nom kidneys.
The predominant influence on the neuronal uptake of
norepinephrine region ¬ also gives desipramine. As already noted,
it is a metabolite of imipramine. By the nature of the action is
similar to the last one. Causes less sedation and m-anticholinergic
effects.
Antidepressants of the group of MAO inhibitors are divided into
non-selective drugs and selective action.
Currently indiscriminate inhibitors of MAO (affects MAO-A and
MAO-B) is used relatively infrequently due to the rather high
toxicity. When choosing an antidepressant preference is usually
given to drugs that affect her ¬ coronal monoamine uptake.
However, in some cases, may be useful ¬ inhibition of MAO
inhibitors, particularly selective.
Non-selective MAO inhibitors inhibit the process of oxidative
deamination of norepinephrine and serotonin, which leads to their
accumulation in the brain tissue values ​¬ considerable amount.
The majority of this group of drugs block the irreversible MAO ¬
reversibly. In this regard, recovery MAO it must be synthesized
anew, which requires considerable time (up to 2 weeks).
). Its maximal inhibition occurs several hours after the intake of
MAO inhibitors. However, the antidepressant effect develops within
7-14 days. Apparently, the mechanism of action of this group of
substances is associated not only with inhibition of MAO, as
between this effect and the en ¬ tidepressivnoy activity is not
always overlap. It is possible that the definition ¬ lennuyu role can
the impact of these drugs on the exchange of GABA.
Along with antidepressant MAO inhibitors are characterized by
pronounced ¬ GOVERNMENTAL psycho-stimulant properties
(cause euphoria, excitement, sleepless ¬ zu).
MAO inhibitors are active antagonists of reserpine in relation to its
sedative, hypotensive and other types of actions. This is due to the
fact that the re ¬ zerpin lowers in the brain catecholamines and
serotonin, and MAO inhibitors eye ¬ shows the opposite effect.
Against the background of the action of MAO inhibitors
dramatically enhanced pressor effect sympathetic-mimetics
(amphetamine, ephedrine, tyramine), including in food pro ¬
product (for example, in the cheese, there are significant amounts
of tyramine). These substances contribute to the release of
adrenergic endings of excessive amounts of noradrenaline ¬ ling,
which accumulates in them as a result of MAO inhibition. Thus
there is a hyper-hypertensive crisis.
Inhibition of MAO inhibitors are influenced by it occurs not only in
the CNS but also in peripheral tissues. Furthermore, these drugs
inhibit the activity of MAO not only, but also a number of other
enzyme systems. Thus, due to inhibition of microsomal liver
enzymes ¬ ments MAO inhibitors prolong the action means for
neingalyatsionnyh anesthesia, antipsychotic phenothiazine series,
opioid analgesics, anti-epileptic and other means.
MAO inhibitors possess antihypertensive activity, which is
apparently due to the decrease in the release of norepinephrine
from varicose thickenings adrenergic ¬ FIR fibers. When they
reduce angina pain (apparently due to block ¬ kirovaniya central
parts of reflections with the heart). MAO inhibitors are absorbed
from the digestive tract is good. Are distinguished primarily by the
kidneys. MAO inhibitors have a relatively high toxicity. This is
manifested mainly
in respect of the liver (can cause severe hepatitis).
Furthermore, they excite the CNS, which is the cause insomnia and
in some cases resulting tremor and convulsions. The use of these
agents may be accompanied by orthostatic hypotension. With the
improper cau ¬ MAO inhibitors should be combined with other
neurotropic agents ¬ mi, since it is often accompanied by adverse
effects (eg, in combination with the type of action of narcotic
substances, sympathomimetic, antidep ¬ ressantami tricyclic
series). Furthermore, the reception MAO inhibitors should be
deleted from the diet foods containing tyramine (cheese, etc.).
Drug dependence in relation to MAO inhibitors does not develop.
As MAO inhibitors have been synthesized derivatives of hydrazine.
However, currently used in medical practice hydrazine single drugs
such nialamide (niamid, nuredal). This is one of the least effective ¬
her antidepressants. However, toxic effects on the liver and its other
side-effects are to a small extent, that is doubtless worthy ¬ stvom
nialamidom.
Another class of chemical compounds refers transaminase
(tranylcypromine, parnat). It is phenylcyclopropylamine, i.e. similar
in structure of phenylalkylamines (e.g. fenaminu). Transaminase - a
strong reversible inhibitor of MAO. It belongs to the most effective
antidepressants in this group. The therapeutic effect of it comes a
little faster than most new hydrazine ¬ (at nialamidom - in 12-14
days, transaminase - in 2-7 days).
Pharmacodynamics transaminase similar to that of other MAO
inhibitors. To this should be added ¬ mu of its certain
sympathomimetic effect (effect of amphetamine-type).
Hepatotoxicity y "negidrazinovyh" compounds is less pronounced
than in preparations of hydrazine.
Antidepressants of indiscriminate group of MAO inhibitors are
contraindicated in diseases of the liver, kidney, stroke, severe
mental stimulation.
In recent years attention of preparations advantageously reversible
inhibitor of MAO-A. These include moclobemide (auroriks) pirazidol,
etc. They are more briefly than the irreversible MAO inhibitors. In
addition, when used reduces the risk of hypertensive crisis when
interacting with sympathomimetic food prois ¬ walking (eg,
tyramine), which is typical of non-selective MAO inhibitors ¬ tors.
Moclobemide is a derivative of benzamide.
Pirazidol - is a tetracyclic compound. The chemical structure, it can
be referred to derivatives of indole. Pirazidola antidepressant
effects, depending on the patient's condition is combined with a
sedative (against the troubles are, anxiety) or challenging (in the
face of oppression) effect. Fur ¬ mechanism of antidepressant
action is explained by its inhibitory effect on the reversible MAO-A
and the ability to inhibit neuronal uptake of norepinephrine. Mholinoblokiruyushaya activity in pirazidola missing. Transferred pre
¬ Parat well. Side effects are rare. Take pirazidol inside.
Stimulants
Stimulants increase the mood, ability to perceive beyond ¬ shnih
irritations, psychomotor activity. They reduce the feeling of tired ¬
STI, enhance physical and mental performance (especially in
fatigue) temporarily reduces the need for sleep.
According to the chemical structure of
psychostimulants include the following groups.
Phenylalkylamines
Benzedrine
Piperidine
derivatives
Pipradol
Merida
Derivative
sydnonimine
Sidnokarb
Methylxanthines
Caffeine
Is a typical stimulant amphetamine (amphetamine sulfate). It seems
a pre ¬ fenilalkilamina ie similar in structure to adrenaline and
noradrenaline. By fenaminu belongs entirely characteristic given to
the whole group psihostimu ¬ liruyuschih substances. The
mechanism of action of amphetamine exciting explain its ability to
release from presynaptic terminals norepinephrine and dopamine.
The released catecholamines stimulate the appropriate receptors
are present in the CNS. In addition, amphetamine, apparently
somewhat reduces neuronal uptake of noradrenaline and
dopamine.
A stimulating effect of amphetamine is attributable largely to its
stimulant effect ¬ tion on the ascending activating reticular
formation of the brain stem. This is manifested in the EEG
desynchronization of bioelectrical activity. However, it is possible
that amphetamine excites neurons of the cerebral cortex directly.
Moreover, it stimulates the formation of specific inhibits limbic
system and neo-striatum.
On the development and implementation of conditioned reflexes
amphetamine in small doses, has a beneficial effect, in large oppresses them. In this case important is the type of nervous
system. For amphetamine characterized its effect on food center,
located in the hypothalamus ¬ Musa, which leads to the
suppression of hunger.
Amphetamine has a direct stimulatory effect on the respiratory
center, which pro ¬ is mostly against his oppression. In this case,
amphetamine acts as an analeptic. Phenamine not only acts on the
CNS but also in peripheral nerve. It exerts an indirect stimulatory
effect on the alpha-and beta-adrenergic receptors. ¬ As already
mentioned, amphetamine refers to sympathomimetics (causes the
release of noradrenaline ¬ Nalini thickening of varicose adrenergic
fibers). It has a direct effect on adrenergic receptors, but it is of
secondary importance. Sympathetic-and amphetamine
Adrenomimeticalkie properties are largely in increasing arterial
pressure ¬ tion. In this regard, amphetamine inferior in activity
adrenaline 100-150 times but its pressor effect considerably
prolonged. Effect on smooth muscle organs other similar
adrenaline, but expressed to a small extent. From the digestive tract
of the drug is absorbed well.
. Quickly penetrates the blood-brain barrier. In the body,
biotransformation an hour ¬ partially. Excreted by the kidneys in a
large part (30-50%) as unchanged. To reduce its concentration in the
blood plasma of 50% requires about 12 hours when the pH shifts
toward acidic urine, excretion rate amphetamine increases.
With prolonged use of amphetamine accumulates, develop
tolerance to it and drug abuse (physical and mental).
Apply amphetamine mainly in neurotic subdepression, as well as
narcolepsy and similar conditions involving sleepiness.
Furthermore, it is sometimes used to improve performance in
fatigue. In this case, it should be noted that the stimulating effect of
amphetamine is accompanied by a large sam ¬ ratoy energy
resources of the body, so after a good rest to recuperate absolutely
necessary.
Amphetamine is sometimes prescribed as a analeptic drug
poisoning substances ¬ arithmetic type of action. To reduce the
appetite amphetamine use is impractical because it causes
excitement, raises blood pressure and is a poten ¬ tial dangerous
drug with respect to the development of drug dependence.
In case of overdose are marked agitation, anxiety, insomnia,
tachycardia, a rhythm disturbance sometimes heart rate.
Amphetamine contraindicated in aterosk ¬ leroze, hypertension,
insomnia, in old age.
Currently, amphetamine is rarely used (due to its ability to cause
drug dependency).
Fenaminu similar in their effect on the central nervous system,
piperidine derivatives pipradol (pipradol) and meridil
(methylphenidate hydrochloride, centedrine). By stimulating asset ¬
sion pipradol not inferior fenaminu. Meridia works less hard. The
apparent advantage pipradol and Merida is the absence of
unwanted peripheral ¬ toric Adrenomimeticalkie effects.
In particular, unlike amphetamine prac ¬ cally they do not affect the
cardiovascular system.
Active psychoactive agent is also sidnokarb. According to the
chemical structure it refers to the group sydnonimine. ¬
psychoactive effect extending sidnokarba develops gradually and
persists for a long time ¬ mja. Euphoria and motor driving is not
observed. Mechanism of action psychostimulant obviously
associated with the activation of noradrenergic system. Compared
with fenaminom sidnokarba have no pronounced peripheral
sympathomimetic effect. This is evident in the relative ¬ but stable
hemodynamics. Sidnokarb well tolerated. If overdose ¬
renormalization possible agitation, anxiety, insomnia, ¬ tion slight
increase in blood pressure. In the evening hours sidnokarb should
not be accepted, as it can disrupt sleep.
The group also includes stimulants caffeine (the compound of the
group ¬ Py methylxanthines). It is an alkaloid contained in leaves of
tea (Thea sinensis), a in the seeds coffee (Coffea arabica), cocoa
(Theobroma cacao), cola (Cola acuminata) in other plants. Caffeine
combined analeptic and psychostimulant properties. Especially
pronounced him a direct stimulating effect on the to ¬ py brain.
Caffeine stimulates mental activity, enhances mental and physical
performance, motor activity, ¬ reproach ourselves to the reaction.
After receiving his vigor appears temporarily eliminate ¬ nyayutsya
or decrease fatigue, drowsiness. The effect on the higher nervous
activity largely depends on the type and dose of caffeine nervous
system. In small doses of caffeine have dominated STI ¬ stimulating
effect, in large - depressing. It should be borne in mind that for a
weak type of nervous system excitation effect is achieved by
introducing small amounts of caffeine, whereas for the strong type
requires much pain ¬ Chiyah dose.
Analeptic activity is associated with the effect of caffeine on the
continued ¬ govatogo centers of the brain. It has a direct stimulatory
effect on the respiratory and vasomotor centers. There are
quickening and deepening the breath, which is particularly evident
at the center of the oppression of breathing. In addition, to ¬ Fein
exciting centers of the vagus nerves. On the spinal cord ¬ drug
action exists only in high doses. By facilitating the transfer of
impact interneural ¬ tation it enhances the spinal reflexes.
Significant place in the pharmacodynamics of caffeine is its impact
on the mid ¬ dechno-vascular system. It consists of the peripheral
and central effects. For example, caffeine has a direct stimulatory
effect on the myocardium. However, at the same time excited
centers of the vagus nerves, so to ¬ finite effect depends on the
prevalence of a particular influence. Usually measured in ¬ tion of
the heart (if they occur at all) are small.
In large doses, caffeine causes tachycardia (ie, dominated by its
peripheral action of), sometimes arrhythmia. Central and peripheral
components in the action of caffeine are in respect of vascular
tone. By stimulating the vasomotor center, coffee ¬ Institute
increases vascular tone, and the direct effects on vascular smooth
muscle tone reduces them. Caffeine has an ambiguous effect on
the various vascular regions. Thus, the coronary blood vessels
dilate more often (especially if cardiac output is increased).
However, some brain vessels toned. The latter apparently explains
beneficial effect of caffeine in migraine. On the other ¬ Gia smooth
muscle organs (bronchi, bile duct), caffeine has a mild ¬ tion
myotropic antispasmodic effect on skeletal muscle - stimulating ¬
separating (central and direct). Even more difficult to change blood
pressure, since it depends on kardiotropnyh and vascular effects of
caffeine. Usually, if the initial partial pressure of arterial ¬ normal,
caffeine does not change or only slightly by ¬ ceeding it.
. If the drug is introduced against the background of hypotension,
blood pressure increased (normalized). Caffeine increases the basal
metabolic rate. Increases glycogenolysis, causing hy ¬
perglikemiyu. Increases lipolysis (free fatty acids in plasma ¬ IU
increases). In large doses, causes the release of adrenaline from the
brain ¬ traction adrenal medulla.
Observed in the application of the central effects of caffeine, the
effect on the smooth and striated muscle, changes in metabolism,
some authors attributed to the accumulation of cAMP. There is it
seems, partly in re ¬ result of phosphodiesterase inhibition and
disturbances in connection with this process, consider ¬ decay of
cAMP. In more caffeine inhibit phosphodiesterase brain and heart,
but this occurs only at very high concentrations exceeding
therapeutic. In recent years the accumulated data confirm
maintainer, more important component of the action of
methylxanthines (caffeine, theophylline) is their antagonism of
adenosine. It is important to note that this is ¬ observed at
therapeutic concentrations of methylxanthines.
In favor of this view is evidenced by the fact that methylxanthines
and adenosine cause pro ¬ oppositely directed effects.
Furthermore, it was shown that the above effects of adenosine
eliminated methylxanthines, which blocks ¬ sealing against
adenosine A - and A2-receptors (are competitive antagonists ¬
Tammy adenosine). Under the influence of caffeine increased
secretion of gastric glands, and may be used for diagnostic
purposes. The use of caffeine in the pathology of the stomach
(gastritis / ulcer, tumor) helps differentiate func ¬ ktsionalnye
violations of organic.
In a small degree of caffeine increases urine output, which is
associated with inhibition of pro ¬ process of reabsorption in the
proximal and distal renal tubular sodium and water. In addition,
caffeine dilates blood vessels and increases renal fil ¬ tration in the
renal glomeruli. Caffeine and especially its water-soluble salts are
well absorbed from the intestine ¬ nick (including the colon). The
main part of it is exposed biotransformation ¬ formation
(demethylated, oxidized). About 10% of the caffeine is released by
the kidneys unchanged. With prolonged use of caffeine develops
Just noticeable pref ¬ circuiting. You may experience psychological
dependence (theism). Caffeine is used to stimulate mental activity,
when wearied, research institutes, migraine, hypotension. It is part
of many combined preparations ¬ Ratov in combination with nonnarcotic analgesics (pill "Citramon-P", etc.), and ergot alkaloids (pill
"Kofetamin").
Side effects are manifested in the form of nausea, vomiting,
restlessness, ¬ impact excitation, insomnia, tachycardia, cardiac
arrhythmias. Caffeine is contraindicated in severe arterial
hypertension, ateros ¬ sclerosis, sleep disorders, glaucoma.