Tricyclic antidepressants are believed to exert their antidepressant action by.. Increasing the effect of neurotransmitters on postsynaptic receptor sites

Tricyclic antidepressants are believed to exert their antidepressant action by
A) Potentiating GABA activity
B) Increasing the effect of neurotransmitters on postsynaptic receptor sites***
C) Blocking alpha adrenergic receptors
D) Increasing the m etabolic breakdown of biogenic amines.
E) Blocking beta adrenergic receptor.
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Tricyclic antidepressants: uses and side effects:
Although today they are less used than SSRIs and other more modern antidepressants, tricyclics were for many decades the pharmacological treatment of choice for depressive disorders.
In this article we will describe what tricyclic antidepressants are, what they are used for and what their most common side effects are.

What are tricyclic antidepressants?
Tricyclics are psychoactive drugs that are used to treat depressive disorders, although in many countries they have been replaced as drugs of choice by other more effective antidepressants. The effects of drugs useful for treating depression are usually related to the agonism of serotonin and norepinephrine.
The name of these drugs comes from their chemical structure: they are composed of three rings of atoms. Years after the appearance of tricyclic antidepressants, tetracyclics also emerged, which are formed by four rings instead of three.
From the moment that imipramine appeared, the first antidepressant of this class, a large number of tricyclics have been manufactured with some differential characteristics. Among the most common are clomipramine, amitriptyline, nortriptyline, desipramine, maprotiline, doxepine, amoxapine, protriptyline and trimipramine.

What is your mecanism of action?
Tricyclic antidepressants are agonists of monoamines, a type of neurotransmitter very relevant in the nervous system of humans. These potentiating effects affect serotonin, norepinephrine and, less significantly, dopamine.
Its main therapeutic activity is due to the inhibition of the reuptake of these neurotransmitters, which increases the availability of monoamines in the synaptic space. However, they also collaterally affect histamine and acetylcholine, on which they exert an antagonism effect.
Due to the low specificity of their mechanism of action, which does not target only the most relevant neurotransmitters as with other antidepressants, tricyclics may be useful for relieving symptoms of depression but also cause very significant side effects and adverse reactions.

History of these drugs:
Tricyclics were discovered in the process of manufacturing antipsychotic medications. In 1950, clomipramine was synthesized, a neuroleptic of tricyclic structure. Information about this drug led shortly after the creation of imipramine, the first tricyclic used specifically to treat depression.
In recent decades the popularity of tricyclics has declined in most of the world because of the discovery of more effective and safe antidepressant drugs, particularly selective serotonin reuptake inhibitors (SSRIs) and fourth generation antidepressants, such as venlafaxine and reboxetine.

Its functions:
Despite their name, tricyclic antidepressants are not only used in cases of depression, but throughout their history they have been applied to a large number of different psychological disorders.

1- Depressive disorders:
The main indication of tricyclics is the treatment of depressive disorders, both major depression and other milder variants, particularly dysthymia. At present they are prescribed especially in melancholic depression and in cases that do not improve by consuming other antidepressants with fewer side effects.

2- Anxiety disorders:
Some tricyclics are occasionally used to treat different anxiety disorders: imipramine has been shown to be effective in generalized and panic anxiety disorder, while clomipramine is still used in cases of obsessive-compulsive disorder (closely related to depression ) and amitriptyline in posttraumatic stress.

3- Chronic pain:
Among the disorders related to chronic pain that have been treated by tricyclic, fibromyalgia and neuropathic pain stand out; It is believed that the agonism of serotonin and norepinephrine indirectly influences the production of endogenous opioids, which have analgesic effects. Amitriptyline seems to be especially useful in this regard.

4- Insomnia:
The sedative side effects of tricyclic antidepressants have led to them being used occasionally to treat insomnia symptoms. However, it is important to keep in mind that there are other more specific drugs for these problems, and especially that psychological therapy is the most recommended way to deal with sleeping difficulties.

5- Eating disorders:
Again, the therapeutic effects of tricyclics in eating disorders are associated with one of its most frequent side effects: weight gain. In particular, clomipramine is sometimes prescribed as part of the therapy for anorexia nervosa.

6- Night enuresis and night terrors:
Imipramine is effective in treating two childhood sleep disorders: nocturnal enuresis and night terrors. These effects are related to decreased delta or slow wave sleep, during which these episodes appear.

Side effects of tricyclic antidepressants:
Although the side effects associated with the use of tricyclic antidepressants depends largely on their agonism or antagonism towards certain neurotransmitters, in this section we will focus on the side reactions associated most commonly with this class of psychoactive drugs as a whole.
As we mentioned in the previous section, among the most common side effects of tricyclic antidepressants are sedation and weight gain; both are due to the inhibition of histamine activity.
Blocking acetylcholine receptors causes side effects such as constipation, urinary retention, dry mouth, blurred vision and memory problems. On the other hand, the inhibition of alpha-adrenergic receptors is related to alterations in blood circulation, especially dizziness and orthostatic hypotension.
Among the serious adverse reactions to the consumption of tricyclics, the neuroleptic malignant syndrome stands out, consisting of the appearance of respiratory, cardiac and muscular disorders that can cause coma and, in approximately one fifth of cases, death. This syndrome seems to be more frequent in people over 50 years.
Also noteworthy is the high addictive potential of tricyclics, because pharmacological tolerance develops easily. The appearance of an intense withdrawal syndrome after abrupt discontinuation of consumption is also a consequence of tolerance. Likewise, the risk of overdose and suicide is strikingly high.
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