ANTIDEPRESSANTS

A Schizophrenic patient can be diagnosed with certainty. A Parkinson’s pt can be diagnosed with certainty. But when we come to depression or anxiety, you can’t measure these things. When pts have these problems, to what extent is it a psychiatry problem and to what extent is it a psychology problem? Even in dealing with your children as they grow up and they go off on some tangent that you think is crazy, and you tell your wife “this is crazy”… but is this really crazy or some kind of psychological problem that can be treated?

Anyway, antidepressants are tri-cyclic compounds (TCA= tri-cyclic antidepressant), and in structure are very similar to the phenothiazines. These compounds were all derived from the efforts of pharmaceutical synthetic chemists working with anti-allergic drugs… they realized that if you take some antihistamine it will put you to sleep, so they realized it has some CNS effects. Then they went on to experiment with specific effects of different compounds.

Depending on what kind of side chain you put on the basic TCA, you have a couple different compounds such as Imipramine or Amitryptyline. They have some effects shared with phenothiazines.

TCA EFFECTS ANALOGOUS TO PHENOTHIAZINES:

1. Disruption of conditioned reflexes

2. Potentiates the sleep induction property of barbiturates

3. Anticholinergic action

TCA EFFECTS NOT SHARED BY PHENOTHIAZINES:

Increases potency of MAO inhibitors (MAO inhibitors are drugs that interfere with degradation of norepinephrine, serotonin, catecholamines. TCAs enhance the presence of adrenergic transmitters)

MECHANISM: there are two antidepressants described, both inhibit the amine pump. When you have transmission and serotonin or norepinephrine is released into the synaptic cleft, some of it goes to the receptor, some is degraded by MAO, and some is taken up via the amine pump. So if this amine pump is blocked, the serotonin or norepinephrine will be there for a long time. This is why MAO inhibitors and TCAs potentiate each other, so transmission is very much enhanced

There are two groups, some are directed towards preventing norepinephrine reuptake, and some (like Prozac) inbibits 5-HT (serotonin reuptake).

Ecstasy (the rave drug) increases the release of serotonin. “Now I’ve never tried this ecstasy drug, but I’d like to hear a description if any of you have. I like to hear those things… one time I read in Time magazine that people feel very good, so why shouldn’t we take it then? Because the priests say you shouldn’t.”

The presynaptic neuron has both Norepinephrine (NE) and 5-HT (which is serotonin). TCAs and MAO inhibitors can inhibit the reuptake so that the neurotransmitters stay in the synaptic cleft for longer. There are also receptors on the presynaptic neuron that bind the neurotransmitters and give a feedback information as far as how much has been released. This introduces further complexity, we don’t know how much these receptors are influenced by these drugs. But the prevailing answer that they want you to give on the multiple choice is that there is an inhibition of the uptake, via the amine pump, of the transmitter from the synaptic cleft.

Why do the drugs take 2-3 weeks to have an effect?

Maybe as a consequence of the original concentration that the number of receptors may be upregulated so that the chronic effect of the drug results in not only an inhibition of reuptake but an increase in the number of receptors so that you will have a better transmission and facilitation of emotional feelings and the anti-depressive effects.

TCA EFFECTS IN MAN:

Improves depression without giving euphoria, and are not addictive. Gives a remission of the depressive state. Takes 2-3 weeks before therapeutic effects occur, indicating that it may upregulate some of the receptors involved in the transmission.

TCA ADVERSE EFFECTS:

Anti-cholinergic effects such as dry mouth, impaired vision, constipation, and high urinary retention occur. TCAs are contraindicated in pts with glaucoma.

Clinical effectiveness appears good, with reduced depression and suicidal tendencies. Implications for dentistry: anticholinergic action (xerostomia); additive depressant effects with other CNS meds.

Category: Pharmacology Notes