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Antidepressants E
Antidepressants E
•Antidepressants
•Mood stabilizers
•Psychostimulants
•Nootropic drugs
•CNS stimulants
(Abstract)
Assoc. Prof. Iv. Lambev
www.medpharm-sofia.eu
Depression is a heterogeneous disorder. A simplified
classification based on presumed origin is as follows:
(1) brief reactive or secondary depression (most common),
occurring in response to real stimuli such as grief, illness, etc;
(2) major depression (melancholic and recurrent depression)
a genetically determined biochemical disorder manifested
by an inability to experience ordinary pleasure or to cope with
ordinary life events;
(3) manic-depressive depression (depression associated with
bipolar affective disorder)
Pharmacologic treatment of depressions is very important, although
a continuing role for electroconvulsive therapy for severe forms of
life-threatening depression is also noted.
manic
Depression is one of the most common psychiatric disorders.
At any given moment, about 3–5% of the population is depressed,
and an estimated 10% of people may become depressed during
their lives. The symptoms of depression are often subtle and
unrecognized both by patients and by physicians. Patients with
vague complaints that resist explanation as manifestations of
somatic disorders and those who might be simplistically described
as “neurotic” should be suspected of being depressed.
Soon after the introduction of reserpine (1948), it became
apparent that the drug could induce depression by inhibiting the
neuronal storage of amine neurotransmitters 5-HT and NE.
Reserpine-induced depression and depleted stores of amine neuro-
transmitters. It was reasoned, depression must be associated
with decreased functional amine-dependent synaptic transmission.
NA (noradrenaline) = NE (norepinephrine)
Rauwolfia serpentina
(a small indian shrub)
•Reserpine
•Ajmaline
Pathogenesis of depression
The idea that depression must be associated with decreased
functional amine-dependent synaptic transmission
provided the basis for amine hypothesis of depression .
By extension, drugs that increased amine function in appropriate
synaptic areas would relieve depression.
The amine hypothesis has provided the major experimental
models for the discovery of new antidepressants.
All currently available antidepressants, except bupropion,
are classified as having their primary actions on the
metabolism, reuptake, or selective receptor antagonism
of 5-HT, NA, or both.
(NE) (5-HT)
(DA)
Moclobemide
(MAO-A)
(3) Selective SSRIs Nialamide
Citalopram, Fluoxetine Mianserin* (MAO-A & B)
(2) Selective NARIs Escitalopram, Fluvoxamine Mirtazapine Selegiline
- - -
Side-effects of SSRIs
(mainly during the 1st and 2nd weeks of treatment): CNS: head-
ache, restleness; CVS: bradycaria; GIT: nausea, diarrhoea
The serotonin syndrome is a rare but dangerous complication
with features restlessness, tremor, hуperthermia, convulsions,
coma and death. Risk is increased by co-administration with
MAOIs, the antimigraine drug sumatriptan, and St. John’s Wort.
Trazodone acts by antagonism of central
presynaptic alpha-2-adrenoceptors.
It is an option for depressed patients where heavy
sedation is required. Trazodone also has the
advantages of lacking antimuscarinic effects and being
relatively safe in overdose. Males should be warned
of the possibility of priapism (painful penile erections),
due to the blockade of peripheral postsynaptic
alpha-1-adrenoceptors.
(1) Methylxanthines
Three methylxanthines are pharmacologically
important: caffeine, theophylline, and theobromine.
All of them occur naturally in certain plants.
(–)
AC PD
ATP cAMP 3’, 5’-AMP
(+) Hypercholesterolemia
(+)
Lipolysis Cholesterol synthesis
Methylxanthines are mild diuretics. They act by inhibiting tubular
reabsorption of Na+ and water. Theophylline and theobromine
are more potent diuretics than caffeine.