ANXIETY AND PANIC ATTACKS: Biological Data
Biological factors, such as genetic background, neurotransmitter and neuroendocrine systems, social factors, and psychological factors, such as, personality traits and ego defense mechanisms, contribute to the pathogenesis of anxiety. Τοwards explaining anxiety, a number of neurone’s systems, neuroanatomical regions and various hormonic levels of mulfunction have been suggested.
The GABA-nergic hypothesis is based on the finding that the benzodiazepines increase the function of GABA-A receptor, allowing the inflow of chloric anions into the cell.
The noradrenergic hypothesis is based on the findings of an abnormal activity of locus cerulus and a presynaptic downregulation of norepinephrine neurons.
The serotonergic theory is based on the assumption that there is hypersensitivity of the 5-HT receptor. From neuroanatomical point of view, it seems that anxiety or panic attacks begin with stimulation of irritable foci in one of three brainstem areas: the medulary chemoreceptors, the noradrenergic pontine locus cerulus or the serotogenic midbrain dorsal raphe. The limbic lobe is believed to be the center of anticipatory anxiety and the prefrontal cortex the region of phobic avoidance. Also, there is convincing evidence that the serotonergic projections inhibit dopamine function in the striatum and cortex inhibiting the synaptic release of dopamine and probably the synthesis of dopamine. The serotonergic receptors are grouped on the basis of shared genetic sequences and second messenger systems in four groups : 1. The 5HT-1 family ( 5HT-1A, 5HT-1D, 5HT-1E and 5HT-1F ) which uses G-protein – mediated signal transduction. 2. The 5HT-2 family ( 5HT-2A, 5HT-2B, 5HT-2C, 5HT-4, 5HT-6, 5HT-7 ) which uses phosphoinositol – mediated signal transduction. 3. The 5HT-3 receptor which uses ion – gated channels and 4. The 5HT-5 family, a new group of 5HT receptors, which contains the 5HT-5A and 5HT-5B receptors.
Abnormalities of both 5HT neurotransmission and HPA axis activity are found in anxiety, but abnormal 5HT neurotransmission seems to be the key factor. Serotonin has also implicated in the pathogenesis of depressive and obsessive-compulsive symptoms which are common features in anxiety disorders. Recent studies suggest that the CRH systems and the locus cerulus-norepinephrine system create a bronchus of positive feedback, that results in a number of clinical and biochemical manifestations of anxiety attacks.
There is a solid pharmacological basis for the observed clinical advantages of most antidepressants. They can be considered as serotonin (5-HT) reuptake inhibitor with potent antidepressant and anxiolytic activity, acting via serotonin binding on the serotonin transporter.
CYP450 Isozyme Inhibition Profiles
1A2 2C9 2C19 2D6 3A4
citalopram + 0 0 + 0
duloxetine + 0 0 ++ 0
escitalopram 0 0 0 0 0
fluoxetine + ++ + to ++ +++ ++
paroxetine + + + +++ +
sertraline + + + to ++ + +
venlafaxine 0 0 0 0 0
ΑΓΧΟΛΥΤΙΚΑ – ΒΕΝΖΟΔΙΑΖΕΠΙΝΕΣ
Εμπορική ονομασία
Γηριατρική δοσολογία
Βενζοδιαζεπίνες μικρού Τ1/2
Λοραζεπάμη
Tavor
2-6
Aλπραζολάμη
Xanax
0.5-6
Βενζοδιαζεπίνες μεγάλου Τ1/2
Κλοραζεπάτη
Tranxene
7.5-30
Βρωμαζεπάμη
Lexotanil
1,5-6
Πραζεπάμη
Centrac
5-30
Διαζεπάμη
Stedon
2-30
Κλοναζεπάμη
Rivotril
0,25-2
Υπναγωγικές Βενζοδιαζεπίνες
Μικρού Τ1/2
Tεμαζεπάμη
Normison
20-40
Τριαζολάμη
Halcion
0,125-0,25
Φλουνιτραζεπάμη
Hipnosedon
0,5-2
Λορμεταζεπάμη
Loramet
0,2
ΑΝΤΙΚΑΤΑΘΛΙΠΤΙΚΑ
Εμπορική ονομασία
Γηριατρική Δοσολογία
Tρικυκλικά
Αμιτριπτυλίνη
Saroten
25-300
Νορτριπτυλίνη
Nortrilen
25-150
Τετρακυκλικά
Μαπροτιλίνη
Ludiomil
25-150
ΝASSA
Mιρταζαπίνη
Remeron
15-90
SSRIs
Φλουοξετίνη
Ladose
10-80
Φλουβοξαμίνη
Dumyrox
25-200
Σερτραλίνη
Zoloft
50-200
Παροξετίνη
Seroxat
5-40
Σιταλοπράμη
Εσιταλοπράμη
Seropram
Entact,Cipralex
10-40
10-20
SNRIs
Βενλαφαξίνη
Efexor
37,5-225
Τραζοδόνη
Τrittico
100-500