Antidepressants . Anxiolytic . Anti - maniac Flashcards
antidepressant effect sets in after
- 2-4 weeks of treatment.
- Not all manifestations of depression respond equally promptly to treatment with antidepressants.
- Abulia is the manifestation of depression that responds promptly to antidepressant treatment, increases the patient’s capacity for initiative, a situation that can increase the risk of suicide in the first
weeks of treatment. - Progressively, the patient’s thymic condition improves, the suffering and the manifestations related to it disappear, the psychomotor activity increases and the patient’s ability to communicate with those around him.
- Delusional ideas respond a little harder to
antidepressant treatment
Antidepressant drugs can have other psychopharmacological effects:
sedative and anxiolytic
or psychostimulant and anxiogenic
pharmacodynamics of antidepressants
- The mechanism of action of antidepressant drugs is not sufficiently known.
- Increases the availability of neurotransmitters in the synaptic cleft, such as serotonin, norepinephrine, or dopamine, either by preventing their reuptake or by preventing their metabolism.
- Also, antidepressants could block :
1 ) muscarinic receptors,
2) α-adrenergic receptors
3) H1-type histaminergic receptors.
Some of the antidepressant drugs, called atypical, may work by blocking presynaptic serotonergic or noradrenergic receptors.
Pharmacokynetics of antidepressants
1) It is generally well absorbed from the digestive tract. 2) The binding to plasma proteins is made in a large proportion, of approx. 90%, and the distribution is
generally wide.
3) Elimination from the body is predominantly by hepatic metabolism.
4) The half-life is generally long, 20-80 hours, which allows a single administration for 24 hours.
Indications of Antidepressants
- major depression and depression from bipolar psychotic disorders.
- Other indications: phobias
(social phobia and school phobia of children with ADHD), - treatment of enuresis, some chronic pain, probably those involving a lot of an
affective component, treatment of cenestopathies and psychosomatic diseases.
Side effects of Antidepressants
- increased risk of suicide and hypomania.
- Other side effects:
tremor,
speech disorders,
seizures,
decreased or increased psychomotor activity, anxiogenic effects,
memory impairment, parasympatholytic
(constipation, risk of bladder in patients with prostate adenoma, dry mouth, blurred vision, worsening glaucoma),
α-adrenolytic or sympathomimetic side effects (orthostatic hypotension and arrhythmias)
Tricyclic antidepressants (TCA)
- work by inhibiting noradrenaline transporter (NET)
and serotonin transporter (SERT), - inhibiting dopamine reuptake and have parasympatholytic, α- adrenolytic and antihistamine H1 effects.
- Some are of the sedative type, such as
amitriptyline,
trimipramine and
doxepine, which produce sedation and anxiolytic effects,
and others are of the psychotonic type, such as
protriptyline, desipramine and clomipramine,
causing increased alertness and anxiety. The antidepressant effect sets in after 2-4 weeks of
treatment.
Selective serotonin reuptake inhibitors (SSRIs)
- inhibit serotonin reuptake,
without inhibiting noradrenaline reuptake,
and without antimuscarinic, α-adrenolytic or
antihistamine H1 effects.
Such are drugs such as
fluoxetine,
sertraline,
paroxetine,
fluvoxamine,
citalopram,
escitalopram. The effectiveness is comparable to that of tricyclic antidepressants.
DIGESTIVE FFECTS -
nausea, diarrhea, vomiting, insomnia, anxiety,
irritability, sexual dysfunction.
Abrupt discontinuation of serotonin reuptake inhibitors may cause withdrawal syndrome with tremor, headache, nausea, nervousness, insomnia.
Serotonin and norepinephrine reuptake inhibitors (SNRIs)
- inhibit the activity of the
transporter for noradrenaline (NET) and serotonin (SERT), - but have NO :
antimuscarinic,
α adrenergic blockers,
or H1 receptor blockers - venlafaxine, desvenlafaxine, duloxetine.
Serotonin and norepinephrine reuptake antidepressants are probably as effective as tricyclic
antidepressants, but better tolerated by the patient.
ADVERSE EFFECTS
Nausea, headache, sleep problems and sexual dysfunction. Not given with MAOIs (induces serotonin
syndrome - > Hyperthermia , muscle rigidity ,CV collapse )
Increased risk of suicide in young patients. Overdose causes CNS depression, seizures,
cardiac dysrhythmias.
Atypical antidepressants
- have an antidepressant effect comparable to other antidepressant drugs, but have very few sympathomimetic side effects (tachycardia, arrhythmias) or parasympatholytic.
Mianserin - blocks α2-presynaptic receptors to facilitate synaptic transmission.
Nefazodone - inhibits :
1) 5-HT1A type presynaptic serotonergic receptors and 2) 5- HT2 receptor serotonin receptors,
3) especially 5-HT2A, as well as atypical antipsychotic drugs (quetiapine).
Bupropion - inhibits NET, SERT but also DAT (dopamine transporter)
as well as VMAT2 (transporter associated with monoamine storage vesicles) and
- increases the release of noradrenaline and dopamine in the synaptic clefts.
Bupropion is combined with another antidepressant if after 8 weeks of treatment.
Monoamine oxidase inhibitors (MAOIs).
The antidepressant effect of these drugs is probably of the same intensity as that of tricyclic antidepressants and is installed with the same latency of 2-4 weeks as in the case of tricyclic antidepressants. Side effects: hypotension, hypertensive attacks, liver damage, polyneuritis, agitation, hyperreflexia, delirium, seizures.
monoamine oxidase A (MAO A),
specific for serotonin and norepinephrine
monoamine oxidase B (MAO B)
specific for dopamine and norepinephrine
Phenelzine and tranylcypromine
irreversibly and nonselectively inhibit MAO and have antidepressant effect.
Chlorgillin and moclobemide
specific inhibitory antidepressants for monoamine oxidase A,
better tolerated than nonspecific monoamine oxidase inhibitors
Specific MAO B inhibitors,
- selegiline,
are used primarily as antiparkinsonian drugs, not as antidepressants.
Mania
is a state opposite to depression, characterized by an exaggerated positive emotional mood, with exaggerated increase in mental and motor activity. Frequently, the state of mania
alternates with the state of depression - bipolar psychosis.
Lithium
used to treat mania - it controls all manifestations of mania without any other psychopharmacological effects. In normal person, lithium does not alter the activity of the central nervous system and, in non-toxic doses, it is practically without effects.
Pharmacodynamics of lithium
The mechanism of action of lithium is unknown - probably interfering
with neurotransmitters with an important role in mental activity,
such as acetylcholine,
dopamine,
norepinephrine,
cyclic adenosine monophosphate (cAMP) or inositol
triphosphate (IP3).
pharmacokinetics of lithium
lithium is practically completely absorbed from the digestive tract, is
distributed in all the water in the body, is not metabolized and is eliminated as such in the
urine.
The half-life is around 20 hours - it can be given only once every 24 hours.
Side effects of lithium
toxic: tremor of the extremities, thyroid disfunction, affects renal tubular function increasing diuresis with nephrogenic insipidus diabetes, interstitial tubulopathy, nephrotic syndrome, sinus node disease, with tachycardia alternating with bradycardia.
indications of lithium
treatment of mania. Latency of clinical effects - approx. 5-10 days; at the beginning of the treatment of the acute mania crisis, lithium is associated with sedative
neuroleptic drugs or other strong sedatives.
Other drugs with antimaniacal effect.
AEDs.
- Carbamazepine has a lithium-like
antimaniacal effect. The combination of carbamazepine with lithium has a greater effect than
either of the two medicines given separately. The antimaniacal effect of carbamazepine
appears to have a shorter latency than lithium and is accompanied by a beneficial sedative
effect in patients with mania.
Valproic acid appears to be as effective as antimaniacal as lithium, with a shorter onset of affect latency (1-4 days), and has a sedative effect.
Atypical antipsychotics (ziprasidone, risperidone, olanzapine, quetiapine, aripiprazole) have been
approved for the treatment of acute mania.
Mood stabilizers : Lithium
in patients with manic-depressive psychosis, decreases the frequency of attacks of
both mania and depression - it is a mood stabilizer.
Antiepileptics as mood stabilizers
1) carbamazepine,
2) valproic acid and
3) lamotrigine.
- Carbamazepine prevents both depressive and manic episodes.
- Valproic acid appears to be more effective in preventing manic episodes than in preventing depressive episodes, while
- lamotrigine appears to be more effective in preventing depressive episodes than in preventing manic episodes.
Atypical antipsychotics
1) olanzapine and
2) quetiapine,
prevent both episodes of depression
and episodes of mania.
1) Risperidone and
2) ziprasidone appear to be more effective in
preventing episodes of mania than in preventing episodes of depression, and aripiprazole
appears to be effective only in preventing episodes of mania and not in preventing episodes of depression.
Anxiety
diffuse fear for no reason, in connection with a possible danger that is not known when it will come or if it will come.
Phobia
is an unwarranted fear of a
real object that does not normally produce fear.
Anxiolytic drugs have an anxiolytic effect at doses that
very little sedative, so that in
these drugs the removal of anxiety appears as the main effect. These drugs do not eliminate
phobias, affective manifestations that respond to antidepressant treatment.
MOA Anxiolytic drugs
The most important anxiolytic drugs currently available act through benzodiazepine receptors or serotonergic receptors.
The main therapeutic indication is the removal of anxiety when it reaches pathological
intensities.
Side effects
sedation,
decreased reflexivity increasing the risk of accidents, especially in certain professions (drivers for example), potentiates the effect of other sedatives, including
alcohol.
Benzodiazepines
- are currently the main chemical group with anxiolytic properties.
- However, not all drugs with a benzodiazepine structure can be categorically included in the
category of anxiolytic drugs, in the sense that they eliminate anxiety at doses that are weakly
sedative.
The most typical anxiolytics with benzodiazepine structure are considered
alprazolam,
diazepam,
oxazepam,
medazepam.
All benzodiazepines have other pharmacodynamic properties such as sedation, relaxation of
striated muscles, or anticonvulsant effect.
MOA of Benzodiazepines
stimulation of benzodiazepine receptors at the level of chlorine channels represented by GABA - A type receptors.
β adrenergic blockers - propranolol
- are also sometimes used as anxiolytics.
Propranolol has not sedative effects, do not affect the ability to learn and memorize, and
decreased anxiety may be due to the elimination of somatic sympatho-adrenergic manifestations of anxiety, such as tachycardia, chest tightness or tremor of the extremities.
Propranolol can increase some motor or intellectual performance disturbed by anxiety,
especially if it is motor performance involving high precision movements.
Buspirone
relatively recent anxiolytic introduced in therapy that has a high affinity for 5-HT1A-type serotonergic receptors (a partial agonist of 5-HT1A-type serotonergic
receptors). The anxiolytic effect usually sets in slowly after 2-3 days of treatment. The most
important side effects are nausea, headache, dizziness and sometimes hyperexcitability.
