Psychopharmacologie Flashcards
Ejaculation retrograde: psychotropes avec quel mécanisme d’action sont en cause?
bloqueurs alpha1
anthicholinergiques
antihistaminergiques
Anorgasmie et éjaculation tardive: quels mécanismes sont en cause?
anti alpha1 stimulation 5HT2A (SSRI) et 5HT2C récepteurs
mécanismes d’action de Mirtazapine
block alpha2 –> augmente stransmission NE et 5HT (via cortex-raphe)
antagonist 5HT2A –> augmente activité 5HT1-R
inhibition 5HT3
Mirtazapine: quels effets sont particulier vs SSRI?
diminution latence sommeil
augmentation durée sommeil
moins de dysfonction sexuelle vs SSRI
plus d’augmentation poids et appetit vs SSRI
effet antiémétique
Mirtazapine: quels effets liés à l’inhibition 5HT3?
antiémétique
stimulation fx cognitives
Mirtazapine: effet secondaire particulier
neutropénie
Mirtazapine: interactions significatives
tabagisme: diminution de [..]
SNRI (Effexor) - augm [..] x3-4
cimetidine - augm [..]
Ketamine: posologie et mécanisme
stimule AMPA (glutamate)
agit sur mTOR et BDNF
0.5 mg/kg IV single dose
quels antidepresseurs sont safe in breasfeeding?
Sertraline
Paroxetine
amitryptyline
imipramine
Vilazodone: mécanisme?
SPARI: serotonine partial agonist/reuptake inhibitor
inhibition SERT + agonist partiel 5HT2A (50/50) = moins de dysfonction sexuelle
comment mirtazapine peut traiter l’akatisie?
à dose 30-60 mg mirtazapine bloque les 5HT2A comme inverse agonist (comme clozapine) et enlève le signal inhibiteur sur la dopamine striatale
quels antiepileptiques interfèrent avec les contraceptifs oraux?
Phenobarbital, phenytoin, carbamazepine, felbamate, oxcarbazepine and topiramate = all enzyme-inducing antiepileptic drugs, decrease oral contraceptives (OCP) = breakthrough bleeding and contraception failure.
Valproic acid, benzodiazepines, gabapentin, lamotrigine, levetiracetam and tiagabine are nonenzyme-inducing antiepileptic drugs that do not affect the efficiacy of OCP. The American College of Obstetrics and Gynecologists (ACOG) states that, “although there are no published data to support this recommendation, it seems prudent to use a 30- to 35-mcg rather than a 20- to 25-mcg estrogen-containing oral contraceptive in women taking enzyme-inducing antiepileptic drugs”. Ref: http://www.aafp.org/afp/2008/0901/p634.html
quel antipsychotique n’a pas d’activité anticholinergique?
Ziprasidone demonstrates no anticholinergic activity, unlike clozapine, olanzapine, loxapine and quetiapine. Ref: Garnder & Teehan (ed). Antipsychotics and their Side Effects. Page 20.
facteurs de risque de diabète chez schizophrenes
Hx familiale
obésité
hypertension
prise des antipsychotique
Diabetes mellitus occurs at a rate that is 4 to 5 times higher in patients with schizophrenia compared to general population. In part, the life-style related risk factors for diabetes in the general population occur at a higher rate in patients with severe mental illnesses (obesity, smoking, physical inactivity, features of metabolic syndrome and poor dietary habits). In addition, the use of antipsychotics also increases the risk. Worryingly, in the CATIE schizophrenia study, a non-treatment rate of 45.3% was observed for diabetes in patients with schizophrenia. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3048500/
Sternbach’s triad for serotoninergic syndrome
altered mental status
neuromuscular abnormalities
autonomic hyperactivity.
Analysis of an extensive series of cases of serotonin toxicity found neuromuscular abnormalities to be the most reliable diagnostic finding. Clonus, hyperreflexia, and muscle rigidity nearly always are evident, and shivering may be present. Of these, hyperreflexia is a characteristic feature while hyperpyrexia is a life-threatening symptom. MAOI and SSRI combinations must be avoided at all costs as the risk of fatal serotonin syndrome is substantial. Ref: Dunkley EJ, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635-642.
quel diurétique a privilégier chez un pt sur Li?
Diuretics can increase serum lithium levels markedly by decreasing its clearance. Thiazides are the worst culprits while loop diuretics are somewhat safer. ACE Inhibitors decrease the excretion of Lithium and can also precipitate renal failure.
The correct answer is: Furosemide or Amiloride
quel Rx aggrave le psoriasis?
Lithium
quel benzo passent par métabosilme phase 2
Lorazepam, temazepam and oxazepam undergo direct phase 2 reactions.
A tricyclic with the best evidence for use in post-stroke depression
nortriptyline
A woman comes into Emergency Department with lethargy, nausea and diarrhoea with weight loss on a hot afternoon. She is taking some unknown psychotropic medication for a long time. She is recently started on ‘water tablets’ for swelling in her legs. Which of the following is a likely cause of her symptoms?
The presentation here is suggestive of lithium overdose or toxicity.
The best intervention for acute lithium toxicity with neurological symptoms
Haemodialysis
The best treatment for lithium-induced tremors
propranolol
tableau clinique de tremor induit par lithium
irregular, nonrhythmic tremor of the distal extremities, variable in both intensity and frequency
It is clinically differentiated from essential tremor and tremors due to anxiety and neuroleptics. The pathophysiologic mechanisms are hypothesized to be of peripheral origin. Propranolol, a blocker of beta-adrenergic receptors, is effective in treating lithium-induced non-toxic tremors on long-term administration.
Which classes of antidepressants are considered to be safe for breastfeeding mothers?
Antidepressants: Secreted in breast milk in very small quantities. Infant serum levels are low. SSRI (Fluoxetine, sertraline, paroxetine and citalopram) and tricyclic antidepressant ( except Doxepin ) are safe. Preferred Tricyclic antidepressants-Amitriptyline and imipramine. Sertraline is the first line of treatment in the USA. The samples for sertraline studies are large. Paroxetine has a lower milk/plasma ratio than fluoxetine and sertraline.
No studies of MAOI’s or bupropion use in breast feeding are available. MAOI’s should be stopped in mothers planning to breast-feed.
Which of the following drugs can alleviate the symptoms of drug craving by means of a partial agonistic action?
Varenicline is a partial nicotinic agonist. It alleviates the symptoms of nicotine craving and withdrawal through its agonist activity while inhibiting the effects of repeated nicotine exposure by its antagonist activity. Buspirone is also a partial agonist (at 5HT-1A), but it is not associated with anti-craving effects. Ref: http://www.medscape.com/viewarticle/559955_3
Which drug is contraindicated in angle closure glaucoma
Topiramate can increase intraocular pressure and can cause acute precipitation of angle closure glaucoma.
an important clinical difference between NMS and serotonin syndrome
Symptoms such as hyperreflexia and myoclonus are attributed to the enhanced release of serotonin in serotonin syndrome and are not seen in NMS.
risk of TD on antipsychotics
With every year of exposure to neuroleptics (typical antipsychotics), the risk of TD is noted to be 2-5%. This is somewhat lower than the risk of dystonia 2-10% that is seen mostly in the early phase of treatment and pseudo-parkinsonism which occurs in around 20% of cases. Approximately 50-55% of patients with Tardive Dyskinesia may show recovery within a year with antipsychotic reduction.
Risk factors for TD
older age of patients
female gender
the presence of organic brain damage
affective disorder
higher in those who have had acute EPSEs (Extrapyramidal side effects) early on treatment
Which measure can help reduce lithium-induced tremors?
Administer the lithium preparation in smaller, more frequent doses.
Propranolol, 30 to 160 mg/d, may also be helpful
Which pharmacological agent has a prominent heteroreceptor based action?
Mirtazapine is a NaSSA (Noradrenergic Specific Serotonergic Antagonist) that has a dual action -
(1) on the Alpha-2 system: blocking the alpha-2 autoreceptors, thus facilitating noradrenergic transmission and blocking the alpha-2 heteroreceptors located on serotonin nerve terminals, thus facilitating serotonin transmission.
(2) Direct antagonism of 5HT2 serotonin receptors, promoting 5HT1 mediated activity.
Which of the SSRI has notable anticholinergic activity?
Paroxetine may induce fewer adverse anticholinergic effects than tricyclics such as clomipramine, but among the SSRIs - it has the highest anticholinergic properties
interaction NSAID et Lithium
NSAIDs increase the plasma levels of lithium (>10 to >40% in some cases) by inhibiting the synthesis of renal prostaglandins and reducing renal blood flow. This increases renal reabsorption of both sodium and lithium.
interaction Lithium et Thiazide diuretics
The levels of lithium usually increase within ten days of a thiazide diuretic being prescribed.
Lithium and ACE
ACE inhibitors can reduce thirst, which can lead to dehydration, and increase renal sodium loss, leading to increased sodium reabsorption by the kidneys, causing an increase in lithium plasma levels.
Drug inducing hyperparathyroidism
Lithium
risk factors for TD
long-term use of typical neuroleptic exposure,
older age,
female gender,
the presence of affective features,
medical illnesses such as diabetes,
previous anticholinergic drug use, and
the presence of movement disorders prior to starting antipsychotics.
ECG changes at therapeutic doses of Li
Reversible flattening and inversion of T-waves are seen even at therapeutic doses but usually produce no clinical consequences. Br. J. Clin. Pharmac. (1980), 9, 599-604
taux d’arret des antidepresseurs et raisons selon CANMAT
nearly 30% of patients discontinue antidepressants within 30 days, and nearly 40% discontinue within 90 days. Lack of response, side effects and stigma are major reasons for the discontinuation. Extensive metabolizers of antidepressants are less prone to side effects; thus, they are less likely to discontinue early than poor metabolizers. Making patients aware of the lag in response time after initiation of treatment, the predicted course of response and adverse events can improve adherence. It is also important to emphasize the need to continue medications even when feeling better. Ref: Lam et al. Journal of Affective Disorders 117 (2009) S26–S43
CPA quidelines on starting doses of antipsychotics in schizophrenia
According to CPA guidelines for schizophrenia,
risperidone must be initiated in doses of 0.5 to 1.0 mg and titrated in doses of 0.5 to 1.0 every 3-4 days, aiming for 2-6mg, maximum being 8mg.
Quetiapine must be initiated in doses of 100 mg and titrated in doses of 100mg daily, aiming for 600 mg, the maximum being 800 mg per day.
Olanzapine must be initiated in doses of 5 to 10 mg and titrated in doses of 2.5 to 5.0 every 3-4 days, aiming for 10-20mg, maximum being 20 mg.
Aripiprazole (not included in CPA guidlines 2005) should be started at a dose of 10mg/day, aiming for 20mg/day, the maximum being 30mg/day (according to Maudsley Prescribing Guidlines 9th edn) Also see Canadian Psychiatric Association. (2005). Clinical practice guidelines: treatment of schizophrenia. Canadian Journal of Psychiatry, 50(13), 7S.
known complication of combining St. John’s Wort with SSRIs
Serotonin syndrome
An initial meta-analysis of St Johns’s Wort (Hypericum perforatum) published in 2001 showed an adjusted RR of 1.94 (1.5 to 2.5) in favour of SJW. But when 3 later studies were added, and the data was re-analysed, this effect size dropped to 1.30 (1.0 to 1.60). A more recent meta-analysis with many new large trials found St. John’s wort to be as effective as tri- or tetracyclic antidepressants and SSRIs in mild to moderate MDD (Linde et al., 2008) but the data was limited for severe MDD. St. John’s wort is certainly more tolerable than the comparator medications. It can increase the effects of conventional SSRIs, but this combination can cause serotonin syndrome and has a risk of inducing hypomania in some patients. Ravindran et al. Journal of Affective Disorders 117 (2009) S54–S64
cardiac effects of lithium
sinus sick syndrome
unmasks or aggravates Brugada (contraindicated if Brugada or family Hx of Brugada)
T wave inversion or flattening (similar to hypokalemia) - no clinical significance
vrai ou faux: biodisponibilité d’Aripiprazole est augmentée par la prise de nourriture
Faux
diminuée
quelles combinaisons d’antidepresseurs avec mirtazapine sont avantagieuses?
Adding mirtazapine to either venlafaxine or SSRI can improve sexual dysfunction and boost remission rates.
STAR*D evaluated a combination of venlafaxine with mirtazapine in open-label condition; and bupropion + citalopram under RCT condition. There is no need to combine SNRI and SSRI in most patients as a low dose of SNRI generally has a serotonergic profile, with no additional advantage gained from adding an SSRI agent.
SSRI et grossesse: effets?
SSRIs are not associated with any notable increase in major malformations (exception- paroxetine). However there is a 13.3% increase in spontaneous abortion (also seen with mirtazapine and bupropion), decreased gestational age (mean 1 week) and low birth weight (mean 175 gms). Paroxetine, particularly high dose first-trimester exposure, is clearly linked to cardiac malformations - VSD and ASD.
Third-trimester use can give rise to neonatal complication due to abrupt withdrawals, which are reversible.
The most common neurological side effect seen when using fluoxetine
tremors
The most common psychiatric side effect of levodopa
Nightmares (30%)
use of benzos during pregnancy: risks?
Benzodiazepines use during the first trimester is associated with a 0.6% risk of an oral cleft, CNS and urinary tract malformation. Neonatal toxicity (withdrawal symptoms), respiratory depression, muscular hypotonia (floppy baby syndrome) are also reported.
What drug should be given mother and neonate after delivery when valproate or carbamazepine is used during pregnancy?
Prophylactic Vitamin K
risk of haloperidol and lithium combination
Although haloperidol and lithium have been used safely together in many patients, there have been some reported cases of encephalopathic syndrome consisting of severe neurotoxic effects and extrapyramidal symptoms, followed by irreversible brain damage, associated with the combination.
The least anticholinergic tricyclic antidepressant is
Desipramine is the least anticholinergic of all TCAs. In the order of increasing anticholinergic activity, we can place nortriptyline, imipramine, doxepine, clomipramine and amitriptyline. Ref: Arnold et al. Psychopharmacology (Berl). 1981;74(4):325-8. Also see Remick, Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(2-3):225-31.
In a patient who is prescribed phenelzine, which of the following medication must be avoided for the fear of drug interaction resulting in serotonin syndrome?
meperidine
MAOIs potentiate the actions of general anaesthetics, sedatives, including alcohol, antihistamines, centrally acting analgesics (particularly pethidine / meperidine due to an enhanced release of 5-HT) and anticholinergic drugs. Thus, sever serotonin syndrome may result with co-administration of pethidine /meperidine and MAOIs.
Peak plasma levels of extended release preparation of divalproex sodium is reached by
Peak plasma levels of extended release preparation of divalproex sodium is reached by 4 to 12 hours. For the regular divalproex sodium preparation, the peak levels are reached by 3 to 8 hours.
Weight gain caused by clozapine is possibly related to
5HT2-c receptor antagonistic activity
The mechanism by which weight gain occurs during treatment with antipsychotics is poorly understood, but the broader receptor affinities of the agents and their antagonism of histamine H1 and serotonin 5-HT2C receptors have been implicated.
