Psychopharmacologie Flashcards
(135 cards)
1
Q
Ejaculation retrograde: psychotropes avec quel mécanisme d’action sont en cause?
A
bloqueurs alpha1
anthicholinergiques
antihistaminergiques
2
Q
Anorgasmie et éjaculation tardive: quels mécanismes sont en cause?
A
anti alpha1 stimulation 5HT2A (SSRI) et 5HT2C récepteurs
3
Q
mécanismes d’action de Mirtazapine
A
block alpha2 –> augmente stransmission NE et 5HT (via cortex-raphe)
antagonist 5HT2A –> augmente activité 5HT1-R
inhibition 5HT3
4
Q
Mirtazapine: quels effets sont particulier vs SSRI?
A
diminution latence sommeil
augmentation durée sommeil
moins de dysfonction sexuelle vs SSRI
plus d’augmentation poids et appetit vs SSRI
effet antiémétique
5
Q
Mirtazapine: quels effets liés à l’inhibition 5HT3?
A
antiémétique
stimulation fx cognitives
6
Q
Mirtazapine: effet secondaire particulier
A
neutropénie
7
Q
Mirtazapine: interactions significatives
A
tabagisme: diminution de [..]
SNRI (Effexor) - augm [..] x3-4
cimetidine - augm [..]
8
Q
Ketamine: posologie et mécanisme
A
stimule AMPA (glutamate)
agit sur mTOR et BDNF
0.5 mg/kg IV single dose
9
Q
quels antidepresseurs sont safe in breasfeeding?
A
Sertraline
Paroxetine
amitryptyline
imipramine
10
Q
Vilazodone: mécanisme?
A
SPARI: serotonine partial agonist/reuptake inhibitor
inhibition SERT + agonist partiel 5HT2A (50/50) = moins de dysfonction sexuelle
11
Q
comment mirtazapine peut traiter l’akatisie?
A
à dose 30-60 mg mirtazapine bloque les 5HT2A comme inverse agonist (comme clozapine) et enlève le signal inhibiteur sur la dopamine striatale
12
Q
quels antiepileptiques interfèrent avec les contraceptifs oraux?
A
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
13
Q
quel antipsychotique n’a pas d’activité anticholinergique?
A
Ziprasidone demonstrates no anticholinergic activity, unlike clozapine, olanzapine, loxapine and quetiapine. Ref: Garnder & Teehan (ed). Antipsychotics and their Side Effects. Page 20.
14
Q
facteurs de risque de diabète chez schizophrenes
A
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/
15
Q
Sternbach’s triad for serotoninergic syndrome
A
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.
16
Q
quel diurétique a privilégier chez un pt sur Li?
A
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
17
Q
quel Rx aggrave le psoriasis?
A
Lithium
18
Q
quel benzo passent par métabosilme phase 2
A
Lorazepam, temazepam and oxazepam undergo direct phase 2 reactions.
19
Q
A tricyclic with the best evidence for use in post-stroke depression
A
nortriptyline
20
Q
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?
A
The presentation here is suggestive of lithium overdose or toxicity.
21
Q
The best intervention for acute lithium toxicity with neurological symptoms
A
Haemodialysis
22
Q
The best treatment for lithium-induced tremors
A
propranolol
23
Q
tableau clinique de tremor induit par lithium
A
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.
24
Q
Which classes of antidepressants are considered to be safe for breastfeeding mothers?
A
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.
25
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
26
Which drug is contraindicated in angle closure glaucoma
Topiramate can increase intraocular pressure and can cause acute precipitation of angle closure glaucoma.
27
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.
28
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.**
29
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
30
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
31
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.
32
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
33
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.
34
interaction Lithium et Thiazide diuretics
The levels of lithium usually increase within ten days of a thiazide diuretic being prescribed.
35
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.
36
Drug inducing hyperparathyroidism
Lithium
37
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.
38
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
39
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
40
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.
41
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
42
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
43
vrai ou faux: biodisponibilité d'Aripiprazole est augmentée par la prise de nourriture
Faux
diminuée
44
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.
45
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.
46
The most common neurological side effect seen when using fluoxetine
tremors
47
The most common psychiatric side effect of levodopa
Nightmares (30%)
48
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.
49
What drug should be given mother and neonate **after delivery** when valproate or carbamazepine is used during pregnancy?
Prophylactic Vitamin K
50
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.
51
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.
52
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.
53
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.**
54
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.
55
Rcommendation for use of ziprazidone in schizophrenia
Ziprasidone appears to be effective in the treatment of secondary negative symptoms with some evidence supporting its use in primary negative symptoms as well. A starting dose of 40mg, and a target dose of 40-80mg for first epsiode and 80-160mg for established schizophrenia is recommended, with maximal dose being 160mg/day. Ref: WFSBP Guidelines. The World Journal of Biological Psychiatry, 2012; 13: 318–378
56
A 85-year-old lady with a history of cerebrovascular disease, atrial fibrillation, and prior myocardial infarction presents with moderately severe agitated depression with features of self-neglect. She is taking warfarin, lisinopril, and has been on a maximum dose of venlafaxine for last four weeks with moderate effect. The most appropriate intervention to manage the depression is
Add mirtazapine
Mirtazapine works well in combination with venlafaxine; it will be the ideal choice in the above scenario.
57
Disulfiram acts on
Aldehyde dehydrogenase
In usual doses, disulfiram acts via inhibition of acetaldehyde dehydrogenase that produces deterrent effects when alcohol is consumed (flush reaction).
58
Propriétés atypiques d'amilsulpride
Amisulpride has atypical antipsychotic activity as it produces very low EPSEs and is more D2/3 selective compared to other typicals. But it does not have 5HT2A blockade like other newer atypicals
59
The term potency of a drug refers to
amount required to produce an effect
60
management of TD
**Discontinuing or a dose reduction for antipsychotics** had been recommended to increase the odds of TD resolution, but this **may lead to an initial worsening of TD in 33% to 53% of patients**. **_Clozapine_** is so fr the best agent incases of intractable TD who still require an antipsychotic. Among atypicals, there is little difference in the propensity to cause TD, but switching between them can be still effctive in reducing TD. It is generally thought that **anticholinergics can worsen TD**, and log term prescription of them is actually a risk factor for TD.
61
interaction entre grapefruit juice and carbamazepine
bioavailability of carbamazepine is increased
Grapefruit juice increases the bioavailability of carbamazepine by inhibiting CYP3A4 enzymes in gut wall and in the liver.Ref: http://www.ncbi.nlm.nih.gov/pubmed/9757152
62
blood effects of carbamazepine
Blood dyscrasias occur in about 2% of patients on carbamazepine, with **transient leucopenia** that resolves with continued treatment being the most common effect, though in some cases this may progress to a **serious bone marrow suppession and aplastic anaemia**.
63
interaction benzo - valproate
valproate displaces protein binding of benzodiazepines, the net effect is an increase in benzodiazepine levels in the plasma
64
interaction benzo - chronic smoking
Chronic smoking induces microsomal enzymes and reduces benzodiazepine levels
65
interaction benzo - ketoconazole et omeprazole
Ketoconazole and omeprazole can reduce benzodiazepine metabolism and result in elevated and prolonged plasma levels.
66
Which one among the following is a weak inhibitor of cytochrome P450?
Paroxetine
Citalopram
Fluoxetine
Fluvoxamine
Citalopram and Escitalopram do not produce cytochrome P 450 inhibition. Fluoxetine, Fluvoxamine and Paroxetine are potent inhibitors of several hepatic cytochrome enzymes. Sertraline is safer, while citalopram is the safest. Citalopram is a weak inhibitor of 2D6.
67
true or false: lithium should be not prescribed to breastfeeding mothers
True
Lithium when used during breastfeeding could produce l**ethargy, hypotonia, hypothermia, cyanosis, and electrocardiography changes in the infant**. For these reasons, it is not advisable to prescribe lithium to breastfeeding mothers. Ref: http://www.aafp.org/afp/2008/0915/p772.html Also see Yatham et al., Bipolar Disorders 2005: 7(Suppl. 3): 5–69
68
Olanzapine is primarily metabolised by the enzyme
CYP1A2
and to a lesser extent by CYP2D6
69
interaction fluvoxamine et clozapine
CYP1A2 inhibition - clozapine increase
Fluvoxamine is a strong CYP1A2 inhibitor and thus increases the ratio of clozapine to its primary metabolite N-desmethylclozapine. Ref: http://www.ncbi.nlm.nih.gov/pubmed/26626327
70
A patient with inadequate response to despiramine is prescribed paroxetine as an add-on antidepressant by her family physician. Which of the following interactions is likely to be important in this case?
CYP2D6 inhibition by paroxetine
Desipramine is extensively metabolized via the CYP2D6 system. When paroxetine is co-administered with desipramine in extensive metboisers, there is a 5-fold decrease in clearance of desipramine as paroxetine is a potent inhibitor of CYP2D6. Ref: http://www.ncbi.nlm.nih.gov/pubmed/8513845
71
The active metabolite of imipramine is
Desipramine
72
Which one among the following has a stimulant-like effect?
Lofepramine
Amitriptyline
Desipramine
Imipramine
Desipramine has relative selectivity for noradrenaline re-uptake and has a stimulant effect
73
A patient on mirtazapine treatment develops rapidly spreading bacterial infection. Which of the following must be immediately checked?
Differential count
Severe neutropenia, defined as less than 0.5 x 10^9/L mature neutrophil cells, is a potentially life-threatening side effect of mirtazapine, occurring with a risk of up to 1 in 1,000 instances
74
clozapine toxicity: signs
drowsiness, lethargy, coma, confusion, agitation, delirium, hyperreflexia, convulsions, hypersalivation, mydriasis, blurred vision, fluctuating body temperature, tachycardia, hypotension, collapse, cardiac arrhythmias, heart block, respiratory depression or failure.
75
A new drug A is a non-competitive antagonist at NMDA receptors. If availability of glutamate at the receptor sites is increased experimentally after administering drug A, which of the following can happen?
Effect of drug A is partially reversed
Noncompetitive antagonists alter the receptor site in some way so the effects can be reversed only partially by increasing the dose of the agonist drug. Non-competitive antagonism reduces both the potency and the efficacy of agonists.
76
interaction floxetine - other drugs
Fluoxetine increases concentration of haloperidol, carbamazepine and phenytoin. Fluoxetine enhances the effects of oral anticoagulants and propranolol
77
SSRI and protein binding
"Fluoxetine, paroxetine and sertraline are highly protein bound (ie, \> 95%). In contrast, the protein binding of citalopram (50%) and fluvoxamine (77%) is considerably less. High protein binding raises the possibility of displacement interaction with other highly protein bound drugs. However, SSRIs are weakly bound primarily to alpha1-acid glycoprotein. Perhaps for this reason, even the highly protein bound SSRIs have not been found to increase the free fraction of concomitantly administered drugs that are also highly protein bound". Ref: Excerpt from http://www.preskorn.com/books/ssri\_s6.html
78
The mechanism of action for Sodium valproate
Valproate acts at sodium channels, at several important steps in GABA metabolism leading to GABA potentiation, and on the activity of histone deacetylase (which influences gene transcription).
79
The pharmacological activity of benzodiazepines depends on its action on which of the following receptors?
## Footnote
GABA-a receptor complex
GABA-a and GABA-b receptor complex
5HT1-A receptor complex
GABA-b receptor complex
GABA-a receptor complex
80
gabapentin in renal disease
Gabapentin doses must be reduced for patients with renal insufficiency as it is solely excreted by kidneys
81
Which of antidementia drugs acts directly on nicotine receptors?
Galantamine, unlike the other anticholinesterases in clinical use, is derived from the alkaloids from the daffodil and snowdrop family. It is a reversible, competitive inhibitor of acetylcholinesterase with some inhibitory action on butyrylcholinesterase. It is also an agonist at nicotinic receptor sites. Although a clinically effective drug, galantamine frequently causes gastrointestinal side effects.
82
Mechanism of action of acamprosate is
Glutamate antagonism
Acamprosate's mechanism is not well understood but is thought to involve interference with excitatory amino acids such as glutamate that may be involved in alcoholic relapse.
83
When prescribing donepezil for a patient with dementia, which of the following must be monitored periodically?
heart rate
Donepezil increases the risk of bradycardia, in a dose-dependent fashion. Patents with bradycardia are more linkely to have falls, syncope, or need a pacemaker. It is important tomonitor heart rate. Ref: http://www.ncbi.nlm.nih.gov/pubmed/19793162
84
Tx of SIADH
water restriction and mild diuresis with a loop diuretic.
85
The mechanism of action of barbiturates is by
Increasing the duration of chloride channel opening
86
SGAs sans effet sur QT
Lurasidone
Abilify
87
QT élevé chez femmes
plus de 470
88
QT élevé chez hommes
plus de 450msec
89
vrai ou faux: tous les antipsychotiues augmentent les risque de sudden death
vrai
x2
90
V ou F: femmes ont plus de risque de TdP des Rx qui prolongent QT
V
91
Quel SSRI a un effet sur QT dose-dépendant?
**Citalopram**
alerte sur 40mg et plus
chez personnes âgées: pas plus de 20 die
**Fluoxetine** - alerte sur usage chez Pt avec risque
92
management of rapid switch BD
Epival
Li+carbamazepine
93
The mechanism of action of barbiturates
Barbiturates act on GABA receptors and serve to **increase the duration of chloride channel opening**
94
definition of clearance
the volume of blood cleared of a particular drug in unit time. It is specific for each drug and does not depend on drug concentration in plasma (because if concentration increases, elimination will also increase under first order kinetics).
Total body clearance depends on renal and non-renal clearance such as sweat, bile etc.
95
particularité de first order kinetics
more drug in the body = more elimination
First-order elimination kinetics **depends on the concentration of only one reactant (drug) and a constant fraction of the drug in the body is eliminated per unit time**. The rate of elimination is proportional to the amount of drug in the body. The majority of drugs are eliminated in this way. For drugs with first order kinetics, **clearance is constant irrespective of dose** consumed because the rate of elimination is directly proportional to plasma level.
96
zero order kinetics - examples drugs
elimination is constant
like cars moving throuth a road block
**ROH**, **phenyroin**, salicylates, cisplatin, **fluoxetin**
97
trazodone: mecanismes action
serotonin antagonist-reuptake inhibitor
antagonist 2HT2A
tres faible affinité au SERT - seulement à fortes doses
alpha 1 blocker
anti-H1
anti-5HT2C
98
difference antre trazodone et nefazodone
nefazodone - inhibiteur NET
trazodone - anti-H1
99
atomoxtine (Straterra): particularité pharmacodynamique
99% bound to plasma albumin
100
excretion de pregabalin (Lyrica)
renale
101
Which of street drugs is called as a dissociative anaesthetic
ketamine
(not same as psychological dissociation)
102
combinaison Li + carbamazepine : side effect
hypothyroidism
Lithium "produces a robust reversal of carbamazepine-induced leukopenia, increasing WBCs, predominantly neutrophils. The combination produced additive antithyroidal effects, resulting in greater decreases in T4 and free T4 than with carbamazepine alone
103
quels psychotropes agissent sur la transformation de codeine en morphine?
CYP2D6 inhibitors
This enzyme is inhibited by certain SSRIs (ex **paroxetine, fluoxetine**) and some TCAs. The CYP2D6 enzyme also breaks down hydrocodone and dihydrocodeine to their active metabolites (hydromorphone and dihydromorphine) which in turn, like morphine, undergo phase 2 glucuronidation
104
Which of the antidepressants can reduce the efficiacy of tamoxifen?
lequel est le plus safe?
CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion)
Venlafaxine is safe
105
symptomes de hyperprolactinémie
galactorrhoea, amenorrhoea, hypogonadism, gynaecomastia, sexual dysfunction and an increased risk of osteoporosis
106
common side effects of MAOI
insomnia, postural hypotension, peripheral oedema, restlessness, nausea, dizziness, sexual difficulties, sweating and tremor
107
effets cardiaques des TCA
wide QRS
AV block
QT increase
T wave changes
no effect on cardiac output
108
quels psychotropes augmentent risque de GI bleed chez vieux?
SSRI
109
which drug can help reducing sweating induced by Effexor and other SNRI?
Terazosin, a blocker of alpha-1 receptors
110
Tetrabenazine: utilisation
Tetrabenazine is a monoamine-depleting agent. It is approved by the FDA for the treatment of chorea in Huntington's disease. It is also used occassionally in treating tardive dyskinesia.
111
Which is true regarding the relapse of mood episodes that occurs after abruptly stopping lithium in patients with bipolar disorder?
Mania occurs more commonly than depression after discontinuing lithium abruptly in patients with bipolar disorder.
112
drugs with a pronounced effect on QTc Prolongation
sertindole, thioridazine, pimozide and droperidol
There have been reports of sudden death with Pimozide due to drug-induced QT prolongation.
113
Which of drug is associated with nephrolithiasis
Topiramate is a weak inhibitor of carbonic anhydrase and can promote the development of renal stones.
114
analgésique à risque de syndrome sérotoinergique
Tramadol increases central and peripheral serotonin levels. In addition, dugs that induce CYP3A4 such as carbamazepine can also increase this risk, in addition to serotonergic drugs such as SSRIs.
115
risque de priapism: quel Rx?
Trazodone
risperidone
116
Quelle est relation dose response des TCA?
Nortriptyline and impiramine have curvilinear dose response relationships, with a therapeutic window for optimal efficacy. **Only desipramine seems to have a linear dose response relationship**. The poor dose–response relationship and narrow therapeutic index of the TCAs **necessitate therapeutic drug monitoring. At present, ithis is recommended for the TCAs imipramine, desipramine, and nortriptyline.**
117
Risk factors for QTc prolongation
female gender, extremes of age, extreme physical exertion, stress or shock, anorexia nervosa, left ventricular hypertrophy, myocardial infarction, hypokalemia, hypocalcaemia and hypomagnesemia, bradycardia, myocarditis and congenital long QT syndrome
118
Among the atypical antipsychotic agents, which ones have less effect on weight gain?
Among the atypical antipsychotic agents, clozapine and olanzapine have the greatest potential to induce weight gain, while **aripiprazole and ziprasidone** the least
119
potentiel des SSRI for NE reuptake inhibition
The least potency for NE reuptake inhibition among SSRIs is seen for escitalopram, followed by citalopram, fluvoxamine, sertraline and fluoxetine. Paroxetine has a higher potency for NE reuptake inhibition than other SSRIs.
120
Akathisia: prise en charge
beta1 blockers - the best - betaxolol
lipophilic beta blockers - propranolol
dopamine agonists - amantadine, rotigotine
benzos- lorazepam
gabapentin
trazodone (antagonist of 5HT2A)
mirtazapine (idem)
modafinil
121
mechanism behind akathisia
5HT-2A agonism
122
treatment of paraphilias
external control
reduce sex drive:
partial reduction: SSRI, Cyproterone (androcur), Provera
ablation of testosterone Lupron, zoladex
Inhibit peripheral testo: finasteride
123
Interaction Abilify et Bupropion
Bupropion (CYP2D6 inhibitor) augmente concentration de l'abilify
124
meilleure combinaison pour éviter effets sur fonctions sexuelles
Vilazodone 20 AM + Mirtazapine 15 HS
while vortioxetine has low risk for sexual side effects at the 5 and 10mg doses, it has higher risk at the 20mg dose. combinaison Vortioxetine 20 + Bupropion 150 : bupropion doubles the dose of vortioxetine pushing it to 40mg dose which increases sexual side
effects
125
Which of the following are least likely to cause serotonin syndrome when combined with another
serotonergic agent?
a. Desipramine
b. Sertraline
c. Levomilnacipran
d. Moclobemide
Desipramine has no SRI activity and is pure NRI. All other listed agents will increase serotonin levels
126
AP avec faible effet sur QT
Lurasidone
Aripiprasole
Paliperidone
Asenapine
127
critères QT
D/C if QT\>500
men \>450, women\>460
128
ATD le moins lié aux protéines
Escitalopram (Cipralex)
129
ATD se lient le plus aux proteines
Fluoxetine, Paroxetine, Sertraline
130
ATD avec le moins d'interactions
Citalopram, Escitalopram, Sertraline
131
black box pour Celexa et Cipralex
CELEXA
max 40 mg pour adulte
max 20 mg pour \>65ans, pb hépatique ou prise de Cimetidine
CIPRALEX
20 mg
10 mg
132
management of hyperhidrosis
clonidine 0.1
terazocin 1-2 mg
benztropine 1 mg
oxybutynin 5 mg qd-tid
133
management of sialorrhea
glycopyrrolate 1 bid
atropine sulfate 1% sublingually
ipratropium 0,03% sublingually
metoclopramide
134
Dx of SIADH
low Na + low serum osmolarity
serum osmolarity \< urine osmolarity
increased urine Na (\>30 mEq)
135
comment distinguer SIADH de la polydipsia?
SIADH: urine concentrée
polydispsia: urine diluée
