Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
154 Cards in this Set
- Front
- Back
|
Definition of affective disorder?
|
Mental illness characterized by pathological changes in mood
Nb! - Not thought, compared with schizophrenia |
|
|
What are the unipolar disorders?
|
1. Depression
2. Mania |
|
|
Definition depression?
|
Pathological depressed mood - life time prevalence = 17%
|
|
|
Definition mania?
|
Excessive elation and accelerated psychomotoric activity (rare)
|
|
|
Definition bipolar disorder?
|
Manic- depressive disorder
= Cycling mood Person experience severe - Highs = Mania - Lows = Major depressive episoides Prevalence = 1-5% Stronger in genetic background |
|
|
Signs of depression?
|
- Depressed mood
- Loss of interest or pleasure - Feelings of guilt or low self-worth - Disturbed sleep or appetite - Low energy - Poor concentration |
|
|
To be characterized as depression - what must be present?
|
1. Depressed mood
2. Loss of interest or pleasure + 5 or more of following criteria: - Significant weight loss / gain - Insomnia / hypersomnia - Psychomotor agitation or retardation, fatigue - Feelings of worthlessness or excessive guilt - Diminished ability to think or concentrate / indecisiveness - Recurrent thoughts of death or suicidal ideation without specific plan / or suicide attempt! |
|
|
What is not depression?
|
- Passing 'blue mood'
- Not a sign of personal weakness - People cannot just pull them together |
|
|
2 neurobiological theories of depression?
|
1. Monoamine (catecholamine) theory
2. 'Receptor theory' |
|
|
Monoamine (catecholamine) theory was suggested in?
|
1965
|
|
|
What is the monoamine (catecholamine) theory for depression?
|
Deficiency of central noradrenergic and/or serotonergic transmission in CNS - as the underlying biological basis
|
|
|
Monoamine theory is supported by?
|
- Pharmacological effects of antidepressants (TCA, MAOI)
- Reserpine against hypertension induced depression in the past |
|
|
Monoamine theory is contradicted by?
|
- Several drugs that increase amount of these NT's but unable to treat depression (cocaine)
- Antidepressants induce rapid NT change - but onset of action seen in patient is significantly delayed |
|
|
What is the 'receptor theory' of depression?
|
Problem in up-regulation of post-synaptic receptors and alterations in their sensitivity
|
|
|
What supports the 'receptor theory'?
|
Antidepressant treatment increase amount of monoamines in CNS - and gradually normalize density / sensitivity of their receptors
But precise pathophysiology remain unsolved!!! |
|
|
3 most famous pharmacotherapies for depression?
|
1. TCA
2. MAOI 3. SSRI |
|
|
TCA means?
|
Tricyclic antidepressants
|
|
|
MAOI means?
|
Monoamine oxidase inhibitors
|
|
|
SSRI means?
|
Selective serotonin Re-uptake inhibitors
|
|
|
Duration of depression treatment?
|
6 months after recovery from 1st episode
Maybe lifelong in recurrent depression |
|
|
Non-pharmachological treatments of depression?
|
- Psychotherapy
- Light therapy - Electroconvulsive therapy (ECT) |
|
|
TCA's principal mechanism of action?
|
Block reuptake of monoamine neurotransmitters:
- Noradrenaline (NE) - Serotonin (5-HT) By competition for binding site of carrier protein: - NET - SERT |
|
|
What other receptors are also blocked by TCA's?
|
H1-receptors
a-receptors M-receptors |
|
|
The 4 most important TCAs are?
|
1. Imipramine
2. Desimipramine 3. Amitriptyline 4. Nortitrptyline |
|
|
Desimipramine is active metabolite of?
|
Imipramine
|
|
|
Nortriptyline is the active metabolite of?
|
Amitryptiline
|
|
|
TCA's are administered how? Why?
|
Orally
- Rapid absorption - Extensive first pass effect |
|
|
TCA's have a strong binding to?
|
- Plasma proteins (95% bound)
- Tissues - high lipophilicity - large distribution |
|
|
Can you use dialysis in acute TCA intoxication?
|
No use - due to the high lipophilicity
|
|
|
Where and by what is TCA's biotransformed?
|
Liver by CYP450 - N-demetyhylation and tricyclic ring hydroxylation
|
|
|
Excretion of TCA's?
|
First glucoronidation --> Then inactive metabolites excreted in urine
|
|
|
Half life of TCA's?
|
10-80 hours - elderly even longer, so risk for accumulation
|
|
|
Adverse effects of TCA's?
|
- Anticholinergic (atropin like) due to M-blockage
- Postural (orthostatic) hypotension due to a-blockage of adrenergic transmission + reflex tachycardia - Sedation due to H1 blockage - Sexual dysfunction |
|
|
Symptoms of M-blockade?
|
- Dry mouth, blurred vision
- Constipation, urinary retention - Palpitations, tachycardia |
|
|
Delay of effect in TCA's?
|
2-4 weeks
|
|
|
Acute intoxication of TCA's affect mostly?
|
CNS and heart
|
|
|
Effects on CNS from acute TCA intoxication?
|
- Atropine like effects
- Excitement, hallucinations, delirium, convulsions - Coma and respiratory depression may follow |
|
|
What cardiac effects does acute TCA intoxication have?
|
- Tachycardia (antimuscarine action)
- Atrial or ventricular extrasystoles - QRS widening - QT elongation - Ventricular fibrillation and sudden death - Hypotension |
|
|
Treatment of acute TCA intoxication?
|
Diazepam (for seizures)
|
|
|
MAOI are derivatives from?
|
Iproniazide
|
|
|
Prinicipal mechanism of action of MAOI?
|
Inhibit intracellular enzyme MAO in CNS neurons - so degradation of catecholamines and serotonin decrease
--> Higher levels of catecholamines and serotonin (systemic monoamine pool) |
|
|
What happens if you give MAOI to non-depressed subjects?
|
Increased motor activity
Euphoria, excitements |
|
|
2 classes of MAOI drugs?
|
1. Irreversible non-selective inhibitors
2. Reversible inhibitors of MAO-A |
|
|
Common name for irreversible non-selective MAO inhibitors?
Characteristics? |
Hydrazides
Long lasting up to 2 weeks |
|
|
Examples of irreversible non-selective MAO inhibitors?
|
Tranylcypromine
Phenelzine |
|
|
Example of reversible inhibitors of MAO-A?
|
Moclobemide
|
|
|
Adverse reactions of MAOI?
|
Postural hypotension
CNS stimulation - Tremors, insomnia, convulsions Weight gain (higher appetite) Severe hepatotoxicity (rare) |
|
|
Most serious problem with MAOI's?
|
The interaction with food
|
|
|
What reaction with food does MAOI's have?
|
Tyramine 'cheese and wine' reaction
Cause - Hypertensive crisis - Severe headache - Potential fatal intracranial hemorrhage |
|
|
What is tyramine?
|
Natural indirect sympathomimetic produced by fermentation
Normally metabolized by MAO in gut and liver - but after MAOI, tyramine bioavailability is much higher |
|
|
With MAOI one should restrict what foods?
|
- Maturing cheeses
- Wine - Beer - Yoghurt - Bananas |
|
|
MAOI cause hypertensive crisis when taken together with?
|
TCA
Levodopa |
|
|
MAOI cause serotonin syndrome when taken together with?
|
TCA
SSRI Opioids (pethidin) |
|
|
What characterize serotonin syndrome?
|
Confusion
Agitation Excitation Tremor Feer Sweating Nausea Diarrhea Sleep disruption |
|
|
MAOI prolongs and profounds effect of?
|
Benzodiazepines
Antihistamines Alcohol |
|
|
Principal mechanism of action of SSRI?
|
Selective inhibition of 5-HT (serotonin) reuptake (SERT)
Both on - Autoreceptors (5-HT 1A) - Postsynaptic receptors (5-HT 2A) |
|
|
Other indications for SSRI other than depression?
|
Anxiety
Bulimia nervosa Gambling Drug withdrawal |
|
|
Most important SSRI+
|
Fluoxetine
Fluvoxamine Paroxetine Sertraline Citalopram |
|
|
Administration of SSRI?
|
Oral - good absorption
|
|
|
Half-life of SSRI?
|
Fluoxetine = 50h
It's metabolite = 240h |
|
|
SSRI increase effect on what other drugs?
|
b-blockers
Benzodiazepines |
|
|
What are some other atypical antidepressants?
|
SNRI
NDRI NaRI SARI |
|
|
SNRI means?
|
Serotonin and noradrenaline reuptake inhibitors
|
|
|
Example of SNRI?
|
Venlafaxine
|
|
|
Characteristics of SNRI?
|
Like TCA - with improved adverse reactions
|
|
|
NDRI means?
|
Noradrenaline and dopamine reuptake inhibitors
|
|
|
Example of NDRI?
|
Bupropion
|
|
|
Characteristics of NDRI?
|
CNS activating effects - used for
- Severe depression + smoking cessation treatment Adverse reactions - Insomnia - Restlessness |
|
|
What does NaRI mean?
|
Noradrenaline reuptake inhibitors
|
|
|
Example of NaRI?
|
Reboxetine
|
|
|
When are NaRI used?
|
Severe depression treatment
Adverse reactions - Dry mouth - Headache - Dysuria - Sweating |
|
|
SARI means?
|
Serotonin antagonist / reuptake inhibitors
|
|
|
Examples of SARI's?
|
Trazodone
Nefazodone (newer and improved) |
|
|
When are SARI's used?
|
In depression with significant anxiety and sleep disturbances - work like TCA
|
|
|
What is serotonin syndrome?
|
Serotonin system overstimulation
|
|
|
What drugs may induce serotonin syndrome?
|
SSRI
MAOI TCA Venlaxafine Nefozadone Pethidine Tramadol |
|
|
Symptoms of serotonin syndrome?
|
Psychiatrical
- Anxiety - Confusion - Hypomania - Agitation Neurological - Tremor - Myoclonus - Hyperreflexia - Ataxia GIT - Nausea - Vomiting CVS - Hypertension tachycardia Fever, sweating |
|
|
Management of serotonin syndrome?
|
Benzodiazepines
5-HT blockers like - Methysergid - Cyproheptadine - Propranolol |
|
|
What are the most famous 'mood stabilizers'?
|
Lithium
Valproate Carbamazepine Lamotrigine |
|
|
Mechanism of action of lithium?
|
Elusive - but effects on 2nd messenger systems (IP3)
|
|
|
Pharmacokinetics of lithium?
|
1. Oral administration
2. Extracellular distribution 3. 95% eliminatino in urine - HL 24H - Second excretatory phase is 2 weeks 4. Only 20% filtered by GF - 80% reabsorbed |
|
|
Acute intoxication symptoms of lithium?
|
GIT
- vomiting - Diarrhea CNS - Confusion - Tremor - Ataxia - Convulsions - Coma Heart - Arrhytmias - Hypotension |
|
|
Lithium toxicity of long-term therapy?
|
Renal toxicity
|
|
|
Adverse reactions of lithium?
|
- Polyuria
- Polydipsia - Weight gain - GIT disturbances - Alopecia |
|
|
Drug interactions of lithium?
|
Thiazides - increase reabsorption thus dander for intoxication!
|
|
|
Schizoaffective disorder?
|
Disorder of both thought and mood
|
|
|
Delusional disorder?
|
Paranoid psychosis
|
|
|
Substance-induced psychotic disorder?
|
Use / withdrawal of:
- Amphetamines - Cocaine - Alcohol - LSD - Psilocybe |
|
|
Definition of schizophrenia?
|
Chronic disorder of thought - characterized by acute psychotic episodes
Periods of impaired psychosocial functionality and residual symptoms in between Typical = Loss of touch with reality |
|
|
Prevalence of schizophrenia?
|
1% of population
|
|
|
Onset of schizophrenia?
|
Adolescence / early adulthood
|
|
|
Etiology of schizophrenia?
|
Unclear
- Genetic component - Neurodevelopmental theory |
|
|
What is neurodevelopmental theory?
|
Aberrant intrauterine brain development, due to infections or hypoxia, causing abnormal neuronal:
- Shape - Positions - Connections |
|
|
Brain morphology of schizophrenia?
|
Brain asymmetry with decreased
- Cortical size - Hippocampal size Increased - Ventricles |
|
|
3 neurotransmitter theories for schizophrenia?
|
1. Dopamine theory (later, most important)
2. Glutamate theory 3. Serotonin theory |
|
|
Glutamate theory?
|
Psychotic-like symptoms induced by NMDA-antagonists like
- Ketamine - Phencyclidine Causing reduced glutaminergic and increased dopaminergic neurotransmitting Impair gating function of GABA neurons |
|
|
Serotonin theory?
|
Schizophrenia-like symptoms induced by LSD, psilocybine
|
|
|
4 dopamine tracts of CNS?
|
1. Mesolimbic
2. Mesocortical 3. Nigro-striatal 4. Tubero-infundibular |
|
|
Innervation of mesolimbic tract?
|
Limbic areas & amygdala
|
|
|
Function of mesolimbic tract?
|
- Arousal
- Memory - Behaviour processing - Spontaneity - Motivation - Self-confidence |
|
|
Effects of dopamin antagonist on mesolimbic tract?
|
Psychosis relief
|
|
|
Innvervation of mesocortical tract?
|
Frontal and prefrontal cortex
|
|
|
Function of mesocortical tract?
|
Communication
Cognition Social functions Stress response |
|
|
Effect of dopamin-antagonist on mesocortical tract?
|
Psychosis relief
|
|
|
Innervation of nigro-striatal tract?
|
Caudate nucleus
Putamen |
|
|
Functions of nigro-striatal dopamine tract?
|
Extrapyramidal system
Movement coordination |
|
|
Effect of dopamin-antagonist on nigro-striatal tract?
|
Movement disorders
|
|
|
Innvervation of tubero-infundibular tract?
|
Pituitary gland
|
|
|
Function of tubero-infundibular tract?
|
Regulation of prolactin secretion
|
|
|
Effect of dopamin-antagonist of tubero-infundibular tract?
|
Hyperprolactin
- Galactorrhea - Gynecomastia |
|
|
Psychotic symptoms are induced by?
|
- Drugs causing dopamine release - e.g. amphetamines
- Dopamin agonists (bromocryptine) and dopamine precursors (L-dopa) |
|
|
Psychotic symptoms are inhibited by?
|
- Drugs blocking dopamine storage (reserpine)
- Dopamine antagonists |
|
|
Types of dopamine receptors?
|
D1 = D1 and D5
D2 = D2-4 |
|
|
Which D-receptor cause antopsychotic action?
|
D2
|
|
|
Most common way of treatment of schizophrenia?
|
D2-antagonism
And also antagonism of 5-HT2 (A/C) |
|
|
Route of administration of antipsychotics?
|
Oral or im. injections 1x / 2x a day
|
|
|
Lipophilicity of antipsychotic drugs?
|
Generally highly lipophilic & bound to plasma proteins
Thus large distribution & risk of accumulation |
|
|
Half-time of most antipsychotics?
|
15-30 hours
|
|
|
Biotransformation of antipsychotics?
|
CYP 450 dependent
- Except ziprasidone |
|
|
Examples of slow-release 'depot' preparations?
|
Flupentixol decanoat
FLuphenazine decanoat Drug is esterified with heptanoid or decanoid acid Dissolved in oil Last 2-4 weeks, as im injection |
|
|
2 groups of typical antipsychotics?
|
1. basal (sedative)
2. Incisive |
|
|
Examples of basal typical antipsychotics?
|
Chlorpromazine
Chlorprotixene Thioridazine |
|
|
Examples of incisive typical antipsychotics?
|
Haloperidol
Fluphenazine Flupenthixol Clopenthixol |
|
|
2 groups of atypical antipsychotics?
|
1. Multi Acting Receptor Targeted Antipsychotic (MARTA)
2. Dopamin and serotonin receptor antagonist |
|
|
Examples of MARTA?
|
Olanzapine
Zotepin Quetiapine Clozapine Antagonists agains D, 5HT, a, H1, M |
|
|
Examples of dopamine and serotonin receptor antagonists?
|
Risperidone
Ziprasidone Aripiprazole |
|
|
Differences between incisive and sedative (typical) antipsychotics?
|
Incisive
- More potent - Selective D2 antagonist - More effective But more extrapyramidal adverse effect Sedative - Weaker D2-antagonist - But block also H1, a1, M - explains sedative effects |
|
|
Differences between atypical and typical antipsychotics?
|
Atypical drugs
- Less extrapyramidal complications - Improved efficacy against negative symptoms, thus useful in resistant group of patients |
|
|
Adverse effects of antipsychotics are classified in?
|
A type - dose dependent
B type - unpredictable |
|
|
List the A-type adverse effects of antipsychotics?
|
1. Extrapyramidal motor disturbances
2. Decreased seizure threshold 3. Sedation and cognitive deficit 4. Antimuscarinic activity 5. Cardiovascular adverse reactions 6. Weight gain + dyslipidemia 7. Diabetes |
|
|
Antipsychotic adverse effect of extrapyramidal motor disturbances comes from?
|
D2 blockage in nigrostriatal pathway
|
|
|
Acute (reversible) extrapyramidal motor disturbances from antipsychotic adverse effects are?
|
1. Parkinson-like symptoms
2. Acute dystonias - muscle spasms - Blepharospasm - Torticollis - Tounge protrusion 3. Akathasia - motor restlessness |
|
|
Treatment of akathasia?
|
Benzodiazepines
|
|
|
Slowly developing (irreversible) adverse effects of antipsychotic drugs are?
|
Tardive dyskinesia
= involuntary movements of face/tounge and limbs - Tounge 'fly catching' - Rabbit lip syndrome - fast speech - Grimasing, blinking like Tourette |
|
|
Antimuscarininc activity of antipsychotics cause?
|
- Blurring of vision
- Increased intraocular pressure - Dry mouth and eyes - Constipation - Urinary retention |
|
|
Cardiovascular adverse reactions of antipsychotic drugs?
|
- Orhthostatic hypotension (a-blockage)
- Drug induced QT syndrome |
|
|
3 B-type (unpredictable) side-effects of antipsychotic agents?
|
1. Neuroleptic malignant syndrome
2. Jaundice 3. Leukopenia and agranulocytosis Other reactions: Urticarial skin reactions Depositions |
|
|
Neuroleptic malignant syndrome?
|
- Muscle rigidity
- Body temperature increase - Mental confusion - Instable blood pressure and tachycardia Death in 15% due to renal or cardiovascular failure |
|
|
Cause of jaundice in antipsychotic drugs?
|
Mild cholestatic hepatitis - obstructive origin - disappears quickly when drug is stopped
|
|
|
Leukopenia and agranulocytosis may be fatal - and induced by what drug?
|
Clozapine
|
|
|
Which antipsychotic may cause urticarial skin reactions?
|
Phenothiazines
|
|
|
Deposition as adverse effect in skin and cornea?
|
Skin
- Melanin, gray discolorations Cornea/lens - Vision disturbances |
|
|
2 selected typical drugs?
|
1. Chlorpromazine
2. Haloperidol |
|
|
Chlorpromazine is used against?
|
Use against
- Schizophernia (positive symptoms) - Bipolar disorder (mania) |
|
|
Chlorpromazine administration?
|
P.O
I.M I.V |
|
|
Effect of chlorpromazine?
|
Autonomic - also block a, M, H1
|
|
|
Chlorpromazine should not be used in?
|
Dementia
MAOI |
|
|
Indication for haloperidol use?
|
- Schizophrenia
- Korsakov syndrome (alcoholics) - Delusional disorders - Psychomotoric calm-down's - Antiemetics |
|
|
2 selected atypical drugs?
|
1. Olanzapine
2. Clozapine |
|
|
What type of drug is olanzapine?
|
MARTA
|
|
|
Indicators for use of olanzapine?
|
- Schizophrenia - both positive and negative
- Manic phase of bipolar disorder |
|
|
Adverse reactions of olanzapine?
|
- Increased body weight
- Dyslipidemia - Diabetes - Sedations |
|
|
Indication for clozapine?
|
Also schizophrenia - specially good for negative symptoms
|
|
|
Adverse effects of clozapine?
|
- Leukopenia and agranulocytosis
- Epileptic seizures - Anticholinergic effects Drug of 3rd choise due to safety concerns |
