Psychotherapeutic Drugs: antipsychotics, antidepressants, bipolar disorder drugs and anxiolytics - Ch. 34, 35, 36 & 38 Flashcards
What are the 3 main emotion/mental health disorders treated with psychotherapeutic drugs?
Anxiety
Mood (affective) disorders
Psychoses
Anxiety
Unpleasant emotional state
-Perception of real or perceived dangers
Mood (affective) disorders
Mania (abnormally pronounced emotions)
Depression (abnormally reduced emotions)
-Bipolar disorder - periodic swings
Psychosis
Major emotion disorder, impaired ability to participate in everyday life
Loss of contact with reality
-Schizophrenia
-Depressive and drug-induced psychoses
What monoamine NTs are depleted in Depression?
Catecholamines
-Norepinephrin (NE)
Indolamines
-Serotonin (5-HT)
What are the kinds of antidepressants?
New-generation
Tricyclic antidepressants (TCA)
Monoamine oxidase inhibitors (MAOIs)
What are the newer-generation antidepressants?
Selective serotonin reuoptake inhibitors (SSRIs)
Mixed serotonin and NE reuptake inhibitors (SNRI)
NE reuptake inhibitors
What re the most commonly prescribed drugs for depression?
SSRIs
Examples of SSRIs?
Sertraline (Zoloft)
fluoxetine (Prozac)
paroxetine (Paxil)
fluvoxamine
citalopram (celexa)
How long can SSRIs take to have effects?
2-6 weeks
What is the mechanism of action of SSRIs?
Selectively inhibit 5-HT reuptake
-Increased serotonin concentration. in the synapse
little or no effect on NE or DA reuptake
What advantage do SSRIs have over tricyclics and MAOIs?
Little to no effect on CV system
What are SSRIs used for?
Major depressive disorder
Bipolar affective disorder (in combination)
Eating disorders
OCD
Panic attacks
Myoclonus (quick, involuntary muscle jerk)
What adverse effects are associated with SSRIs?
CNS: headache, nervousness, insomnia, fatigue
GI: nausea
Sexual dysfunction, weight gain
Serotonin syndrome
What are symptoms serotonin syndrome?
Cognitive: Confusion, agitation and restlessness
Autonomic: tachycardia, hypertension, hyperthermia, sweating
Neuromuscular: clonus, hyperreflexia, tremor
-Occur within 2-72 hours
Examples of SNRI?
Venlafaxine
duloxetine
Tricyclic antidepressants are considered what type of drug?
Second-line
-fail SSRIs or other newer-gen
-Adjunct therapy w/ newer-gen drugs
What are Tricyclic antidepressants used for?
Depression
Childhood enuresis
OCD
Adjunctive analgesics
Trigeminal neuralgia
Examples of Tricyclic antidepressants?
Amitriptyline
imipramine
desipramine
clomipramine
Which Tricyclic antidepressants is used for childhood enuresis?
Imipramine
Which Tricyclic antidepressants is used for OCD?
clomipramine
What do Tricyclic antidepressants do?
Blockade of NE reuptake
Blockade of 5-HT reuptake
Receptor block of:
Mucarinic (cholinergic) receptors
alpha1-adrenoreceptors
H1 receptors
What adverse effects are associated with Tricyclic antidepressants?
Sedation
Anticholinergic effects
Orthostatic hypotension
Why do Tricyclic antidepressants cause sedation?
H1 receptor blockade
-wears off after 1-2 weeks
What are symptoms of anticholinergic effects?
Blurred vision
dry mouth
constipation
urinary retention
tachycardia
Why do Tricyclic antidepressants cause orthostatic hypotension?
Alpha1-adrenoceptor blockade
Tricyclic antidepressants should be used with caution in people who have what existing disorders?
Cardiac dyrhythmias (anticholinergic effects)
Seizures
Tricyclic antidepressants can be ______?
Lethal if overdosed
70% to 80% die before reaching the hospital
Death is from seizures or cardiac dysrhythmias
Is there an antidote for Tricyclic antidepressants overdose?
No antidote for acute toxicity
What is used to treat Tricyclic antidepressants overdose?
Decrease drug absorption with activated charcoal
speed elimination by alkalinising urine
manage seizures/dysrhythmias with drugs
basic life support
What are the first generation drugs for depression?
MAOIs
-Phenelzine
What are MAOIs now used for?
Treatment of depression when not responsive to the rdrugs
Disadvantage associated with MAOIs?
Potential to cause hypertensive crisis when taken with tyramine (cheese effect)
What is the mechanism of action of MAOIs?
Inhibit MAO enzyme in CNS and peripheral tissue
Reduced breakdown of monoamines in neurone, more released from neurones
What does MAO enzyme do?
Metabolizes monoamine (DA, 5-HT, NE) neurotransmittors
What adverse effects are associated with MAOIs?
orthostatic hypotension (most common)
CNS stimulation: Insomnia, anxiety
Cheese effect
What foods/drinks do MAOIs interact with?
Food/drinks containing Tyramine leads to hypertensive crisis
What is hypertensive crisis?
Most serious problem with MAOIs
-Severe headache, hypertension, tachycardia
Possible cerebral hemmorhage, stroke and death
What foods have Tyramine?
Aged mature cheeses (cheddar, blue, Swiss)
Smoked/pickled or aged meats
Yeast extracts (marmite)
red wines
Fava beans (Italian broad beans)
What must happen when switching from an SSRI to MAOI?
Must be a 2-5 week βwash outβ drug free period between the two drug therapies
What must happen when switching from MAOI to a TCA/SSRI?
2 week wash out drug free perioid
Maintain diet restriction 2 weeks after MAOI cessation
What are other drugs used for depression?
Bupropion
Mirtazapine
Vortioxetine
What is bupropion?
block of DA and NE reuptake
What is mirtazapine?
Increases release of 5-HT
antagonism at certain 5-HT receprtors
What is vortioxetine?
Complex modulation of 5-HT neurotransmission
Block 5-HT reuptake, agonist against some 5-HT and antagonist at other 5-HT receptors
What are some anxiolytic drugs?
Benzodiazepines (BZDs)
Antidepressants; SSRIs, SNRI
Buspirone in GAD
Antiseizure drugs in GAD and PTSD
Antipyschotics in GAD and PTSD
What drugs used for seizures are also used in GAD?
Valproate
Gabapentin
What antipsychotics are also used GAD and PTSD?
Olanzepine
Risperidone
What do Benzodiazepines (BZDs) do?
Depress activity in brainstems and limbic system (CNS depressant)
βsedative-hypnoticβ
Immediate relief
How are benzodiazepines used?
Sparingly, long-term
What effects do increasing dosages of BZDs have?
- Anxiolytic
- Sedation
- Hypnotic (promote sleep)
- Stupor (near-unconsciousness or insensibility)
What are benzodiazepines used for?
Anxiety
Sedation
Muscle relaxation
Seizure control
Adjuvant for depression
Alcohol withdrawal
What benzodiazepines are used as anxiolytics?
lorazepam (Ativan)
alprazolam
diazepam (Valium)
clonazepam
What is the mechanism of action of Benzodiazepines?
Enhances effect of GABA (GABA = decrease excitability in neurons)
Decreased neuronal excitability
decrease CNS activity
Why are BZDs safer than barbiturates in overdose?
BZDs = little respiratory depression given PO
When do benzodiazepines cause respiratory depression?
When administered IV
or combined with opioids, alcohol and barbiturates
What adverse effects are associated with BZDs?
Decreased CNS activity: Drowsiness, loss of coordination, dizziness, confusion, manual skills affected
Can be addictive (less than barbiturates)
Examples of mood stabilisers (used for bipolar)?
Lithium carbonate
Drugs used for other indications:
seizure drugs
atypical antipsychotics
antidepressants (SSRIs)
What is the first-line treatment of mania and manic depressive illness?
Lithium
-May be used with other meds to stabilise mood
What is lithiums therapeutic index?
Narrow therapeutic range
toxicities above 2 mmol/L
death at 2.5 mmol/L
What should maintenance serum levels of lithium range between?
0.4 and <1.5 mmol/L
-Most treated in 0.6-0.8 mmol/L range
What adverse effects are associated with lithium <1.5 mmol/L?
Fine finger tremor
polyuria
thirst
GI upset
What long-term adverse effects are associated with lithium?
Renal impairment
Goiter and hypothyroidism
What are symptoms of Lithium toxicity >1.5 mmol/L?
Persistent GI upset (early sign)
Course hand tremor
Neurologic effects: Confusion, sedation, incoordination, seizures, coma
What drugs used in seizures are also used for bipolar disorder?
Valproate
Carbamazepine
What atypical antipsychotics are also used in bipolar disorder?
Olanzapine and quetiapine
What drugs for depression are also used for bipolar disorder?
Controversial!!
Fluoxetine (not used alone)
What are some psychotic disorders?
Schizophrenia
Schizoaffective disorder
Depressive or drug-induced psychoses
What positive symptoms (exaggerations) are associated with Schizophrenia?
Delusions
paranoia
hallucinations
disorganised or catatonic behaviour
What negative symptoms (loss or decrease) are associated with Schizophrenia?
Flat emotions
Social withdrawal
Lack of speech and self-care
Avolition (no motivation)
What cognitive symptoms are associated with schizophrenia?
Disorganised thoughts and speech
memory and learning difficulties
What are antipsychotics also known as?
Neuroleptics
What are antipsychotics used for?
Serious mental illnesses
-schizophrenia
-bipolar affective disorder
-depressive and drug-induced pyschoses
-autism
Movement disorders
-Touretteβs syndrome
Nausea, vomiting, intractable hiccups
What are the three major objectives of schizophrenia drug therapy?
Suppression of acute episodes
reduce relapse
Maintenance of the highest possible level of functioning
What are adjunctive drugs to antipsychotics used in schizophrenia drug therapy?
Benzodiazepines (BZDs)
Antidepressants
When do initial effects of schizophrenia drug therapy occur?
1 to 2 days
When does substantial improvement from schizophrenia drug therapy occur?
~2 to 4 weeks
When do full effects of schizophrenia drug therapy develop?
may not develop for several months
Which schizophrenia symptoms may respond better to schizophrenia drug therapy?
Positive symptoms respond better than negative or cognitive
What are the classifications of antipsychotics?
First generation (Typical, conventional) FGA
Second generation (Atypical) SGA
Examples of first generation typical antipsychotics?
Chlorpromazine (Largactil)
haloperidol
Examples of second generation atypical antipsychotics?
Clozapine (clozaril)
Resperidone
What is the mechanism of action of typical antipsychotics?
Dopamine (D2) receptor antagonists
-Block receptors in CNS
-Block histamine receptors
-block cholinergic receptors
-block alpha 1-adrenoceptors
Where do typical antipsychotics block receptors in the CNS?
limbic system, basal ganglia (emotion, cognitive, motor function)
nigrostriatial pathway (motor function)
What is responsible for typical antipsychotics most serious adverse effect?
DA receptor antagonism
What is typical antipsychotics mosts serious adverse effect?
Extrapyramidal Motor disturbances
What are early onset extrapyramidal symptoms?
Acute dystonias (abnormal muscle tension)
Pseudoparkinsonism (tremors, rigidity, bradykinesia)
Akathisia - motor restlessness
What can reduce early onset extrapyramidal symptoms?
Anticholinergics
benzotropine
diphenhydramine
What are long-term (months/years of treatment) extrapyramidal symptoms?
Tardive (βslow or delayedβ) dyskinsia
-worm like tongue movement, lip smacking
-speaking, eating problems
-mostly irreversible
What adverse effect of typical antipsychotics can occur 4-14 days after therapy starts?
Neuroleptic Malignant Syndrome
Symptoms of Neuroleptic Malignant Syndrome?
Lead pipe rigidity
sudden high fever (>41Β°C)
BP irregularities, cardiac dysrhythmias
seizures, coma
What other CNS adverse effects are associated with typical antipsychotics?
Sedation
delirium
What dermatological adverse effects are associated with typical antipsychotics?
Photosensitivity
skin rash
hyperpigmentation
pruritus
What atypical antipsychotic has very little extrapyramidal motor disturbances?
Clozapine
What atypical antipsychotic has extrapyramidal motor disturbances?
risperidone
Resperidal Consta (IM depot injection every 2 weeks)
What are some newer atypical antipsychotic drugs in Canada?
lurasidone -minimal anticholinergic action
asenapine (SL only)
What is the mechanism of action of atypical antipsychotics?
Block 5-HT2 (serotonin) receptors
Les effect on DA receptors (less motor disturbances)
Block H1 receptors (sedation)
Bock cholinergic receptors (constipation)
Block alpha1-adrenoceptors (hypotension)
What adverse effects are associated with Clozapine?
Haematological:
agranulocytosis (WBC)
anemia
Drooling
What adverse effects are associated with all antipsychotics? (generally associated with atypical)
Weight gain
Metabolism disturbances
-blood glucose management
-plasma lipids
What can you not take with antipsychotics?
CNS depressants
alcohol