Psychotherapeutic Drugs Flashcards
Antipsychotic agents - MoA
Therapeutic effects of these drugs are believed to result from competitive blockade of dopamine receptors and serotonin (5HT) receptors.
When first adm the drugs cause an increase in dopamine synthesis, release and metabolism, this probably due to a compensatory response to the acute blockade of postsynaptic dopamine receptors produced by antipsychotic drugs. Over time continued dopamine receptor blockade leads to inactivation of dopaminergic neurons and produce depolarization blockade –> reduced dopamine release from mesolimbic and nigrostriatal neuron –> alleviate positive symptoms of schizophrenia while causing EPSs. Eventually the reduction in dopamine release caused by depolarization blockade leads to dopamine receptor up-regulation and super sensitivity to dopamine agonists –> development of a delayed type of EPS called tardive dyskinesia.
In mesocortical and nigrostriatal pathways, 5-HT2 receptors mediate presynaptic inhibition of dopamine release. Blockade of these receptors by atypical antipsychotic drugs may increase dopamine release in these pathways. In the mesocortical pathway, this action may alleviate the negative symptoms of schizophrenia. In the nigrostriatal pathway, increased dopamine release counteracts the EPs caused by D2 receptor blockade.
Antipsychotic agents - Clinical use
Schizophrenia and other forms of psychosis; drug-induced psychosis and psychosis associated with manic phase of bipolar disorder
Severely agitated patients, including those with dementia and severe mental retardation.
Some are also used in the treatment of nausea and vomiting (because the phenothiazines have antiemetic activity)
Add-on medications to those w depression treated w antidepressants
Antipsychotic agents - Adverse effects
In the peripheral autonomic nervous system, antipsychotic drugs also block muscarinic receptors and a1- adrenoceptors.
Antagonism of a1: dizziness, orthostatic hypotension and reflex tachycardia
Muscarinic antagonism: blurred vision, dry mouth, constipation, urinary retention.
H1 antagonism: Drowsiness, sedation, increased appetite, weight gain.
Development of motor abnormalities after adm of high potency typical antipsychotic.
Neuroleptic malignant syndrome: severe form of drug toxicity, life threatening characterized by: muscle rigidity, elevated temperature, altered consciousness, autonomic dysfunction(tachycardia, diaphoresis, tachypnea, urinary and fecal incontinence) –> this syndrome resembles malignant hyperthermia. Managed by discontinuing treatment w offending antipsychotic drug + adm of dantrolene to prevent further muscle abnormality and providing supportive care.
Antipsychotic agents - Contraindications
Dementia-related psychosis in elderly and pregnancy after second trimester (increased risk of abnormal motor movements or withdrawal effects in neonates)
Typical Antipsychotic agents (1st generation)
Chlorpromazine Fluphenazine Thioridazine Haloperidol Trifluoperazine Thiothixene Loxapine
Typical Antipsychotic agents - MoA and Effects
Equal or greater affinity for D2 receptors than for 5-HT2 receptors. Antagonism of D2 receptors in mesolimbic pathways is thought to repress the positive symptoms of schizophrenia, blockade of D2 receptors in the basal ganglia is believed to be responsible for the parkinsonian and other EPSs that sometimes occur in pt taking antipsychotics.
EFFECTS:
Pt become less agitated and experience fewer auditory hallucinations.
Grandiose/ paranoid delusions subside and can disappear completely in some pt w continued treatment.
Sleeping and eating patterns become normalized + behavioral improvement occurs in the form of decreased hostility, combativeness and aggression.
Can have some effect on negative symptoms.
Increases prolactin levels by blocking dopamine receptors in tuberoinfundibular pathway
Typical Antipsychotic agents - Adverse effects
Blockade of dopamine receptors in the striatum –> EPSs;
Akathisia (motor restlessness, feel compelled to pace, shuffle their feet, shift positions –> unable to sit quietly)
Pseudoparkinsonism (rigidity, bradykinesia, tremor)
Dystonia (abnormal muscle tension –> affects neck and facial muscles incl tongue, pharynx, larynx and eyes –> oculogyric crisis; eyeballs become fixed in one position, usually upward ;glossospasm, tongue protrusion, torticollis (contracted state of cervical muscles –> twisting of neck + unnatural position of head.
Tardive dyskinesia (after months of years of treatment): abnormal oral and facial movements; tongue protrusions, lip smacking. Later stages; abnormal limb and truncal movements
Increased Prolactin levels –> Gynecomastia in men & menstrual irregularities
Poikilothermy: body temp approach ambient temp –> hyperthermia or hypothermia. (via effects on hypothalamus)
Typical Antipsychotic agents - Treatment of Adverse effects
Lowering the dose Change into an atypical antipsychotic Adm of drug to counteract the effects: Benztropine (anticholinergic) Diphenhydramine (antihistamine) Amantadine (increases dopamine release).
Tardive dyskinesia: Lowest doses for shortest period of time, discontinued periodically. Drugs effective in treatment:
Amantadine, clozapine, physostigmine, Benzodiazepines
Chlorpromazine - Interactions
Additive effects w antiadrenergic, anticholinergic and CNS depressants.
Decreases serum levels of lithium.
Concurrent use of a b-blocker or an antidepressant may increase serum levels of both drugs.
Fluphenazine - Clinical use
Pt who are not compliant w oral med or are unable to take oral drugs.
Fluphenazine - Interactions
Additive effects w antiadrenergic and CNS depressants.
Concurrent use of a b-blocker or an antidepressant may –> serum levels of both drugs.
Thioridazine - Adverse effects
Cardiac arrhythmia
elevated serum prolactin levels and poikilothermy and pigmentary retinopathy
Cardiac toxicity
Haloperidol - Clinical use
Tourette syndrome in addition to schizophrenia
Haloperidol - Interactions
Barbiturates and carbamazepine decrease serum levels. Quinidine increase serum levels.
Thiothixene - Interactions
Additive effects w antiadrenergic and CNS depressants.
Concurrent use of a b-blocker may increase serum levels of both drugs.
Loxapine - Interactions
Concurrent use of an antidepressant may increase serum levels of both drugs.
Atypical Antipsychotic Agents (2nd generation)
Clozapine Olanzapine Molindone Risperidone Ziprasidone Lurasidone Iloperidone Asenapine Aripiprazole Quetiapine Paliperidone Pimavanserin
Atypical Antipsychotic Agents - MoA
Greater affinity for 5-HT receptors than for D2 receptors, and some atypical drugs have increased the affinity for D3 and D4 receptors.
Atypical Antipsychotic Agents - Clinical use
Besides schizophrenia; acute manic episodes ass w bipolar disorder (monotherapy or adjunct to lithium or valproate)
Treatment-resistant depression
Clozapine - MoA
Potent antagonists of a large nr of receptors.
Therapeutic effects result from blockade of D4 receptors and 5-HT2 receptors.
Clozapine - Clinical use
Greater activity against negative symptoms of Schizophrenia
Clozapine - Adverse effects
Agranulocytosis
Sedation and autonomic side effects (due to antagonism of histamine, muscarinic and a1-adrenoceptors)
Olanzapine - MoA
Chemical analog of clozapine.
Twice the affinity for 5-HT2 receptors as it does for D2 receptors.
Can also block D3 and D4 receptors.
Olanzapine - Clinical use
As effective as haloperidol in alleviating positive symptoms of schizophrenia
Superior to haloperidol in alleviating negative symptoms
Treatment-resistant depression in comb w fluoxetine
Olanzapine - Adverse effects
Sedation and weight gain.
Higher doses: akathisia, pseudoparkinsonism, dystonias
Molindone - Interactions
Additive effects w anticholinergic and CNS depressants. Concurrent use of a b-blocker or an antidepressant may increase serum levels of both drugs.
Risperidone, Ziprasidone, Lurasidone, Iloperidone and Asenapine - MoA
Antagonize D2 and serotonin 5-HT2A receptors.
Risperidone, Ziprasidone, Lurasidone, Iloperidone and Asenapine - Clinical use
Positive and negative symptoms of Schizophrenia
Risperidone, Ziprasidone, Lurasidone, Iloperidone and Asenapine - Adverse effects
Less sedation, more orthostatic hypotension and higher incidence of EPSs
Elevated serum prolactin
QT prolongation –> cardiac dysrhythmias, torsade de pointes
Aripiprazole - MoA
Partial agonist at dopamine and 5-HT1A, but 5-HT2A antagonist
Aripiprazole - Clinical use
Irritability in autistic children
Treatment-resistant depression
Quetiapine - Clinical use
Treatment-resistant depression
Paliperidone - MoA
Major active metabolite of risperidone. Antagonist at D2 and 5-HT2A receptors.
Pimavanserin - Clinical use
Hallucinations and delusions ass w Parkinson disease
Antidepressant Drugs - Clinical use
All forms of depression
Anxiety disorders: panic disorder, phobic disorder, obsessive-compulsive disorder.
Sleep disorders: somnambulism and night terrors (repress excessive REM sleep and dreaming), enuresis (increase awareness of need to urinate –> facilitate waking up)
Chronic pain syndromes (mood-elevating effect and analgesic activity)
Eating disorders
Tricyclic Antidepressants
Amitriptyline Clomipramine Imipramine Desipramine Nortriptyline
Tricyclic Antidepressants - Clinical use
Depression
Tricyclic Antidepressants - Adverse effects
Autonomic side effects by blocking muscarinic and a1 receptors.
Some of them also produce sedation
Lower the seizure threshold and can induce seizures
Overdose: Life threatening cardiac dysrhythmia with wide QRS complex tachycardia. Marked autonomic effects, hypotension and sinus tachycardia, excessive sedation and seizures.
Tricyclic Antidepressants - Interactions
Serum levels elevated by concurrent administration of antipsychotic drugs, calcium channel blockers, cimetidine, and SSRIs, which compete with TCA for metabolic enzymes in the liver
Serum levels decreased by barbiturates, carbamazepine and phenytoin because of up-regulation of hepatic metabolic enzymes
Tricyclic Antidepressants - Antidote
Sodium bicarbonate
Amitriptyline, Clomipramine, Imipramine (tertiary amines) - MoA
Block serotonin reuptake to a greater extent
Amitriptyline - Indication
Depression and moderate to severe agitation and/or anxiety in a formulation with perphenazine
Amitriptyline, Clomipramine, Imipramine (tertiary amines) - Adverse effects
Produce more sedation and autonomic side effects than secondary amines
Clomipramine - Indication
Obsessive-compulsive disorder
Desipramine and Nortriptyline (secondary amines) - MoA
Block norepinephrine uptake more than they block serotonin reuptake
Selective serotonin reuptake inhibitors
Fluoxetine Fluvoxamine Paroxetine Sertraline Citalopram Escitalopram Vortioxetine
Selective serotonin reuptake inhibitors - MoA
Block the neuronal reuptake of serotonin and have much less effect on the reuptake of norepinephrine
Selective serotonin reuptake inhibitors - Indication
Depression
Certain anxiety disorders, such as panic disorder and obsessive-compulsive disorder
Selective serotonin reuptake inhibitors - Contraindication/caution
Seizure disorders, hepatic disorders, diabetes and bipolar disorder.
SSRIs should not be taken with triptan agents
Selective serotonin reuptake inhibitors - Adverse effects
Nervousness
Dizziness
Insomnia
Occasionally cause male sexual dysfunction in the forms of priapism and impotence
Serotonin syndrome when administered with MAOIs and its characterized by agitation, restlessness, confusion, insomnia, seizures, severe hypertension, and GI symptoms
Selective serotonin reuptake inhibitors - Interactions
Metabolized by CYP P450
Increases levels of alprazolam, diazepam, carbamazepine, phenytoin
Increase the hypoprothrombinemic effect of warfarin
Should not be given with MAOIs- serotonin syndrome.
Fluoxetine - Indication
Depression
Bulimia nervosa
Anorexia nervosa
Obsessive-compulsive disorder.
Fluoxetine - Adverse effects
Impair regulation of blood glucose levels in diabetic patients.
It can also cause SIADH, chararterized by persistent hyponatremia and elevated urine osmolality.
Fluoxetine - Interactions
Inhibit CYP2D and increase serum levels of antipsychotic drugs, TCAs and dextromethorphan
Fluvoxamine - Indication
Obsessive-compulsive disorder
Depression
Panic disorder
Paroxetine - Indication
Low-dose paroxetine was recently approved for the treatment of vasomotor symptoms (“hot flashes” and night sweats) in perimenopausal women
Paroxetine - Adverse effects
Cause more sedation
Sertraline - Special consideration
Preferred in elderly patients, because its elimination is not affected by aging. little effect on CYT P450
Citalopram and Escitalopram - Adverse effects
Increase the QT interval, risk for torsade de pointes
Serotonin and norepinephrine reuptake inhibitors
Duloxetine Venlafaxine Desvenlafaxine Milnacipran Levomilnacipran
Serotonin and norepinephrine reuptake inhibitors - MoA
Inhibits both neuronal serotonin and norepinephrine reuptake
Duloxetine and Venlafaxine - Indication
Major depressive disorder
Diabetic peripheral neuropathic pain
Generalized anxiety disorder
Fibromyalgia (only duloxetine)
Desvenlafaxine and Levomilnacipran - Indication
Major depression
Milnacipran - Indication
Fibromyalgia
Monoamine oxidase inhibitors
Isocarboxazid Phenelzine Tranylcypromine Moclobemide Selegiline
Monoamine oxidase inhibitors - MoA
Bind irreversibly to monoamine oxidase (enzyme responsible for degradation of the biogenic amine neurotransmitters, norepinephrine, dopamine, and serotonin)
MAO-A: preferentially oxidizes serotonin but will also metabolize norepinephrine and dopamine
MAO-B: preferentially metabolizes dopamine
Monoamine oxidase inhibitors - Adverse effects
Hypertensive crisis characterized with occipital headache, palpitations, neck stiffness or soreness, nausea and vomiting, sweating and photophobia.
Monoamine oxidase inhibitors - Interactions
Due to interactions with many foods and drugs, the MAOIs are indicated for patients who have failed to respond to other drugs.
Hypertensive crisis can occur after administration of sympathomimetic amines or food containing tyramine
Which MAOI inhibit both MAO-A and MAO-B?
1st generation:
Isocarboxazid
Phenelzine
Tranylcypromine
Isocarboxazid
Phenelzine
Tranylcypromine (1st gen) - Indication
Depression
Moclobemide - MoA
Reversibly Inhibit MAO-A
Moclobemide - Indication
Depression
Selegiline - MoA
Inhibit MAO-B
Selegiline - Indication
Parkinson disease
Transdermal patch for depression
Other Antidepressant Drugs
Bupropion Mirtazapine Trazodone Vilazodone Hypericin
Bupropion - MoA
Weak inhibitor of neuronal reuptake of dopamine, norepinephrine and serotonin. It also acts as a noncompetitive antagonist at nicotinic cholinergic receptors.
Bupropion - Indication
Smoking cessation
Inducing weight loss in obese patients in combination with naltrexone
Bupropion - Adverse effects
Agitation
Insomnia
Nausea
Weight loss
Mirtazapine - Classification and MoA
Tetracyclic antidepressant
Block presynaptic a2 adrenergic autoreceptors and heteroreceptors and thereby increase the neuronal release of norepinephrine and serotonin. It increases central norepinephrine concentration to a greater degree than TCAs, and it is also a potent antagonist of 5-HT2 and 5-HT3 receptors.
Mirtazapine - Clinical use
Depression
Anxiety
Mirtazapine - Adverse effects
Elevates hepatic enzyme levels
Agranulocytosis
Trazodone - MoA
Selectively inhibit the neuronal reuptake of serotonin and also act as antagonist at the 5-HT2A receptor.
Trazodone - Adverse effects
Sedation
Orthostatic hypotension
Vilazodone - MoA
Selectively inhibit the neuronal reuptake of serotonin, also partial agonist of the 5-HT1A receptor
Hypericin - MoA
Inhibit MAO and can also block neuronal reuptake of serotonin.
Mood-Stabilizing Drugs
Lithium
Carbamazepine
Valproate
Mood-Stabilizing Drugs - Clinical use
Bipolar disorder
Lithium - MoA
Acts by suppressing the formation of second messengers involved in neurotransmitter signal transduction. Lithium reduces the formation of IP3 by inhibiting two enzymes in the inositol phosphate pathway.
Lithium also inhibits the uptake of inositol into the cell. By reducing the IP3 formation, lithium reduces the neuronal response to serotonin and norepinephrine, whose effects are partly mediated by IP3
Lithium - Clinical use
Manic symptoms of bipolar disorder
Lithium - Adverse effects
Overdose:
Neurotoxicity and cardiac toxicity leading to dysrhythmia
Nausea and vomiting
Side effects:
Drowsiness, weight gain, fine hand tremor, polyuria, hypothyroidism.
Hand tremor can be controlled with B-blocker.
Lithium - Interactions
NSAIDs and diuretics decrease lithium clearance by about 25% and increase lithium levels
Central Nervous System Stimulants
Amphetamine Dextroamphetamine Methamphetamine Lisdexamfetamine Phentermine Methylphenidate Modafinil Armodafinil Atomoxetine Guanfacine Clonidine
Amphetamine - MoA
Increases release of norepinephrine and dopamine from nerve terminals
Amphetamine, Dextroamphetamine and Methylphenidate - Clinical use
ADHD
Narcolepsy
Obstructive sleep apnea/hypopnea syndrome
Shift work sleep disorder
Methamphetamine - Clinical use
ADHD
Obesity
Lisdexamfetamine - Clinical use
ADHD
Phentermine - Clinical use
Appetite suppressant in the treatment of obesity
Methylphenidate, Modafinil and Armodafinil - MoA
Increase the levels of catecholamine in central and peripheral synapses, inhibit dopamine reuptake.
Modafinil and Armodafinil - Clinical use
Narcolepsy
Obstructive sleep apnea/hypopnea syndrome
Shift work sleep disorder
Atomoxetine - MoA and Clinical use
Selective norepinephrine reuptake inhibitor
ADHD
Guanfacine and Clonidine - MoA and Clinical use
a2-adrenoceptor agonist
ADHD
Hypertension
Central Nervous System Stimulants - Adverse effects
Risk of cardiovascular incidents ranging from hypertension to MI
Increased risk of sudden death in children and adolescents being treated for ADHD with stimulants.
Young children: decreases in growth and weight gain
TCA - MoA
Block the neuronal reuptake of norepinephrine and serotonin; blockade of the reuptake transporters NET (norepinephrine transporter) and SERT (serotonin transporter).
