TRANS 070: PSYCHOPHARMACOLOGY Flashcards
subtype of antipsychotic drug that produces a high incidence of extrapyramidal side effects (EPS) at clinically effective doses
Neuroleptic
is the primary indication for antipsychotic drugs
Schizoprenia
INDICATIONS OF ANTIPSYCHOTIC DRUGS
- Schizophrenia is the primary indication for antipsychotic drugs
- Schizoaffective disorders
- Manic phase in bipolar affective disorder
- Monotherapy of acute bipolar depression
- Adjunct in the treatment of unipolar depression
- Agitation (e.g., haloperidol)
- Inability to distinguish between what is real and what is not
- Presence of delusions (false beliefs)
- Various types of hallucinations, usually auditory or visual, tactile, or olfactory
- Grossly disorganized thinking in a clear sensorium
psychosis
- Characterized mainly by a clear sensorium but a marked thinking and perceptual disturbance
- Most common psychotic disorder, present in about 1% of the population
- Considered to be neurodevelopmental disorder
- Studies have established that this is a genetic disorder with high heritability
Schizoprenia
Psychosis is not unique to schizophrenia and is [not present/always present] in all patients with schizophrenia at all times.
not present
identify if this is positive or negative symptom in Schizoprenia?
Hallucinating visually, audibly
Delusional Thinking
Disorganized Thinking
Agitated or Repetitive Movements
Positive
identify if this is positive or negative symptom in Schizoprenia?
Flat Affect
Anhedonia
Extreme Isolation
Resemble Clinical Depression
Negative
is a key factor in the mechanism of action of the main class of second-generation antipsychotic drugs,
5-HT2A-receptor blockade
prototype of 5HT 2A receptor blockade
clozapine is the prototype.
These drugs are inverse agonists of the 5-HT2A receptor; that is, they block the constitute activity of these receptors.
Clozapine. 5HT 2A receptor blockers
These receptors modulate the release of dopamine, norepinephrine, glutamate, GABA, and acetylcholine, among other neurotransmitters in the cortex, limbic region, and striatum.
5HT 2A
[Stimulation/Inhibition] of the serotonergic receptors leads to inhibition of cortical and limbic dopamine release.
Stimulation
Evidence suggest that [excessive/decreased] limbic dopaminergic activity plays a role in psychosis
excessive
[diminished/increased] cortical or hippocampal dopaminergic activity has been suggested to underlie the cognitive impairment and negative symptoms of schizophrenia
Diminished
major excitatory neurotransmitter in the brain
Glutamate
are noncompetitive inhibitors of the NMDA receptor that exacerbate both cognitive impairment and psychosis in patients with schizophrenia. (2)
Phencyclidine and Ketamine
Selective 5-HT2A antagonists, as well as atypical antipsychotic drugs, are much [more potent/less potent] than D2 antagonists in blocking these effects of PCP
more potent
hypofunction of NMDA receptors, located on GABAergic interneurons, leading to [increased/diminished] inhibitory influences on neuronal function, contributed to schizophrenia.
Diminished
Also known as neuroleptics, conventional or typical antipsychotics
First Generation Antipsychotics
Alleviate positive symptoms of schizophrenia
Have significant potential to cause extrapyramidal side effects and tardive dyskinesia
First Gen Antipsychotics
is the primary difference between FGAs and second-generation antipsychotics
propensity to cause movement disorders
- Low activity at histaminic and muscarinic receptors
- Associated with little sedation, weight gain, or anticholinergic activity, but a high risk for extrapyramidal side effects
high potency FGA (first gen antipsychotics)
haloperidol, fluphenazine are examples of?
High Potency FGA
Have high histaminic and muscarinic activity with a corresponding increased prevalence of sedation and anticholinergic effects
• Have lower risk of extrapyramidal side effects
Low Potency FGA
Chlorpromazine is an example of what drug classs?
Low Potency FGA
When you give FGAs you must also treat extrapyramidal side effects. T or F?
T
Aliphatic phenothiazine antipsychotic which blocks postsynaptic mesolimbic dopaminergic receptors in the brain
Chlorpromazine
exhibits a strong alpha-adrenergic blocking effect and depresses the release of hypothalamic and hypophyseal hormones
Chlorpromazine
Prototypical 1st gen antipsychotic and the FIRST ANTIPSYCHOTIC MEDICATION. First synthesized in France in 1952
Chlorpromazine
T or F? No antipsychotic has been shown to be significantly more effective than chlorpromazine in treating schizophrenia with the notable exception of clozapine
T
• Usual dose for schizophrenia of Chlorpromazine?
• Usual dose for schizophrenia: 200 – 800mg daily, in 2-4 divided doses
popular brand name of chlorpromazine?
Thorazine
adverse effects of chlorpromazine?
ADVERSE EFFECTS:
- EPS, sedation, weight gain, dry mouth, blurred vision, urinary retention, constipation, orthostatic hypotension
Butyrophenone antipsychotic that non-selectively blocks postsynaptic dopaminergic D2 receptors in the brain
• Available in oral and parenteral (IM, IV preparations)
Haloperidol (haldol)
what preparation is used as a rapid tranquilizer to control acute episodes of agitation and violence in patients with schizophrenia. (Dose: 2.5mg – 10mg
IM
Piperazine phenothiazine antipsychotic which blocks non-selectively postsynaptic mesolimbic dopaminergic D2 receptors in the brain
FLUPHENAZINE DECANOATE
Commonly used as a depot injection in cases of noncompliance to daily oral antipsychotic therapy
FLUPHENAZINE DECANOATE
Dose of FLUPHENAZINE DECANOATE
Dose: 6.25 to 25 mg every 2 weeks; the effects of a single injection may last 4 to 6 weeks
Adverse effects? FLUPHENAZINE DECANOATE
ADVERSE EFFECTS:
- EPS, increased risk for tardive dyskinesia
involuntary choreoathetoid movements of the mouth, tongue, face, extremities, or trunk, including lip-smacking, tongue writhing, or thrusting jaw movements, facia grimacing, and trunk or extremity writhing
Tardive dyskinesia
fever, muscle rigidity, mental status changes, and autonomic instability, generally accompanied by rhabdomyolysis and creatine kinase elevation
Neuroleptic malignant syndrome
menstrual irregularities, infertility, galactorrhea, loss of libido, and erectile and ejaculatory dysfunction
Prolactin Elevation
Constitute the bulk of antipsychotics nowadays
Generally, have lower risk of extrapyramidal side effects and tardive dyskinesia compared with first generation antipsychotics
SECOND GENERATION ANTIPSYCHOTICS (SGA1)
Alleviate both positive and negative symptoms of schizophrenia
SECOND GENERATION ANTIPSYCHOTICS (SGA1)
useful for treatment-resistant schizophrenia
Clozapine
is the most powerful antipsychotics under second generatio
Clozapine
Second generation antipsychotics as a group usually has [more/less] extrapyramidal symptoms; the side effects are usually metabolic
less
MOA of SGA
Post synaptic blockade of brain dopamine (D2) receptors,
Aripirazole and Brexipiprazole: MOA?
Aripirazole and Brexipiprazole: D2 receptor partial agonist
MOA Cariprazin
Cariprazin: D3/D2 receptor partial agonist
MOA Pimavenserin
Serotonin HT2A inverse agonist and antagonist
Prototype SGA
CLOZAPINE (CLOZARIL)
strongest affinity for muscarinic receptors (kaya madaming anticholinergic symptoms) among the SGAs and patient reports of side effects are most frequent
CLOZAPINE (CLOZARIL)
May cause agranulocytosis in up to 2% of patients
Dose-related lowering of seizure threshold
- Associated with potentially fatal cases of myocarditis and cardiomyopathy
- Changes in blood pressure, heart rate
- Anticholinergic side effects: Dry mouth, sialorrhea (excessive salivation), constipation
CLOZAPINE (CLOZARIL)
Pagnaka CLOZAPINE. Madalas may CBC monitoring to check
• Broad efficacy
Madaalas na madalas ginagamit as first line treatment
• Little to no extrapyramidal system dysfunction at low doses
RISPERIDONE (RISPERDAL
which ADR effect?
- Highest risk for EPS (extrapyramidal symptoms) among 2nd generation antipsychotics
- Highest risk for prolactin elevation among 2nd generation antipsychotics (together with paliperidone)
- Hypotension with higher doses
Risperidone (Risperidal)
Madalas ginagamit kasama ng Risperidone (Risperidone, Olanzapine, Quetiapine)
Very similar efficacy profile with Risperidone kaya sometimes they are used interchangeably
• Effective against negative as well as positive symptoms
• Little or no extrapyramidal system dysfunction
OLANZAPINE (ZYPREXA)
• High potential to cause weight gain and metabolic problems such as diabetes, hypercholesterolemia
Okay lang na AE and weight gain pag payat ang patient give Olanzapine para kumain sya ng kumain, but if Px has cardiovascular risk opt to give Risperidone or Quetiapine
• Dose- related lowering of seizure threshold
which Adverse effect?
OLANZAPINE (ZYPREXA)
Ang problema ay sobrang sedating nya to the point na it is commonly used OFF LABEL to treat Insomnia
For the treatment of bipolar disorder dun sya magaling na magaling talaga. Adjunct to bipolar depression, treatment of bipolar disorder
QUETIAPINE (SEROQUEL)
Hindi common sa Philippines • Less weight gain than clozapine • Parenteral form available (you can give if the patient is admitted) ADVERSE EFFECT: • QTc prolongation
ZIPRASIDONE (GEODON)
Indications for admitting a patient with psychiatric condition: Any of the 3 is present, admit the patient.
- Suicidality
- Homicidality
- Neuroleptic Malignant Syndrome (mental status change, muscle rigidity, fever, autonomic nervous system dysfunction associated with the use of antipsychotics)
One of the newer Second-Generation Antipsychotic (SGA)
Good drug less potential for metabolic side effects while retaining the efficacy for both positive and negative symptoms.
• Lower weight gain liability, long half life
• Novel mechanism potential
ADVERSE EFFECTS:
• Uncertain, novel toxicities possible
ARIPIPRAZOLE (ABILIFY)
Lithium, treatment for bipolar disorder, is a metal and the pharmacologic preparation is
lithium carbonate
• First agent shown to be useful in the treatment of the manic phase of bipolar disorder
- Sometimes used adjunctively in schizophrenia
- Used for the acute phase illness as well as for the prevention of recurrent manic and depressive episodes
- Has slow onset of action but very effective
The therapeutic window is very narrow
LITHIUM/ LITHIUM CARBONATE
Adverse effects of lithium?
ADVERSE EFFECTS: • Tremors (may be alleviated by giving beta blockers: propranolol and atenolol) • Decreased thyroid function • Polydipsia/ polyuria • Nephrogenic diabetes insipidus • Edema
OTHER AGENTS FOR BIPOLAR DISORDER
carbamazepine
lamotrigine
Valproic Acid
ANTIDEPRESSANT AGENTS (4)
- Selective Serotonin Reuptake Inhibitors
- Serotonin- Norepinephrine Reuptake Inhibitors
- Tricyclic Antidepressants
- Monoamine Oxidase Inhibitors
Suggest that depression is related to a deficiency in the amount of function of cortical and limbic serotonin (5-HT), norepinephrine (NE) and dopamine (DA)
what hypothesis?
MONOAMINE HYPOTHESIS OF DEPRESSION
are the most commonly prescribed first-line agents in the treatment of both MDD and anxiety disorders
SSRI
MOA: Highly selective blockade of serotonin transporter (SERT) with little effect on norepinephrine transporter (NET)
SSRI
Uses of SSRI?
Uses: in the treatment of major depression, anxiety disorders, panic disorder, obsessive compulsive disorder, some personality disorders, post-traumatic stress disorder, perimenopausal vasomotor symptoms, eating disorder (Bulimia)
When you give SSRIs for the treatment of depression, it takes at least ____ weeks before the drug exhibits a clinically significant effect
2 weeks.
Should be able to manage the expectations of the patients, do not give SSRIs for less than 2 weeks
Adverse effects of SSRI?
Nausea, gastrointestinal upset, diarrhea, and other gastrointestinal symptoms
• Diminished sexual function and interest
• Headaches, insomnia or hypersomnia
Contraindication of SSRI?
SSRIs are contraindicated in patients with hypersensitivity as well as patients who received monoamine oxidase inhibitors (MAOI) in the previous 2 weeks
If you give SSRI together with MAOI, you can have serotonin syndrome that manifest as [hypotensive/hypertensive] crisis among other symptoms.
Htn
First selective serotonin reuptake inhibitor (SSRI) approved for major depression (MDD
FLUOXETINE (PROZAC)
Approved for the treatment of bulimia (binge eating followed by vomiting)
• Least propensity to cause undesired weight gain
FLUOXETINE (PROZAC)
Do not prescribe Fluoxetine with ________
Tamoxifen
Do not prescribe with Tamoxifen!
There is an interaction between Tamoxifen and Fluoxetine. Reduces the effectiveness of Tamoxifen (given to prevent the growth of breast cancer)
Famous brand name is Celexa
• Usual dose: 20-40mg OD
ADVERSE EFFECTS:
• May cause dose-dependent QT interval prolongation that can lead to arrhythmias
Citalopram
Mas sikat than citalopram, brand name is Lexapro
Famous because of very little propensity to induce drug-drug interaction
Common agent given when the patient is taking a lot of other medications for different conditions. E.g.: HIV positive patients
Does not require S2 license, even GP’s can prescribe this drug
• Single isomer formulation of citalopram
• Usual dose: 10-20mg OD (given at least 2 weeks)
Escitalopram
• Usual dose: 20-40mg OD
• Associated with weight gain
Baligtad kay Fluoxetine (Prozac)
• Associated with fetal cardiac septal defects if taken during pregnancy
• Discontinuation syndrome (dizziness, paresthesias) if patient is taking it long term, then treatment is suddenly discontinued
Paroxetine
• Duloxetine, Venlafaxine, Levomilnacipran
Duloxetine and Venlafaxine are the most commonly used
SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
- May also be used as first line agents for MDD, like SSRIs
- MOA: treat depression by initially blocking presynaptic serotonin and norepinephrine transporter proteins
- Effects: Acute increase in serotonergic and adrenergic synaptic activity similar to SSRIs
- Uses: Major depression, chronic pain disorders, fibromyalgia, perimenopausal symptoms
SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIs)
Adv effects of SNRI?
ADVERSE EFFECTS:
• Noradrenergic effects, including increased blood pressure and heart rate and CNS activation such as insomnia, anxiety and agitation
• All the SNRIs have been associated with a discontinuation syndrome resembling that seen with SSRI discontinuation
E.g., Imipramine, Clomipramine which are usually third-line agents for depression
Powerful agents
• MOA: Mixed and variable blockade of NET and SERT
TRICYCLIC ANTIDEPRESSANTS (TCAs)
• Uses: Major depression NOT RESPONSIVE TO OTHER DRUGS, chronic pain disorders, incontinence, OCD (but not as first-line agents)
TRICYCLIC ANTIDEPRESSANTS (TCAs)
• E.g.: Bupropion, Amoxapine, Maprotiline, Mirtazapine
Third to fourth line agents for depression
• MOA: increased norepinephrine and dopamine activity
• Effects: Stimulate presynaptic release of catecholamines but no effect on 5-HT
• Uses: Major depression, smoking cessation (Bupropion)
TETRACYCLIC ANTIDEPRESSANTS
- Approved in 1997 as a treatment for smoking cessation
- As effective as nicotine patches in smoking cessation, but with unknown MOA for this effect
- May have some benefits in treating obesity
(Bupropion)
• E.g.: Isocarboxazid, Phenelzine, Selegiline
• Used in the treatment of major depression unresponsive to other drugs
• Very slow elimination
Associated with many interactions with drugs for hypertension, dyslipidemia, psychotropic medications, kaya mahirap sya gamitin. You have to properly weigh the risk and benefit.
MONOAMINE OXIDASE INHIBITORS (MAOIs)
ADVERSE EFFECTS:
• Orthostatic hypotension
• Weight gain
• Anorgasmia (inability to generate an orgasm)
• Discontinuation syndrome (withdrawal effects)
The many potential drug interactions
MONOAMINE OXIDASE INHIBITORS (MAOIs)
To induce weight gain, choose:
For weight loss:
The rest are weight neutral
To induce weight gain, choose Mirtazapine or Paroxetine
For weight loss: Bupropion
The rest are weight neutral
Drugs used for Substance abuse issues
Bupropion for Nicotine
Mirtazapine for methamphetamine
Drugs used for ADHD
Bupropion, Venlafaxine
Drugs used for Pain
Duloxetine, Venlafaxine, Amitriptyline (TCAs)
Drugs used for Migraine
Amitriptyline
Drugs used for Avoid sexual dysfunction
Bupropion
Mirtazapine
Drugs used for Avoid seizures
Bupropion
Drugs used for Pediatric
< 18 y/o
Note that all antidepressants have a black box warning for increased suicidal ideation in adolescents
Medical treatment most commonly used in patients with severe major depression or bipolar disorder that has not responded to treatments
Involves a brief stimulation of the brain to induce convulsion while the patient is in anesthesia
It can also be used when the patient cannot wait for 2 weeks to observe the effects of antidepressants
ELECTROCONVULSIVE THERAPY (ECT)
• First drugs to be abused (preceding stimulants) and are still
among the most commonly used for nonmedical purposes
opioids
is rapidly
metabolized to morphine)
diacetylmorphine (heroin)
examples are: Morphine, heroin (diacetylmorphine, which is rapidly
metabolized to morphine), codeine, and oxycodone
Opioids
usually found in cough syrup before
Codeine
the derivatives of this is now antitussive
Opoids
for treatment of opioid addiction? opioid antagonist
o Reverses the effects of a dose of morphine or heroin
within minutes
o May be lifesaving in the case of a massive overdose
o Provokes an acute withdrawal (precipitated abstinence)
syndrome in a dependent person who has recently taken
an opioid
Naloxone
adverse effect of Opioid that leads to death?
Respiratory depression
causes disinhibition of dopamine neurons, mainly by
presynaptic inhibition of GABA neurons
THC - 9-
tetra-hydrocannabinol (THC)
Onset of effects of THC after smoking marijuana occurs
within minutes and reaches a maximum after ______-
1-2 hours
most prominent effects of marijuana
Most prominent effects are euphoria and relaxation
• Liquid ecstasy, grievous bodily harm, or date rape drug
• First synthesized in 1960 and introduced as a general
anesthetic
• Causes euphoria, enhanced sensory perceptions, a feeling
of social closeness, and amnesia, before causing sedation
and coma
• Has been used in date rapes because it is odorless and can
be readily dissolved in beverages
GAMMA-HYDROXYBUTYRIC ACID (GHB)
• Induce, perceptual symptoms, including shape and color
distortion
• Psychosis- like manifestations (depersonalization,
hallucinations, distorted time perception) have led some to
classify these drugs as psychotomimetic
• They also produce somatic symptoms (dizziness, nausea,
paresthesia, and blurred vision)
• Some users have reported intense reexperiencing of
perceptual effects (flashbacks up to several years)
LSD
• Lysergic acid diethylamide (acid, battery acid, dots)
_________addiction occurs primarily through smoking of
tobacco, although through chewing tobacco
nicotine
Selective agonist of the nicotinic acetylcholine receptor
(nAChR) that is normally activated by acetylcholine
nicotine
prevents nicotine from exerting its actions; impairs capacity to drive and has been associated with suicidal ideations
Varenicline
- Commonly prescribed as anxiolytics and sleep medications
- Represent a definite risk for abuse
- addiction to this drug has Symptoms that include irritability, insomnia, phonophobia, and photophobia, depression, muscle cramps, and even seizures. Typically, these symptoms taper off within 1-2 weeks
BENZODIAZEPINES
48-72 hours after cessation, an alcohol withdrawal delirium may become apparent in which the person hallucinates, is disoriented, and shows evidence of autonomic instability
associated with 5-15%mortality
(delirium tremens)
Treatment of ethanol withdrawal is supportive and relies on ___________
oxazepam and lorazepam
In alcohol patients in whom monitoring is not reliable and liver function is adequate, a longer-acting benzodiazepine such as _____________ is preferred
chlordiazepoxide
o Long -acting opioid antagonist, blocks u-opioid receptors
o Reduced the rate of relapse to either drinking or alcohol dependence and to reduce craving for alcohol, especially in patients with high rates of naltrexone adherence
o Dose:50mg OD PO, IM injection once q4 weeks also available
Naltrexone
o First medicine approved by the Food and Drug Administration (FDA) for the treatment of alcohol abuse and alcohol dependence
o Acts inhibiting aldehyde dehydrogenase
Disulfiram (Antabuse)
in Disulfiram, Alcohol is metabolized as usual, but acetaldehyde accumulates. Thus, disulfiram causes extreme discomfort in px who drink alcoholic beverages. T or F?
t
o Used in Europe for several years to treat alcohol dependence
o Has many molecular effects including actions on GABA, glutamate, serotonergic, noradrenergic, and dopaminergic receptors
o Dose:333mg tablets, 1-2tabs BID to TID
Acamprosate
Developed as general anesthetics; use-dependent, noncompetitive antagonism of the NMDA receptors
• Crystalline powders in their pure forms, but on the street they are also sold as liquids, capsules, or pills, which can be snorted, ingested, injected, or smoked
• The effects of these substances became apparent when patients undergoing surgery reported unpleasant vivid dreams and hallucinations after anesthesia
• Psychedelic effects last for about 1 hour and also include increased blood pressure, impaired memory function, and visual alterations
Ketamine and Phencyclidine
AKA “K”, “Special K”, “Vitamin K”, “Kit kat”
o Horse tranquilizer
Ketamine
AKA Angel Dust
Phencyclidine
- Nitrites, ketones, aliphatic and aromatic hydrocarbons
- Present in a variety of household and industrial products
- Inhaled by “sniffing”, “huffing”, or “bugging”
- Exact mechanism of action of most volatile substances remains unknown
- Some studies show that it can decrease your brain mass
Inhalants
AKA • “coke”, “blow”, “coca”, “snow”, “nose candy”
Cocaine
- Alkaloid found in the leaves of Erythroxylon cola, a shrub indigenous to the Andes
- Used clinically as a local anesthetic and to dilate pupils in ophthalmology
Cocaine
is a water-soluble salt that can be injected or absorbed by any mucosal membrane
• When heated in an alkaline solution, it is transformed into the free base: “crack cocaine,” which can then be smoked
Cocaine Hydrochloride
Rewarding effects of cocaine:
block of the dopamine transporter (DAT), by increasing dopamine concentrations in the nucleus accumbens
• Users typically lose their appetite, are hyperactive, and sleep little
antagonist for cocaine?
To date, no specific antagonist is available
o Management of intoxication remains supportive
AKA “shabu”, “meth”, “chalk”
Methamphetamine
Group of synthetic, indirect-acting sympathomimetic drugs that cause the release of endogenous biogenic amines (e.g. dopamine and noradrenaline)
AMPHETAMINES
Exert their effects by reversing the action of biogenic amine transporters in the plasma membrane
• interfere with the vesicular monoamine transporter (VMAT) which causes levels of dopamine (or other transmitter amine) in the cytoplasm to increase
• Often produced in small clandestine laboratories
o Precise chemical identification difficult
• Typically taken initially in pill form by abusers; can also be smoked or injected
AMPHETAMINES
effectss of amphetamines?
Within hours after oral ingestion, amphetamines increase alertness and cause euphoria, agitation, and confusion
• Hypertensive crisis and vasoconstriction may lead to stroke
o Depletion of nasal septum: vasoconstriction → tissue necrosis
• Chronic use: tolerance may develop → dose escalation → toxicity
AKA MDMA? “Molly”, “E”
ECSTASY (MDMA)
• MDMA: methylenedioxymethamphetamine
Has a preferential affinity for the serotonin transporter (SERT) and therefore most strongly increases the extracellular concentration of serotonin followed by marked intracellular depletion for 24 hours after a single dose
o Sobrang high tapos biglang down
MDMA/ ecstasy
Withdrawal is marked by a mood “offset” characterized by depression lasting up to several weeks
Ecstasy
