5.1 - Central Nervous System (Anxiolytics, Antidepressants, Antipsychotics) Flashcards
What is anxiety?
Difficulty to control apprehension/worry occurring more days than not (6+ months)
Symptoms:
–> Restlessness
–> Easily fatigued
–> Difficulty concentrating
–> Irritability
–> Muscle tension
–> Sleep disturbances
What drugs are anxiolytics?
Benzodiazepines, non-benzodiazepines, buspirone
What are the sedative hypnotics?
Barbituates
What sympathetic blockers are used to treat anxiety?
Propanolol, clonidine
What are the three benzodiazepines that act on GABA-A?
Lorazepam (Ativan), Clonazepam, Diazepam
What is GABA? What receptors does it act on?
Main inhibitory NT in the brain
GABA-A
–> When stimulated, increased opening of chloride channels, making cells more negative (less excitable)
GABA-B
–> Inhibits neuronal activity
What is baclofen? What does it act on?
Stimulates GABA-B to reduce muscle spasticity
What are the sites on a GABA receptor?
GABA receptor, benzodiazepine receptor, non-benzodiazepine receptor, barbituate site
What are the clinical uses of benzodiazepines?
Sedation (before surgery)
Reduce anxiety
Muscle relaxation
What are the adverse effects of benzodiazepines?
–> Drowsiness, ataxia
–> Danger of drug accumulating in body (esp w long t1/2)
–> Dangerous when combined with alcohol
–> Can cause anterograde amnesia
–> Risk of substance use disorder and tolerance (14+ days)
–> Prolonged use may lead to withdrawal syndrome if discontinued suddenly (Insomnia, restlessness, sweating, tremors, tachycardia
What is the antidote to benzodiazepines overdose?
Flumazenil
–> Benzodiazepine receptor antagonist
–> Can trigger seizures
What is psychological (behavioural) dependence?
Emotional reliance on a drug to produce pleasure or relieve discomfort
–> State of need driven by the rewarding effects of the drug (taps into reward system)
–> Can lead to cravings and compulsive use despite harmful effects
What is physical dependence?
State of adaptation to the presence of a drug leading to the development of tolerance as well as marked withdrawal syndrome following the abrupt cessation of a drug.
What is flunitrazepam?
Rohypnol
–> 10x more potent than diazepam
–> Approved for use in Europe/South America
often slipped in drinks
What is gamma hydroxybutyrate?
Found in the brain and acts on GABA receptors
–> Often contains toxic residues leftover from their chemical synthesis
Often slipped in drinks
What happens when flunitrazepam and gamma hydroxybutyrate are mixed with alcohol?
Can cause:
–> Fainting
–> Anterograde amnesia
–> Resp depression/bradycardia/hypotension
What kind of drugs are zopiclone and zolpidem? What are they used for? What are the adverse effects?
Non Benzodiazepines
–> Anxiolytic drugs that do not share same chemical structure as benzodiazepines but act on the same receptor GABA-A
–> Used to treat insomnia without decreasing stages of restorative sleep
Fewer adverse effects affecting coordination/memory
Generally, shorter duration and onset of action benzodiazepines
What does buspirone do? What are the side effects?
Decreases the release of serotonin (5-hydroxytryptamine or 5-HT)
Less sedative, does not act quickly, fewer interaction with alcohol, and less abuse than benzodiazepines.
Side effects: dizziness and lightheadedness
What alpha-2 agonist is used to treat anxiety? What does it do for anxiety?
Clonidine
–> May reduce physical symptoms but not particularly effective at reducing anxiety at the emotional level
Which B-blocker is used to treat anxiety?
Propanolol
–> Used to treat social phobia, performance anxiety, and anxiety related to the memory of stressful events
What kind of drug is phenobarbital? What is its use?
Barbiturate
–> Sedative hypnotic
Pronounced Sedative Effect
–> Was used as IV anesthetic, also in death penalty
–> Gradual tolerance leads required dose for effect to be greater than the lethal dose
What are the adverse effects of phenobarbital?
–> Lethargy, cardiovascular and respiratory depression
–> Induction of CYP enzymes
Adrenergic anxiolytics are useful at relieving what symptoms of anxiety?
Feelings of anxiety, dilated pupils, tachycardia, tremor, and remembering on stressful events
Depression is classified as…
Depressed mood or apathy + Four of the following:
–> Psychomotor retardation or restlessless
–> Weight/appetite disturbances
–> Sleep disturbances
–> Fatigue
–> Feelings of guilt or worthlessness
–> Executive dysfunction
–> Suicidal ideation
One hypothesis about depression suggests that what kinds of NTs are low?
Amines
–> Na, Da, 5HT
What is a synonym for serotonin?
5-hydroxytryptamine
What is the process of synthesizing serotonin?
Tryptophan –> 5-hydroxytrytophan –> 5-hydroxytryptamine
What are the MAO inhibitors used to treat depression? What is the mechanism of action?
Phenelzine, pargyline
–> Irreversible inhibition of monoamine oxidase, resulting in increased release of NA, DA, 5HT in synaptic cleft
What interaction of drugs can result in malignant hyperthermia?
Meperidine + irreversible MAO inhibitor (phenelzine, pargyline)
What are the adverse effects of irreversible MAO inhibitors and tyramine?
Hypertensive crisis of NA caused by displacer tyramine and the inhibited MAO cannot eliminate the excessive levels of NA
What is tyramine?
An NA displacer found in fermented cheeses and meats, yeast, red wine, and beer.
Can cause hypertensive crisis when combined with irreversible MAO inhibitors (Phenelzine, pargyline)
What is moclobemide? What is it used for?
Reversible MAO-A inhibitor
–> Decreased risk of toxic adverse effects associated with tyramine bc it releases MAO if NA levels are too high
What is selegiline? What is it used for?
Reversible MAO-B inhibitor
–> Used to treat Parkinsonism
What kind of NT does MAO-A preferentially target?
NA and 5HT (some DA)
What kind of NT does MAO-B preferentially target?
DA
What are the monoamines?
Serotonin, NE, E, DA
What kind of drugs are amitriptyline and imipramine?
Tricyclic Antidepressants
–> Inhibit reuptake of serotonin, NE, and DA
–> Very lipid soluble with long half-life (is slowly released from adipose tissue where it builds up)
–> Narrow therapeutic index, several adverse effects
What are the adverse effects of tricyclic antidepressants?
Anti-histaminic
–> Weight gain and fatigue
Anti-muscarinic
–> Constipation, blurred vision, xerostomia, fatigue (anti-sludge)
Anti-adrenergic
–> a1 effects: hypoTN, dizziness
+ decreased libido
+ can block sodium channels, can be toxic to heart
Name all the SSRIs relevant to this class.
Fluoxetine
Citalopram
Escitalopram
Paroxetine
Sertraline
SSRIs do not have as many adverse effects as Tricyclic antidepressants. What are their adverse effects?
–> Anorexia/diarrhea
–> Insomnia
–> Sexual dysfunction
–> Anxiety
What is an enantiomer?
A mirror-imaged composition of the atoms in a molecule - Some companies purify the active enantiomer from a mixture
What kinds of drugs are venlafaxine, duloxetine, and desvenlafaxine? Adverse effects?
5HT + NA Reuptake Inhibitors
–> Mech of action resembles tricyclic antidepressants
–> Possibly faster therapeutic effect
Adverse effects:
–> Nausea, anorexia, agitation, sexual dysfunction
What kind of drug is Buproprion? Adverse effects?
An NA + DA reuptake inhibitor
–> Useful to reduce cravings in pts trying to quit smoking, also used as an antidepressant
Adverse Effects:
–> Sympathetic stimulation (Headache, tachycardia, tremors, agitations, suppressed apetite)
–> Sleep disruptions
–> Xerostomia
What are non-pharmaceutical treatments for depression?
–> Repetitive Transcranial Magnetic Stimulation (rTMS)
–> Electroconvulsive therapy (ECT)
What is repetitive Transcranial Magnetic Stimulation? Adverse effects?
Treatment for depression
–> Magnetic pulses are used to increase activity in parts of the brain
Adverse effects: Headache
What is electroconvulsive therapy? Adverse effects?
Treatment for depression
–> small electrical currents stimulate brain
–> pt will receive anesthesia and muscle relaxants prior to therapy - usually used to severe and refractory depression
Adverse effects:
–> Headaches
–> Muscle Soreness
–> Amnesia
What is the main medication used to treat Bipolar disorder? What are its adverse effects?
Lithium
–> Narrow therapeutic index
–> Must ensure good kidney function
Adverse effects:
–> Nausea, thirst, polyruria, fine tremor (exaggerated to seizure at high dose)
What are the positive symptoms of psychosis?
–> Auditory and visual hallucinations
–> Inappropriate gesticulation
–> Repetition of movement
–> Strange language
–> Pressure of speech
–> Disorganized behaviour
–> Agitation
What are the negative symptoms of psychosis?
–> Passivity
–> Lack of initiative
–> Alogia (poverty of speech)
–> Anhedonia (Lack of pleasure)
–> Frozen facial expression
–> Lack of concentration
–> Social isolation
What is alogia?
Poverty of speech
What is anhedonia?
Lack of pleasure
What is the believed pathophysiological explanation for schizophrenia?
Excessive DA
What kind of medication is chlorpromazine and haloperidol?
Typical antipsychotics (also called neuroleptics)
How do typical antipsychotics treat schizophrenia?
-symptoms
-mech of action
Block DA receptors in the brain
–> They improve positive symptoms, but do not improve negative ones
What are extrapyramidal symptoms? What drugs are they associated with?
Associated with typical antipsychotics
–> Parkinsonism (tremors at rest, rigidity, akinesia)
Dystonia
–> Inappropriate muscle contraction, grimacing
Akathesia
–> Feeling of inner restlessness and inability to stay still
How can EPS associated with typical antipsychotics be treated?
Sometimes, extrapyramidal symptoms can be treated with anticholinergic drugs like benztropine
What are the adverse effects of typical anti-psychotics
Extrapyramidal symptoms
Malignant Neuroleptic Syndrome
–> Hyperthermia, muscle rigidity, coma
With longterm use, tardive dyskinesia
–> involuntary, repetitive movements (blinking, lip smaking, tongue movements)
Anti-M, Anti-H1, and alpha1 blocker effects
Increases secretion of prolactin (consequence of blocking DA)
Photosensitivity
What kinds of drug are the following:
clozapine, olanzapine, quetiapine, risperidone, aripiprazole
Atypical antipsychotics
–> Improve the positive and negative symptoms of schizophrenia/psychosis
–> Fewer extrapyramidal effects
What are specific adverse effects of clozapine?
Agranulocytosis, may cause drowsiness, metabolic risks (appetite, obesity, dyslipidemia, insulin resistance, diabetes, CDV disease)
What are the adverse effects specific to quetiapine?
Drowsiness
What are the adverse effects specific to olanzapine?
Metabolic risks (appetite, obesity, dyslipidemia, insulin resistance, diabetes, CDV disease)
May cause drowsiness
Aripiprazole:
Mechanism of action
Adverse Effects
Atypical Antipsychotics
–> Partial agonist at dopamine receptor
–> Increased risk for pathological gambling and hypersexuality
What is nordazepam? Give an example of a medication that has it as a metabolite.
An active metabolite of some benzodiazepines that will increase the half life of the drug and has an adverse effect of accumulating in the body
–> diazepam
What drugs are used to treat depression?
–> MAO Inhibitors
–> Tricyclic Antidepressants
–> SSRIs
–> SNRIs
What plant is cocaine derived from?
Extracted from leaves of the coca plant
What is the mechanism of action of cocaine compared to amphetamines?
Similar effects to amphetamines
–> amphetamine displaces DA, NA, and 5HT stored in vesicle
–> cocaine inhibits reuptake of DA, NA, and 5HT in synapse
What are the two forms of cocaine used?
Cocaine hydrochloride - white powder taken intranasally
Cocaine base “crack” - Heated for use and taken IV or inhaled
What are the effects of cocaine?
Sympathomimetic effects:
–> Agitation, tremor, ventricular dysrhythmias, intense vasocontraction that can lead to angina, MI, or hemorrhagic stroke), cardiac stimulation, hyperpyrexia, convulsions
What routes are methamphetamines taken?
p.o., snorted, smoked, i.v.
What are the effects of methamphetamines?
Arousal, euphoria, sense of increased mental capacity, decreased appetite, visual and auditory hallucination, erratic behaviour, psychotic state
Sympathomimetic actions, ventricular dysrhythmias, intense vasoconstriction (angina, hemorrhagic stroke, MI)
Bruxism and xerostomia can lead to tooth decay
What routes is MDMA taken?
orally, snorted, injected, rectal suppository
What are the effects of MDMA? What others drugs is it structurally similar to?
Structurally similar to methamphetamine (stimulant) and mescaline (hallucinogen)
–> Low dose: mild LSD-like psychological effects
–> higher dose: amphetamine-like effects
What are the adverse effects of MDMA?
May injure serotonergic neurons, stimulate the heart, hyperthermia
Seizures, spasmodic jerking, jaw clenching, bruxism, confusion, anxiety, panic, paranoia
Serotonin Syndrome
What are the symptoms of serotonin syndrome?
Diaphoresis, tachycardia, diarrhea, pyrexia, psychomotor agitation, shivering, hyperrreflexia/tremor that is greater in lower extremities), mydriasis, confusion
In more serious cases: delirium, muscular rigidity, clonus (repeated involuntary muscular contractions)
