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Clinical Pharmacology Year V NIŠ > Neuropsychopharmacology > Flashcards

Neuropsychopharmacology Flashcards

1
Q

What is Alzheimer’s disease and its symptoms?

A
  • neurodegenerative condition: the most common condition to lead to dementia
  • Cognitive decline: loss of memory, aphasia, ataxia, disorientation
  • Behavioural changes: hallucination, depression, sleep fragmentation, aggression
  • Functional symptoms: inability to care for self and perform daily tasks
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2
Q

What are the types of AD?

A
  • Sporadic AD: late onset (> 65 years)- APoE4 carriers
  • Familial AD: early onset with rapid progression with dominant inheritance- APP, PS1/PS2 mutations)
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3
Q

What are the core pathological hallmarks for AD in the brain?

A
  • Accumulation of extracellular plaques consisting of amyloid beta proteins
  • Neurofibrillary tangles consisting of hyperphosphorylated tau
  • Loss of cortical neurons
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4
Q

What is the pharmacological goal for the treatment of AD?

A
  • Unable to alter the underlying neurodegenerative process
  • Able to provide modest short-term benefits
  • Support slowing down of symptom development
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5
Q

What drugs are commonly used to treat cognitive symptoms of AD?

A
  • AchE inhibitors
  • Galantamine, Donepezil & Rivastigmine: indicated for mild to moderate AD
  • “GALanttly DOwn the RIVer”
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6
Q

What are the side effects of the AchE inhibitors used to treat mild-moderate AD?

A
  • Nausea
  • Vomiting
  • Vertigo
  • Diarrhea
  • Tremors
  • Bradycardia
  • Muscle cramps
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7
Q

What drug is used for moderate to severe AD? Side effects

A
  • NMDA antagonist: Memantine
  • often may be used in combination with Donzepil
  • Side effects: Nausea, vomiting, headache & confusion
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8
Q

What first-choice drugs may be used for the treatment of behavioural symptoms of AD?

A

First Choice:
- Agitation: citalopram and risperidone
- Apathy- Methylphenidate
- Depression: a higher dose of citalopram, sertraline
- Insomnia: Zolpidem, Zaleplon

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9
Q

What Second choice drugs may be used for treatment of the treatment of behavioural symptoms of AD?

A

Second Choice:
- Agitation: Apripiprazole, Olanzapine
- Apathy: Modafinil
- Depression: Aripiprazole, Paroxetine, Duloxetine
- Insomnia: Trazodone, Suvorexant

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10
Q

What is anxiety?

A
  • an unpleasant state of worry, tension or uneasiness from fear of a known or unknown source
  • symptoms are sympathetic: tachycardia, sweating, trembling and palpitations
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11
Q

Which drugs are used as anxiolytics?

A
  • Benzodiazepines
  • Antidepressants: SSRI, SNRI
  • Buspirone
  • Pregabalin
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12
Q

What are the MOA of Benzodiazepines?

A

-indirect GABA A receptor agonists; → ↑ GABA action → ↑ opening frequency of chloride channels → hyperpolarization of the postsynaptic neuronal membrane → ↓ neuronal excitability
- decrease the duration of N3 phase in NREM sleep, thereby reducing the occurrence of sleepwalking and night terrors

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13
Q

What are the pharmacological effects of Benzodiazepines?

A
  • Anticonvulsant
  • Muscle relaxant
  • Reduce anxiety
  • Sedation
  • Anterograde amnesia
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14
Q

Can Benzodiazepines be used during pregnancy?

A
  • No
  • they can cross the placenta and caused CNS depression of newborn
  • not to be given when pregnant or breastfeeding
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15
Q

What are some common benzodiazepines?

A
  • Diazepam
  • Lorazepam
  • Alprazolam
  • Flurazepam
  • Clorazepate
  • Triazolam
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16
Q

What are the adverse effects of benzodiazepines?

A
  • drowsiness
  • confusion
  • ataxia
  • possible cognitive deficits after short-acting Benzo’s
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17
Q

What happens if Benzodiazepines are increased in dosage for longer periods?

A
  • Develop dependence
  • Signs of dependence, cease medication, withdrawal symptoms
  • Resume medication, fear of withdrawal symptoms, creates dependence (back to signs of dependence)
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18
Q

What are the symptoms of withdrawal from Benzodiazepines?

A
  • Confusion
  • Anxiety
  • Agitation
  • insomnia, restlessness
  • rarely seizures
  • shortly acting Benzo’s (e.g. triazolam) create more abrupt and severe withdrawal reactions
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19
Q

Which drug is a benzodiazepine antagonist?

A
  • Flumazenil
  • blocks GABA A receptor; reverse effects of Benzo’s
  • rapid onset of action but short duration (half-life around 1 hour)
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20
Q

What antidepressants may be used as anxiolytic agents?

A

SSRI: Paroxetine, Escitalopram
SNRI: Venlafaxine, Duloxetine

  • given in combo with Benzo’s during the first week of treatment
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21
Q

What is Buspirone?

A
  • not given for short action or acute anxiety due to slow onset of action
  • more for chronic generalised anxiety disorder (GAD)
  • requires constant use for at least up 2 weeks for effects to take place
  • partial agonist of pre and post-synaptic 5HT 1a receptors
  • antagonist of D2 AND 5HT 2a receptors
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22
Q

What is pregabalin?

A
  • treatment of GAD, epilepsy, neuropathic pain etc
  • low riks for addiction development not tolerance
  • increases expression of glutamic acid decarboxylase to convert glutamate to GABA
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23
Q

What is the pharmacological management of insomnia?

A
  • Hypnotic agents: benz, melatonin receptor agonist, Z drugs etc
  • Antidepressant with sedating properties
  • Antihistamine drugs
24
Q

What Z drugs are used for insomnia? MOA? Adverse effects?

A
  • Zolpidem and Zaleplon
  • MOA: bind to GABA A receptors to enhance neuronal hyperpolarization
  • rapid onset of hypnosis with amnestic effects or day after somnolence
  • Side effects: dizziness, dry mouth , headache etc
25
Q

What Benzo’s are used to treat insomnia? Adverse effects?

A
  • Triazolam, Flurazepam, Oxazepam, Midazolam
  • Adverse effects: withdrawal, drowsiness, headache, attention deficiency, tremor, ataxia etc
26
Q

What orexin receptor anatagonists are used for insomnia? MOA? Adverse effects?

A
  • Suvorexant, lemborexant (both are hypnotics)
  • Bind to specific ORX1 and ORX2 receptors in brain to promote sleep
  • adverse effects: drowsiness, headache, driving impairment
27
Q

What melatonin receptor agonists are used for insomnia? MOA? Side effects?

A
  • Ramelteon, Tasimelteon
  • selectively activate MT1 and MT2 receptors in suprachiasmatic nucleus in the brain to induce sleep
  • adverse effects: withdrawal, headache, fatigue, drowsiness
28
Q

Which antihistamines are used for insomnia? MOA? Side effects?

A
  • Diphenhydramine, Doxylamine, Hydroxyzine
  • mild insomnia, used via OTCP
  • bind and block H1 receptors in the brain to promote sedation and sleep
  • Side effects: dry mouth, hallucination, fatigue
29
Q

Which antidepressants are used for insomnia? MOA? Side effects?

A
  • Doxepin, Trazodone, Mirtazapine, Amitriptyline
  • Antagonist of 5HT2 and 3, A1 and H1
  • Reuptake inhibition of 5HT and NA
  • Side effects: prolonged sedation, orthostatic HTN, dry mouth, headache, constipation
30
Q

What is depression?

A
  • Depression is a state of mood disorder, characterised by persistent feelings of sadness, hopelessness, and loss of interest in activities an individual once enjoyed
  • a sense of fatigue, depressed mood, significant weight loss/gain without intention, lack of focus etc
31
Q

What antidepressants are used for the management of depression?

A
  • SSRI e.g. paroextine or fluoxetine (1st line)
  • SNRI e.g. venlafaxine, duloxetine (1st line)
    -NDRI e.g. Bupropion (1st line)
  • NA-specific serotonergic antidepressants (NaSSA) e.g. mirtazapine (1st line)
  • TCA e.g. amitriptyline (2nd line)
  • MAOI e.g. selegiline (3rd line)
32
Q

What SSRIs are used for depression management? MOA? Adverse effects?

A
  • Paroxetine, Fluoxetine, sertraline etc.
  • Inhibition of 5HT reuptake in the synapse to increase serotonergic transmission
  • indicated: major depression, PTSD, eating disorder, anxiety etc
  • adverse effects: nausea, diarrhea, headache, insomnia, weight gain (paroxetine), discontinuation syndrome & serotonin syndrome
33
Q

What is discontinuation and serotonin syndrome?

A
  • discontinuation syndrome: abrupt cessation of SSRI leads to anxiety, headache, malaise and sleep disturbance
  • serotonin syndrome: when used with MAOI- hyperthermia, diarrhoea, muscle rigidity. sweating, myoclonus, mood alteration
34
Q

Which SNRIs are used for depression management MOA? Side effects?

A
  • Venlafaxine, Duloxetine, Desvenlafaxine etc.
  • Moderate blockade of SERT and NA transporters to acutely increase serotonergic and adrenergic transmissions
  • Indicated in major depression, chronic pain, perimenopausal symptoms
  • Side effects: sedation, XS sweating, nausea, headache, diarrhea, insomnia etc
35
Q

What NDRI is used for depression management? MOA? Side effects?

A
  • Bupropion
  • Blockage of dopaminergic and NA reuptake transporters to increase dopaminergic and adrenergic neurotransmission
  • Indication: major depression, cigarette smoking cessation
  • Side effects: headache, tremors, dry mouth, XS sweating
36
Q

Which NaSSA is used for depression management? MOA? Side effects?

A
  • Mirtazapine
  • antagonism of presynaptic A2 and post-synaptic 5HT2 & 3 receptors in CNS to increase serotonergic neurotransmission
  • indicated in major depression, increased anxiety, insomnia
  • side effects: dry mouth, headache, increased appetite, weight gain

*when given with MAOI: can induce HTN, hyperthermia and seizures

37
Q

What atypical antidepressants are used for depression management? MOA? Side effects?

A
  • Nefazodone Trazodone
  • weak inhibition of SERT
  • antagonist of post-synaptic 5HT 2a receptors, H1 & A1: increase serotonergic neurotransmission
  • indicated in major depression, sedation and insomnia
  • side effects: headache, dizziness, sedation, nausea, ortho. hypotension
38
Q

What TCAs are used for depression management? MOA? Side effects?

A
  • amitriptyline, imipramine, Nortryptiline etc.
  • increase MAO-mediated neurotransmission by inhibition of NA and 5HT reuptake and blocking NA, 5HT, H and muscarinic receptors
  • require 2 weeks or longer to show effects on mood elevation
  • adverse effects: blurred vision, dry mouth, urinary retention, constipation, tachycardia etc.
39
Q

What MAOI are used or the management of depression? MOA? Side effects?

A
  • Selegiline (MAO-B selective), Phenelzine, Tranylcypromine etc.
  • irreversibly/reversibly inactivate enzymes MAO-A & MAO-B, therefore NTs can accumulate in presynaptic neurons and synapse
  • used in major depression and selegiline used in PD
  • Side effects: blurred vision, dry mouth, constipation

*with serotonergic agent may induce serotonin syndrome

40
Q

What is the treatment protocol for depression in elderly patients?

A

1st line: SSRI (except fluoxetine) or SNRI, Bupropion, Mirtazapine
2nd line: Fluoxetine, Trazodone
3rd line: TCAs Maprotiline

Common side effects: extrapyramidal symptoms especially with SSRIs

Drug dose should be slowly increased to an effective dose for the individual or until the first occurrence of adverse effects

41
Q

What is Bipolar disorder (BD) ? Types?

A

Type 1: 1 or more manic or mixed episodes with altered mood, euphoria, increased energy, rapid speech, reduced need for sleep
- mixed rapid alteration of manic and depressive symptoms

Type 2: 1 or more hypomanic episodes, elevated mood with talkativeness, racing thoughts and reckless behaviour

Cyclothymia: persistent mood swings for at least 2 years with numerous periods of hypomania and depressive states

42
Q

What mood stabilizers are used for BD?

A
  • Lithium, Carbamazepine, Valproic acid and Lamotrigine
43
Q

How is lithium used for BD mood stabilization? MOA? Side effects?

A
  • inhibits Monoamine reuptake
  • inhibits inositol phosphates
  • increase GABAergic and decrease Glutaatergic signalling
  • effective in treating patients with mania and hypomania
  • side effects: headache, dry mouth, dizziness, fatigue, sedation, polyuria etc

Lithium is a maintenance drug known to lower risk of suicide

*prolonged use can be toxic to kidney, liver and thyroid function

44
Q

How is carbamazepine used for BD mood stabilization? MOA? Side effects?

A
  • used in outpatients for acute symptoms of mania (200-600mg/day) and hospitalized patients (800-100mg/day)
  • adverse effects: fatigue, nausea, skin rash, ataxia etc
  • inactivates Na channels
45
Q

How is valproic acid used for BD mood stabilization? MOA? Side effects?

A
  • inhibits GABA transaminase → ↑ GABA → ↓ neuronal excitability and Inactivates Na+ channels
  • adverse effects: GI disturbances, fine tremors, sedation, hair shedding, increased appetite and weight gain
46
Q

How is lamotrigine used for BD mood stabilization? MOA? Side effects?

A
  • adverse effects: dry mouth, nausea, headache
  • acute mania syndrome- start with 2mg for the first 2 weeks up to 50 mg onwards
47
Q

What atypical anti-psychotics may be used for BD? MOA? Side effects?

A
  • Risperidone, Cariprazine, Olanzapine etc
  • D2 receptor antagonism and 5-HT2A receptor antagonism
  • Interaction with several other receptors (i.e., D3, D4, α-adrenergic, and H1 receptors)
  • Side effects: metabolic effects, prolonged QT, hyperprolactinemia etc.
48
Q

How is BD managed in the acute phase with mania/hypomania or mixed episodes

A
  • mood stabiliser or atypical anti-psychotics
49
Q

How is BD managed in the maintenance phase with mania/hypomania or mixed episodes or depressive episodes?

A
  • Quetipine and lithium/valporic acid
  • Olanzapine monotherpay
    or Lamotrigine and valproic acid/carbamazepine
50
Q

How is BD managed in the acute phase with depressive episodes?

A
  • Olanzapine/fluoxetine
  • Quetipine
51
Q

What is schizophrenia?

A
  • strong form of psychosis
  • delusions, hallucinations (often acoustic) and disorder thinking and behaviour
  • Strong genetic component
52
Q

What is the pharmacology of antipsychotic drugs?

A
  • 1st and 2nd generation
  • both inhibit dopaminergic D2 receptors in the brain
  • 2nd generation block 5HT 2a receptors (interaction with receptors also e.g. H, A and D3)
53
Q

What are the pharmacological effects of antipsychotic drugs?

A
  • Antipsychotic effects: reduce hallucinations and delusions (clozapine can reduce impaired attention and cognition and apathy)

-extrapyramidal effects: PD like, dystonia, motor restlessness

-antiemetic effect: due to D2 receptor blockade in chemoreceptors trigger zone in medulla

  • anti-Ch effect: blurred vision, dry mouth, confusion, constipation

Others: weight gain, ortho hypotension, increased prolactin release, sexual dysfunction, neuroleptic malignant syndrome

54
Q

What are the therapeutic indications for antipsychotics?

A
  • Schizophrenia
  • nausea and vomiting prevention
  • agitated and disruptive behaviour, secondary to other disorders
55
Q

What are the guideline for treating Schizophrenia?

A
  • First choice: 2nd generation antipsychotics (except Clozapine)
  • Second choice: 1st generation antipyschotics
  • Third choice: Clozapine
56
Q

What are 1st and 2nd generation antipsychotics used for schizophrenia management?

A

1st Generation:
- Chlorpromazine: low D2 potency
- Haloperidol: high D2 potency
- Molindone: high D2 potency
- Fluphenazine: high D2 potency

2nd Generation:
- Clozapine
- Quetiapine
- Olanzapine
- Risperidone

*all 5HT 2a > D2 receptor antagonism - along with 5HT1a, D1, D4, M and A adrenergic interaction receptors

Clinical Pharmacology Year V NIŠ (9 decks)

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