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Pharm > NOP test 2 > Flashcards

NOP test 2 Flashcards

1
Q

SSRIs

A

Fluoxetine and Sertraline

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2
Q

SNRIs

A

Duloxetine

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3
Q

Tricyclics

A

Amitriptyline

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4
Q

MAOIs

A

Phenelzine and Selegiline

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5
Q

Which types of depression do you use antidepressants with?

A
  • Major depression and maybe bipolar depression

- Use only with reactive depression if necessary

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6
Q

Fluoxetine: MOA, Uses, and PK

A
  • SSRI
  • MOA: Highly selective inhibition of 5HT repute
  • Uses: Major depressive disorder., OCD, Bulimia nervosa, Panic Disorder, and PMDD
  • PK: Inhibits 2D6 and requires 5-6 wks to reach steady state and to wash out.
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7
Q

Fluoxetine: Adverse effects

A

-AE: Black box warning for suicide
-5HT2 receptor effects: (tolerance develops to most SD) agitation, akathesia, initial anxiety, panic, insomnia and SEXUAL DYSFUNCTION
-5HT3 (tolerance develops)
nausea, gi distress, diarrhea, headache, wt loss
-LONG TERM WEARING of efficacy

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8
Q

Fluoxetine: Contraindications

A
  • Pregnancy (3rd trimester pulmonary HTN)
  • Tamoxifen uses 2D6
  • Drugs that increase 5HT levels (MAOI) due to Serotonin syndrome
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9
Q

Sertraline

A
  • SSRI very similar to fluoxetine with less side effects
  • may be more efficacious in severe depression
  • approved for PTSD and bulimia is off label
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10
Q

Duloxetine: MOA, Uses, and PK

A
  • SNRI ( same mech as tricyclics with less side effects
  • MOA: Blocks 5HT and NE reuptake but more selective of SERT
  • USES: MDD, generalized anxiety disorder, and several pain disorders (peripheral myopathy, fibromyalgia, and chronic pain)
  • PK: Blocks 2D6 (tamoxifen) metabolites are inactive w/ half life of 11-12 hrs (shorter than fluoxetine)
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11
Q

Duloxetine: AE and contraindications

A
  • AE: Suicide risk, sexual dysfunction, HTN crisis or MI
  • Contraindication: don’t take w/ other drugs that increase [Serotonin], and narrow angle glaucoma, don’t take with drugs that need NET for their action (methyldopa)
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12
Q

Tricyclic Antidepressants

A
  • Amytriptyline

- Side effects limit patient compliance and overdose can be lethal due to CV effects

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13
Q

Amytriptyline: Uses, MOA, and PK

A

USES: MDD, and off-label for some pain disorders
-MOA: inhibit 5HT and NE reuptake (more selective for SERT)
PK: Metabolized by 2D6, half –> nortriptyline. Other metabolites are active –> long half life (30 hrs)

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14
Q

Amytriptyline: Adverse effects and Toxicity

A

ADVERSE EFFECTS
-Suicide risk
-Anticholinergic (tachycardia)
-Alpha 1 antagonist (ortho Hypo and drowsiness)
-Antihistamine (Sedation and Wt gain)
-Sexual dysfunction and transition to mania in bipolar patients
TOXICITY
-Acute poisoning is common and potentially life threatening (Cardiotoxic treat with Na Bicarb if QR widening)

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15
Q

Amytriptyline: Drug interactions and contraindications

A

DRUG INTERACTIONS:
-MAOIs or other drugs that increase serotonin.
-Drugs that prolong QT (thioridazine)
-Can reverse Anti-HTN effects of some drugs.
Contraindications: CV problems and pre-exisiting CV conditions

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16
Q

Phenelzine: MOA, USES, and PK

A

MOA: Irreversible inhibition of MAO (A&B) = drug action continues after drug has been cleared
USES:
-MDD: onset is faster than w/ other anti-depressants
-Agoraphobia, Bulimia, Panic Disorder, Social phobia
PK:
-Transformed by acetylation in liver with 50% slow acetylators

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17
Q

Phenelzine: AE, Toxicity

A

AE:
-Increased suicide
-Ortho Hypo and sedation common
-Central stimulation, wt gain, and insomnia/euphoria
Toxicity: CNS stimulation –> hallucinations, delirium, convulsions, coma, (USUALLY NOT LETHAL)

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18
Q

Phenelzine: Food and Drug Interactions

A
  • Cheese RXN: Large amounts of tyramine –> NE release –> HTN crisis
  • Sympathomimetic Amines: potentiates amphetamines –> HTN. L-DOPA should be withdrawn 2-4 weeks prior to MAOI
  • DO NOT COMBINE WITH OTHER ANTI-DEPRESSANTS
  • DO NOT COMBINE WITH CNS DEPRESSANTS IN GENERAL
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19
Q

Phenelzine: Contraindications

A
  • Drugs that increase 5HT
  • Drugs that increase NE or EPI
  • Dextromethorphan (5HT syndrome of pyschosis)
  • Meperidine (Death)
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20
Q

Selegiline: MOA, USE, and PK

A

-MOA: irreversible inhibition of MAO A&B
-USES: MDD and Parkinson’s at low doses
PK: 2B9–> active metabolites
-Regen or new enzymes is required

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21
Q

Selegiline: AE

A

AE:

  • Increased risk of suicide
  • Same food and drug interactions as phenelzine
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22
Q

Bupropion: USES, MOA

A

USES:
-MDD (treat sexual dysfunction due to other meds but not as effective in presence of anxiety)
-SAD
-When other ADs produce cognitive slowing
MOA:
-Inhibits DAT and NET, with greater specificity for DAT

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23
Q

Bupropion: AE,

A

AE:

  • Suicide
  • WT Loss
  • Tachycardia
  • Lowers seizure threshold
  • inhibits 2D6
  • Serotonin syndrome w/ MAOIs or other drugs that elevate 5HT
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24
Q

Mirtazapine: MOA

A
  • Antagonist at presynaptic alpha 2 antagonist –> increase release of 5HT and NE
  • Antagonist at presynaptic 5HT2 –> increase release of DA and NE
  • Inhibition of postsynaptic 5HT3 –> antiemetic effects
  • Antagonist at H1 receptor –> sedation and wt gain.
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25
Q

Mirtazapine: Uses

A

-MDD: Patients with insomnia, no ortho hypo, lower incidence of sexual dysfunction

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26
Q

Mirtazapine: AE

A
  • Increase Suicide
  • Somnolence (H1 Blockade)
  • Weight gain
  • No significant affect on CYPs
  • increase triglycerides and cholesterol.
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27
Q

Mirtazapine: Toxicity and Drug interactions

A

-Toxicity: Overdose drowsiness, disorientation, ataxia, nausea and vomiting
Drug Interactions: Drugs that elevate 5HT levels Serotonin syndrome

28
Q

Which anti-psychotics are most effective?

A

-They are all equally effective (with the exception of clozapine) so selection depends more on patient tolerability

29
Q

Typical Anti-Psychotics

A
  • First generation
  • associated with EPSE and Tardive dyskinesia
  • Cheaper
30
Q

Atypical Anti-Psychotics

A
  • Lower risk of EPSE/TD and more effective for negative symptoms, but more adverse metabolic side effects.
  • More expensive
31
Q

Typical and atypical anti-psychotics MOA

A
  • D2 receptor antagonist
  • requires 60% occupancy for effect
  • Atypical drugs differ in that serotonin receptor affinity is higher than D2 receptor affinity (accounts for higher efficacy with neg symptoms and lower EPSE risk)
32
Q

Neuroleptic Malignant Syndrome

A
  • Side effect of neuropsychotic
  • Life threatening
  • More common with typical
  • Mental status change, Hyperthermia, extreme muscle rigidity, and autonomic dysfunction
  • Tx: drug withdrawal and supportive therapy
33
Q

Antipsychotic side effects

A

-QT interval prolongation
-Adverse metabolic effects
-Increased mortality in elderly with dementia related psychosis
Autonomic effects: Anticholinergic, anti-adrenergic, anti histaminergic

34
Q

EPSE

A
  • Akathisia: Feeling of restlessness difficulty sitting still (Dose reduction, beta, or BZD)
  • Parkinsonism: Tremor, rigidity, shuffling gait, bradykinesia (anti-parkinsonian, anti-cholinergic)
  • Dystonias: Acute muscle spasms of neck, back, and eyeballs (anti parkinsonism, anti-cholinergic)
  • Tardive Dyskinesias: Oral-Facial dystonias, chorioathetosis (no treatment, permanent)
35
Q

Halperidol

A
  • Typical anti-pyschotic
  • High potency (higher risk of EPSE but less sedating)
  • Approved for schizophrenia, severe behavioral problems in kids, tourettes
36
Q

Chlorpromazine

A
  • Lower potency (lower risk of EPSE but more sedating)
  • approved for psychosis, and nausea/vomitting and severe behavioral problems in kids
  • Off label control behavior in elderly children with dementia
37
Q

Clozapine

A
  • Atypical Anti-psychotic
  • Recalcitrant schizophrenia and suicidal behavior in patients with schizoaffective disorder (6 mos. for full response)
  • Usually last line due to agranulocytosis
  • Virtually no risk of EPSE/TD
38
Q

Other atypical antipsychotics

A

-Risperidone -olanzapine -quetiapine, ziprasidone

39
Q

Apiprazole

A

-Partial D2 agonist

40
Q

Drug selection for Schizophrenia

A
  • Mono therapy of Aripiprazole, risperidone, quetiapine, ziprasidone (atypical agents)
  • One not really better than another, but olanzapine usually reserved due to its metabolic side effects
  • Typical agents can be used when effective in patients and absence of EPSE
41
Q

Refractory Schizophrenia

A
  • failure of at least 2 mono therapy trials

- Clozapine is effective in 30-60% patients

42
Q

Drugs used to treat Mania

A
  • LITHIUM
  • Anticonvulsants (valproate, carbamazepine)
  • Antipsychotics
  • Benzodiazepines: used mostly as adjunct for agitation, insomnia, or anxiety
43
Q

Drugs use in Severe acute mania

A

-Combo of lithium or valproate & antipsychotic

44
Q

Drugs used in Hypomania

A

-Monotherapy with atypical antipsychotic is recommended

45
Q

Lithium: MOA

A
  • Prototype mood stabilizer
  • MOA: Unknown for most part
  • Inhibits neuronal signaling pathways IP3 –> reducing GPCR synaptic transmission activity and glycogen synthase kinase-3 pathway
  • Reduces Manic symptoms and stabilizes mood in bipolar pts (no affect on regular individuals
46
Q

Lithium: PK

A
  • Serum levels must be monitored to prevent toxicity (0.8-1.2)
  • Renal elimination with dosage based on CrCL
47
Q

Lithium Adverse effects: (acute, long term, and overdose)

A
  • Acute: tremor, mild nausea, polyurea/dipsia, wt gain, mild cog impairment
  • Long-Term: Nephrogenic Diabetes insipidus, thyroid dysfunction, hypercalcemia, arrhythmias in pots with preexisting CV dz
  • Overdose: Increase risk with renal impairment, dehydration and sodium depletion,
  • Present with nausea, vomiting, diarrhea, arrhythmias, lethargy ataxia, confusion, and seizures
  • Thiazides, NSAIDS, ACEIs increase lithium levels
48
Q

Mechanisms of Action of Anti-Seizure Drugs

A
  • Block Neuronal gated Na+ Channels: Limited repetitive firing by promoting inactivated state, but action is voltage (greater effect if depolarized) and use dependent (mostly affects repetitive firing neurons). Great of FOCAL and SECONDARILY GENERALIZED SEIZURE
  • Block Ca 2+ channels: T-Type channels inhibits absence seizures and HVA Ca ++ suppresses glutamate release (FOCAL SEIZURES)
  • Enhance GABAergic transmission
  • Antagonize Glutaminergic Transmission: suppress glutamate mediated synaptic excitation by antagonizing neuronal NMDA and AMPA receptors
49
Q

Traditional Agents

A
  • Older drugs that all block Na+ channels
  • Phenytoin
  • Valproic Acid
  • Carbamazepine
  • Ethosuximide
  • Lorazepam
50
Q

Phenytoin (Traditional): MOA and PK

A

-MOA: blocks Na+ channels
PK:
-Oral formulation
-IV: Fosphenytoin
-Non-linear elimination, plasma protein binding and hepatic CYP metabolism
-Plasma drug conc. increases disproportionately as dose is elevated (toxicity)

51
Q

Phenytoin (Traditional): Therapeutic use and Drug interactions

A
  • Therapeutic Use: Focal and tonic clonic seizure and status epilepticus, NOT effective against absence seizures, Cardiac arrhythmia
  • Drug Interactions: Increases CYP 3A4 clearance –> ineffective birth control
  • Decrease CYP2C9 clearance which leads to increased bleeding with warfarin
52
Q

Carbamazepine (Traditional): MOA and PK

A
  • MOA: Blocks Na+ channels
  • PK: Linear Kinetics and more reliable blood levels
  • Met: by CYP3A4 and induces its own metabolism
53
Q

Carbamazepine (Traditional): Therapeutic Uses and Adverse effects

A
  • Therapeutic Uses: Generalized tonic clonic seizures, simple and complex focal seizures, trigeminal neuralgia, and bipolar disorder
  • Adverse Effects:
  • Most frequent: Drowsiness, ataxia, vertigo, diplopia, and blurred vision, nausea/vomiting and diarrhea
  • Hyponatremia (SIADH)
  • Rash (Black box warning test for allele in asians)
  • Blood Dyscrasias (boxed warning for aplastic anemia and agranulocytosis
54
Q

Valproic Acid (Traditional): MOA and USE

A
  • MOA: Blocks Na+ Channels, Blocks T-Type Ca++ Channels, Stimulates GABA synthesis while inhibiting degradation
  • USES: Absence Seizure, Myoclonic, focal and tonic clonic seizures
  • Bipolar disorder
  • Migraine prophylaxis
55
Q

Valproic Acid (Traditional): Adverse Effects and Drug Interactions

A

AE:
-GI solved by using enteric coated divalproex
-CNS: Sedation, Ataxia, tremor, and weight Gain
-Hepatic Toxicity and Pancreatitis: Boxed warnings especially in children under 2 years
-Teratogenic: Boxed warning for neural tube defects
Drug Interactions:
-Phenytoin displaces Valproic acid from albumin and decreases it metabolism

56
Q

Ethosuximide (Traditional): MOA and Uses

A

MOA:
-Blocks T-Ca++
Uses:
-Uncomplicated Absence seizures

57
Q

Ethosuximide (Traditional): Adverse Effects

A

AE:

  • GI Complaints and CNS complaints
  • Rare: SLE, Leucopenia, aplastic Anemia, and SJS
58
Q

Status Epilepticus treatment

A
  • IV Lorazepam to terminate seizure episode due to longer duration of action
  • IV Phenytoin for prolonged control after termination
59
Q

Gabapentin (newer): PK, Uses and Adverse Effects

A
  • PK: Excreted unchanged in Urine
  • Uses: Add on of focal and generalized seizure, Postherpetic myalgia, tons of off label uses
  • Adverse effects: Sedation, dizziness, but mostly well tolerated
60
Q

Lamotrigine (NEWER): MOA, and PK

A

MOA: blockade of Na+ channels –> less glutamate release, Ca++ Channel block and 5-HT3 antagonist
-PK: Glucuronidation which is increased by enzyme inducers

61
Q

Lamotrigine (NEWER): USES and ADVERSE EFFECTS

A

USES: Lennox-Gastaut Syndrome, Monotherapy for partial and secondarily generalized tonic-clonic seizures in adults, alternative to ethosuximide for absence, Bipolar maintenance
ADVERSE EFFECTS: Dizziness, ataxia, blurred vision, nausea, and vomiting, Rash SJS, Teratogen

62
Q

Levetiracetam (NEWER): PK, Therapeutic Uses, and Adverse effects

A

PK:
-Mostly devoid of drug interactions
USES: Add-on for partial or generalized tonic-clonic and myoclonic seizures
ADVERSE EFFECTS: Fatigue, dizziness, can cause HTN, Behavioral symptoms

63
Q

Tiagabine (NEWER): MOA, USE, and Adverse Effects

A

MOA: Blocks glutamate reuptake (GAT-1) thus prolongs inhibitory effect
USES: Add-on for refractory partial seizure w/wo secondary generalization (may promote seizures in those who don’t have epilepsy)
AE:
-Dizziness, somnolence, tremor, and enhance absence seizure activity

64
Q

Topiramate (NEWER): MOA, and PK

A

MOA:
-Blocks Na chan., Neuronal hyperpolarization, Carbonic anhydrase inhibitor
PK:
-Excreted unchanged in urine

65
Q

Topiramate (NEWER): USES and ADVERSE EFFECTS

A 
USES:
-Monotherapy for partial and generalized tonic-clonic seizures, -Adjunct for lennox-gaustaut syndrome
-Prophylaxis for migraines
AE:
-Renal calculi from CA inhibition
-Cog impairment
66
Q

Felbamate (Newer): MOA, USE, and ADVERSE EFFECTS

A

MOA:
-Antagonist of NMDA
-Postive modulator of GABA receptors
USE:
-Monotherapy of poor control severe focal and second. gen. seizures that are refractory
-Adjunct for Lennox-Gastaut
AE: Life threatening aplastic anemia and liver failure

67
Q

Vigabitrin: MOA, USE, and ADVERSE EFFECTS

A 
MOA:
-Irr. inhib. of GABA transaminase
USE:
Refrac. complex partial seizures
Mono therapy for infantile spasms
ADVERSE EFFECTS: Progressive and permanent bilateral vision loss

Pharm (8 decks)

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