Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Antidepressants and Lithium > Antidepressants and Lithium > Flashcards

Antidepressants and Lithium Flashcards

1
Q

Fluoxetine

A
  • SSRI
  • potent inhibitors of CYP2D6 (drug interactions)
  • metabolite norfluoxetine has LONG half-life of 7 to 9 days
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Paroxetine

A
  • SSRI

- potent inhibitors of CYP2D6 (drug interactions)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Sertraline

A

SSRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Citalopram

A

SSRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Escitalopram

A

SSRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Fluvoxamine

A
  • SSRI

- treatment of OCD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Venlafaxine

A
  • SNRI

- extensively metabolized via CYP2D6

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Duloxetine

A

SNRI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Imipramine

A
  • Tricyclics (TCAs)

- more selective for serotonin transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Amitriptyline

A

TCA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Clomipramine

A
  • Tricyclics (TCAs)

- treatment of OCD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Desipramine

A
  • Tricyclics (TCAs)

- more selective for NE transporter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Nortriptyline

A

TCA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Trazodone

A
  • 5-HT2 Antagonist
  • LSD is an agonist
  • prodrug that is converted to 5-HT2A antagonist
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Mirtazapine

A
  • 5-HT2 Antagonist
  • antagonist of presynaptic alpha2 autoreceptor, enhances release of NE and 5-HT
  • acts strongly on H1 receptor, so we can use this medication as a sedative
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Bupropion

A
  • class all by itself
  • enhances both NE and DA neurotransmission
  • inhibits reuptake transporters for both NE and DA as well (VMAT2)
  • useful for smoking cessation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Phenelzine

A
  • MAOI

- a hydrazide that combines irreversibly with MAO to provide long-lasting inhibition (covalent modification)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Tranycypromine

A
  • MAOI

- does not bind irreversibly, but still has prolonged effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Reserpine

A
  • medication for high BP
  • blocks the ability of the neurotransmitter to be concentrated in the vesicle and then causes the neurotransmitter to not be released and induces depression in the individual
  • anti-psychotic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Block reuptake of neurotransmitters

A
  • TCAs
  • SNRIs
  • SSRIs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Block breakdown of neurotransmitters

A

MAOIs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Limitation of Monoamine Hypothesis

A
  • clinically useful antidepressants act rapidly at pharmacologic sites of action, yet clinical effects require 3 or more weeks of therapy
  • while reserpine rapidly depletes neurotransmitter, several weeks of treatment are required to induce depression
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Possible explanation for delay in clinical effect

A
  • desensitization of presynaptic autoreceptors
  • control in part the synthesis and release of neurotransmitters
  • because the autoreceptor binds the same neurotransmitter that cell is releasing
  • in short term you have an increase in the neurotransmitter in the synaptic cleft and may limit the amount of neurotransmitter released
  • but then the autoreceptors become desensitized and the cell down-regulates the number of receptors and the hypothesis is that over long term treatment you lose the inhibition of control and release and then you release additional serotonin or norepinephrine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Serotonin Synthesis and Catabolism

A
  • synthesized from tryptophan
  • present in high concentrations in platelets and GI tract
  • lesser amounts in brain and retina
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Amphetamine

A
  • inhibitor of monoamine storage
  • substrate of reuptake transporter
  • inside the cell it inhibits the transporter that reserpine inhibits, so when transporter is blocked you get a build up of neurotransmitter in the cell cytoplasm and then the excess of neurotransmitter in the nerve terminal causes the system to reverse and causes norepinephrine to release
  • net result is that amphetamine causes a decreased release of vesicular transport and an increased release of non-vesicular transport
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

SSRI

A
  • selective serotonin reuptake inhibitors
  • inhibit 5-HT reuptake selectively as compared to NE reuptake
  • relatively selective for 5-HT transporter, thus side effects limited to effects on 5-HT mediated responses
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

SNRI

A
  • serotonin-norepinephrine reuptake inhibitor
  • inhibit reuptake transporters for both NE and 5-HT
  • TCAs also fall into this category, but are less selective
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

MAOI

A
  • inhibitor of monoamine degradation
  • monoamine oxidase (MAO) metabolizes monoamines
  • phenelzie is a hydrazide that combines irreversibly with MAO to provide long-lasting inhibition (covalent modification)
  • tranylcypromine does not bind irreversibly, but still has prolonged effect
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

MAOI drug interactions

A
  • individuals taking MAOIs must be very wary of intake of tyramine
  • at high levels, tyramine can reverse reuptake transporters (as amphetamines) causing uncontrolled catecholamine release and possible hypertensive crisis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Type A MAO

A

NE, 5-HT, tyramine

31
Q

Type B MAO

A

more selective for dopamine

32
Q

TCAs

A
  • inhibit reuptake transporters for both NE and 5-HT (like SNRIs)
  • tend to interact with variety of other receptors, therefore broad range of side effects
  • imipramine is more selective for serotonin
  • desipramine is more selective for NE
  • so you can give both imipramine and desipramine to inhibit both transporters
33
Q

5-HT2 Antagonists

A
  • trazodone (prodrug that is converted to 5-HT2A antagonist)
  • nefazodone (black box warning due to hepatotoxicity)
  • mirtazapine
34
Q

Pharmacologic Differences Among Antidepressants

A
  • SSRIs block activity of serotonin and have very little effect on NE
  • SSRIs have very little effects on other receptors
  • SNRIs have no effect on other receptors while older TCAs have activity on the other receptors
  • so the SNRIs have fewer side effects
35
Q

Autonomic Sympathetic Effects of Antidepressants

A
  • inhibit NE reuptake in ANS, in addition to CNS

- MAOIs increase NE in sympathetic nerve terminals

36
Q

Sedation Effects of Antidepressants

A

-common CNS effect of TCAs and some HCAs (H1 receptor)

37
Q

Muscarinic Receptor Blockade Effects of Antidepressants

A
  • occurs with all TCAs

- newer agents (HCAs) less potent

38
Q

Cardiovascular Effects of Antidepressants

A

-hypotension due to alpha-adrenergic blockade, depression of cardiac conduction

39
Q

Seizure Effects of Antidepressants

A

-convulsive threshold lowered with TCAs and MAOIs

40
Q

Clinical Uses of Antidepressants

A
  • depression (no shit)
  • anxiety disorders (including panic disorder)
  • OCD (fluvoxamine for OCD; clomipramine (SNRI) especially beneficial)
  • PTSD (SSRI; addition of antipsychotic may be helpful; MAOIs and TCAs also used)
41
Q

Adverse Effects Associated with SSRIs

A
  • predicted from enhanced serotonergic tone
  • GI symptoms (nausea, diarrhea)
  • sexual dysfunction
  • decreased libido
  • headache
  • insomnia or hypersomnia
  • weight gain
  • hyponatremia in elderly
  • increased risk of bleeding
  • teratogenic potential with paroxetine
42
Q

Adverse Effects Associated with SNRIs

A
  • SSRI effects PLUS noradrenergic effects
  • increased BP and HR
  • CNS activation (insomnia, anxiety, agitation)
43
Q

Adverse Effects Associated with TCAs

A
  • SNRI effects PLUS effects due to interaction with other receptors
  • anticholinergic effects
  • orthostatic hypotension
  • sedation
44
Q

Adverse Effects Associated with 5-HT Antagonists

A
  • trazodone (sedation, GI disturbances, orthostatic hypotension)
  • mirtazapine (significantly sedating, increased appetite and weight gain (attractive for use in elderly))
  • nefazodone exhibits hepatotoxicity
45
Q

Adverse Effects Associated with Bupropion

A
  • agitation
  • insomnia
  • anorexia
46
Q

Adverse Effects Associated with MAOIs

A
  • orthostatic hypotension
  • weight gain
  • sexual disturbances
  • interactions with tyramine-containing foods can precipitate hypertensive crisis
  • can provoke Serotonin Syndrome in combination with SSRI or SNRI
47
Q

Serotonin Syndrome

A
  • SSRI + MAOI
  • SNRI + MAOI
  • SSRI (or SNRI) + drug with MAOI activity such as linezolid or serotonergic drug such as dextromethorphan, sumatriptan, tramadol, or St. John’s Wort
  • altered mental status, fever, tachycardia, hypertension, agitation, tremor, myoclonus, hyperreflexia, ataxia, incoordination, diaphoresis, shivering, GI symtpoms
48
Q

Antidepressant Safety in Children

A
  • fluoxetine is only 2nd generation drug approved by FDA for treated MDD in children (2 to 12 yrs) and adolescents (13 to 18 yrs)
  • concerns raised of increased risk of SI amongst children taking SSRIs and SNRIs
  • led to addition of FDA required Black Box warning on all antidepressant drugs
  • risk of suicide elevated amongst depressed pts
  • controversial decision
  • monitor suicidal behavior in any case
49
Q

Antidepressants and Pregnancy

A
  • maternal depression associated with intrauterine growth problems, low birth weight
  • Paroxetine (SSRI) classified as category D (positive evidence of risk)
  • other SSRIs classified as category C (risk cannot be ruled out)
  • reports of adverse events when SSRIs used in 3rd trimester
  • some evidence of self-limited neonatal behavioral syndrome with SNRI exposure in 3rd trimester
  • MAOIs (category C) but risk of drug or food interactions leading to hypertensive crisis leads some physicians to recommend against use
50
Q

Pharmacodynamic Drug Interactions with Antidepressants

A
  • those with sedative effects are additive with other sedatives, particularly alcohol and BZs
  • MAOIs sensitize pts to indirect sympathomimetics like tyramine and to sympathomimetics such as ephedrine
  • SSRI (or SNRI) plus MAOI can lead to serotonin syndrome
51
Q

Pharmacokinetic Drug Interactions with Antidepressants

A
  • paroxetine and fluoxetine are potent inhibitors of CYP2D6
  • many drugs are substrates for 2D6 including TCAs, some antipsychotics (haloperidol, risperidone), codeine/oxycodone, beta-blockers
  • fluvoxamine and others are inhibitors of CYP3A4
52
Q

Overdose of TCA

A
  • extremely dangerous

- prescribed on “no refill” basis, small quantities

53
Q

Overdose of MAOIs

A
  • intoxication rare

- requires supportive txt

54
Q

Overdose of SSRIs

A
  • OD fatalities rare

- intoxication requires supportive txt

55
Q

Overdose of bupropion

A

-seizures

56
Q

Overdose of Mirtazapine

A
  • sedation
  • disorientation
  • tachycardia
57
Q

Overdose of newer antidepressive agents

A

often involve other drugs, including alcohol

58
Q

Pharmacokinetics of Antidepressants

A
  • rapid oral absorption
  • reach peak plasma concentration in 2-3 hrs
  • t1/2 on order of 0.5 to 1 day
  • tightly bound to plasma proteins
  • metabolized by liver
  • eliminated by kidney
59
Q

Pharmacokinetics of SSRI

A
  • metabolite of fluoxetine, norfluoxetine, has LONG half-life of 7 to 9 days
  • wouldn’t give pt an MAOI 2 days after stopping SSRI because SSRI would still be in system and can run risk of serotonin syndrome
60
Q

Pharmacokinetics of SNRI

A
  • venlafaxine extensively metabolized via CYP2D6

- parent drug and metabolite have half-life of ~11 hrs

61
Q

Pharmacokinetics of TCAs

A
  • extensively metabolized, long t1/2’s
  • dosed once daily at night due to sedating effects
  • demethylation of tertiary amines leads to active metabolites
62
Q

Pharmacokinetics of 5-HT2 Antagonists

A
  • trazodone has short half-life (3-6 hrs) requires split dosing for depression.. single dose at night for hypnotic effects
  • mirtazapine is metabolized by CYP 2D6, 3A4, 1A2… dosed in evening due to sedating effects
63
Q

Pharmacokinetics of Bupropion

A
  • substantial first pass metabolism and active metabolites

- alternative routes of administration available

64
Q

Choice of Drugs (1st line)

A
  • SSRI
  • SNRI
  • bupropion
  • mirtazapine
65
Q

Choice of Drugs (2nd line)

A
  • switch drugs (different class)
  • combine two classes (carefully!)
  • add another drug class (atypical antipsychotic)
66
Q

Txt for Bipolar Disorder

A
  • drugs that increase catecholamine activity exacerbate mania
  • drugs that reduce NE or DA activity tend to reduce mania
  • lithium (mechanism unclear)
  • antiepileptics and antipsychotic agents exhibit efficacy
  • antidepressants must be used cautiously in bipolar pts to avoid induction of mania
  • ** pts treated for PD where dopamine is upregulated have a tendency to exhibit psychotic behavior over time
67
Q

Lithium Pharmacodynamics

A
  • enters cells via Na+ channels
  • may enhance some actions of 5-HT
  • may decrease NE and DA turnover
  • mimics other small monovalent cations; can disrupt proteins and transporters that require cation cofactors
  • may reduce synaptic transmission
  • effects of lithium on inositol regeneration are well-studied, but may not be central to therapeutic action (lithium seems to have effect on enzymes that convert IP2 to IP1 and IP1 to inositol… unclear on mechanism by how it does this)
68
Q

Lithium Pharmacokinetics

A
  • completely absorbed in 6 to 8 hrs
  • distributed in total body water, slow entry to intracellular compartments, no protein binding
  • excreted entirely in urine
  • plasma half-life = 20 hrs
  • target plasma concentration usually 0.6 mEq/L to 1.4 mEq/L; toxicity seen at 2 mEq/L (this has a very narrow therapeutic window or therapeutic index)
69
Q

Lithium Drug Interactions

A
  • diuretics decrease renal clearance by 25%

- some NSAIDs decrease clearance by increasing Li+ reabsorption in proximal tubules

70
Q

Lithium Toxicity and Adverse Effects

A
  • tremor is common at therapeutic doses; controlled with propranolol or atenolol (beta-blockers)
  • reversibly decreases thyroid function
  • inhibits K+ entry to myocytes causing abnormal repolarization, extracellular hyperkalemia, intracellular hypokalemia
  • reversible polydipsia and polyuria
71
Q

Lithium Contraindications to Use

A
  • pts with severe dehydration or sodium depletion
  • pts with significant cardiovascular disease
  • pts with significant renal impairment
  • during lactation
72
Q

Vilazodone

A
  • SSRI and 5-HT agonist

- approved for treatment of depression in 2011

73
Q

Nefazodone

A
  • 5-HT antagonist

- black box warning due to hepatotoxicity

Antidepressants and Lithium (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions