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Pharmacology Mod 5 > Antidepressant and Antimanic drugs > Flashcards

Antidepressant and Antimanic drugs Flashcards

1
Q

what is the mechanisms of antidepressants

A

NE and 5-HT signalling
Most effective antidepressants maintain NE and or 5-HT signlat (Block metabolism (MAOI), or block reuptake (TCA, SSRI

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2
Q

what is the mechanism of antimanics

A

reduce neuronal activity

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3
Q

What are the types of Anti-depressants

A

MAOIs
TCAs
SSRIs
SSNRIs
NDRIs
Alpha-2 receptor anatagonists

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4
Q

What are MAOIs

A

monoamine oxidase inhibitors
phenylzine and Selegiline

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5
Q

what are TCAs

A

tricyclic antidepressants
Amitriptyline
imipramine

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6
Q

what are SSRIS

A

selective serotonin reuptake inhibitors
fluoxetine
citalopram
sertraline
paroxetine
esctalopram

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7
Q

what are SSNRIs

A

Serotonin-NE reuptake inhibitors
venlafaxine
duloxetine
desvenlafaxine
levomilnacipran

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8
Q

what are NDRIs

A

NE-DA reuptake
Bupropoin(wellbutrin)

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9
Q

whare are alpha-2 receptor antagonists

A

mirtazapine

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10
Q

What are MAOI MOA

A

associated with mitochondria in neurons and glial cells
MAO A is more common than MAO B
antidepressant MAOIs are irreversible and nonselective MAO inhibitors affecting NE, 5-HT and DA

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11
Q

what are the adverse effects of MAOIs

A

interactions with foods and other drugs - tyramine and sympathomimetic drugs
weight gain
orthostatic hypotension
insomnia
hepatotoxicity (phenelzine)
sexual dysfunction
Narrow therapeutic index

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12
Q

What are Tyramine containing foods

A

aged cheese
draft beer
dried/aged foods
smoked foods
tofu

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13
Q

what drug interactions do MAOIs have

A

sympathomimetics: ephedrine, amphetamine (hypertensive crisis)
Antidepressants: re-uptake inhibitors (hypertensive crisis and Serotonin syndrome)

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14
Q

What is TCAs MOA

A

SERT (5-HT re-uptake transporter) blocker
NET (NE transporter) blocker

results in enhanced NE and 5-HT signaling - alpha 1 and 5-HT1

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15
Q

what are TCA adverse effects

A

H1R blocker: drowsiness, sedation, weight gain
MAchR blocker: blurred vision, dry mouth, constipation, urinary retention, tachycardia, cognitive dysfunction
alpha 1 and 2 AR partial blocks: postural hypotension, dizziness, relfex tachycardia
Na+ channel block: cardiac conduction delays -HIGHLY DANGEROUS IN OVERDOSE
narrow TI

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16
Q

What are the tertiary amines

A

Amitriptyline and Imipramine
metabolized by CYP450 demethylation

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17
Q

What are TCA drug interactions

A

other antidepressants
Cardiovascular drugs (Na+ channel blockers)
antimuscarinic drugs
CYP450 interactions

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18
Q

What are the MOA for SSRIs

A
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19
Q

What are the adverse effects of SSRI medicatiosn

A

GI disturbances
long-term weight gain
anxierty, agitation, insomnia, suicidal throughts
headache
sweating
sexual dysfunction
“black box” warning for use in children/adolescents for increased suicidal thoughts
Serotonin syndrome

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20
Q

what type of SSRI has the lowest risk in children

A

fluoxetine (prozac)

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21
Q

what medication are people switched to who are affected by SSRI sexual dysfunction

A

Bupropoin (wellbutrin) for decreased libido

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22
Q

what is serotonin syndrome symptoms

A

hyperreflexia
CNS excitation
mental state: anxiety/agitation
autonomic excitation: hypertension, hyperthermia

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23
Q

what is the treatment of Serotonin syndrome

A

Benzodiazepine - sedation
cyproheptadine (first get anti-histamine with serotonin antagonistic properties)

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24
Q

when is serotonin syndrome most often seen

A

over dose or drug combination of SSRI with MAOI

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25
Q

What the the most common side effects of SNRIs

A

nausea

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26
Q

what is high doses of SNRIs associated wtih

A

treatment emergent hypertension - do not give to CAD

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27
Q

what is venlafaxine used for

A

Major depression,
GAD,
panic disorders,
social phobias

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28
Q

what is duloxetine used for

A

major depression
GAD
pain relieving drug for
diabetic peripheral neuropathy
fibormyalgia
MSK pain
OA

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29
Q

what is the only antidepressant medication available without direct serotonergic effects

A

Bupropion (wellbutrin)

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30
Q

what is Bupropoin used to treat

A

depression and nicotine dependence

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31
Q

what is a side effects of Bupropion

A

anxiety

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32
Q

why is Trazodone not commonly used in full antidepressant doses

A

too sedating for most patients to tolerate in full antidepressant doses

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33
Q

what is trazodone used for in lower doses

A

hypnotic

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34
Q

what is Nafazodone

A

generally very well tolerated among patients with depression, anxiety and insomnia BUT “black bock” warning for hepatotoxicity

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35
Q

what is mirtazapine

A

unique (pre-synpatic) MOA
increase release of EN and 5-HT
less Nausea and sexual dysfunction
also has anti-histamine effect causing sedation
weight gain is often a significant problem

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36
Q

what types are medications used to treat anxiety disorders

A

SSRI, SNRI, TCAs, MAOI, SSRIs

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37
Q

what drugs are used for insomnia + depression

A

trazodone, mirtazapine

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38
Q

what are drugs used for pain syndromes

A

TCAs, SNRIs

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39
Q

what drugs are used for ADD

A

Bupropion

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40
Q

what drugs are used for eating disorders

A

SSRIs, Mirtazapine

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41
Q

what medication is used for nicotine dependence

A

Bupropion (wellbutrin)

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42
Q

what are important antimanic drugs

A

lithium
anticonvulsants
atypical antipsychotics

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43
Q

what are anticonvulsants used for antimanic management

A

carbamazepine
lamotrigine
valproic acid

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44
Q

what are atypical antipsychotics used for antimanic management

A

quetiapine
risperidone

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45
Q

what are mood stabilizers used for

A

bipolar disorder

acute mania
acute dpression
mixed bipolar sates
prophylaxis against manic recurrence
prophylaxis against depressive recurrence

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46
Q

what are the classes of mood stabilizers

A

Class A: stabilize from ABOVE baseline - anti-manic without causing depression
Class B: stabilize from BELOW baseline - antidepressant without precipitating/accelerating mania

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47
Q

what is lithium used for

A

efficacy in bipolar disorder
best for prophylaxis against manic recurrence
can be used in acute manic states
poorest for acute depression, mixed states

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48
Q

what is the MOA of Lithium

A

blocks recyling of inositol phosphates
thus, signaling Gq coupled receptors is desensitized

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49
Q

what are the AE of Lithium

A

pass through BBB and can pass to unborn fetus and milk of nursing mothers
renal effects
tremor
weight gain
hypothyroidism - TSH needs to be checked
V/D, ataxia, come - intoxication
Drug interactions with antidepressants and diuretics

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50
Q

what are anticonvulsants to treat

A

mania and seizures

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51
Q

What are antiolytic medications used

A

GABA modulators
Non-Benzodiapepine - GABA - agonist Hypnotics
Non-GABA anxiolytics

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52
Q

what are GABA modulators used for anxiety

A

Benzodiazepines
(diazepam, clonazepam, lorazepam, temazepam)

53
Q

what is a benzodiazepine antagonists

A

flumazenil

54
Q

what are non-benzodiazepine GABA-agonist hypnotic

A

Zolpeidem

55
Q

what are NON-GABA anxiolytics

A

antidepressants (TCA, MAOI, SSRI)
Trazadone
Mirtazapine
Buspirone
Propranolol

56
Q

what is GAD

A

generalized anxiety disorder
general symptoms of motor tension, autonomic hyperactivity for atleast one month

57
Q

what type of medications may induce anxiety

A

stimulants
nasal decongestants/asthma treatments
dopaminergic
or drug withdrawal

58
Q

when are benzodiazepines used

A

acute anxiety
short term treatment
while waiting for longer-term preventatives to become fully active
or as an adjunct to preventative treatment when needed

59
Q

what are barbitates used for

A

historical treatment of anxiety, insomnia and is still used in epilepsy and anesthesia induction

60
Q

what is the best option for fast relief of panic attack

A

Benzodiazepine

61
Q

why do we use caution in long-term use of Benzodiazepines?

A

concerns for tolerance, dependence and abuse

62
Q

what are important Benzodiazepines

A

diazepam
clonazepam
alprazolam
lorazepam
temazepam

63
Q

what are the therapeutic uses of Benzodiazepine

A

anxiety attacks
insomnia
agitation
alcohol withdrawal
sedation for variety of procedures and anesthetic induction
status epilepticus and some epilepsy
post-injury muscle tension

64
Q

what are the adverse effects of Benzodiazepine

A

sedation (unless desired)
ataxia/falls (elderly concern)
impaired motor performance (driving)
impaired cognition/confusion (not good for test anxiety)
anterograde amnesia (short half-life)
disinhibition of impulses
relatively safe in overdose

65
Q

how do we treat benzodiazepine overdoses

A

flumazenil - benzodiazepine receptor antagonists

66
Q

what medications are flumazenil not effective against

A

barbiturate overdose

67
Q

what are controversies with benzodiazepines

A

tolerance
withdrawal
abuse and dependence

68
Q

what are the fast onset benzodiazepines

A

diazepam and temazepam

69
Q

what are slow onset benzodiazepine

A

clonazepam

70
Q

what are intermediate onset benzodiazepines

A

alprazolam and lorazepam

71
Q

what is Buspirone

A

NON-GABA anxioloytic
non-sedating anxiolytic
effective only with chronic use
partial agonist at pre- and post-synaptic 5-HT1A receptors - some antagonist activity at D2 receptors
show some antidepressant and antipsychotic activities

72
Q

what are the pharmacokinetics of buspirone

A

rapidly absorbed orally
extensively hepatic metabolism to form several active metabolytes
well tolerated by elderly but may have low clearance

73
Q

what are the adverse effects of buspirone

A

Dizziness, headache, GI upset
combo with MAOIs can cause tachycardia and hypertension

74
Q

what is propranolol

A

Beta adrenoreceptor antagonist
decreases sympathetic overactivity
decreased HR and BP
used for performance anxiety

75
Q

what medications treat GAD

A

SSRI, SNRI, Buspirone, Benzodiazepine

76
Q

what medicatiosn treat phobic anxiety

A

benzodiazepines
TCA and MAOI

77
Q

what medications treat panic disorders

A

benzodiazepines
TCA and MAOI

78
Q

what medications treat OCD

A

SSRI

79
Q

what medications treat PTSD

A

SSRI, buspirone

80
Q

what medication treats performance anxiety

A

propranolol

81
Q

what medication treats sedation

A

benzodiazepines

82
Q

what medications reduce REM sleep and NREM sleep

A

Benzodiazepines and Barbiturates

83
Q

how quickly does hypnotic medication tolerance occur

A

tolerance occurs within 1-2 weeks

84
Q

what is a short acting benzodiazepine used for sleep

A

Temazepam

85
Q

what is temazepam used for

A

fast acting but used to decrease sleep latency
short term use - not a treatment for chronic insomnia

86
Q

what non-benzodiazepine hypnotics are used for sleep

A

zolpidem, eszoplicone, zaleplon
they are agnoists that bind similar to benzodiazepines, but to only a subset of GABAa receptors that are associated with sleep
produce pure sedation

87
Q

what are the adverse effects of Zolpidem/eszoplicone

A

safety: high therapeutic index unless combined with other CNS depressants
can cause daytime drowsiness
concerns for complex sleep behaviors (sleep walking/driving)
can exaggerate the deleterious hypoxic effects of obstructive sleep apnes
abuse potential

88
Q

what are the pharmacokinetics of zolpidem/eszoplicone

A

readily absorbed orally
short elimination half-life
metabolized by CYP450 oxidation - may have interaction with drugs that use/affect these enzymes

89
Q

what are other drugs with hypnotic activity

A

antihistamine: diphenhydramine
hypnotic antidepressants: doxepin (TCA), trazodone(5-HT2 antagonist), Mirtazepine (SNRI with antihistamine effects)

90
Q

what is the only antidepressant FDA approve for insomnia

A

Doxepin (TCA)

91
Q

what are first generation antipsychotic drugs

A

classical D2 antagnoists

92
Q

what are second generation antipsychotic drugs

A

atypical antipsychotics

93
Q

what is the treatment for neuroleptic malignant syndrome

A

bromocriptine

94
Q

what are the classical D2 antipsychotic antagonists

A

haloperidol

95
Q

what are the atypical antipsychotics

A

risperidone
olanzapine
clozapine
quetiapine
aripiprazole

96
Q

what are characteristics of schizophrenia

A

Positive symptoms: disordered thinking, delusions, paranoia, hallucinations(esp. auditory)
Negative symptoms: emotional withdrawal, depression

97
Q

what are adverse effects of D2 antagonists

A

acute dystonic reactions
parkinsonian symptoms (tremor or rigidity)
akathisia (restlessness)
hyperprolactinemia

98
Q

what are side effects of Haloperidol

A

sedation: early onset, tolerance
hypotension
extrapyramidal effects: tremor, akinesia, akithesia, tardive dyskinesia, neuroleptic malignant syndrome

99
Q

what is Tardive dyskinesia

A

looks like someone is always chewing something

100
Q

what is neuroleptic malignant syndrome

A

hyperpyrexia (101-107 degrees)
autonomic instability
confusion, altered sensorium
elevated creatinine kinase levels from muscle breakdown
renal failure due to myoglobinuria

101
Q

what increases the risk of neuroleptic malignant syndrome

A

higher likelihood with 2 or more concomitant antipsychotics

102
Q

what is the treatment of neuroleptic malignant syndrome

A

often in ICU
aggressive IV hydration and diuresis
discontinuation of the offending medications
IV BROMOCRIPTINE
dantrolene sodium for intractable hyperpyrexia

103
Q

what is Risperidone

A

blocks D2=5-HT2 (better for negative symtpoms)
high potency
few side effects: still have risk for extrapyramidal side effects but lower than haloperidol

104
Q

what is Clozapine

A

blocks D4=5-HT2
low potency
effective against both positive and negative symptoms
very low risk of extrapyramidal effects

105
Q

what does clozapine increase risk of

A

agranulocytosis, so often reserved for patients with extrapyramidal effects of haloperidol

106
Q

what is Quetiapine

A

antagonist to D1, D2, 5-HT1A and 5-HT2
similar effectiveness as Risperidone with less chance of motor side effects
Side effects: very sedating, other D2-related side effects
choice in psychotic patients suffering from sleep disorders

107
Q

at is Olanzapine

A

properties similar to Quetiapine, with slightly more effectivness, but also more intense side effects

108
Q

what are difficulties in treating schizophrenia

A

family/community support and psychotherapy are essential
compliance is a problem: side effects and paranoid delusions of poisoning is common

109
Q

what is an opiate

A

drugs derived from opium
ex. morphine, heroin, codeine

110
Q

what is an opioid

A

substances that have morphine-like activity and act on opioid receptors

111
Q

what are the kinds of opioids

A

natural, endogenous opioid peptides and synthetic

112
Q

what is the MOA of opioids

A

opens K+ channel, blocks Ca2+ channels, receptor coupled to Gi = decrease in cAMP, leads to hyper-polarization and inactivation of neuron

113
Q

what are the CNS effects of opioids

A

analgesia, drowsiness, change in pain reaction, euphoria, cough suppression

114
Q

what are the side effects of opioids

A

N/V constipation, itching, respiratory suppression

115
Q

what is codeine

A

pro-drug
converted to morphine in the liver by CYP450
need for metabolism causes “ceiling effect”
patients who do not express much CYP2D will not have effectiveness
CYP2D blocked by antidepressant SSRIs, so codeine is not effective
less potent than morphine
oral
analgesic, antitussive, antidiarrheal

116
Q

what is the choice of opioids for inpatient chronic pain patients

A

morphine (2 Hour t1/2)

117
Q

what is the choice of opioids for outpatient chronic pain

A

long acting opioid
methadone or time-release oxycodone (15-40h T1/2)

118
Q

what is the opioid for acute short-term pain

A

rapid onset, short-acting
codeine or oxycodone (2-6 hours t1/2)

119
Q

what is the opioid for general anesthesia

A

potent
short acting
Fentanyl (2-4 h t1/2)

120
Q

what opioids are metabolized by CYP3A

A

methadone, oxycodone and fentanyl

121
Q

what opioids are metabolized by CYP2D

A

codeine (low in some patients)

122
Q

how is morphine metabolized

A

by glucouronidation
FIRST PASS EFFECT leads to low oral availability
advantage: low drug interactions

123
Q

what are opioid drug interactiosn

A

other opioids
other CNS depressants (anxiolytics and hypnotics)
Antidepressants (TCA and MAOI)
antipsychotics
CYP inhibitors for orally active opioids

124
Q

what opioids are common in avuse

A

heroin
fentanyl
oxycontin

125
Q

what is methadone

A

synthetic derivative of morphine
orally active, long acting
less euphoria
used in the treatment of addiction

126
Q

what is buprenophine

A

partial agonist/antagonist
slow onset of action, slow departure from receptors
reduces craving and blocks effects of heroin

127
Q

what are the symptoms of opioid overdose

A

stupor, coma
pinpoint pupils (miosis)
depressed respiration
needle marks

128
Q

what is dextromethorphan

A

centrally acting cough suppressant
d isomer of morphine derivative
no analgesia or addictive properties unless severaly abused

129
Q

what is loperimide

A

Imodium
methadone skeleton
phenylpiperidine moiety
achieves antidiarrheal activity
cannot cross BBB

Pharmacology Mod 5 (3 decks)

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