KG - Pharm 3, Exam 1, Antidepressants Flashcards
1
Q
what is the amine neurotransmitter DOPAMINE responsible for?
A
- REWARD, MOTIVATION, EUPHORIA, MOVEMENT
- target of cocaine & amphetamines
2
Q
what is the amine neurotransmitter NE responsible for?
A
- REWARD, AROUSAL, ALERTNESS, DECISIONS
- FLIGHT OR FRIGHT
3
Q
what is the amine neurotransmitter SEROTONIN responsible for?
A
- MOOD, EMOTION, MEMORY, SLEEP, COGNITION
- target of MDMA, LSD
4
Q
what is the monoamine hypothesis?
A
- depression caused by under activity of amines in the brain (DA, NE, serotonin)
5
Q
moa: uptake inhibitors, short term & long term
A
- serotonin levels increase but so does feedback inhibition (balances synaptic amine levels)
- LONG TERM = antidepressants DOWN REGULATE auto-receptors, increases firing rate of serotonin neuron
6
Q
TCAs: moa
A
- INHIBIT RE-UPTAKE OF NE & 5-HT
- BLOCK ALPHA-ADRENERGIC, HISTAMINE, MUSCARINIC RECEPTORS
7
Q
TCAs: use
A
- depression - limited use bc toxic & potential to overdose
- CHRONIC PAIN (TMJ)
- fibromyalgia
- enuresis
8
Q
why are TCAs used for chronic pain?
A
- bc a SMALL DOSE can be used
9
Q
Amitriptyline & Imipramine: info
A
- TERTIARY AMINES
- PRIMARILY INHIBIT 5-HT RE-UPTAKE
- produce more seizures than secondary amines
- more sedating than secondary amines
10
Q
Nortriptyline & Desipramine
A
- SECONDARY AMINES
- PRIMARILY INHIBIT NE RE-UPTAKE
11
Q
How do you choose a TCA?
A
- based on adverse effects
12
Q
How do you discontinue antidepressant use?
A
- taper off gradually
13
Q
TCAs: pharmacokinetics
A
- oral
- long half lives
- once daily dosing
- METABOLIZED BY CYP2D6 (DRUG INTERACTIONS COMMON!)
14
Q
TCAs: side effects (histamine, cholinergic, alpha adrenergic)
A
- BLOCK ALPHA ADRENERGIC, HISTAMINE, CHOLINERGIC RECEPTORS (leads to pharmacologic effects)
- -> HISTAMINE = drowsiness, fatigue, sedation
- -> CHOLINERGIC = blurred vision, tachycardia, constipation, urinary retention, dry mouth, palpitations, memory impairment, probs w/ cognition
- -> ALPHA = cardiac depression, TORSADE DE POINTES, postural hypotension, dizziness, reflex tachycardia
15
Q
TCAs: side effects, cont
A
- weight gain
- TORSADE DE POINTES (arrhythmias)
- SIADH
- SEXUAL DYSFUNCTION
- decr seizure threshold
- tolerance to sedation & anticholinergic effects
- ANALGESIA
16
Q
antidote for torsades de pointes?
A
- Mg or isoproterenol
17
Q
TCAs + MAOIs = ______
A
- SEROTONIN SYNDROME = severe CNS toxicity w/ hyperpyrexia, convulsions, coma (stop TCAs 2-4 wks before starting MAOIs)
- TCAs compete for metabolism w/ SSRIs
18
Q
TCAs: drug interactions
A
+ MAOIs = serotonin syndrome
+ sympathomimetics (ie: amphetamine) = HTN
+ alcohol/CNS depressants = extra sedative effects
+ anticholinergics = potentiated effects
–> compete w/ SSRIs
19
Q
SSRIs: moa
A
- selectively inhibit 5-HT reuptake
20
Q
SSRIs: uses
A
- depression
- panic disorder
- OCD, social anxiety = PAROXETINE
- bulimia
- alcoholism
- children & teens
21
Q
DOC depression?
A
SSRIs
22
Q
SSRIs: pharmacokinetics
A
- well absorbed by gut
- metabolized by CYP450s
- inhibit CYP2D6 (fluoxetine, paroxetine)
- lots of drug interactions
23
Q
Fluoxetine (Prozac): info
A
- Norfluoxetine = active metabolite (half life 7-9 days)
- half life 2-3 days
- MORE DRUG INTERACTIONS THAN OTHER SSRIs
- impairs blood glucose in diabetics
24
Q
Sertraline (Zoloft): info
A
- extensive first pass metabolism
- half life 26 hrs
- LEAST LIKELY SSRI TO INTERACT W/ OTHER DRUGS
- preferred in elderly
25
Citalopram: info
DOC for depression
26
SSRIs: side effects
- MILD side effects (less than TCAs)
- GI
- weight loss/gain
- SIADH
- CNS STIMULATION w/ fluoxetine/sertraline, sedation w/ other drugs
- SEXUAL DYSFUNCTION/DISINTEREST
- no cardiac probs
- photosensitivity
27
SSRIs: drug interactions
- inhibition CYP3A4, CYP2D6 (fluoxetine)
- -> TCAs - inhibition metabolism increases toxicity
- -> Warfarin - increased risk bleeding
- -> phenytoin, carbamazepine - incr levels and toxicity
- MAOIs = SEROTONIN SYNDROME
- St. John's Wort, Amphetamines = SEROTONIN SYNDROME
- beta blockers = heart block, hypotension
- opioids = inhibits conversion to active compound
28
SNRIs: moa
- inhibit NE & 5-HT re-uptake
29
SNRI drugs?
- Venlafaxine (chance cardiac toxicity, incr BP)
| - Duloxetine (chance hepatotoxicity)
30
MAOIs: moa
- IRREVERSIBLY INHIBIT MAOs & MAOs METABOLIZE NE, DA, & 5-HT
- MAO-A metabolizes NE & 5-HT in BOTH CNS and GI tract
- MAO-B selectively metabolizes DA in CNS
31
Phenelzine: info
- INHIBITS MAO-A & MAO-B
- INCREASES NE & 5-HT
- use for depression that hasn't responded to other drugs
- DRUG OF LAST CHOICE - SERIOUS SIDE EFFECTS
32
selegiline: info
- SELECTIVELY INHIBITS MAO-B
- INCREASES DOPAMINE
- fewer side effects
- used in Parkinson's
33
MAOIs: pharmacokinetics
- long half life
| - effects persist after stopping drug
34
MAOIs: adverse effects (TYRAMINE)
- TYRAMINE metabolized by MAO in GI TRACT
- MAOIs inhibit tyramine metabolism
- increased peripheral noradrenergic effects
- AVOID FOODS w/ TYRAMINE (RED WINE, BEER, AGED CHEESE, ETC...)
HYPERTENSIVE CRISIS!
35
MAOIs: adverse effects, cont
- tremors, sedation, excitation, insomnia
- ORTHOSTATIC HYPOTENSION
- WEIGHT GAIN
- ANTICHOLINERGIC EFFECTS (blurred vision, dry mouth)
36
MAOIs: drug interactions
- w/ TCAs/SSRIs/St. John's Wort - SEROTONIN SYNDROME
- OTC COLD MEDS can lead to severe HTN
- OPIOIDS & DEXTROMETHORPHAN - can lead to hyperpyrexia, serotonin syndrome
37
Bupropion: moa
- PREFERENTIALLY INHIBITS DOPAMINE RE-UPTAKE
38
Bupropion: use
- COMBINED w/ SSRIs (sometimes)
| - ADHD, alcoholism (decreases craving), smoking
39
Bupropion: pharmacokinetics
- extensive first pass metabolism
- metabolized by CYP2B6
- inducer CYP2D6
40
Bupropion: side effects
- SEIZURES (MOST SERIOUS)
- CNS EFFECTS (anxiety, insomnia, restlessness, tremor, psychosis)
- tachycardia
- sexual dysfunction (rare)
41
Mirtazapine: moa
- NORADRENERGIC & SPECIFIC SEROTONERGIC ANTIDEPRESSANT
- BLOCKS PRESYNAPTIC ALPHA 2 RECEPTORS (normally would inhibit release of NE & 5-HT)
- INCREASES RELEASE NE, 5-HT
- BLOCKS 5-HT2a, 5-HT3 RECEPTORS
- blockade of these receptors eliminates side effects of SSRIs
42
Mirtazapine: info
- HISTAMINE ANTAGONIST (produces sedation)
| - relieves side effects serotonin
43
Atomoxetine: moa
- SELECTIVE INHIBITOR OF NE RE-UPTAKE
| - active metabolite that is DA/D2 antagonist
44
Atomoxetine: info
- TREATMENT ADHD
| - last drug of choice depression
45
Atomoxetine: side effects
- liver damage possible, but rare
| - side effects like TCAs
46
Trazodone: moa
- 5-HT2a RECEPTOR ANTAGONIST
47
Trazodone: info
- sedating, not good antidepressant
- antianxiety, antipsychotic
- OFF LABEL USE = HYPNOTIC/SLEEP AID
- pain management
48
Trazodone: side effects
- SEDATION
- dizziness, hypotension, nausea
- PRIAPISM (rare) - limits use in males
49
St. John's Wort: info
- may be effective for MILD depression
- DO NOT COMBINE WITH OTHER ANTIDEPRESSANTS! - SEROTONIN SYNDROME
- can prolong effects general anesthetics
