Clinical Pk Exam 3- Antidepressants

Front 1

choosing antidepressants- rationale based on...

Back 1

based on side fx, not efficacy

Front 2

first choice antidepressants (3)

Back 2

The SSRIs, secondary amines, and atypical antidepressants

Front 3

second and last choice antidepressants

Back 3

Second choice or severe depression: TCAs

MAOIs

Front 4

dosing antidepressants (3)

Back 4

start low to assess tolerance of side fx

increase dosage rapidly, as tolerated

maintain typical dose for 4-8 weeks (takes a while to work)

Front 5

indications for taking serum lvls for antidepressants (unequivocal) (2)

Back 5

patients at risk for toxicity (cardiac pt)

patients who are not responding to usual doses

Front 6

indications for taking serum lvls for antidepressants that are mayyyybee (2)

Back 6

pt where prompt response is critical
determining compliance/metabolic availability

Front 7

absorption and ba of antidepressants (2)

Back 7

rapid- 2-4 hours peak Tmax

variable BA due to extensive first pass

Front 8

Vd of most antidepressants

Back 8

up to 60 L /kg

Front 9

distribution of antidepressants (2)

Back 9

highly lipophillic - wide distribution

tend to concentrate in cardiac and cerebral tissue

Front 10

protein binding of antidepressants

Back 10

highly bound to AAG and lipoproteins

Front 11

metabolism and elimination of antidepressants (2) CL rate and primary means of clearance

Back 11

high CL
primarily cleared by metabolism

Front 12

liver metabolism pathways involved (4)

Back 12

Oxidation, hydroxylation, demethylation, then
glucuronidation:

Front 13

CYPs/enzymes involved in metabolism (4)

CYP inhibition

Back 13

UGT
CYP2D6, 2C19, 3A4

inhibits 2D6

Front 14

half lives of antidepressants

Back 14

rates of metabolism vary widely so can range anywhere from 12 to 190 hrs

Front 15

active metabolites of imipramine (3)

Back 15

2-hydroxy Imipramine; Desipramine; 2-hydroxy Desipramine

Front 16

active metabolites of desipramine

Back 16

2-hydroxy desipramine

Front 17

active metabolites of amitriptyline (2)

Back 17

nortriptyline
10-OH nortriptyline

Front 18

active metabolite of nortriptyline

Back 18

10-OH nortriptyline

Front 19

doxepin active metabolite

Back 19

Desmethyldoxepin (cis and trans isomers)

Front 20

things that alter tricyclic PK (4)

Back 20

genetics (primary)
smoking (induces CYP1A2, minor metabolic pathway)
age
metabolic CL...isn't this genetics

Front 21

antidepressants are often Rx'ed in combination with what drugs (5)

Back 21

Antipsychotics, anxiolytics, mood stabilizers
cardiovascular drugs, antibiotics

Front 22

what drugs should you AVOID administering with?

Back 22

MAOI

Front 23

TCAs ** KNOW THIS** and MAOIs main AE/contraindication

Back 23

- they have serious side effect on the heart- arrhythmias (can be contraindicated if pt has had major heart procedures or infarctions)

Front 24

not going to be asked active metabolites

Back 24

---

Front 25

why is it hard to determine PK profile for antidepressants?

Back 25

they all have active metabolites

Front 26

CYP2D6
CYP2C19
CYP3A4

dosage adjustments for poor metabolizers?

Back 26

CYP2D6- for poor metabolizers have to reduce dose by 20-70%
CYP2C19- reduce rec dose in PM by 50-70%
CYP3A- CYP3A4 not polymorphic

Front 27

drug interactions- possible issues (PK and pD)

Back 27

PK: Inhibition (Induction)
PD: Arrhythmia (esp with MAOI/TCA)

Front 28

effect of st johns wort on imatinib (or...any drug it interacts with) on PK parameters (3)

Back 28

Cmax- decrease
Tmax- increases k (induction) so decreases Tmax
AUC- decrease

Front 29

Fluoxetine (Prozac) inhibits... (3)

Back 29

CYP2D6
CYP3A4
CYP2C9

Front 30

fluoxetine drug interactions with what CYP2D6 drugs (4)

Back 30

increases AUC of TCAs, clozapine, haloperidol, propranolol

Front 31

fluoxetine drug interactions with which CYP3A4 drugs (2)

Back 31

increases AUC of carbemazapine and risperidone

Front 32

fluoxetine drug interactions with CYP2C9 drugs (2)

Back 32

increases AUC of phenytoin, warfarin

Front 33

Side effects of antidepressants- 6 receptor targets

Back 33

NE uptake blockade
dopamine uptake blockade
serotonin uptake blockade
H1 blockade
muscarinic (Ach) block
alpha1 block

Front 34

NE related side fx (2)

Back 34

Tremors
Tachycardia

Front 35

dopamine related side fx (3)

Back 35

Psychomotor activation
Psychoses
Increased attention/concentration

Front 36

serotonin related side fx (3)

Back 36

Gastrointestinal disturbances
Anxiety (dose – dependent)
Sexual dysfunction

G.A.S

Front 37

H1 block side fx (3)

Back 37

Sedation, drowsiness
Weight gain
Hypotension

Front 38

Ach block side fx (6)

Back 38

Blurred vision
Dry mouth
Sinus tachycardia
Constipation
Urinary retention
Memory dysfunction

Front 39

alpha1 block side fx (3)

Back 39

Postural hypotension
Reflex tachycardia
Dizziness

Front 40

cardiac fx of antidepressants (3)

Back 40

Cardiac conduction delay
Pro-Arrhythmic at high doses
Minimal effects on cardiac output

need to monitor EKG

Front 41

tricyclics OD sx (6)

Back 41

coma/shock
respiratory depression with apnea
agitation/delirium
neuromuscular irritability and seizures
bowel and bladder paralysis
conduction issues/ventricular arrhythmias

Front 42

contraindication of TCAs

why?

Back 42

heart disease, and recent acute myocardial infarction (within 6 weeks)

because even therapeutic doses show evidence for cardiac toxicity

Front 43

issues that interfere with plasma conc. monitoring for TCAs (3)

Back 43

-active metabolites which make it hard for us to monitor plasma lvls
-need 3-4 weeks for effect to begin

-must use SS plasma conc. Which will be delayed 3-5 half lifes..so wil take too long

Front 44

TCA relationship of plasma lvl and therapeutic response (2)

Back 44

For most of the tricyclics, the relationship between plasma levels and
therapeutic response remains poorly defined.
- For some, tentative therapeutic ranges of plasma levels have been
proposed.

Front 45

clinical app of PK data (4) (as in...why or why not use it)

Back 45

dosage selection is largely empirical- so not much contribution there

loading doses-not much effect and can be harmful

reduce doses in elderly

Measurement of plasma levels only useful in certain instances

Front 46

3 reasons to use PK data

Back 46

pt at greatest risk for heart toxicity (old, heart disease)

suspected noncompliance, drug interactions, persistent side fx, therapeutic failures

overdosage

Front 47

practical application of PK data for antidepressants- like how to actually use the data for dosing

Back 47

Maintenance dosage requirements can be estimated from the plasma
level taken 24 hours after a single test dose (follows the report of good
correlations between plasma concentrations at 24 hours and final
steady-state concentrations)

Front 48

% of pt that respond satisfactorily to antidepressants

Back 48

Only 50 to 70% of patients respond satisfactorily to treatment with
antidepressants

Front 49

time it takes for antidepressants to work

Back 49

- Takes 2-4 weeks before an antidepressant response occurs, though
anxiety and sleep disturbance may not be helped within a few days.

Front 50

difference in efficacy of antidepressants?
what are the important differences?

Back 50

- Little evidence for any claimed differences in efficacy.
- Important differences, however, with regard to adverse effects, as
previously discussed.