#4 PD Interactions

Question 1

What are the TWO types of MAOI interactions?

Answer 1

1. Indirect-acting sympathomimetics

2. Serotonergic drugs

Question 2

What is the only REVERSIBLE MAOI mentioned?

Answer 2

Moclobemide

Question 3

Name some IRREVERSIBLE MAOIs

Answer 3

1. Isocarboxazid (marplan)
2. Phenelzine (nardil)
3. Selegiline (eldepryl)
4. Tranylcypromine (Parnate)

Question 4

This MRSA antibiotic is a MAO-A & B inhibitor

Answer 4

Linezolid

increases pressor effect of sympathomimetics

Question 5

Which 2 drugs can have a synergistic effect increasing BP?

Answer 5

Linezolide + Pseudoephedrine

[both can individually increase BP. Together they are synergistic]

Question 6

This is the only given MAO-A inhibitor that does NOT inhibit MAO-B

Answer 6

Moclobemide

Question 7

These are the two MAO-B inhibitors that do NOT inhibit MAO-A

Answer 7

Rasagiline, Selgiline (under 10 mg per day)

Question 8

Avoid taking this antibiotic with Sudafed

Answer 8

Linezolid

[note: NO interaction with dextromethorphan]

Question 9

T/F:

Serotonin Syndrome is always drug related

Answer 9

TRUE

Question 10

Serotonin syndrome can be confused with this occurrence

Answer 10

Neuroleptic Malignant syndrome

Question 11

These are the 5 highlighted symptoms of Serotonin syndrome

Answer 11

1. tremor
2. myoclonus
3. rigidity
4. sweating
5. agitation

Question 12

What do all these drugs have in common? 
Dextromethorphan
Buspar
TCA's
SSRIs 
Tramadol 
Meperidine
Sibutramine
Trazadone 
Vilazodone

Answer 12

SEROTONERGIC drugs

Question 13

Paroxetine is an inhibitor of what enzyme?

Answer 13

2D6

Question 14

The [3A4/2D6] metabolite of tramadol is active?

Answer 14

2D6

(the 3A4 metabolite is INACTIVE)

Question 15

[O/N]-desmethytramadol is processed by 2D6 and is ACTIVE

Answer 15

O-desmethyl tramadol

Question 16

Paroxetine + tramadol can cause what SE?

Answer 16

Serotonin syndrome

Question 17

T/F: Dextromethorphan has case reports of causing serotonin syndrome with SSRIs

Answer 17

TRUE

Question 18

What common OTC analgesic increases BP?

Answer 18

NSAIDs

Question 19

T/F:
ACEI are most sensitive to BP effects of NSAIDS, followed by ARBs, BB, and diuretics.
CCBs have minimal effects.

Answer 19

TRUE

Question 20

This class of drugs will reduce the effectiveness of ACEIs

Answer 20

NSAIDS

Question 21

ACEI + NSAID will lead to a(n) {INCREASE/DECREASE] in GFR?

Answer 21

DECREASE

Question 22

This major HTN Class seems to have the least effect from NSAID administration

Answer 22

CCB

Question 23

T/F:

Metabolic inhibition significantly INCREASES QTC prolongation

Answer 23

FALSE

Question 24

Name 4 drugs most often involved in QT prolongation DDIs

Answer 24

1. Ondansetron
2. Amiodarone
3. Metronidazole
4. Haloperidol

Question 25

What categories of drugs are expected to INCREASE QTc at therapeutic concentrations?

Answer 25

``` Class I antiarrhythmic agents Class III antiarrhythmic agents Other: -Moxifloxacin -Ceritinib -Lumefantrine ```

Question 26

List 7 antiarrhythmic agents expected to increase QTc at therapeutic concentrations.?

Answer 26

``` Class I antiarrhythmic agents -quinidine -procainamide -disopyramide Class III antiarrythmic agents -amiodarone -sotalol -Ibutilide -Dofetilide ```

Question 27

Which antibiotic is expected to INCREASE QTc at therapeutic concentrations?

Answer 27

Moxifloxacin

Question 28

What categories of drugs may produce extended QTc intervals, especially at elevated plasma concentrations?

Answer 28

1. antibiotics 2. TCAs 3. Antipsychotics 4. GI agents

Question 29

Name 2 antibiotics which may produce extended QTc intervals, especially at elevated plasma concentrations?

Answer 29

1. Clarithromycin | 2. Erythromycin

Question 30

Name 2 antidepressants which may produce extended QTc intervals, especially at elevated plasma concentrations?

Answer 30

1. Imipramine | 2. Desipramine

Question 31

Name 4 antipsychotics which may produce extended QTc intervals, especially at elevated plasma concentrations?

Answer 31

1. haloperidol 2. Pimozide 3. Thioridazine 4. Ziprasidone

Question 32

Name a GI agent which may produce extended QTc intervals, especially at elevated plasma concentrations?

Answer 32

Cisapride

Question 33

T/F: | Patients on multiple QTc prolonging drugs will experience an additive effect

Answer 33

FALSE

Question 34

AVOID use of 2 QTc prolonging drugs if they have BOTH PD & ______ QTc prolonging effect.

Answer 34

PK

Question 35

Cisapride + Erthromycin and quinidine + thioridazine are 2 examples of what type of interactions?

Answer 35

PD & PK prolonging effect [use together if benefit outweighs risk]

Question 36

What QT prolongation strategy should you use with two drugs: Dofetilide + Propafenone?

Answer 36

BOTH are antiarrhythmic agents that are expected to INCREASE QT at therapeutic concentrations: AVOID

Question 37

What QT prolongation strategy should you use with these two drugs: quindine + thioridazine

Answer 37

``` Quinidine = 2D6 INHIBITOR; can cause QT prolongation at normal concentrations Thioridazine = 2D6 substrate; can cause QT prolongation at HIGH concentrations ``` ANY drug expected to INCREASE QTc + a drug that may INCREASE QTc with PK and PD interaction potential: AVOID

Question 38

What QT prolongation strategy should you use with these two drugs: Procainamide + Haloperidol

Answer 38

``` Procainamide = antiarrhythmic @ normal concentration Haloperidol = antipsychotic @ elevated concentration ``` Drug expected to INCREASE QTc at therapeutic concentrations + a drug that may INCREASE QTc w/o PK interaction: Use only if the benefits outweighs risk

Question 39

What QT prolongation strategy should you use with these two drugs: Cisapride + Erythromycin

Answer 39

``` Cisapride = GI agent; 3A4 SUBSTRATE Erythromcyin = antibiotic; 3A4 INHIBITOR DDI = PK interaction ``` Drug expected to INCREASE QTc at therapeutic concentrations and have a PK interaction: Use only if the benefits outweighs risk

Question 40

What QT prolongation strategy should you use with these two drugs: Clozapine + Ziprasidone

Answer 40

Both antipsychotics Any 2 drugs that may INCREASE QTc & do NOT have a PK interaction: Assess risk and monitor as indicated

Question 41

T/F: | Risk of bleeding increased when anticoagulants are added together or combined with NSAIDS

Answer 41

TRUE

Question 42

Name 2 drugs which are NOT anticoagulants but significantly INCREASE risk of bleed with warfarin?

Answer 42

1. amiodarone | 2. Bactrim (2C9 INHIBITOR)

Question 43

T/F: | Warfarin & Levothyroxine have a dangerous DDI and must NOT be used together

Answer 43

FALSE | [adjust doses based on labs as usual]

Question 44

Reversible MAOI (1)

Answer 44

Moclobemide all others are IRREVERSIBLE

Question 45

Linezolid + Sudafed DDI

Answer 45

Linezolid = IVA w/mild MAOI activity = increases BP Sudafed = increases BP Linezolide + Sudafed = INCREASED BP, more than what would be if purely additive = Synergistic

Question 46

Paroxetine + tramadol DDI

Answer 46

PK: tramadol is 2D6 Substrate; paroxetine is 2D6 inhibitor PD: both have 5HT properties Paroxetine + tramadol = risk for serotonin syndrome via both PK & PD interactions [magnitude of PK DDI depends on 2D6 polymorphisms]

Question 47

What happens when you use paroxetine to inhibit 2D6 metabolism of tramadol?

Answer 47

Tramadol =2D6=active analgesic metabolite Tramadol =3A4 = inactive More Tramadol goes down 3A4 path= LESS analgesia

Question 48

Tramadol + terbinafine DDI

Answer 48

``` Terbinafine = 2D6 inhibitor; 5HT properties Tramadol = 2D6 minor substrate; inhibits 5HT reuptake ``` = INCREASED [tramadol] exposure Both PK & PD interactions = risk of serotonin syndrome

Question 49

Tramadol + Itraconazole DDI

Answer 49

Itraconazole = 3A4 inhibitor Tramadol's metabolite gets cleared by 3A4 = NO change in tramadol, but INCREASED [metabolite] = risk for serotonin syndrome

Question 50

NSAIDS that INCREASE BP more (2)

Answer 50

Indomethacin | Piroxicam

Question 51

If... Drug A = known to prolong QTc Drug B= known to prolong QTc Then....

Answer 51

AVOID COMBO

Question 52

If... Drug A = known to prolong QTc Drug B= MAYBE to prolong QTc + additional PK interaction Then....

Answer 52

AVOID COMBO

Question 53

If... Drug A = known to prolong QTc Drug B= known to prolong QTc & NO PK interaction Then....

Answer 53

Use cautiously if benefit > risk

Question 54

If... Drug A = MAYBE prolong QTc Drug B= MAYBE prolong QTc + PK interaction Then....

Answer 54

Use cautiously if benefit > risk

Question 55

If... Drug A = MAYBE prolong QTc Drug B= MAYBE prolong QTc & NO PK interaction Then....

Answer 55

Use and Monitor

Question 56

Dofetilide + propafenone okay?

Answer 56

Both are known to cause QT prolongation = AVOID USE

Question 57

Quinidine + thioridazine okay?

Answer 57

Quinidine = known thioridazine = maybe + PK interaction = AVOID

Question 58

Procainamide + haloperidol okay?

Answer 58

Procainamide = known haloperidol = maybe NO PK interaction= Caution, use if benefit > risk

Question 59

Cisapride + erythromycin okay?

Answer 59

Cisapride = maybe Erythromcyin = maybe + PK interaction = Caution, use if benefit> risk

Question 60

Clozapine + ziprasidone okay?

Answer 60

Clozapine = maybe Ziprasidone = maybe = Use + Monitor