#4 PD Interactions Flashcards
What are the TWO types of MAOI interactions?
- Indirect-acting sympathomimetics
2. Serotonergic drugs
What is the only REVERSIBLE MAOI mentioned?
Moclobemide
Name some IRREVERSIBLE MAOIs
- Isocarboxazid (marplan)
- Phenelzine (nardil)
- Selegiline (eldepryl)
- Tranylcypromine (Parnate)
This MRSA antibiotic is a MAO-A & B inhibitor
Linezolid
increases pressor effect of sympathomimetics
Which 2 drugs can have a synergistic effect increasing BP?
Linezolide + Pseudoephedrine
[both can individually increase BP. Together they are synergistic]
This is the only given MAO-A inhibitor that does NOT inhibit MAO-B
Moclobemide
These are the two MAO-B inhibitors that do NOT inhibit MAO-A
Rasagiline, Selgiline (under 10 mg per day)
Avoid taking this antibiotic with Sudafed
Linezolid
[note: NO interaction with dextromethorphan]
T/F:
Serotonin Syndrome is always drug related
TRUE
Serotonin syndrome can be confused with this occurrence
Neuroleptic Malignant syndrome
These are the 5 highlighted symptoms of Serotonin syndrome
- tremor
- myoclonus
- rigidity
- sweating
- agitation
What do all these drugs have in common? Dextromethorphan Buspar TCA's SSRIs Tramadol Meperidine Sibutramine Trazadone Vilazodone
SEROTONERGIC drugs
Paroxetine is an inhibitor of what enzyme?
2D6
The [3A4/2D6] metabolite of tramadol is active?
2D6
(the 3A4 metabolite is INACTIVE)
[O/N]-desmethytramadol is processed by 2D6 and is ACTIVE
O-desmethyl tramadol
Paroxetine + tramadol can cause what SE?
Serotonin syndrome
T/F: Dextromethorphan has case reports of causing serotonin syndrome with SSRIs
TRUE
What common OTC analgesic increases BP?
NSAIDs
T/F:
ACEI are most sensitive to BP effects of NSAIDS, followed by ARBs, BB, and diuretics.
CCBs have minimal effects.
TRUE
This class of drugs will reduce the effectiveness of ACEIs
NSAIDS
ACEI + NSAID will lead to a(n) {INCREASE/DECREASE] in GFR?
DECREASE
This major HTN Class seems to have the least effect from NSAID administration
CCB
T/F:
Metabolic inhibition significantly INCREASES QTC prolongation
FALSE
Name 4 drugs most often involved in QT prolongation DDIs
- Ondansetron
- Amiodarone
- Metronidazole
- Haloperidol
What categories of drugs are expected to INCREASE QTc at therapeutic concentrations?
Class I antiarrhythmic agents Class III antiarrhythmic agents Other: -Moxifloxacin -Ceritinib -Lumefantrine
List 7 antiarrhythmic agents expected to increase QTc at therapeutic concentrations.?
Class I antiarrhythmic agents -quinidine -procainamide -disopyramide Class III antiarrythmic agents -amiodarone -sotalol -Ibutilide -Dofetilide
Which antibiotic is expected to INCREASE QTc at therapeutic concentrations?
Moxifloxacin
What categories of drugs may produce extended QTc intervals, especially at elevated plasma concentrations?
- antibiotics
- TCAs
- Antipsychotics
- GI agents
Name 2 antibiotics which may produce extended QTc intervals, especially at elevated plasma concentrations?
- Clarithromycin
2. Erythromycin
Name 2 antidepressants which may produce extended QTc intervals, especially at elevated plasma concentrations?
- Imipramine
2. Desipramine
Name 4 antipsychotics which may produce extended QTc intervals, especially at elevated plasma concentrations?
- haloperidol
- Pimozide
- Thioridazine
- Ziprasidone
Name a GI agent which may produce extended QTc intervals, especially at elevated plasma concentrations?
Cisapride
T/F:
Patients on multiple QTc prolonging drugs will experience an additive effect
FALSE
AVOID use of 2 QTc prolonging drugs if they have BOTH PD & ______ QTc prolonging effect.
PK
Cisapride + Erthromycin
and
quinidine + thioridazine are 2 examples of what type of interactions?
PD & PK
prolonging effect
[use together if benefit outweighs risk]
What QT prolongation strategy should you use with two drugs:
Dofetilide + Propafenone?
BOTH are antiarrhythmic agents that are expected to INCREASE QT at therapeutic concentrations:
AVOID
What QT prolongation strategy should you use with these two drugs:
quindine + thioridazine
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
What QT prolongation strategy should you use with these two drugs:
Procainamide + Haloperidol
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
What QT prolongation strategy should you use with these two drugs:
Cisapride + Erythromycin
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
What QT prolongation strategy should you use with these two drugs:
Clozapine + Ziprasidone
Both antipsychotics
Any 2 drugs that may INCREASE QTc & do NOT have a PK interaction:
Assess risk and monitor as indicated
T/F:
Risk of bleeding increased when anticoagulants are added together or combined with NSAIDS
TRUE
Name 2 drugs which are NOT anticoagulants but significantly INCREASE risk of bleed with warfarin?
- amiodarone
2. Bactrim (2C9 INHIBITOR)
T/F:
Warfarin & Levothyroxine have a dangerous DDI and must NOT be used together
FALSE
[adjust doses based on labs as usual]
Reversible MAOI (1)
Moclobemide
all others are IRREVERSIBLE
Linezolid + Sudafed DDI
Linezolid = IVA w/mild MAOI activity = increases BP
Sudafed = increases BP
Linezolide + Sudafed = INCREASED BP, more than what would be if purely additive
= Synergistic
Paroxetine + tramadol DDI
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]
What happens when you use paroxetine to inhibit 2D6 metabolism of tramadol?
Tramadol =2D6=active analgesic metabolite
Tramadol =3A4 = inactive
More Tramadol goes down 3A4 path= LESS analgesia
Tramadol + terbinafine DDI
Terbinafine = 2D6 inhibitor; 5HT properties Tramadol = 2D6 minor substrate; inhibits 5HT reuptake
= INCREASED [tramadol] exposure
Both PK & PD interactions = risk of serotonin syndrome
Tramadol + Itraconazole DDI
Itraconazole = 3A4 inhibitor
Tramadol’s metabolite gets cleared by 3A4
= NO change in tramadol, but INCREASED [metabolite] = risk for serotonin syndrome
NSAIDS that INCREASE BP more (2)
Indomethacin
Piroxicam
If…
Drug A = known to prolong QTc
Drug B= known to prolong QTc
Then….
AVOID COMBO
If…
Drug A = known to prolong QTc
Drug B= MAYBE to prolong QTc + additional PK interaction
Then….
AVOID COMBO
If…
Drug A = known to prolong QTc
Drug B= known to prolong QTc & NO PK interaction
Then….
Use cautiously if benefit > risk
If…
Drug A = MAYBE prolong QTc
Drug B= MAYBE prolong QTc + PK interaction
Then….
Use cautiously if benefit > risk
If…
Drug A = MAYBE prolong QTc
Drug B= MAYBE prolong QTc & NO PK interaction
Then….
Use and Monitor
Dofetilide + propafenone okay?
Both are known to cause QT prolongation = AVOID USE
Quinidine + thioridazine okay?
Quinidine = known
thioridazine = maybe + PK interaction =
AVOID
Procainamide + haloperidol okay?
Procainamide = known
haloperidol = maybe NO PK interaction=
Caution, use if benefit > risk
Cisapride + erythromycin okay?
Cisapride = maybe
Erythromcyin = maybe + PK interaction =
Caution, use if benefit> risk
Clozapine + ziprasidone okay?
Clozapine = maybe
Ziprasidone = maybe
=
Use + Monitor