Term
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Definition
the administration of many drugs together
the practice of prescribing multiple drugs to patients suffering from more than one condition
the prescription or dispensation of unnecessarily numerous or complex medicines
the use of multiple drugs to treat one or a limited number of conditions |
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Term
| 5 principal prescribing situations in which polypharmacy may occur in psychiatry |
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Definition
1) treatment of multiple symptoms
ex) depression with psychosis
2) treatment of multiple illnesses
ex) diabetes and hyperlipidemia
3) treatment of phasic illnesses
ex) bipolar disorder (different phases)
4) preventing or treating ADRs caused by other medications
ex) sexual dysfunction caused by SSRI
5) attempting to accelerate the onset of action or augment the effects of a preceding drug
ex) lithium takes a while to start working, so add a BZD initially |
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Term
| drug interaction complications |
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Definition
lack of efficacy
poor tolerability
SERIOUS ADVERSE EVENTS:
sudden death
seizures
cardiac rhythm disturbances
serotonin syndrome
neuroleptic malignant syndrome
delirium |
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Term
the study of the time course of a drug in the body
how the body acts on drugs
ADME |
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Definition
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Term
| factors that affect absorption |
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Definition
absorption is the process of a drug reaching the bloddstream
oral medications are usually absorbed in the stomach or small intestine
factors that affect absorption:
alterations in GI pH
presence or absence of food in stomach
rate of bowel motility |
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Term
| absorption drug interactions |
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Definition
LEVOTHYROXINE + MULTIVITAMIN (iron/Ca)
decreased absorption of thyroid hormone
chelation reaction
DIVALPROEX DELAYED RELEASE + ANTACID
dissolve enteric coating of Depakoe = increased GI distress
ZIPRASIDONE + FOOD
50% increase in absorption (bioavailability)
SERTRALINE + FOOD
40% increase in absorption (bioavailability)
ASENAPINE (SUBLINGUAL) + FOOD/WATER
drinking water or eating food 2-5 minutes after administration decreases asenapine exposure by 10-20% |
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Term
| factors that affect distribution |
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Definition
distribution is how a drug is distributed throughout the body to various organs or sites of action
getting to the site of action:
through the bloodstream capillaries
diffuse to site of action
circulate bound to proteins (albumin) in the blood:
only the free drug is "active"
if a drug is highly protein bound, there is little free drug available
when one adds a highly protein bound drug, it can displace a previously bound drug
higher free/active drug is concerning with NARROW THERAPEUTIC INDEX DRUGS |
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Term
| highely protein bound drugs |
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Definition
most concerned with narrow therapeutic index drugs:
AMITRIPTYLINE
DIGOXIN
PHENYTOIN
WARFARIN
others:
asenapine
aspirin
chlorpromazine
diazepam
diphenhydramine
furosemide
glyburide
ibuprofen
imipramine
indomethacin
ketoconazole
naproxen
nifedipine
nortiptyline
oxazepam
thyroxine
valproic acid |
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Term
| distribution drug interactions |
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Definition
VALPROATE + PHENYTOIN
valproate displaces phenytoin from plasma protein binding sites = increased free levels (unbound) of phenytoin = increased risk for phenytoin toxicity (nystagmus, unstable gait, nausea, sedation, tremor)
VALPROATE + ASPIRIN
aspirin displaces valproate from plasma protein binding sites = increased free levels (unbound) of valproate = increased risk for valproate toxicity (nausea/vomiting, tremor, confusion, incoordination) |
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Term
| factors that affect metabolism |
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Definition
metabolism is the chemical modification of drug occurring in biological environment facilitating deactivation and excretion of drug
liver -> primary site of drug metabolism
CYP450 = a group of heme containing enzymes embedding in lipid bilayer of endoplasmic reticulum of hepatocytes
involved in oxidative metabolism (phase I) of drugs |
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Term
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Definition
occurs as a result of COMPETITIVE BINDING at the enzyme's binding site
competitive inhibition depends on:
the affinity of substrate for the enzyme being inhibited
the t1/2 of the inhibitor drug (acute alcohol ingestion = metabolism within 24 hours of single dose, amiodarone inhibition does not surface for months)
MOST inhibition interactions HAPPEN RIGHT AWAY, but drugs with long t1/2s may happen later |
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Term
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Definition
occurs when CYP450 activity is increased by medications, usually through INCREASED PRODUCTION OF THE ENZYME
an inducer may cause the level of a coadministered drug to decrease below the level needed for therapeutic effect, resulting in loss of clinical efficacy
1-3 weeks for an induction interaction to happen |
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Term
| CYP3A4 inhibitors (potent) |
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Definition
clarithromycin
erythromycin
CCBs - diltiazem, verapamil
protease inhibitors - ritonavir |
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Term
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Definition
carbamazepine
phenobarbital
phenytoin
primidone
rifampin
St. John's Wort |
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Term
| CYP1A2 inhibitors (potent) |
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Definition
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Term
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Definition
carbamazepine
phenobarbital
phenytoin
primidone
rifampin
SMOKING (hydrocarbons) |
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Term
| CYP2D6 inhibitors (potent) |
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Definition
CIMETIDINE
FLUOXETINE
PAROXETINE
amiodarone
quinidine
ritonavir
terbinafine |
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Term
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Definition
| NO SIGNIFICANT INDUCERS OF 2D6 |
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Term
| CYP2C inhibitors (potent) |
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Definition
amiodarone
fluconaxzole
fluoxetine
fluvoxamine
isoniazind
metronidazole
ritonavir
trimethoprim/sulfamethoxazle |
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Term
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Definition
carbamazepine
phenobarbital
phenytoin
rifampin |
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Term
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Definition
poor metabolizers:
Caucasians
Asians |
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Term
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Definition
poor metabolizers:
Caucasians
African Americans
Asians |
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Term
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Definition
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Term
| antipsychotic 1A2 SUBSTRATES |
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Definition
olanzapine
clozapine
haloperidol
asenapine
if the patient is a chronic smoker, have to increase the dose of the substrates |
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Term
| antipsychotic CYP2D6 SUBSTRATES |
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Definition
risperidone
clozapine
olanzapine
aripiprazole
iloperidone
fluphenazine
haloperidol
perphenazine
thioridazine |
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Term
| antipsychotic 3A4 SUBSTRATES |
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Definition
clozapine
quetiapine
aripiprazole
ziprasidone: predominantly metabolized via reduction by aldehyde oxidase = safer drug in terms of drug interactions
iloperidone
lurasidone
chlorpromazine
haloperidol |
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Term
| antidepressant 1A2 INHIBITORS |
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Definition
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Term
| antidepressant 2D6 INHIBITORS |
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Definition
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Term
| antidepressant 3A4 INHIBITORS |
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Definition
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Term
| antidepressant 2C9/2C19 INHIBITORS |
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Definition
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Term
| antidepressant SSRIs with less drug interactions |
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Definition
| sertraline, citalopram, escitalopram |
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Term
| anticonvulsant CYP450 INDUCERS |
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Definition
phenytoin
phenobarbital
carbamazepine
(oxcarbazepine)
(topiramate) |
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Term
| metabolic drug interactions |
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Definition
1) one drug negatively affects the other's oxidative metabolism by inducing CYP enzyme activity (induction interactions)
2) one drug negatively affects the other's oxidative metabolism by inhibiting CYP enzyme activity (inhibition interactions) |
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Term
| when to watch for drug interactions |
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Definition
[image]
inhibitor interaction happens right away
inducer interaction will take more time |
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Term
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Definition
ALPRAZOLAM + ST. JOHN'S WORT
CYP3A4 induction interaction = decreased alprazolam blood levels (decreased efficacy)
ETHINYL ESTRADIOL (ORAL CONTRACEPTIVE) + CARBAMAZEPINE
CYP3A4 induction interaction = decreased estrogen hormone blood levels (breakthrough bleeding, unintended pregnancy)
OLANZAPINE OR CLOZAPINE + CIGARETTE SMOKING
CYP1A2 induction interaction = decreased olanzapine or clozapine blood levels (decreased efficacy) |
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Term
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Definition
FLUOXETINE/PAROXETINE + RISPERIDONE
CYP2D6 inhibition interaction = increase (75%) in risperidone blood levels
increased risk of EPS
FLUVOXAMINE + OLANZAPINE
CYP1A2 inhibition interaction = increased olanzapine blood levels
FLUOXETINE/PAROXETINE + METOPROLOL
CYP2D6 inhibition interaction = increased metoprolol blood levels
SIMVASTATIN + NEFAZODONE
CYP3A4 inhibition interaction = increased simvastatin blood levels |
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Term
| grapefruit juice interactions |
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Definition
HMG-CoA reductase inhibitors (statins):
atorvastatin, lovastatin, simvastatin
CYP3A4 inhibition interaction = increased statin blood levels (fatigue, myalgias, and increased risk for rhabdomyolsis)
buspirone:
CYP3A4 inhibition interaction = increased buspirone blood levels (somnolence, dizziness, headache, nausea) |
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Term
| example of a metabolic drug interaction |
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Definition
DISULFIRAM + ETHANOL
interference of hepatic oxidation of acetaldehyde = increased acetaldehyde concentration
HA, dyspnea, throbbing in neck, N/V, sweating, thirst, tachycardia, hypotension, blurred vision, vertigo, weakness, anxiety, confusion, arrhythmias possible |
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Term
| glucuronidation drug interaction |
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Definition
VALPROIC ACID INHIBITS GLUCURONIDATION
INCREASES LAMOTRIGINE BLOOD LEVELS
if valproic acid is given with lamictal, you have to 1/2 the dose of lamictal to 12.5 mg/day or 25 mg every other day
increases lorazepam, oxazepam, temazepam blood levels |
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Term
| factors that affect elimination |
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Definition
elimination is the process by which drugs are eliminated from the body
most drugs/metabolites are excreted through urine (kidneys)
in psychiatry, most common elimination interactions will involve LITHIUM, gabapentin, or topiramate |
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Term
| elimination drug interactions |
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Definition
LITHIUM + NSAIDS (ibuprofen, naproxen)
increase lithium blood levels by up to 50% (reabsorption of lithium through kidneys)
LITHIUM + DIURETICS (HCTZ)
increase lithium blood levels by 50% (diuretic = sodium depletion which causes an increase in renal reabsorption of lithium)
LITHIUM + ACE INHIBITORS OR ARBS
increase lithium blood levels by up to 300% (volume depletion = decreased lithium excretion through kidneys)
LITHIUM + CAFFEINE OR THEOPHYLLINE
decrease lithium blood levels by increasing renal clearance of lithium by ~20%
lithium toxicity when > 1.5 |
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Term
the study of how a drug acts on its site(s) of action to produce pharmacologic effects
how drugs act on the body
drug molecule forms a complex with receptor in target organ or tissue causing a pharmacological response to occur |
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Definition
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Term
| types of pharmacodynamic drug interactions |
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Definition
DUPLICATION (AGONISM):
2 medications with same receptor effects = their therapeutic effects and adverse effects are intensified
OPPOSITION (ANTAGONISM):
2 medications with opposing receptor effects interact and reduce the effectiveness of one or both medications |
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Term
| antipsychotic receptor binding profiles |
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Definition
olanzapine:
H1 and M1
sedation and anticholinergic effects
quetiapine:
H1
sedation
clonzapine:
H1 and M1
risperidone:
alpha1
chlorpromazine:
H1, alpha1, M1
not well tolerated |
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Term
| antidepressant receptor binding profiles |
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Definition
amitriptyline:
H1, M1, alpha1
less well tolerated
clomipramine:
H1, M1, alpha1
less well tolerated
imipramine:
H1
mirtazapine:
H1
sedation
nefazodone:
H1, alpha1 |
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Term
| pharmacodynamic drug interactions: histamine (H1) interactions |
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Definition
QUETIAPINE + DIPHENHYDRAMINE
CLOZAPINE + HYDROXYZINE |
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Term
| pharmacodynamic drug interactions: muscarinic (M1) interactions |
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Definition
OLANZAPINE/CLOZAPINE + BENZTROPINE
clozapine causes excessive salivation AND is a strong M1 blocker
if clozapine is given with benztorpine (to stop excess salivation) the anticholinergic ADRs will be even worse
AMITRIPTYLINE + DIPHENHYDRAMINE |
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Term
| pharmacodynamic drug interactions: alpha1 interactions |
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Definition
QUETIAPINE + TRAZODONE
CHLORPROMAZINE + RISPERIDONE |
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Term
| pharmacodynamic drug interactions: beta interactions |
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Definition
PROPRANOLOL + ALBUTEROL INHALER
antagonistic effect = decreased bronchodilation effects of albuterol = bronchospasm |
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Term
| pharmacodynamic drug interactions: NE interactions |
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Definition
MAOIS (TRANYLCYPROMINE) + STIMULANTS (PSEUDOEPHEDRINE OR METHYLPHENIDATE)
MAOIS + TYRAMINE-CONTAINING FOODS (aged cheeses, aged meats, pickled meats/fish, alcohol (beer, wine)
sympathomimetics enhance catecholamine release = increased NE levels = hypertensive crisis |
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Term
| pharmacodynamic drug interactions: serotonin interactions |
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Definition
SSRIs
SNRIs
MAOIs
TCAs
lithium
St. John's Wort
tramadol
sibutramine
ecstasy
dextromethorphan
L-tryptophan
nefazodone
trazodone
buspirone
linezolid
triptans
SSRIS + WARFARIN (anticoagulants)
MOA: inhibition of serotonin uptake by platelets
monitor for s/sx of bleeding |
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Term
other synergistic drug interactions
(not dynamic b/c isn't the same receptor) |
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Definition
Cardiac Rhythm Disturbances:
ZIPRASIDONE/HALOPERIDOL/THIORIDAZINE + TCAS
synergistic QTc prolongation
Blood Dyscrasias:
CARBAMAZEPINE + CLOZAPINE (CONTRAINDICATED TOGETHER)
agranulocytosis
Respiratory Depression:
BENZODIAZEPINES + OTHER SEDATIVE HYPNOTICS (barbiturates, alcohol, choral hydrate)
Sexual Dysfunction:
SSRI (5HT agonism) + ANTIPSYCHOTIC (increased prolactin)
Lowered Seizure Threshold:
AMITRIPTYLINE (TCAS) + CLOZAPINE
BUPROPION + CLOMIPRAMINE (TCA)
Circulatory Collapse:
MEPERIDINE + MAOIS
Stimulation (insomnia):
BUPROPION + BUSPIRONE
FLUOXETINE + PSEUDOEPHEDRINE
Weight Gain:
LITHIUM + OLANZAPINE
MIRTAZAPINE + QUETIAPINE
CARBAMAZEPINE + VALPROIC ACID
Tremor:
LITHIUM + HALOPERIDOL
lithium induced tremor - intention hand tremor, when the patient moves
haloperidol induced tremor - jazz snap, pill rolling, RESTING hand tremor
VALPROIC ACID + BUPROPION
valproic acid induced tremor - intention hand tremor |
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Term
| drugs frequently involved in serious drug interactions |
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Definition
carbamazepine
cyclosporine
erythromycin
fluconazole/ketoconazole
statins
MAOIs
meperidine
phenytoin
protease inhibitors (ritonavir)
rifampin
SSRIs
theophylline
warfarin |
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Term
| always check potential interactions with any narrow therapeutic index drug including: |
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Definition
warfarin
digoxin
levothyroxine
lithium
carbamazepine
phenytoin
TCAs/MOAIs
theophylline |
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Term
| when to watch for drug interactions |
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Definition
when a patient is on numerous medications
lifestyle changes
when a new drug is added
when a drug is discontinued
when the dose of a drug is increased
when the dose of a drug is decreased |
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