Term
| Why does Li require monitoring? |
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Definition
It has a narrow TI, wide inter-individual variations (in Cl & Vd), & intra-individual variations (age & duration of therapy). |
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Term
| Which salt form of Li is solid & which is liquid? |
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Definition
Li carbonate is solid Li citrate is liquid |
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Term
| What is the bioavailability for regular formulations of Li? liquid? SR? |
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Definition
>95% for regular & liquid Li >80% for SR LI |
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Term
What are the advantages of taking SR Li? What are the disadvantages? |
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Definition
Advantages improved compliance. decreased adverse effects associated w/ peak & rising serum concentrations (tremor & nausea). increased urine concentration in kidneys. Disadvantages increased diarrhea on an empty stomach |
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Term
Rank the Li formulations wrt speed of absorption time |
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Definition
fastest - liquid 2nd - oral 3rd - SR |
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Term
| Explain why distribution is a 2-compartment model for Li |
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Definition
| The 1st phase is extracellular; the 2nd phase is unevenly distributed to the kidney, bone, brain, & thyroid. |
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Term
| Why is the Vd for Li decreased in geriatric pts? |
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Definition
| B/c they have a small amount of total body water & Li is a water soluble drug. |
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Term
Is Li contraindicated during pregnancy? Is Li contraindicated in breast-feeding mothers? |
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Definition
Only during the 1st trimester & 1 week before delivery. Yes, b/c it's excreted in the breast milk. |
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Term
Discuss Li wrt elimination |
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Definition
It's not metabolized, & it's not bound to plasma proteins, so it's 100% filtered. 80% is reabsorbed in the proximal tubule. The 1/2 life is 12h for acute mania, 18-27h for maintenance of bipolar, & 30-50h in the elderly. Also, less is cleared during the night, due to the circadium rhythm of the GFR, & in the supine position (laying down). |
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Term
What does decreased Na intake due to Li levels? |
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Definition
When Na is decreased, there's increased Na & water reabsorption, which = Li reasborption |
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Term
| What does dehydration do to Li levels? |
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Definition
When you're dehydrated, the kidney reasborbs water, & Li follows water, so Li reasborption is increased. |
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Term
| Why would you be concerned about giving Li to someone who was going to be sweating alot? |
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Definition
| B/c Li is excreted w/ the sweat. So, you would want to monitor a pt like this. |
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Term
| What do thiazide diuretics do to Li levels? |
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Definition
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Term
| What do NSAIDs do to Li levels? Explain |
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Definition
| NSAIDs normally decrease the formation of PGE2. PGE2 normally vasodilates the afferent arteriold. So, w/ NSAIDs, there is less PGE2, less vasodilation, & less clearance of Li. Thus, Li levels are increased. |
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Term
| How do ACE inhibitors affect Li levels? |
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Definition
| ACE inhibitors cause Na excretion, which means increased Li. |
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Term
| What are the 2 examples given for methylxanthines & what do they do to Li levels? |
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Definition
| Caffeine & theophylline decrease Li levels |
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Term
What are the therapeutic levels of Li for: acute mania? chronic dosing? geriatic? |
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Definition
0.8-1.2mEq/L 0.6-1.0mEq/L 0.4-0.6mEq/L |
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Term
| When is the best time to take a sample of [Li]? Why is this the best time? |
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Definition
In the AM, 12h after a PM dose. By this time, the dose has been completely absorbed & distributed |
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Term
What happens when neurotoxic Li levels reach the following values: 1.5-2.0? 2.5-3.0? >3.0? |
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Definition
1.5-2.0 - muscle weakness, nausea, irritability 2.5-3.0 - confusion, slurred speech, unsteady gait, blurred vision (you look drunk) >3.0 - ataxia, parkinsonian movements |
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Term
At what concentration of Li is dialysis recommended? Once the serum levels get below 1mEq/L post-dialysis, when & why should you take another measurement? |
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Definition
3.5-4mEq/L Once the levels get below 1, you should take another measurement in 6-8h b/c this drug tends to have distributional rebound (the levels could go back up). |
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Term
When should serum levels be drawn for: someone w/ acute mania? maintenance? after a dosage change? |
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Definition
Every 2-3 days Every 1-2 wks during first 4-8wks (whenever concentration is stabilized); then, once q 6 months. 1 week |
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Term
| How does Li affect the thyroid? Why should levels be monitored q 6 months? |
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Definition
It decreases thyroid hormone, which increases TSH. If TSH is too high, pt could get hyperthyroidism or a goiter. So, monitor q 6 months. |
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Term
| Discuss the fixed dosing method |
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Definition
The starting dose is 300mg tid. If CLcr is 10-50ml/min, give 50-75% of the recommended daily dose. If CLcr is <10ml/min, give 25-50% of recommended daily dose. A drawback of the fixed dosing method is that most pts are subtherapeutic during the 5-7 days it takes to reach ss. Many of the pts taking this drug need it to work faster. |
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Term
| Which of the SSRIs has the lowest F? How does this affect the dose? |
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Definition
| Sertraline has the lowest F, so it will require the highest dose. |
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Term
| Which active metabolite has a significant half life? How is this significant? |
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Definition
| Norfluoxetine has a 1/2 life of 7-15 days. Norfluoxetine, then, is considered equipotent (it has = activity) w/ its parent drug. This is significant for efficacy, toxicity, & drug interactions. |
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Term
| Which of the SSRIs is the most potent inhibitor of CYP2D6? Why is this important? |
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Definition
| Fluoxetine can inhibit its own metabolism, which reduces its clearance. We need to make sure to take this into consideration when thinking about drug interactions. |
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Term
| Can SSRIs be used w/ MAOIs? |
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Definition
| No, this could cause serotonin syndrome |
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Term
| Explain the interaction b/w fluoxetine & anticonvulsants (carbamazepine & valproic acid). |
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Definition
| Plasma levels of anticonvulsants increase up to 50%, b/c fluoxetine inhibits oxidative metabolism |
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Term
T or F: Renal disease increases the AUC & Cpmax of paroxetine? fluoxetine? sertraline? |
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Definition
| It's only T for paroxetine |
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Term
Should SSRI levels be measured? Explain. |
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Definition
| No, b/c they have a flat relationship, meaning there's no relationship b/w the concentration & effect (however, there is a relationship b/w concentration & toxicity). They either work or they don't. |
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Term
| What are the w/drawal symptoms for fluvoxamine, paroxetine, & sertraline? Why isn't fluoxetine included? |
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Definition
fatigue, abdominal cramps, distension, insomnia, flu-like symptoms, HA, nausea, irrtability, & shock-like symptoms. These symptoms aren't seen in fluoxetine, b/c of its long 1/2 life |
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Term
What are the indications for the benzodiazepines? |
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Definition
Hypnotics at high doses Anxiolytics at moderate doses sedatives at low doses muscle relaxant alcohol w/drawal anticonvulsant |
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Term
| Which would be preferred for seizures: diazepam or lorazepam? Why? |
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Definition
| Diazepam is more lipophilic than lorazepam, so it is rapidly absorbed. However, it is considered to be erratically absorbed, b/c it bounces back and forth over the BBB. Lorazepam should be used for seizures, b/c it is rapidly & completely absorbed. |
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Term
What would be the optimal choice of benzodiazepine for an older person? What are some benzos that could be given to an older person? |
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Definition
The elderly have decreased oxidative metabolism, decreased albumin (which means increased free drug), & decreased renal function. So, the optimal drug will have a short 1/2 life, few hepatic biotransformations (conjugation would be preferred), & no active metabolites. Lorazepam, Oxazepam, Temazepam, & estazolam |
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Term
| What are some benzos that could be used in the elderly? |
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Definition
lorazepam, oxazepam, temazepam, estazolam |
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Term
What do all of the long-acting benzos have in common? Which long-acting benzos have extra long 1/2 lives? |
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Definition
Their metabolic pathway is oxidation & they all have active metabolites. Clorazepate & prazepam |
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Term
| What are some common withdrawal symptoms of benzos? |
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Definition
| anxiety, irritability, muscle pains, metallic taste, paranoia, hallucinations |
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Term
| How should aminoglycosides be administered? |
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Definition
Intravenous intermittent infusion for at least 30-60 minutes. Infusion for more than 60 will reduces error. We want high peaks for response & low peaks to prevent toxicity. Make sure that you recognize that it's intermittent & not continuous (which can cause toxicity). IM would also work for younger, healthy people; but, it shouldn't be done in anyone over 40. |
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Term
Aminoglycosides best fit a 3-compartment model. Explain. |
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Definition
| There is a distribution phase, a fast elimination phase (drug is eliminated), & a slow elimination phase (drug is accumulated in kidney & released over time). |
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Term
T or F Aminoglycosides readily cross membranes |
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Definition
False They are polar, so they don't cross membranes well. They are poorly distributed to places that require them to cross membranes (eg, eyes, CNS). They can get into fluids (synovial, peritoneal, pleural, etc). |
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Term
| discuss aminoglycoside elimination |
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Definition
99% is excreted renally. Uptake can occur in the proximal tubule via pinocytosis. Pinocytosis occurs after the charge on the aminoglycoside binds to the kidney. Urinary concentrations are 20-100X > than in the blood. elimination is highly variable, so simply calculating CLcr will not work. Dosing, then, has to be individualized. |
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Term
| What are the factors that affect aminoglycoside dispostion? |
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Definition
renal function age distribution (Vd decreases when Kel increases) fever (CO & GFR go up, drug levels go down) hematocrit IBW gender (females have lower Vd/kg, so they are at greater risk for toxicity). |
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Term
| How is aminoglycoside disposition affected by obstetrics? |
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Definition
| Pregnant women have increased GFR |
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Term
| How is aminoglycoside disposition affected by burns? |
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Definition
Burns increase elimination |
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Term
| How is aminoglycoside disposition affected by pediatrics? |
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Definition
| In pediatrics, drugs have large Vds & shortened elimination half-lifes |
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Term
How is aminoglycoside disposition affected by geriatrics? |
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Definition
geriatric pts are highly variable & must be monitored closely |
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