Unit 10 TDM and Toxicology Flashcards

The dose of a medication which will have the intended effect for 50% of the population

The dose which will cause toxic symptoms in 50% of the population

The dose which is lethal in 50% of the population

Cytochrome P450 Oxidase enzymes (CYP450)

Phase I - Oxidizing or reducing a compound

Phase II - Inactivation of a compound by adding a functional group to it

Volume of distribution, tells how widely the substance is spread throughout your body

How much of a substance you get rid of in a specific amount of time

How long it takes for the plasma concentration to decrease by half

The test gives you a result which is positive or negative

The test gives you a numerical value as a result

Because it displaces oxygen on our hemoglobin and holds on tightly so that we can no longer transport oxygen in our blood

100% oxygen

Red face, headache, shortness of breath

The heart and the brain

Oxidative phosphorylation (i.e. the ability for oxygen to accept electrons in the electron transport chain). Results in tissue death, seizures, and coma.

Open flames in an enclosed space

So many. Primarily gastrointestinal motility, acidity of the drug, gastric acidity,

This is when a drug is measured after 1-4 hours and is considered to be completely absorbed, reaching it's peak concentration

this is when a drug is measured immediately prior to the next dose, at theoretically the lowest concentration

A constant percentage of substance is eliminated over time

A constant amount of substance is eliminated over time

alcohol

5

When the drug intake equals drug excretion

What the drug does to the body

What the body does to the drug

Nausea, vomiting, cardiac arrhythmias

note: is a cardiac glycoside used to improve cardiac contraction in patients with congestive heart failure. Side effects of increased concentrations (>3 ng/mL) include nausea, vomiting, premature ventricular contractions (PVCs), and atrioventricular node blockade.

Nausea, vomiting, tinnitus, thrombocytopenia, and cardiac arrhythmias

note :is a drug used to treat cardiac arrhythmias. It is generally administered as a slowly-absorbed oral pill. Trough levels are assessed. Toxicity begins at twice the upper limit of the therapeutic range. Side effects include nausea, vomiting, tinnitus, thrombocytopenia, and PVCs.

Digoxin and Quinidine

Aminoglycosides and Vancomycin

Nephrotoxicity and Ototoxicity

note:are a group of antibiotics used to treat gram-negative bacterial infections.
Big toxicities to remember with these are Nephrotoxicity and Ototoxicity; kidney and hearing.

Nephrotoxicity, otoxicity, and Red Man Syndrome

note: is at the pinnacle of antibiotics and one of the kingpins that we use to treat the “untreatable” infections. It is administered intravenously and can cause “red man syndrome” (erythema or the whole body), Nephrotoxicity, and Ototoxicity. Same as the aminoglycosides, but just add that it causes the cool red man syndrome thing and you’re good.

Hirsuitism, gingival hyperplasia, vitamin D deficiency, folate deficiency

note: is an anti-seizure, Anti-Epileptics, drug and used in brain injury to prevent further loss of functional tissue. Seizures can occur in sub-therapeutic or supratherapeutic doses. Other side effects include hirsutism (become a hairy man beast like bigfoot), gingival hyperplasia, vitamin D deficiency, and folate deficiency.

Rashes, nausea, vertigo, and a deadly leukopenia

note: is an effective anti-seizure drug, but is only used in refractory cases that do not respond to other antiepileptic drugs. Side effects can include rashes, nausea, vertigo, and the most serious is the deadly leukopenia.

Used for absence seizures Causes nausea, vomiting, anorexia, dizziness, lethargy

note: is used for controlling petit mal seizures. These are the seizures that don’t
cause wild flailing but the patient stares blankly not moving, and are also called absence seizures. This drug has the standard litany of side effects for most drugs; nausea, vomiting, anorexia, dizziness, lethargy. You would be safe to bet that most oral drugs cause these symptoms, so they’re not really special like some of the others I’ve outlined.

Phenytoin, Carbamaepine, and Ethosuximide

Lithium, Tricyclic antidepressants, and clozapine

Anemia, renal impairment, apathy, lethargy, hypothyroidism, seizures

note: is a common mood-altering medication used for bipolar disorder. Lithium has a half-life of 10-35 hours and has a narrow therapeutic index, meaning that side effects present just above the effective concentration. These include apathy, lethargy, renal impairment, hypothyroidism, and seizures.

Seizures, arrhythmias, and loss of consciousness

note: are used to treat depression, and the most pertinent ones are imipramine, amitriptyline, and doxepin. TCAs hang out in the body a VERY long time; half-life of 17-40 hours. Side effects include seizures, arrhythmias, and loss of consciousness.

Seizures

note: is a drug used in refractory schizophrenia as an antipsychotic. Excess dosing can result in seizures.

renal dysfunction

note:is an immunosuppressive agent used to prevent host-versus-graft rejection.
Half-life is approximately 12 hours, and toxicity results in renal dysfunction

note: is another oral immunosuppressive agent but it is 100 times more potent . Although it is still effective at lower concentrations, It's toxicity still results in renal dysfunction

inhibits DNA synthesis in all cells

note: This works well for cancer, because those cells are rapidly dividing and they will take more MTX and suffer more. The peak concentrations are measured 1 hour after the dose is given orally. Side effects will include a cytotoxic effect to most cells in the body. We have a procedure to halt the MTX effect on our cells called leucovorin rescue, where we basically infuse the patient with folic acid which effectively stops the deadly action of MTX on our cells.

leukovorin rescue

Cyclosporine, tacrolimus, methotrexate

Theophylline

Seizures

note: is an older drug, but shows up with high frequency on standardized exams. It is used to dilate the bronchial passages to alleviate respiratory problems, but can cause seizures. Since the advent of inhaled glucocorticoids, It is rarely used anymore.

Drug B is the correct answer. This problem actually has two challenges to be overcome, the first is units, the second is Vd . Let’s get everything to the same units first.10 mg/dL = 0.1 g/L 20 ug/mL = 0.02 g/L The Vd for Drug A is 1 g (administered drug) / 0.1 g/L (plasma concentration) = 10 L The Vd
for Drug B is 1 g / 0.02 g/L = 50 L. This means that more of Drug B is distributed throughout the lipid-rich regions of the body and is not found in the aqueous plasma. The Volume of Distribution throughout the body is greater and will hang out longer

The decrease in GI motility will increase the absorption of morphine into her bloodstream.

5, isn’t this interesting that it takes 5 half-lives for a drug to effectively be eliminated from the body and it takes 5 dosages to reach a stable steady-state concentration. This is assuming that the patient took all 5 doses at the proper times though, which may or may not happen.

Zero order elimination. It would be eliminated at a constant rate of 0.01 g ETOH / 100 mL blood / 1 hour in a person who has not chronically abused alcohol and developed a tolerance to it. In patients who develop an alcohol tolerance, this rate can increase to as fast as 0.06 g ETOH / 100 mL blood/ 1 hour ... that’s a 6-fold increase! Holy Batman!

The decrease in GFR will lead to a decrease in the elimination of the drug. His serum Digoxin levels should stay between 0.8 - 2 ng/mL in the serum. Higher levels will predispose him to some fairly daunting cardiac problems, including premature ventricular contractions and AV node blockages.

Aminoglycosides and Vancomycin

The answer comes from the metabolism of alcohol. She only had the action of alcohol dehydrogenase to metabolize the liquor. The CYP450 enzymes in the liver can be induced, which were likely present in higher quantities in her friends who probably drink often. She will likely have a hangover in the morning as well, and will probably choose new friends after the glorious experience of repeatedly puking after she wakes up.

Steroids bind to intranuclear receptors and cause transcription of DNA into RNA. This allows for proteins to be made from the RNA via translation. Because steroids start a cellular process inside the nucleus, they do NOT have immediate activity

Benzoylecgonine

Theoretically, yes because oxycodone and codeine do cross react in the screening immunoassay, just at very low rates. The likelihood of this scenario being true is NOT high. He most likely just found, bought, or somehow procured codeine pills, but it probably was NOT oxycodone that caused a positive immunoassay for codeine.

Glutathione, this substance generally takes care of all free radicals
floating around in your body, unless of course, it is trying to keep your liver safe from certain death by trying as hard as it can to deal with the reactive oxygen species given off by Tylenol metabolism. I’m sure it’s kind of like the Battle for Middle Earth in Lord of the Rings. Your liver is faced with scores upon scores of a deadly opponent, and your small band of glutathione is all that’s there to protect it from certain destruction.

N-acetyl-p-benzoquinoneimine

The toxic dose curve fits between the effective dose curve and the lethal dose curve which makes sense because you would expect to feel sick from a substance before you die from your exposure to it. That’s not always the case,nbut a good rule of thumb.

CYP450 enzymes would likely conjugate the drug to an ion to make it water soluble and readily excreted in the urine.

Quantitative, because it gives you a number! 0.08% is drunk driving in Utah! An easy way to tell if the test is a quantitative test is that you’ll get a number whereas you will get either a (+) or a (-) on a qualitative test. Think breathalyzer for quantitative and pregnancy test for qualitative.

CO poisoning is the most likely cause of this patient’s headache and red complexion. This is commonly seen in patients with old propane heaters in poorly-ventilated areas of their home. Some people also get CO poisoning by running their car engine in their garage with the garage door closed. If there is a flame source with inadequate ventilation, CO could be the cause.

CO binds hemoglobin 200 times stronger than oxygen does. The CO
concentration doesn’t have to overwhelm the concentration of Oxygen to displace it on hemoglobin. The only chance that Oxygen has to overcome the effects of CO is to be inhaled in nearly 100% concentration so that the CO can diffuse off the hemoglobin and be breathed out in the lungs

The cause of this patient’s symptoms would likely become clear upon collecting a quick history from the patient. Intentional poisoning for suicide is occasionally seen, however smoke inhalation is by far the most common cause for harmful cyanide exposure. Workers in the metal trades (especially electroplating), mining, jewelry making, photography, and agriculture can have significant industrial
cyanide exposures. Ingestion of food that contains cyanide is rare. The drug nitroprusside, used to dilate blood vessels, can produce toxic levels of cyanide in the body