ETX 30 FINAL

Water is essential for human life; however, water can be toxic if too much is consumed in a short period of time. This concept is an example of what key principle of toxicology and pharmacology:

The dose makes the poison

Which of the following drugs has the safest therapeutic index?

Cetirizine (Zyrtec): ED50: 0.2mg/kg; TD50: 55mg/kg

Toxins are generally safer than toxicants because toxins are naturally produced from plants, bacteria, or animals and toxicants are synthetic.

False

Eating and smoking Tetrahydrocannabinol (THC, the psychoactive chemical in marijuana), will produce different biological responses. Why is this?

THC will get into the bloodstream faster by smoking than by eating; THC will have a more predictable biological response by smoking than by eating

The difference between the amount of 11-OH-THC when smoking or eating THC is a result of what?

First Pass Metabolism

Your friend tells you to take Oscillococcinum to treat your flu-like symptoms. The recommended dose is 1 tube. How much duck liver is in 1 tube of Oscillococcinum?

The duck liver will be diluted so many times that the tube consists of all sugar

Which of the following is not an example of a pharmacokinetics study

Determining the mechanism of action of a drug

Oxycodone (an opioid agonist) is metabolized through the CYP3A4 enzyme into a weaker opioid agonist than oxycodone. Which of the following is true:

Grapefruit juice can decrease the half-life of oxycodone

Ibuprofen (Advil) has a half-life of ~2 hours.  Half an hour after taking a 400mg pill of ibuprofen, the peak plasma concentration is 10 ug/ml. Advil has pain-killing activity at a plasma concentration above 3 mg/ml. Approximately how often would you need to take another pill to maintain the pain relief activity of Ibuprofen?

Every 4 hours

Individual variability in caffeine metabolism may be the result of:

Smoking, which will decrease the half-life of caffeine

Which of the following is true about adenosine

Caffeine is an antagonist of the adenosine receptor

A large Charged Lemonade from Panera contains ~250mg of caffeine. After drinking 5 large Charged Lemonades:

An individual would display signs of toxicity, including increased urinary output, anxiety, tachycardia

The majority of college students who have used amphetamine-like stimulants have a prescription.

False

Off-label use of a drug indicates that

The FDA has not conducted a careful evaluation of the benefits and risks for the off-label use

What is one of the ways Amphetamines lead to increased dopamine levels in the synaptic cleft

By inhibiting dopamine reuptake

Lisdexamfetamine (Vyvanse) is a prodrug that is converted in red blood cells to dextroamphetamine. Which of the following is true?

Lisdexamfetamine has less abuse potential than dextroamphetamine when administered intravenously

How does propranolol impact performance anxiety?

By blocking the fight or flight response

Propranolol half-life is 3-6 hours and is primarily metabolized by CYP1A2. We also know that smoking cigarettes can increase the activity of the CYP1A2 enzyme. How would smoking affect the metabolism of propranolol?

Increase propranolol metabolism, reduce the duration of action/decrease half-life

The bioavailability of propranolol was assessed by a single-dose (80 mg) study in healthy volunteers who either took the drug 1) on an empty stomach, 2) immediately after a protein-rich breakfast, or 3) together with a carbohydrate-rich, protein-poor breakfast. Which group would have the highest plasma concentration of propranolol?

Protein-rich breakfast

My friend Tommy Bahama has been doing the keto diet, which makes his urine a pH of 4. His doctor also recently put him on Adderall to help with his ADHD, but he didn’t disclose his diet in his appointment. He is noticing that the dose he was prescribed wears off quickly during the day. Why is this?

Acidic urine promotes elimination leading to a shorter half-life

only people with ovaries produce estrogen and progesterone and only people with testes produce testosterone

False

NES/T is currently in Phase II trials for use as a hormonal contraceptive in people who produce sperm.  This hormonal contraceptive combines Nestorone (to inhibit testosterone production) with synthetic testosterone. The addition of synthetic testosterone is included to increase blood testosterone levels, while keeping testicular testosterone levels low.  This addition is important because

Blood levels of testosterone are necessary for libido, sexual function, and muscle growth

Tricyclic Antidepressants were originally developed as a therapeutic for Tuberculosis, but later were shown to have antidepressant effects as they are antagonists of some serotonin, adrenergic, and histamine, muscarinic targets. Why was the development of SSRI’s such an advanced shift from TCAs used for antidepressants?

SSRIs are more selective for serotonin than TCAs and have a higher therapeutic index

Joe Schmoe was recently prescribed propranolol for his high blood pressure by his primary care physician. As we remember, propranolol is metabolized by primarily by CYP1A6 and also CYP2D6. A few weeks later, he went to the psychiatrist, who prescribed him Fluoxetine (Prozac), an SSRI that inhibits activity of CYP2D6. How would this change the metabolism of both drugs?

No change in fluoxetine metabolism, decreased metabolism of propranolol

What is not one of the differences between different drugs within the SSRI class?

Selectivity for the serotonin transporter over other neurotransmitter transporters

Drugs (including benzodiazepines) are always designed to act through a defined mechanism of action and for a specific disease indication.

False

GABA binds to a binding site on the GABA A receptor that is between the alpha and beta subunits to open the ion gate. Benzodiazepines bind to a binding site between the alpha and gamma subunits to open the ion gate. Therefore, benzodiazepines are:

Allosteric agonists

Different drugs within the benzodiazepine class can have different biological effects. Which is NOT one of the reasons for these differences:

Some benzodiazepines predominately act through a receptor that is not the GABA A receptor

Combining benzodiazepines with other depressants (e.g. alcohol or opioids) can increase overdose risks because:

Combination of benzodiazepines and depressants can increase risk of respiratory depression (slowing or stopping breathing)

Phencyclidine (PCP) and ketamine differ in that:

Ketamine is less potent than PCP

Ketamine acts as an allosteric antagonist to the excitatory NMDA receptor. This means that:

Ketamine binds to a different site as glutamate to prevent the activation of the NMDA receptor

In The CUT article “Leave Your Body at the Door”, NYU professor, Dr. Joseph Palamar, is quoted as saying “[Ketamine] is also extremely potent; the difference between a goofy buzz and total body paralysis is [a small amount].” This statement is an example of ketamine having:

A low therapeutic index (here the effective dose is a goofy buzz and the toxic dose leads to total body paralysis]

Fentanyl, propranolol, and ~1/3 of FDA approved drugs target:

G-protein coupled receptors

Heroin has less of a biological effect when delivered orally compared to by i.v. injection because:

Heroin undergoes first-pass metabolism when delivered orally

A subset of the population is considered “ultrarapid metabolizers” that have increased activity of CYP2D6, the enzyme that converts codeine to morphine.  Compared to the rest of the population, when these “ultrarapid metabolizers” are exposed to codeine, they will:

Have increased analgesic (pain reducing) effect

The addition of functional groups to morphine make the chemical more lipophilic. This increased lipophilicity makes codeine and heroin:

Better at passing through cell membranes and crossing the blood-brain barrier

Which of the following is true regarding the regulation of blood glucose levels:

After a meal containing glucose, the incretin, GLP-1, is secreted from the intestine in order to increase insulin secretion, which decreases blood glucose levels

Which is NOT an outcome of the GLP-1 receptor agonist, Semaglutide (Ozempic/Wegovy):

Increased hemoglobin A1C

If orally administered alone, the peptide, semaglutide (Ozempic/Wegovy) is not efficacious  because:

It is degraded by the acidic pH and proteolytic enzymes in the stomach

Botulism neurotoxin (BoNT) is

Bacteria

How does Botulism neurotoxin prevent Acetylcholine release?

By cutting up SNARE proteins and preventing vesicle exocytosis

Which of the following is not possibly treated by Botox:

Seasonal allergies

the safest drugs/chemicals come from natural (plant, bacteria, or animal) sources.

False

Which of the following is considered a supplement by the FDA:

Vitamin D capsules for oral ingestion

When does the FDA involvement in supplement regulation begin

After market: the FDA takes action against adulterated or misbranded supplements

Which of the following is NOT an example of an allowed structure/function claim on a supplement label, when accompanied by the statement “This statement has not been evaluated by the FDA. This product is not intended to diagnose, treat, cure, or prevent any disease”:

Berberine can reverse type 2 diabetes

Alcohol is not considered a Schedule I drug, because:

Historical, political, and financial reasons