BIO200H5 Lecture Notes - Lecture 8: Liver Failure, Prodrug, Alkalosis

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9 Nov 2018

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If the drug is a pro-drug (which has to be metabolized in the body for the active form), it probably has a toxic effect. Some genetic variation: some races have different genetics to make them a higher or lower metaboliser of a drug, there are certain parameters that we have to take into consideration when prescribing a drug (a- Slide 12: have to know equation, how much of the drug is going to be trapped in the circulatory system, how much is going to be permeated into the cell. Sometimes alkalinity or acidity of the blood will determine the permeation. Slide 13: clearance = elimination, rate of elimination in any tissue, each of these organs have their own rate of elimination. Slide 14: experiment, we are going to use a beaker and a syringe. Lets say the fluid in the beaker is blood: top left, there is no output.

Related Questions

Need help with biology questions:

1. To increase the excretion of an acidic drug, what would you do to the urine?

	A.	Make it more basic
	B.	None of the above
	C.	Make it neutral
	D.	Make it more acidic

2. G-Protein coupled receptors directly act on which of the following secondary messenger molecules:

	A.	cAMP
	B.	ATP
	C.	ADP
	D.	GTP
	E.	None of the above or more than one of the above

3. Drug A and Drug B both produce the same level of biological/physiological response. Drug A produces this effect with 100 mg/kg dose. Drug B produces this effect with 50 mg/kg dose. Which of the following is true?:

	A.	Drug B is more efficacious than Drug A. Both drugs are equally potent.
	B.	Drug A is more efficacious than Drug B. Both drugs are equally potent.
	C.	Drug A and B are equally efficacious. Drug A is more potent than Drug B.
	D.	Drug A and B are equally efficacious. Drug B is more potent than Drug A.

4. The stomach has a ______ pH, whereas the small intestines have a _______ pH. The colon has an approximately ___________ pH.

	A.	High; low; neutral
	B.	Low; high; neutral
	C.	Low; neutral; neutral
	D.	None of the above

5. Which receptor is most likely to reduce norepinephrine levels when activated?

	A.	alpha 2 adrenergic
	B.	alpha 1 adrenergic
	C.	dopamine D1 receptors

6. Which of the following statements are FALSE?

	A.	If the Vd of a drug is between 60 and 80 L the drug has likely distributed to the total body water of a 200 kg man.
	B.	In the enterohepatic system the activity of bacteria to remove conjugates from a drug in the gut will decrease the clearance of the drug.
	C.	Lipid drugs are more likely to be reabsorbed by the kidney from the urine.
	D.	A weak basic drug (pKa = 6) will be mostly ionized in urine of a pH= 3 and only the non- ionized drug will be eliminated.
	E.	The major conjugate in Phase 2 metabolism is glucuronide.

7. Isoproterenol (Î²-agonist) is a vasodilator that increases HR. What happens to systolic and diastolic pressures upon IV administration of isoproterenol?

	A.	â systolic; â diastolic
	B.	â systolic; â diastolic
	C.	â systolic; â diastolic
	D.	â systolic; â diastolic
	E.	None of the above

8. If you want to increase the blood concentration of a drug A, you can perform which of the following procedures:

	A.	Inhibit Drug A metabolism with Drug B
	B.	Enhance Drug A reabsorption from renal proximal tubule by changing ionization of Drug A with Drug B
	C.	Allow competition of Drug B with Drug A for active renal secretion processes
	D.	Increase the binding of Drug A to serum albumin
	E.	All of the above

9. Which of the following describes Phase I metabolism?

	A.	Inactive products are always produced in this phase.
	B.	Large molecules such as glucuronic acid are conjugated to drugs in this phase.
	C.	This phase may produce active metabolites from prodrugs.
	D.	This phase only occurs in the liver.

10. Which of the following is NOT an enzyme involved in the biosynthesis of biogenic amines?

	A.	Phenylethanolamine N-methyl Transferase
	B.	Dopamine Î²-hydroxylase
	C.	Tyrosine dehydroxylase
	D.	DOPA decarboxylase
	E.	All of the above

11. Why would an antibiotic at the same concentration be more active against bacteria in water than in serum or plasma? (Activity is measured in a test tube)

	A.	activity of the antibiotic is increased in water.
	B.	due to drug-protein interaction in serum
	C.	the antibiotic is more stable in water
	D.	all of the above
	E.	none of the above

12. Ion channels are targets for drugs. Which drug class targets Na+ channels?

	A.	Benzodiazepines
	B.	Beta blockers
	C.	Local anesthetics
	D.	Antihypertensive drugs (cardiac and smooth muscle)
	E.	Glibenclimide (diabetic drug)

13. _________________ not metabolized by catechol-O-methyltransferase (COMT).

	A.	Dopamine
	B.	Epinephrine
	C.	Phenylephrine
	D.	Norepinephrine
	E.	All of the above are metabolized by COMT.

1) The neurotransmitters acetylcholine and norepinephrine are digested by enzymes that are located at the axon synapse or within the axon terminal of the neurons.

a)What are the names of these different types of enzymes?

b)Where are they located and what is the result of their enzymatic activity?

2) Explain how the Investigational New Drug process works as well as the four different phases of clinical trials. Why are some drugs still taken off the market after approval by the FDA?

3) A single IV injection of 100 mg drug with a half-life of 4 hours is administered to a young adult.

a) Plot drug concentration versus time on a graph making certain to clearly label.

b) How long will it take to eliminate > 95% of the drug?

c) If the volume of distribution is 4L, what is the clearance of the drug?

4) Many drugs are metabolized in the liver through the microsomal metabolizing system.

a) What specific enzymes are involved in this metabolism?

b) What are the main functions of these enzymes?

c) What are some factors that can contribute to individual drug metabolism variation? Explain.

5) Think of an emergency situation requiring immediate and intense physical exertion.

a) List as many body organs as you can and predict the desired level of activity [increased or decreased].

b) Which neurotransmitter would produce these effects and through what receptors?

6) It is interesting that a drug can produce a therapeutic effect and an undesired side effect in one situation, and that the same drug side effect may be considered a therapeutic effect in another situation. Explain this phenomenon using the drug promethazine as an example.

7) A patient brought into the emergency room is experiencing severe hypotension. Blood pressure reads 90/50.

a) What class of drugs is indicated for treatment and why?

b) What precautions should be observed when these drugs are administered?

c) What would be the first indication that too much drug has been administered?

8) Only certain drugs are capable of crossing the blood brain barrier.

a) How is the blood brain barrier different than barriers found in other areas of the body? Be specific.

b) What properties of drugs will make it more likely to cross the blood brain barrier? Explain your answers.

9) A 32-year-old, presents to the Emergency Department by ambulance with vomiting, confusion, salivation, and respiratory distress. The patient states that he was feeling fine until today when I started getting ill. He then vomits. During a physical exam you record the following information: Heart rate 45; Blood pressure 90/60; Respiratory rate 25; Temperature 36.6C; Pupils constricted. During your exam, 4 more ambulances arrive with patients with similar symptoms. You find out they were all riding in the same care on the Red Line when they began feeling ill.

a) What do you feel is happening and why?

b) Would you expect their symptoms to improve over time? Why or why not?

c) What drug would you prescribe to treat these patients and why?

10) Betty has diabetes and asthma. She also has developed high blood pressure, for which doctor just prescribed propranolol. One of your duties as a physicianâs assistant is to make sure patients are not prescribed drugs that are contraindicated because of other health problems.

a) What should you tell the doctor about Bettyâs prescription for propranolol and why?

b) Is there a more appropriate drug for Betty? Explain you answer.

Please answer the question after reading the paragraph.

We have a global health challenge in our hands today, and that is that the way we currently discover and develop new drugs is too costly, takes far too long, and it fails more often than it succeeds. It really just isn't working, and that means that patients that badly need new therapies are not getting them, and diseases are going untreated. We seem to be spending more and more money. So for every billion dollars we spend in R&D, we're getting less drugs approved into the market. More money, less drugs. Now we have a whole pipeline of different organ chips that we are currently working on in our labs. Now, the true power of this technology, however, really comes from the fact that we can fluidically link them. There's fluid flowing across these cells, so we can begin to interconnect multiple different chips together to form what we call a virtual human on a chip. Now we're really getting excited.We're not going to ever recreate a whole human in these chips, but what our goal is is to be able to recreate sufficient functionality so that we can make better predictions of what's going to happen in humans. For example, now we can begin to explore what happens when we put a drug like an aerosol drug. Those of you like me who have asthma, when you take your inhaler, we can explore how that drug comes into your lungs, how it enters the body, how it might affect, say, your heart. Does it change the beating of your heart? Does it have a toxicity? Does it get cleared by the liver? Is it metabolized in the liver? Is it excreted in your kidneys? We can begin to study the dynamic response of the body to a drug. Organs on chips could also change the way we do clinical trials in the future. Right now, the average participant in a clinical trial is that: average. Tends to be middle aged, tends to be female. You won't find many clinical trials in which children are involved, yet every day, we give children medications, and the only safety data we have on that drug is one that we obtained from adults. Children are not adults. They may not respond in the same way adults do. There are other things like genetic differences in populations that may lead to at-risk populations that are at risk of having an adverse drug reaction. Now imagine if we could take cells from all those different populations, put them on chips, and create populations on a chip. This could really change the way we do clinical trials. And this is the team and the people that are doing this. We have engineers, we have cell biologists, we have clinicians, all working together. We're really seeing something quite incredible at the Wyss Institute. It's really a convergence of disciplines, where biology is influencing the way we design, the way we engineer, the way we build. It's pretty exciting.

Question: For years, technology and medicine have joined together to pave the way or even solve some of the worldâs greatest issues in healthcare. These issues include but are not limited to incurable diseases and disorders like AIDS and cancer. According to Geraldine Hamilton however, we as a population are spending too much money to develop drugs and solutions to these issues, only to be at a deficit with the drugs actually produced. She believes that one of the keys is how we test these drugs and finding more efficient ways to do so. As a result, she suggests the use of organs on chips, an innovation created and pioneered by her lab. The use of organs on chips could change the way new drugs are released and tested, thus possibly furthering the process of creating solutions to healthcareâs problems. Where is the fine line between technology and human innovation? Is human innovation gradually becoming depending on technology? (At least two paragraphs, a paragraph is at least 5 sentences long.)

BIO200H5 Lecture Notes - Lecture 8: Liver Failure, Prodrug, Alkalosis

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