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Dave has a particularly efficient CYP2D6 enzyme system in his liver. Based on this information one would predict that he would:

A. Be efficient at metabolizing most psychoactive medications

B. Have trouble with the biotransformation of many drugs

C. not be particularly efficient at metabolizing psychoactive medications

D. be efficient at metabolizing some psychoactive medications more than others

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Reid Wolff
Reid WolffLv2
28 Sep 2019

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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.

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

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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.

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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 physician’s 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 Betty’s prescription for propranolol and why?

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

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1

Antonio uses Adderal to treat his ADHD. Scott stole some of Antonio's medication so he could study for an exam. Which of the following best describes Scott's behavior relative to this incident?

A

Drug dependence

B

Drug abuse

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Drug addiction

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2

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2

______________ is the key player in the reward system of the brain.

A

Serotonin

B

None of these answers are correct

C

Adrenaline

D

Dopamine

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3

Several factors influence how drug users experience the drug effects. The four more important factors are which of the following?

A

Physiological, social, genetics, and cultural

B

Psychological, genetics, social, and cultural

C

Pharmacological, physiological, psychological, and social

D

Pharmacological, cultural, social, and contextual

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4

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4

Drug abuse usually follows 4 steps of drug use. This is known as the spectrum of psychoactive drugs. What 4 steps are part of this spectrum?

A

Beneficial, casual, problematic, chronic dependence

B

Beneficial, casual, abusive, addictive

C

Beneficial, problematic, chronic dependence, and abusive

D

Social, abusive, dependent, addictive

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5

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5

The main neurotransmitter in the reward system is thought of being which of the following?

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Dobutamine

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Epinephrine

C

Glutamate

D

Dopamine

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6

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6

The rate at which a drug is distributed in the body depends on which of the following?

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Its solubility properties

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Its tendency to attach to proteins in tissues

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Its ability to pass across membranes

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Its molecular size

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7

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7

A period of medical treatment, usually including a 9-12 step program, during which a person is helped to overcome physical and psychological dependence on alcohol or drugs is known as part of the ______________ process.

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Withdrawal

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Intoxication

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Oxidation

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Detoxification

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Drug addiction is defined as which of the following?

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Pathological condition in which one compulsively uses a drug, despite its negative effects

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Using any prescribed drug or over the counter medication for healing purposes

C

Using a drug excessively, or for purposes for which it was not medically intended

D

Constant use of a chemical to ensure a constant state of happiness

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9

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9

The rate at which a drug is distributed in the body depends on which of the following properties?

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It's solubility properties

B

Pass across membranes

C

It's molecular size

D

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10

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The most commonly abused set of drugs in the USA is which of the following?

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Non prescription over the counter drugs

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Case Study Section 4 – Nitrogen Metabolism Based on “A Sickeningly Sweet Baby Boy: A Case Study on Autosomal Recessive Inheritance” by Jacqueline Washington and Anne Zayaitz (National Center for Case Study Teaching in Science) The Patient: Mathew Miller is a 7-day-old infant that is rushed to the emergency room by his parents Emma and Jacob Miller, Mennonites from Lancaster County, PA. Emma’s pregnancy and delivery with Mathew was normal but he started having trouble nursing and now has completely stopped feeding. By the time they reach the emergency room Mathew’s limbs were rigid and he had had a seizure. The initial examination showed no infection and his x-rays were normal. The family history collected by the Doctor revealed that Emma and Jacob had had a previous son, Samuel that died at 9 days-of-age. There also is a history of unexplained childhood mortality on both sides of the family; Emma’s mother had two sisters who died in the first year of their lives and Jacob’s father had a sister who died at 7 months of age. Emma also points out to the Doctor that Mathew’s diaper has a funny smell to it. Blood and urine samples were taken for testing and skin biopsies from Mathew, Emma, and Jacob were taken and tested for enzyme activity. The tests results showed that:

• Mathew’s urine had elevated levels of the branched chain amino acids and their α-keto acid derivatives (which caused the sweet smell in his diapers)

• Both Emma and Jacob’s skin biopsies had nearly normal levels of branched chain amino acid metabolism/enzyme activity

• Mathew’s enzyme activity was less than 2% of normal

Question 1: What is the most likely diagnosis for Mathew?

A. Argininemia

B. Diabetes mellitus '

C. Maple syrup urine disease

D. Phenylketonuria

Question2: What enzyme did the skin biopsy test measure?

A. Carbamoyl phosphate synthetase I

B. Alanine aminotransferase

C. Phenylalanine hydroxylase

D. Branched-chain α-keto acid dehydrogenase complex

Question 3: This enzyme functions VERY similarly to two other enzymes that we have discussed, what are they?

A. Phosphofructokinase-1 and fructose 1,6-bisphosphatase (FBPAse-1)

B. Pyruvate dehydrogenase complex and α-ketoglutarate dehydrogenase complex

C. Urease and arginase

D. Isocitrate dehydrogenase and malate dehydrogenase

Question 4: How did Mathew (and presumably Samuel) inherit the disease if both Emma and Jacob have normal enzyme activity levels?

A. Emma and Jacob must both be carriers for the disease but their one normal gene is enough to maintain enzyme activity levels.

B. The disease can happen spontaneously, there is no genetic link.

C. Jacob is not really the father of the boys.

D. The disease can skip generations.

Question 5: What would be the best diet for Mathew to follow to control his disease?

A. Atkin’s diet (low carbohydrates, high fat, and high protein)

B. Low protein

C. Low fat

D. No special diet will control the disease

Over the next 4 years Mathew’s metabolic disease is controlled by his special diet but he still suffers approximately 3 metabolic crises a year. These occur when amino acids accumulate in his blood leading to the swelling of his brain. Even something as simple as a cold or the flu can affect his amino acid levels and send his metabolism into crisis. Jacob and Emma decide that “We cannot continue to live in constant fear that a minor infection or a simple cold or ear infection could kill our son. Even though we are doing everything we are supposed to, he is still getting sick and we are afraid we may lose Mathew.” They learn that some children with Mathew’s disease have undergone liver transplants and are effectively cured.

Question 6: How/why would a liver transplant effectively cure Mathew’s condition?

A. A new liver would be able to spread it’s genes throughout the body and correct the genetic disorder.

B. A new liver would more effectively respond to metabolic hormonal control.

C. A new liver would express the functional enzyme needed to metabolize the amino acids causing Mathew’s condition.

D. A new liver would produce more hemoglobin to transport oxygen more effectively.

The family is directed to Dr. Morton of Children’s Hospital of Pittsburgh, where transplant experts agree to list Mathew for a liver transplant. Jacob and Emma learn that children who receive a liver transplant have to take strong immunosuppressive drugs for the rest of their lives. It was also clear that there was a 40% possibility that Mathew could reject the liver and need a second transplant (which also might be rejected) or he could die from surgical complications.

Question 7: Assuming the liver transplant was successful and Mathew did not reject the new liver, what type of diet would Mathew be able to/need to eat?

A. He would still need to eat his special diet but he would be at less risk of a metabolic crisis

B. He could eat a normal diet

C. He would need to change to a high protein diet like Atkin’s

D. He would be on an all liquid diet

Question 8: Emma and Jacob decide they want to try to have another child. What would be the chance that this child would also have the disorder that Mathew and Samuel have/had?

A. 0 %

B. 25%

C. 50%

D. 75%

E. 100%

Question 9: If Mathew grew up, got married, and decided to have children, what would be the chance that his children would have the disorder? A. 0%, the liver transplant would have cured him

B. 25%

C. 50%

D. 100%

E. It would depend on his wife, if she was normal than there would be a 0% chance of his children having the disorder but 100% would be carriers, if she was a carrier than there would be a 50% chance of his children having the disorder and a 50% chance that they would be a carrier.

Question 10: The disorder is found in 1 in 200,000 infants throughout the US but 1 in 200 in the Amish and Mennonites of Lancaster County, PA. Why is there such a difference in the prevalence of the disease?

A. There are environmental factors associated with being Amish or Mennonites that increase the prevalence.

B. There is a large amount of genetic similarity within these populations because they tend to marry within the population so recessive disorders such as this are more likely.

C. The gene mutation is preferentially carried in Caucasians so when you average the prevalence across all races in the US the prevalence drops.

D. It is unknown why the prevalence is so much greater in Amish and Mennonites.

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