PHARM midterm 2 critical thinking questions

Wk 1-3: yellow highlight
Wk4-6: blue highlight

Ropinirole is a dopamine agonist. Compare how ropinirole works versus how levodopa works to treat Parkinson's disease.

-Ropinirole is able to cross the blood-brain barrier, therefore it is able to mimic the action of dopamine without becoming dopamine.

-levodopa gets converted after it crosses the BBB the nget converted into dopamine naturally. Levodopa is a prodrug that changes into dopamine using dopamine decarboxylase.

What are two key differences between a phase I versus phase II clinical trial? What is a significant similarity between them?

-Phase 1:
closely monitored; HEALTHY
tested on less than 100 healthy people
TO PATIENTS THAT NEED TO BE HELPED

-Phase 2
tested
BLIND TESTING BY FDA

-Both need to closely monitored

What is the key difference between a phase II versus phase III clinical trial? What are two significant similarities between them?

a. The key difference between a phase 2 and a phase 3 clinical trial is that phase 3 adds more patients and a longer period of time usually follows.

BLIND TEST BY FDA

b. Two significant similarities between them are: they are tested on affected patients and they are both monitored carefully.

c. ALL THREE PHASES BLIND TESTED BY FDA

Why does pH affect the solubility of many drugs?

-For drugs containing amines (most drugs) this means:

-Lower than that pH, the ammonium ion form will predominate
-Higher than that pH, the neutral amine form will predominate

How does serum albumin affect drug levels? How is it related to drug polarity?

a. Serum albumin is a blood plasma protein with a pocket that reversibly binds/carries lipophilic drugs. Binding is reversible, not permanent and binds natural molecules (ex Bilirubin). Serum albumin is too big to leak out of capillaries. The drug only moves into tissues after dissociating from albumin which can often be slow. Drug dosages are adjusted to take this into account. Also can slow down metabolism/inactivation of a drug by the liver

b. Serum albumin is related to drug polarity because it primarily takes place in the liver. It makes the drug more polar, more soluble in blood, urine and feces, and often inactivates it- easily filtered by the kidney into the urine

- less likely to be reabsorbed by the kidney

- Works on many non-biological molecules, not just drugs

What would be the likely result of crushing an enteric coated pill and mixing it with applesauce before feeding it to a patient? What would be the likely effect of doing this with a sustained release pill?

a. The likely result of crushing an enteric coated pill and mixing it with applesauce before feeding it to a patient is that it won't be able to reach its desired destination and have the wanted effect.

b. The effect of doing it with a sustained release pill would be that since the pills dissolve more slowly so the coatings dissolve at different rates so that the life of the drug is extended

Some patients have unusually high levels of a particular cytochrome P450 isozyme. Explain how that would affect the half-life of a drug that is metabolized by that isozyme.

The unusually high levels of a particular cytochrome P450 isozyme would affect the half-life of a drug that is metabolized by that isozyme because it would metabolize too quickly, and the drug would not be absorbed correctly.

How does competition for serum albumin affect drug levels? How is it related to drug polarity?

-Serum albumin can affect drug levels due to its size being too big to leak out of capillaries allowing drugs to slowly move into tissues after disassociating with serum albumin. Because of this, it can slow down metabolism/inactivation of a drug in the liver.

-It is related to drug polarity because it is a blood plasma protein with a pocket that reversibly binds/carries lipophilic drugs, therefore relates to the polarity of blood in order to transport the drug throughout the body.

A patient takes two drugs that are both metabolized by the same cytochrome P-450 isozyme. How will this affect the rate of metabolism? Compare this to the rate of metabolism if the drugs were taken individually

-Because the patient is taking two drugs that both need to be metabolized by the same cytochrome P450 isozyme, competition for inactivation occurs, resulting in the drugs fighting one another to be metabolized. This can cause one drug to be metabolized more than the other resulting in unequal dosages of the drugs causing one or both drugs to be ineffective.

-If the drugs were taken individually, then there would be no problem using the cytochrome P450 isozyme to metabolize the drug in order to get the drugs full effect using the recommended dosage. This way, the bioavailabilty of the drug remains the same since it has no competition with another drug.

Explain briefly how a drug's rate of metabolism will most likely be affected
a) if they are a regular alcohol drinker and sober when they take the drug
b) when they are drunk
c) if they have cirrhosis of the liver.

1.) if they are a regular alcohol drinker and sober when they take the drug
-Because they are a regular drinker, their liver is constantly active, therefore the half-life of a drug is reduced due to it being metabolized quicker.

2.) when they are drunk
-When the person is drunk, their liver is also trying to breakdown the alcohol as well, so when taking a drug while drunk, the drug has a longer half-life. This correlates to competition for inactivation.

3.) if they have cirrhosis of the liver.
-If the person has cirrhosis of the liver, the drug would have trouble being metabolized, therefore, the drug would have a prolonged half-life.

How does salmeterol differ from albuterol in terms of speed of action and duration of action? What are the advantages of each?

-Albuterol is a fast-acting beta 2 agonist that is used to stop an asthma attack using an MDI.

-Salmeterol is a long onset acting beta 2 agonist that is used prophylactically to prevent asthma attacks, not stop them.

Briefly describe an example where a muscarinic antagonist and an adrenergic agonist have approximately the same clinical effect.

-Atropine, which is a muscarinic agonist, is used to treat bradycardia or to restart someone's heart. It is similar to metoprolol, a β1 adrenergic agonist, that is used to increase heart rate and the force of contraction of the heart.

Dry mouth is a common adverse effect reported for oxybutynin (Ditropan), which is used to treat incontinence. Explain why dry mouth shouldn't be surprising for this drug.

-Dry mouth shouldn't be a surprise for this drug because it is a long-acting drug in order to help a patients urinate, therefore they are excreting urine/fluids resulting in dry mouth.

Describe how levodopa/carbidopa pills act effectively to supplement dopamine levels in the brain of a PD patient. Include some relevant details

-Levodopa/carbidopa pills are effective because it requires a lower dosage therefore, less levodopa is loss in the GI tract and peripherally all while still providing the same amount of levodopa to the brain. Peripheral conversion of levodopa outside the brain can cause adverse side effects, therefore carbidopa helps with that.
-how and why

-Levadopa: what it does and why

-Carbidopa: inhibits decarboxylase and DOES NOT cross the BBB: inhibits decarboxylase outside the brain, reach the brain without the side effects/ converted in the body

Selegiline is an "MAO-B" inhibitor. Compare how selegiline works versus how levodopa works to treat Parkinson's disease.

Selegiline slows down MAO-B which produces higher dopamine levels

levodopa travels throughout the body before it reaches the brain.

Midazolam (Versed) is known for causing short-term amnesia, more so than other benzodiazepines. In what situation is this side-effect useful? What other effect of benzodiazepines is helpful in some contexts, but undesirable in others? Explain briefly.

- putting someone under anesthesia because you don't want the patient to remember the pain or procedure.

Benzodiazepines cause physical and psychological dependency when used to treat anxiety long-term, but continue to work long-term. When used to treat seizures, they tend to lose efficacy over time, ie. the seizures return after several months, and/or the dosage needs to be increased. Does this info suggest metabolic tolerance, or pharmacodynamic tolerance? Explain briefly.

-metabolic tolerance: taking the drug over a long period of time causes a change in the way the body reacts

-an increase in the way that benzodiazepines are broken down: a decrease in the drug's half-life

Generally speaking, how do most anti-seizure drugs work? Why does it make sense that many anti-seizure drugs cause side-effects like sedation and ataxia?

-Most anti-seizure drugs work: they make the brain less excitable

-side effect: sedation and ataxia
-occur because it puts the brain to rest therefore, the brain isn't actively being active to do things, except stay at rest.

Why is haloperidol no longer recommended for long-term treatment of schizophrenia? What is the physiological basis of that? What purpose is haloperidol still used for?

-Long-term use of haloperidol can cause tardive dyskinesia. The physiological basis is similar to Parkinson's like symptoms. It is now currently used as a sedative for aggressive paranoia episodes.

-STILL USED FOR ACUTE EPISODE OF PARANOIA

How are some anti-emetic drugs related to antipsychotic drugs? How are they different? What special feature of the CTZ relates to this?

-Anti-emetic drugs are similar to antipsychotic drugs because their actions are the same however anti-emetic drugs don't cross the blood-brain barrier, they act on the chemical trigger zone of the medulla oblongata, that is not protected by the blood-brain barrier.

Why is lithium carbonate not available for qdaily prescription? Why are there frequently problems with patient compliance with it?

-.Lithium carbonate is not available for daily prescription because you need frequent dosing of it due to the kidneys filtering out lithium ions effectively. There are frequent problems with patients compliance, because it has a low therapeutic index as well as various side-effects. Although it works effectively, it could be too effective where a patient see their life in different shades of grey.

-REASON FOR LOW PATIENT COMPLIANCE: MAKES YOU PEE ALOT ; LEVEL OUT THE PATIENTS MOODS

-SIDE EFFECTS: HEAD ACHE, NAUSEA, WEIGHT GAIN, MAKES YOU PEE ALOT

- NUMEROUS ADVVERSE AFFECTS

-WATER SOLUBLE: RAPIDLY EXCRETED IN URINE

Describe what happens in an opioid overdose and in naloxone treatment of that.

An opioid overdose involves respiratory depression which is normally the cause of death. Naloxone is a pure antagonist of opioid and is used to lessen the adverse effects of narcotic overdose especially respiratory depression, however it can cause cold turkey withdrawal symptom effects.

What is the main similarity between naloxone and methadone? How are they different?

The main similarity between naloxone and methadone (slow acting pill) is that they both help with the side effects of opioid. They're different because naloxone is used to treat the side effects of opioid overdose while methadone is another opioid that is used to treat the withdrawal symptoms of opioids, so it can still cause a euphoric affect.

-opposites to each other in every way
-Block: naloxone // causes overdose symptoms
-Stimulate: methadone //induces overdose

Why are local anesthetics often mixed with epinephrine? What is a common sideeffect of doing that?

Local anesthetics are often used with epinephrine because together they cause local vasoconstriction to keep the anesthetic from spreading. The common side-effect of this is tachycardia.

Discuss the clinical significance of the terms COX-1 vs. COX-2. Name the one COX-2 specific NSAID still on the market What problem caused the other two to be pulled off the market?

-COX-1 isozyme mainly affects stomach mucus production while COX-2 produces prostaglandins in other parts of the body that are responsible for pain sensitivity, fever, and inflammation.
-clinically: we care because inhibiting COX 1 causes stomach ulcers but also relieve pain
Clinically: leave COX 2
-celebrex still on the market //used for long term arthritis
-Vioxx and Bextra not on the market
-COX 1 inhibitors inhibit platelet aggregation
-The COX-2 inhibitor that is still on the market it celecoxib (Celebrex) that is used for long-term arthritis. The problem that caused for Vioxx and Bextra to be pulled off the market is because they showed a larger increase in mortality due to strokes and MI's.

Compare uses, advantages and disadvantages of aspirin versus acetaminophen.3

-Ketorolac is useful in releasing serious pain and is only available by prescription unlike ibuprofen. It has much higher efficacy and can be administered in many ways. It also has a longer half-life, however, due to its strong efficacy, it is recommended for its shirt-term use only because it can cause thinning of the stomach lining resulting in stomach ulcers.