Pharmacokinetics Ppt: Slides 64-95, Megan's Portion

The liver is the main metabolic organ in the body. It plays a crucial role in breaking down nutrients, producing energy, and detoxifying harmful substances. It metabolizes carbohydrates, proteins, and fats, and stores vitamins and minerals. Additionally, the liver produces bile, which aids in digestion and absorption of fats. Overall, the liver is essential for maintaining overall metabolic balance and proper functioning of the body.

In a one compartment model, all drug administration occurs directly into the central compartment and distribution of the drug is instantaneous throughout the volume. This means that there is only one compartment or space in the body where the drug is distributed, and it is assumed that the drug is evenly distributed throughout this compartment. This simplifies the pharmacokinetic analysis and calculations, as there is no need to account for multiple compartments or complex distribution processes.

CYP3A4 is the correct answer because it is an enzyme that is found in high concentrations in the intestinal mucosa and is involved in the first-pass metabolism of drugs such as chlorpromazine and clonazepam. This means that CYP3A4 plays a significant role in breaking down these drugs in the intestines before they are absorbed into the bloodstream.

Inducers of CYPs (cytochrome P450 enzymes) increase the activity of these enzymes, leading to an increase in drug metabolism. This means that drugs are broken down more quickly in the body, resulting in a decrease in their effectiveness and potentially requiring higher doses for the desired therapeutic effect. Inducers can include certain medications, herbal supplements, and environmental factors, and their impact on drug metabolism should be considered when prescribing or adjusting medication regimens.

In most clinical situations, the drug concentration [C] is much smaller than the Michaelis constant (Km). This indicates that the drug concentration is significantly lower than the substrate concentration at which the enzyme is working at half of its maximum velocity. In other words, the drug concentration is not saturating the enzyme, and therefore, the enzyme is not working at its maximum efficiency.

both. There are Phase I reactions which use the P450 system and ones that do not.

In a one compartment model, the clearance from the compartment is a first-order process. This means that the rate at which the drug is eliminated from the body depends on the concentration of the drug in the compartment. As the concentration decreases, the elimination rate also decreases. This is characteristic of a first-order process, where the elimination rate is proportional to the drug concentration.

During Phase II reactions, drugs are metabolized by enzymes in the liver, which often leads to the addition of certain molecules, such as glucuronic acid or sulfate. This process increases the drug's polarity and makes it more water-soluble, facilitating its elimination from the body. Therefore, the consequence of Phase II reaction is an increase in the drug's elimination.

A drug is eliminated from the body through two main processes: metabolism and excretion. Metabolism involves the breakdown of the drug into various metabolites, which are then eliminated from the body. Excretion, on the other hand, refers to the removal of the drug or its metabolites from the body through urine, feces, sweat, or breath. Therefore, the correct answer is excretion, as it is the only process mentioned that is solely responsible for the elimination of drugs from the body.

Inhibitors of CYPs (cytochrome P450 enzymes) cause a decrease in drug metabolism. CYPs are responsible for the metabolism of many drugs in the liver, and inhibitors of these enzymes can interfere with their activity. When CYP activity is inhibited, the metabolism of drugs is slowed down, leading to higher drug levels in the body and potentially increased drug toxicity. Therefore, the correct answer is a decrease in drug metabolism.

A drug that makes an inactive drug active is called a prodrug. Prodrugs are biologically inactive compounds that are converted into an active form within the body. This conversion can occur through various mechanisms such as enzymatic reactions or chemical transformations. The purpose of using prodrugs is to enhance the drug's therapeutic effects, improve its stability, or reduce its side effects. By converting an inactive drug into an active form, prodrugs can increase the drug's bioavailability and improve its pharmacokinetic properties.

Phase I and Phase II drug metabolism both involve processes that aim to make hydrophobic drugs more polar. Phase I reactions, such as oxidation, reduction, and hydrolysis, introduce or expose functional groups that increase the polarity of the drug. Phase II reactions, such as glucuronidation, sulfation, and methylation, further increase the polarity by conjugating the drug with highly polar molecules. These modifications enhance the solubility of the drug, facilitating its elimination from the body through urine or bile. Therefore, both Phase I and Phase II drug metabolism contribute to the conversion of hydrophobic drugs into more polar forms for efficient elimination.

The correct answer is liver, smooth ER, oxidizes, NAD/NADPH. The Flavin containing monoxygenase system is mainly present in the liver, but some is also expressed in the gut and lung. It is located in the smooth endoplasmic reticulum. This system oxidizes compounds containing sulfur and nitrogen. It uses NAD/NADPH as cofactors.

The rate of drug metabolism and elimination is directly proportional to the concentration of free drug, known as first order kinetics. This means that as the concentration of free drug increases, the rate of metabolism and elimination also increases. In first order kinetics, the rate of elimination is dependent on the concentration of the drug, leading to an exponential decrease in drug concentration over time. This type of kinetics is commonly observed for drugs that are metabolized by enzymes in the body.

In zero order kinetics, the rate of metabolism remains constant over time regardless of the concentration of the substrate (in this case, the free-drug concentration). This means that the enzyme is saturated and working at its maximum capacity. Therefore, the given statement indicates zero order kinetics.

=NORMAL process

According to her ppt, the most important Phase II conjugation reaction is glucuronidation by UDP-Glucuronosyltransferase. This reaction involves the transfer of a glucuronic acid molecule from UDP-glucuronic acid to a substrate molecule, resulting in the formation of a glucuronide conjugate. Glucuronidation is a major pathway for the metabolism and elimination of many endogenous compounds and xenobiotics. It plays a crucial role in detoxification and clearance of drugs, toxins, and other foreign substances from the body.

A conjugated drug is usually inactive. Conjugation refers to the process of attaching a molecule or group to a drug molecule, which can alter its properties. In the case of conjugated drugs, the attached molecule or group typically reduces the drug's activity or renders it inactive altogether. This modification is often done to improve the drug's stability, increase its solubility, or enhance its targeting to specific cells or tissues. Therefore, a conjugated drug is generally not active on its own.

First-pass metabolism is the type of drug metabolism that is important for the activation or breakdown of a drug. It occurs when a drug is metabolized in the liver before it enters the systemic circulation. This process can greatly affect the bioavailability and effectiveness of a drug, as well as determine the dosage that should be given to a patient. Therefore, understanding first-pass metabolism is crucial in determining the appropriate dosage for a patient.

Phase I reactions generally add a hydroxyl group on the drug to slightly increase water solubility. This is because the addition of a hydroxyl group (-OH) increases the polarity of the molecule, making it more soluble in water. This increased solubility allows the drug to be more easily transported and eliminated from the body. Additionally, the hydroxyl group can also serve as a site for further metabolism or conjugation reactions in Phase II metabolism.

After Phase I metabolism, a drug undergoes various chemical reactions that modify its structure. Oxidation, hydrolysis, and reduction are common events that can occur during Phase I metabolism. However, protonation is not a typical event in Phase I metabolism. Protonation refers to the addition of a proton to a molecule, which typically occurs during Phase II metabolism. Therefore, according to the notes, protonation is the event that will NOT happen to a drug after Phase I metabolism.

The correct answer is family, subfamily, specific isozyme. This is the correct nomenclature for CYP enzymes, where the family is identified first, followed by the subfamily, and then the specific isozyme.

Phase II reactions generally add a large polar group to the hydroxyl group on the drug to greatly increase water solubility. This is because adding a large polar group, such as a sulfate or glucuronide, increases the polarity of the drug molecule, making it more soluble in water. Increased water solubility is important for the elimination of drugs from the body, as they can be easily excreted through urine or bile. Adding another hydroxyl group, an amine group, or a fat soluble group would not have the same effect on water solubility.

The correct answer is "drug microsomal metabolizing system." DMMS stands for drug microsomal metabolizing system. This term refers to the enzymatic system present in the liver that is responsible for metabolizing drugs and other foreign substances. The microsomal metabolizing system plays a crucial role in drug metabolism, as it helps to break down drugs into smaller, more easily eliminated molecules. This system is important in determining the effectiveness and toxicity of drugs in the body.

see slide 78

Phenobarbital and Rifampin are two common inducers for Warfarin, Ibuprofen, Tolbutamide, and Phenytoin. These drugs are known to increase the metabolism of other medications by inducing certain liver enzymes, such as cytochrome P450 enzymes. Phenobarbital is a barbiturate that is commonly used as an anticonvulsant, while Rifampin is an antibiotic used to treat tuberculosis and other bacterial infections. Both drugs can enhance the breakdown of Warfarin, Ibuprofen, Tolbutamide, and Phenytoin in the liver, leading to reduced levels and potentially decreased efficacy of these medications.

The correct answer is "All of the above, minus Timbits!" because aspirin, phenytoin, and ethanol are all examples of drugs that exhibit zero order kinetics. Zero order kinetics means that the rate of drug elimination remains constant regardless of the drug concentration in the body. This is in contrast to first order kinetics, where the rate of elimination is proportional to the drug concentration. Timbits is not a drug and therefore not relevant to the question.

slide 81 kinetics

Metabolism is the process by which the body breaks down substances, such as drugs, and transforms them into different forms. One of the effects of metabolism is the conversion of inactive drugs into active forms, which can then exert their intended effects in the body. Another effect is the detoxification of toxic drugs, which involves converting them into non-toxic forms that can be easily eliminated from the body. However, the given answer states that metabolism does not make a toxic drug non-toxic, which contradicts the known effects of metabolism. Therefore, the given answer is incorrect.

In a Phase I reaction, Diazepam would receive a hydroxyl group from CYP450. In a Phase II reaction, Diazepam would receive a sugar group from glucuronidation.

They don't really have inducers and are not commonly susceptible to induction.

After drugs are distributed, they are eliminated through metabolism and elimination. This means that the drugs undergo biotransformation in the body and are then eliminated from the body. They are not redistributed back to the tissues or absorbed further into the body. Instead, they are broken down and eliminated through processes such as urine or feces.

Think Al.d, Al.o

Inducers of CYPs increase drug metabolism, leading to the production of metabolites. If the metabolite is active, it can result in increased drug activity. If the metabolite is inactive, it may not contribute to the drug's activity. However, the given answer states that there is an increased drug activity if the metabolite is inactive, which contradicts the expected outcome. Therefore, this choice is NOT one of the consequences of inducers of CYPs.

After Phase I metabolism, a drug is most often inactivated. Phase I metabolism involves oxidation, reduction, or hydrolysis reactions, which introduce or expose functional groups on the drug molecule. These reactions typically increase the polarity of the drug, making it more water-soluble and easier to eliminate from the body. Inactivation of the drug occurs when these reactions render the drug less pharmacologically active or completely inactive. Therefore, it is common for drugs to undergo inactivation during Phase I metabolism.

Didn't know I was in Chem 101 again

The correct answer is 1-5 because the oxidation reactions not catalyzed by Cytochrome P450 include the Flavin containing monoxygenase system, Alcohol dehydrogenase, Aldehyde oxidation, Xanthine oxidase, and Amine oxidases. Flavin oxidases are not mentioned in the list of oxidation reactions not catalyzed by Cytochrome P450.

Monoamine oxidase is found in nerve terminals/mitochondria, while Diamine oxidase is found in liver microsomes. Both enzymes are involved in the metabolism of endogenous substances.

Inhibitors of CYPs cause a decrease in drug metabolism, which leads to increased plasma drug concentrations. This can result in increased drug activity if the metabolite is inactive and decreased drug activity if the metabolite is active. However, it does not lead to an increased therapeutic drug effect. In fact, a decreased therapeutic drug effect is a consequence of decreased drug metabolism, not CYP inhibitors.

The consequence of Phase I reaction is a change in the drug's activity. Phase I reactions involve the modification of the drug's structure, such as oxidation, reduction, or hydrolysis. These modifications can alter the drug's pharmacological properties, including its potency, efficacy, and toxicity. Therefore, the drug's activity is likely to be different after undergoing Phase I metabolism.