Pharmacology: Administration and Distribution of Drugs

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Questions and Answers

What is a disadvantage of intravenous administration of a drug?

It produces a slow distribution of the drug

It is less invasive than other routes of administration

It allows the drug to bypass the blood-brain barrier

It places the drug directly into the circulatory system, leading to rapid distribution (correct)

What is a characteristic of subcutaneous and intramuscular injections?

They show slow distribution of the drug (correct)

They are less effective than oral administration

They bypass the circulatory system

They produce a rapid distribution of the drug

What is the function of the blood-brain barrier?

To increase the flexibility in formulating dosage forms

To slow down the distribution of the drug

To allow all compounds to pass through

To protect the brain from exposure to a large number of metabolites and chemicals (correct)

What is an advantage of intraspinal and intracerebral routes of administration?

They allow the drug to bypass the blood-brain barrier Signup and view all the answers

What is a potential advantage of the prodrug approach?

It can increase the flexibility in formulating dosage forms Signup and view all the answers

What is a limitation of parenteral routes of administration?

They may not cross the blood-brain barrier Signup and view all the answers

What is a characteristic of intravenous administration?

It places the drug directly into the circulatory system Signup and view all the answers

What is a potential drawback of intravenous administration?

The drug may be distributed to unwanted places in the body Signup and view all the answers

What is the effect of increasing the effective concentration of warfarin at the receptor?

Increased clot formation time Signup and view all the answers

What is the key factor that determines the concentration of a drug in tissue depots?

Lipophilicity of the drug Signup and view all the answers

What happens to thiopental after its initial administration?

It disappears into tissue protein and redistributes into body fat Signup and view all the answers

What is the effect of structural changes in the barbiturate series that favor partitioning into lipid tissue stores?

Decreased duration of action but increased CNS depression Signup and view all the answers

What is the primary route of entry for most molecules absorbed from the gastrointestinal tract into the circulatory system?

Portal vein Signup and view all the answers

What is the fate of the remaining thiopental after its initial release from tissue depots?

It is metabolized in the liver and excreted Signup and view all the answers

What is the characteristic of barbiturates with the slowest onset of action and longest duration of action?

More polar side chains Signup and view all the answers

What is the primary function of the liver in drug metabolism?

Metabolism of drugs Signup and view all the answers

What is the typical form of methylprednisolone?

Tablets Signup and view all the answers

What is the role of esterases in the case of methylprednisolone acetate?

To hydrolyze the acetate ester to the active methylprednisolone Signup and view all the answers

What is the characteristic of methylprednisolone sodium succinate?

It is a prodrug that is hydrolyzed to the active methylprednisolone Signup and view all the answers

Why is acitretin recommended for women who would like to become pregnant?

It can clear from the body within a reasonable time frame Signup and view all the answers

What is the effect of protein binding on the drug's effective solubility?

It can make a drug with poor water solubility a very effective agent Signup and view all the answers

What happens to the drug once it enters the systemic circulation?

It can stay in solution or be bound to serum proteins Signup and view all the answers

What is the effect of protein binding on the drug's availability to the sites of biotransformation?

It decreases the drug's availability to the sites of biotransformation Signup and view all the answers

What is the characteristic of etretinate?

It has a 120-day terminal half-life Signup and view all the answers

What is the result of geometric isomers in drugs?

Differ in their capabilities for interacting with a biological receptor, distribution, metabolism, and excretion Signup and view all the answers

What is the main difference between cis- and trans-diethylstilbestrol?

Their estrogenic activity Signup and view all the answers

What is the effect of conformational isomers on functional groups or interaction with biological receptors?

They cause differences in reactivity or interaction Signup and view all the answers

What is the result of conformational flexibility in open-chain neurohormones?

They produce multiple biological effects Signup and view all the answers

What is the characteristic of groups attached to aromatic ring?

They are restricted to the plane of this ring Signup and view all the answers

What is the effect of pKa values and rate of lipid solubility characteristics on geometric isomers?

They are related Signup and view all the answers

What is the difference between geometric and conformational isomers?

Geometric isomers are due to rotation around a double bond, while conformational isomers are due to rotation around a single bond Signup and view all the answers

What is the result of conformational isomers in certain semirigid ring systems?

They show significant differences in biological activities Signup and view all the answers

What is the function of the CYP reductase in the mixed-function oxidase system?

To supply the reducing equivalents needed for the metabolic oxidation of foreign compounds Signup and view all the answers

What is the name of the iron-containing porphyrin component of the CYP enzyme?

Protoporphyrin IX Signup and view all the answers

What is the purpose of the NADH-linked cytochrome b5 in the mixed-function oxidase system?

To supply the reducing equivalents needed for the metabolic oxidation of foreign compounds Signup and view all the answers

What is the major organ involved in the metabolism of xenobiotics?

Liver Signup and view all the answers

What is the name of the enzyme that is responsible for transferring an oxygen atom to the substrate RH?

CYP oxidase Signup and view all the answers

What is the name of the reaction involved in the mixed-function oxidation of aromatic compounds?

Aromatic hydroxylation Signup and view all the answers

What is the reason for the versatility of the hepatic CYP mixed-function oxidase system?

Substrate nonspecificity of CYP and the presence of multiple forms of the enzyme Signup and view all the answers

What is the name of the complex formed when the reduced (Fe+2) form of the CYP enzyme binds with carbon monoxide?

P450-CO complex Signup and view all the answers

Study Notes

Parenteral Administration

Intravenous administration places the drug directly into the circulatory system, leading to rapid distribution throughout the body.
Subcutaneous and intramuscular injections show slow distribution of the drug, as it must diffuse from the site of injection into systemic circulation.
Parenteral routes produce a depot in the tissues from which the drug must reach the blood or lymph.

Blood-Brain Barrier (BBB)

The BBB is composed of membranes of tightly joined epithelial cells lining the cerebral capillaries, protecting the brain from exposure to a large number of metabolites and chemicals.
Parenterally administered drugs may not cross the BBB.
It is possible to bypass the BBB by injecting the drug directly into specific organs or areas of the body, such as intraspinal or intracerebral routes.

Prodrug Design

Prodrug design can alter the solubility characteristics of a drug, increasing the flexibility in formulating dosage forms.
Examples of prodrug design include:
- Methylprednisolone: slightly water-insoluble, used in tablets.
- Methylprednisolone acetate: essentially water-insoluble, used in topical ointments and sterile aqueous suspensions for intramuscular injection.
- Methylprednisolone sodium succinate: water-soluble, used in oral, intravenous, and intramuscular dosage forms.

Protein Binding

Once a drug enters the systemic circulation, it can undergo protein binding, usually to albumin.
Protein binding can have a profound effect on the drug's effective solubility, biodistribution, and biological half-life.
Example: warfarin, with its high protein binding, increases the effective concentration at the receptor, leading to an increased prothrombin time and potential hemorrhage.

Tissue Depots

The drug can be stored in tissue depots, such as neutral fat, which constitutes 20-50% of body weight.
The more lipophilic the drug, the more likely it will concentrate in these pharmacologically inert depots.
Example: thiopental, a lipophilic barbiturate, rapidly disappears into tissue protein, redistributes into body fat, and then slowly diffuses back out of the tissue depots.

Drug Metabolism

All substances in the circulatory system, including drugs, metabolites, and nutrients, pass through the liver.
The liver is the primary organ involved in the metabolism of xenobiotics.
The mixed-function oxidase system, which includes the cytochrome P450 (CYP) enzymes, is responsible for the oxidative metabolism of foreign compounds.

Isomerism

Geometric isomers (cis-trans isomerism or E-Z isomerism) of drugs can differ in their capabilities for interacting with biological receptors, distribution, metabolism, and excretion.
Conformational isomers (anti, eclipsed, and gauche) exist due to rotation of atoms or groups of atoms around a single bond.
Differences in reactivity of functional groups or interaction with biological receptors may be caused by differences in steric requirements of the receptors.

Cytochrome P450 (CYP)

CYP is a superfamily of heme proteins responsible for transferring an oxygen atom to the substrate.
The CYP enzymes are found in high concentrations in the liver, but are also present in other tissues, such as lung, kidney, intestine, skin, placenta, and adrenal cortex.
The CYP system is able to metabolize an almost unlimited number of diverse substrates by various oxidative transformations.

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Description

This quiz explores the administration and distribution of drugs in the body, specifically in regards to intravenous administration and its effects.