Biopharmaceutics

Question 1

Pharmacokinetics definition

Answer 1

Pharmacokinetics is the study of the action and movement of drugs within the body, including the mechanisms of absorption, distribution, metabolism, and excretion of drugs.

It defines the processes by which the
body ingests a drug, breaks down the drug, distributes it throughout the body, uses it, and then excretes the waste products of the drug.

Question 2

Drug Absorption

Answer 2

The movement of a drug from its site of administration into the bloodstream is absorption.

In most cases, this is the first step the body
takes to begin processing a drug. For absorption to occur, a drug must be
transported across one or more biological membranes to reach the blood
circulation. This process can take place via passive (diffusion) or active
transport.

Question 3

Passive Transport

Answer 3

The most common and important mode of traversal of drugs through membranes is passive transport or diffusion.

Diffusion is the process in which particles in a fluid move from an area of higher concentration to an area of lower concentration, resulting in an even distribution of the particles in the fluid.
This mechanism requires little or no
energy. In the body, diffusion depends upon lipid solubility (ability to be dissolved in a fatty substance) of the drug. Cell membranes consist of a fatty bi-layer through which drugs must pass for diffusion to occur.
Agents that are relatively lipid-soluble diff use more rapidly than less lipid-soluble
drugs.

Question 4

Active Transport

Answer 4

Active transport is a process that moves particles in fluid through membranes from a region of lower concentration to a region of high concentration. It uses specific carrier molecules (proteins) in the cell membranes and requires energy.

Question 5

Absorption of Medications Through the Digestive System

Answer 5

Oral administration of drugs is the most convenient, economical, and common route of administration.

Absorption of most drugs administered
orally takes place through the digestive system. Drugs given orally are usually
absorbed across the stomach or upper intestinal wall and enter blood vessels of hepatic portal circulation.

Hepatic portal circulation carries
blood directly to the liver where it is immediately exposed to metabolism by
the liver enzymes before reaching the systemic circulation. Th is exposure
is called the first-pass effect; the drug reaches the liver, where it is partly
metabolized before being sent to the body for systemic effects.

Drugs that are administered parenterally or sublingually do not undergo a first-pass
effect. Therefore, parenteral medications are often given in lower doses than
those given orally.

Question 6

Factors Influencing Absorption

Answer 6

Acidity of the Stomach

Presence of Food in the Stomach

Dosage of Drugs

Drug Bioavailability

Routes of Administration

Question 7

Factors Influencing Absorption - Acidity of the Stomach

Answer 7

Drugs with an acidic pH, such as aspirin, are easily absorbed in the acid environment of the stomach, whereas alkaline medications
are more readily absorbed in the alkaline environment of the small intestine.

Milk products and antacids tend to change the pH of the stomach. Therefore, some drugs are not absorbed properly. The
infant who is taking formula or milk may need to take medications on an empty stomach because the regular feedings will change the stomach acid level.

Question 8

Factors Influencing Absorption - Presence of Food in the Stomach

Answer 8

The presence of food in the stomach or intestine can have a profound influence on the rate and extent of drug absorption.

Food in the stomach decreases the absorption rate of medications, while an empty stomach increases the rate.

Sometimes the drug must be put into effect quickly, requiring the stomach to be empty.

If the medication causes irritation of the stomach, food should be eaten to serve as a buffer and decrease irritation.

Question 9

Factors Influencing Absorption - Dosage of Drugs

Answer 9

Drugs administered in high concentrations tend to be more rapidly absorbed than those administered in low concentrations.
The relationship between drug dose and blood, or other biological fluid concentrations, is called the dose-effect relationship.

Question 10

Factors Influencing Absorption - Drug Bioavailability

Answer 10

Bioavailability is a term that indicates measurement of both the rate of drug absorption and total amount of drug that
reaches the systemic blood circulation from an administered dosage form.

The route of drug administration in this matter is essential. If a drug is administered by intravenous injection, all of the dose enters the blood circulation. This is not true for drugs administered by other routes, especially for drugs given orally.

Solid drugs such as tablets and capsules must dissolve. This is a major source of difference in drug bioavailability.

Poor solubility of a drug or incomplete absorption of a drug in the gastrointestinal tract, and rapid metabolism of a drug during its first pass through the liver are other factors that influence bioavailability.

Question 11

Factors Influencing Absorption - Routes of Administration

Answer 11

Absorption will vary based upon the route of administration.

Some oral drugs are administered sublingually (under the tongue) or buccally (inner lining of cheek); these drugs are absorbed through the mucous membranes directly into the bloodstream to protect the drug from decomposition and deterioration in the stomach or liver.

Topical drugs may be absorbed through several layers of skin for local absorption. For example, nitroglycerin commonly
is applied to the skin in the form of an ointment or transdermal patches; it is absorbed rapidly, and provides sustained blood levels.

When the drug is injected directly into the bloodstream (vein or artery) and distributes throughout the body, it acts rapidly;
the process of absorption is bypassed.

The drug may be injected deeply into a skeletal muscle. The rate of absorption depends on the vascularity of the muscle site, and the lipid solubility of the drug.

If it is injected beneath the skin, drug absorption is less rapid, because the subcutaneous region is less vascular than the muscle tissues.

Question 12

Drug Distribution

Answer 12

The process by which drug molecules leave the bloodstream and enter the tissues of the body is called distribution.

When a drug reaches the bloodstream, it is ready to travel through blood, lymphatics, and other fluids to its site of action. Drugs interact with specific receptors.

Some drugs are frequently bound to plasma proteins (albumin) in the blood. If these drugs are bound to albumin, they are known as inactive drugs, while those that are unbound are called pharmacologically-active drugs. If binding is extensive
and firm, it will have a considerable impact upon the distribution and excretion of the drug in the body. Only when the protein molecules release the drug can it diffuse into the tissues, interact with receptors, and produce a therapeutic effect.

The brain and placenta possess special anatomical barriers that prevent many chemicals and drugs from entering. These barriers are referred to as the blood-brain barrier and fetal-placental barrier.

Sedatives, antianxiety drugs, and anticonvulsants readily cross the
blood-brain barrier to produce their actions on the central nervous system.
Alcohol, cocaine, caff eine, nicotine, and certain prescription drugs easily cross the placental barrier and can potentially harm the fetus.

Question 13

Drug Metabolism

Answer 13

Drug metabolism is a chemical reaction wherein a drug is converted into compounds, and then easily removed from the body.

It occurs once the drug reaches the liver, before the drug reaches its intended site within the body.

Most drugs are acted upon by enzymes in the body, and are converted to
metabolic derivatives during metabolism. The process of conversion is called
biotransformation.

The liver is the major site of biotransformation.
Many biotransformations in the liver occur in the smooth endoplasmic reticulum
of the hepatocytes. Liver enzymes react with the drugs creating metabolites.
The majority of these metabolites are inactive and toxic.

Drug metabolism influences drug action, such as duration of drug action, drug interactions, drug activation, and toxicity or side effects. In most cases, biotransformation can terminate the pharmacological action of the drug and increase removal of the drug from the body.

Question 14

Drug Excretion

Answer 14

The final step of pharmacokinetics is excretion, which is the removal of
drugs from the body.

Drugs may be excreted from the body by many routes, including urine, feces (unabsorbed drugs, and those secreted in the bile), saliva, sweat, milk, lungs (alcohols and anesthetics), and tears.

Any route may be important for a given drug, but the kidney is the major site of excretion for most drugs.

Unchanged drugs or drug metabolites can be eliminated by the kidneys. The main role of the kidney is to remove all non-natural and harmful agents in the bloodstream while keeping a balance of other natural
substances. Kidney impairment can significantly prolong drug action and
causes drug toxicity.

Renal excretion of drugs and their metabolites may undergo three processes:
(1) filtration
(2) secretion
(3) reabsorption

Question 15

Drug Excretion - Drug Filtration

Answer 15

Urine formation begins in the glomerulus and Bowman’s capsule in the kidneys.

Filtration causes water and dissolved substances to move from the glomerulus into Bowman’s capsule.

Filtration occurs when the pressure on one side of a membrane is greater than the pressure on the opposite side.

Small substances such as water, sodium, potassium, chloride, glucose, uric acid, and creatinine move through the wall of the glomerulus very easily.
These substances are filtered in proportion to their plasma concentration. In other words, if the concentration of a particular substance or drug in the plasma is high, many of these substances are filtered.

Approximately one-fifth of the plasma reaching the kidney is filtered. The
rate of filtration is referred to as the glomerular filtration rate (GFR) and is
normally 125–130 milliliters per minute (mL/min).

Question 16

Drug Excretion - Drug Secretion

Answer 16

Although most of the water and dissolved substances enter the tubules of the kidneys as a result of filtration across the glomerulus, a second process moves very small amounts of substances from the blood into the tubules. This is called tubular secretion.

It involves the active secretion of substances such as potassium ions (K+), hydrogen ions (H+), uric acid, the ammonium ion, and drugs from the peritubular capillaries into the tubules.

Secretion occurs primarily in the proximal convoluted tubule. This is an active process mediated by two carrier systems, one specific for organic acids and one specific for organic bases.

Therefore, the pH of the urine may affect the rate of drug excretion by changing the chemical form of a drug to one that can be more readily excreted or to one that can be reabsorbed.

Penicillins or barbiturates are weak acids, and available as sodium or potassium salts.
These agents can be better excreted if the urine pH is less acid.

On the other hand, any drug which is available as sulfate, hydrochloride, or nitrate salts, such as atropine or morphine, can be excreted better if the urine
is more acidic.

By altering the pH of urine, increased elimination of certain drugs can be facilitated, thus preventing prolonged action or overdosage of a toxic compound.

Another technique to alter the rate of excretion of a drug is to produce a competitively blocking effect. For example, probenecid may be used to block the renal excretion of penicillin. This prolongs the effect of the antibiotic by maintaining a higher therapeutic plasma level.

Secretions of drugs are active transport systems. They require energy and may become saturated.

Question 17

Drug Reabsorption

Answer 17

Reabsorption may occur throughout the tubules of the nephrons. It causes water and selected substances to move from
the tubules into the peritubular capillaries.

The mechanism is passive diffusion, therefore, only the unionized form of a drug is reabsorbed. It is dependent upon its lipid solubility.

For example, the kidneys selectively reabsorb substances such as glucose, proteins, and sodium, which they have already secreted into the renal tubules. These reabsorbed substances return to the blood.

Question 18

Drug Clearance

Answer 18

Drug clearance describes drug elimination (excretion plus metabolism).

It is defined as elimination rate over time divided by the drug’s concentration.
Drug clearance can also be described as being equal to the volume of fluid
completely cleared of a drug per a unit of time. It is usually expressed in mL/minute or L/hour.

Plasma clearance divided by blood clearance equals blood concentration divided by plasma concentration. Total clearance equals the sum of clearances of individual body processes. The eliminated drug amount is proportional to the clearance of the respective elimination process.

Question 19

Pharmacodynamics

Answer 19

Pharmacodynamics is the study of the biochemical and physiological effects of drugs. It is also defined as the study of a drug’s mechanism of action.

After administration, most drugs enter the blood circulation, and expose almost all body tissues to their possible effects.

All drugs produce more than one effect in the body. The primary effect of a drug is the desired or therapeutic effect. Secondary effects are all other effects, whether desirable or undesirable (causing harmful effects), produced by the drug.

Most drugs have an affinity for certain organs or tissues, and exert their greatest action at the cellular level in those specific areas, which are called target sites.
Most often, there are links between pharmacokinetics and pharmacodynamics
that demonstrate the relationship between drug dose and blood, or other biological fluid concentration.

The pharmacologic response by itself
does not provide information about some very important determinants of that response; for example, dose, drug concentration in plasma or at the site
of action. Pharmacokinetic and pharmacodynamics can determine the dose effect relationship.

Question 20

Drug Action

Answer 20

Drugs produce their effects by altering the normal function of the cells and tissues of the body. They do not create new cellular functions. Instead, they change existing cellular functions.

Drug action is generally described relative to a physiological state that was in existence when a drug was administered. Some drugs accumulate in specific tissues because they have an affinity for a tissue component. The most common way that drugs exert their action is by forming chemical bonds with certain receptors in the body. This usually occurs only if the drug and its receptor have a compatible chemical shape.

Drugs with molecules that fit precisely into a given receptor elicit a comparable drug response and are known as agonists.
Those that do not fit perfectly produce only a weak response or no response at all.
Not all drugs that bind to specific cells cause a functional change in the cell. These drugs act as antagonists to the natural process and work by blocking a sequence of biochemical events.

Some drugs may act by affecting the enzyme functions of the body.
When drugs are metabolized in the liver, they produce antimetabolites.
These antimetabolites interrupt or inhibit the actions of particular enzymes,
thus producing a desired therapeutic effect.

Question 21

Factors Affecting Drug Action

Answer 21

There are various factors that are important in determining the correct drugs for a patient, such as:

drug half-life
age
sex
body weight
time of day administered (diurnal)
presence of illnesses
psychological factors
tolerance
toxicity of drugs
idiosyncrasy
drug interactions.

Question 22

Factors Affecting Drug Action - drug half-life

Answer 22

The half-life of a drug is a related measurement used to ensure that maximum therapeutic dosages are given.

The half-life of a drug is the time it takes for the concentration of the drug in plasma to be reduced by one half (50 percent).

It is an indication of how long a medication will produce its effect in the body.

The larger the half-life value, the longer it takes for a drug to be eliminated. This is one of the most common methods
used to explain drug actions.

The half-life of each drug may be different:
for example, a drug with a short half-life, such as two or three hours, will need to be administered more often than one with a long half-life, such as eight hours.

Another method of describing drug action is by the use of graphic depiction of the plasma concentration of the drug versus time.

Question 23

Factors Affecting Drug Action - Age

Answer 23

Newborns and elderly individuals show the greatest effects of a drug’s actions.
Because of their ages and either immature or impaired body systems, they are more sensitive to medications that affect the central nervous system, and are at risk for developing toxic drug levels.

Calculations of drug dosages for these two groups must be carefully measured, and treatment usually starts with very small doses.

Question 24

Factors Affecting Drug Action - Sex

Answer 24

Both men and women respond to drugs differently.

A pregnant woman is at risk for taking some medications because of damage to the developing fetus.
In addition, certain drugs may have side effects that can stimulate uterine contractions, causing premature labor and delivery.

Men absorb intramuscular drugs more quickly. Intramuscular drugs remain
in women’s tissues longer than in men’s tissues, because of higher body fat
content.

Women and men differ in the way they are affected by other types of drugs as well.

Question 25

Factors Affecting Drug Action - Body Weight

Answer 25

Basically, the same dosage has less effect on a patient who weighs more than the normal range for their height, and a greater effect on an individual who weighs less.

This is because body weight is an important factor for drug action, and some medication doses must be adjusted based on body weight.

Pediatric medications are designed for the body weight or body surface of children. If adult medications are used for children, the correct dosage must be calculated and adjusted for the child’s body weight.

Question 26

Factors Affecting Drug Action - Diurnal Body Rhythms

Answer 26

Diurnal (during the day) body rhythms play an important part in the effects of some drugs, because they can affect the intensity of a person’s response to a drug.

For example, sedatives given in the morning will not be as effective as when administered before bedtime.

On the other hand, corticosteroid administration is preferred in the morning, because this best mimics the
body’s natural pattern of corticosteroid production and elimination.

Question 27

Factors Affecting Drug Action - Presence of Illnesses

Answer 27

Patients with liver or kidney disease may respond to drugs differently, because the body is not able to detoxify and excrete chemicals properly.
The liver and kidneys are the major sites of elimination of chemical substances.

Other illnesses that affect the physical health of the liver and kidneys must also be considered.

Question 28

Factors Affecting Drug Action - Psychological Factors

Answer 28

Psychological factors involve how patients feel about the drug(s) they are prescribed, and the different ways they respond to them. If an individual believes in the therapy, even a placebo (sugar pill, or sterile water thought to be a drug) may help to bring about relief. Some patients cooperate in following the directions for a specific drug, and a patient’s mental attitude can reduce or increase an expected response to a drug.

Question 29

Factors Affecting Drug Action - Tolerance

Answer 29

Tolerance is the phenomenon of reduced responsiveness to a drug. The body becomes so adapted to the presence of the drug that it cannot function properly without it.

The only way to prevent drug tolerance from occurring is to avoid the repeated use of a drug. The signs of drug tolerance consist of an increased amount required by the body to achieve the desired effects.

Certain drugs that stimulate or depress the central nervous system are prone to causing drug tolerance.

Question 30

Factors Affecting Drug Action - Drug Toxicity

Answer 30

Almost all drugs are capable of producing toxic effects. There is a range between the therapeutic dose of a drug and its toxic dose. This range is measurable by the therapeutic index, which is used to explain the safety of a drug.

The therapeutic index is expressed in the form of a ratio:
IMAGE 2

The larger the difference between the two doses, the greater the therapeutic index. For example, if the therapeutic index is 3 (such as 30 mg /10 mg), it means that three times the dose of a drug will be lethal
to a patient.

Question 31

Factors Affecting Drug Action - Idiosyncratic Reactions

Answer 31

When a patient has experienced a unique, strange, or unpredicted reaction to a drug, this is termed an idiosyncratic reaction.

Idiosyncratic reactions may be caused by underlying enzyme deficiencies from genetic or hormonal variation.

Question 32

Factors Affecting Drug Action - Drug Interactions

Answer 32

Drug interactions are defined as effects of medications taken together.

When two or more drugs are prescribed together, this generally results in one of the following:
1. The drugs have no effects on each other’s action.
2. The drugs increase each other’s effect.
3. The drugs decrease each other’s effect.

Any of these results may also be affected by the ingestion of food.

Most drugs do not interact with other drugs or food, but when such interactions do occur, some may be life-threatening.

Plasma protein binding can be a source of drug interaction if several drugs compete for binding sites on protein molecules.
Drug interactions may result in elevated concentrations of drugs by displacement of protein-bound drugs or by reduced rates of drug disposition, therefore, resulting in toxic drug concentrations.

Some drug interactions are wanted, and the medications are prescribed together to produce the desired effect. For example, probenecid is given with penicillin to increase the absorption of penicillin.

Other interactions are unintended and unwanted, producing possible dangers for the patient.

Drug interactions may also cause a more rapid drug disappearance, with plasma concentrations decreasing to below minimum effective values. For example,
some antibiotics make birth control pills less effective.

Question 33

Side Effects and Adverse Effects of Drugs

Answer 33

Side effects are usually referred to as mild but annoying responses to the medication. Adverse reactions or adverse effects usually imply more severe symptoms or problems that develop because of a drug. Adverse effects may require the patient to be hospitalized, or may even threaten the patient’s life.

Certain side effects such as nausea may disappear if the dosage is reduced.
Some side effects such as drowsiness may go away aft er the patient takes the
medication for a while.

Occasionally, side effects are very problematic, thus the dispensing of the drug to the patient is stopped or changed to a different drug. An example of this can be hyperactivity or inability to sleep, bleeding,
nephrotoxicity, or hepatoxic development.

Question 34

Hypersensitivity or Allergy

Answer 34

Allergies or hypersensitivity reactions are another unpredictable reaction that some drugs such as aspirin, penicillin, or sulfa products may cause in some patients.

Hypersensitivity reactions generally occur when a patient has received a drug and the body has developed antibodies against it. After this process of antibody production, if the patient is re-exposed to the drug,
the antigen-antibody reaction produces, itching, hives, rash, or swelling of the
skin. This is a common type of allergic reaction.

Question 35

Anaphylactic Reaction

Answer 35

An anaphylactic reaction to a drug is a severe form of allergic reaction that is life threatening. The patient develops severe shortness of breath, and may even have cardiac collapse.

An anaphylactic reaction is a medical
emergency because the patient may suffer paralysis of the diaphragm, swelling of the oropharynx, and an inability to breathe.