UNIT 2 (BIOPHARMACEUTICALSㅡFATE OF DRUG)

Question 1

• the study of the physicochemical properties of the drug and the drug product, in vitro, on the bioavailability of the drug, in vivo, to produce a desired therapeutic effect.

Answer 1

BIOPHARMCEUTICS

Question 2

• It is the study of the kinetics of absorption, distribution, metabolism, and excretion (ADME) of drugs and their corresponding pharmacologic, therapeutic, or toxic effects in animals and man.

Answer 2

PHARMACOKINETICS

Question 3

• The absorption process is driven by the concentration gradient across the membrane, with the passage of drug molecules occurring primarily from the side of high concentration.

Described by _____________

Answer 3

• Fick’s first law of Diffusion

Question 4

• involves the aqueous channels or pores through which hydrophilic drugs can pass.

○ Occurs in the jejunum and proximal tubules of kidneys

○ Absent in the stomach and the lining of the urinary bladder

Answer 4

Filtration

Question 5

• Drugs are better absorbed in __________ form.

Answer 5

unionized

Question 6

• This type of transport is thought to involve membrane components that may be enzymes or some other type of agent capable of forming a complex with the drug (or other agent) at the surface membrane.

Answer 6

SPECIALIZED TRANSPORT MECHANISM

Question 7

• Under normal circumstances, a drug may be expected to remain in the stomach for 2 to 4 hours (_________________) and in the small intestine for 4 to 10 hours

• The gastric emptying time for a drug is most rapid with a fasting stomach, becoming slower as the food content is increased.

Answer 7

gastric emptying time

Question 8

• ↑ increase GET

Answer 8

▪ High fat /fatty foods

▪ Cold food

▪ Gastric ulcers

▪ Stress

▪ Vigorous exercise

▪ Lying on the left side

▪ Drugs (Antidiarrheal

/antimotility agents)

▪ Hunger

Question 9

• ↓ decrease GET

Answer 9

▪ Spicy foods

▪ Extreme temp. of meal

▪ Gastrectomy

▪ Depression

▪ Mild Exercise

▪ Lying on right side

▪ Motility enhancing agents:

(metoclopramide, domperidone, cisapride)

▪ Diabetes Mellitus

Question 10

• They form a subtype of solid solvates in which water molecules are incorporated into the crystal lattice of a compound

o The possibility of solid APIs to exist at different levels of hydration represents another way to improve the APIs’ properties by altering their solid state structures.

Answer 10

● Hydrates

Question 11

● The drug–protein complex-

● reversible,

● involves albumin (globulins also participate in the binding of drugs, particularly some of the hormones)

● Entails formation of relatively weak bonds (van del Waals, hydrogen, ionic)

● Binding capacity is saturable

Answer 11

Protein-binding

Question 12

o NOT exposed to the body’s detoxification (metabolism) processes

o NOT filtered through the renal glomeruli

Answer 12

BOUND DRUG

Question 13

o Serves as a reservoir or depot (only released when the level of free drug in the blood is no longer adequate to ensure protein saturation)

Answer 13

INACTIVE PORTION

Question 14

● the major process by which foreign substances, including drugs, are eliminated from the body

● Biotransformation indicates the chemical changes to drugs within the body as they are metabolized and altered by various biochemical mechanisms.

Answer 14

Metabolism

Question 15

▪ an inactive parent compound, may be converted to an active therapeutic agent by chemical transformation in the body.

Answer 15

Prodrugs

Question 16

● refers to both metabolism and excretion

● The kidney is the most important organ for excreting drugs and their metabolites.

Answer 16

Elimination

Question 17

The rate of reabsorption is _____________ to the concentration of drug in un-ionized form.

Answer 17

proportional

Question 18

• Refers to the comparison of bioavailabilities of different formulations, drug products, or batches of the same drug products

Answer 18

Bioequivalence

Question 19

• Describes the rate and extent to which an active drug ingredient or therapeutic moiety is absorbed from a drug product and becomes available at the site of action

Answer 19

Bioavailability

Question 20

Bioavailability data

Answer 20

the amount or proportion of drug absorbed from a formulation or dosage form

the rate at which the drug was absorbed

the duration of the drug’s presence in the biologic fluid or tissue correlated with the patient’s response

the relationship between drug blood levels and clinical efficacy and toxicity.

Question 21

• According to the FDA (5), the in vivo bioavailability of a drug product may be determined by:

Answer 21

o measurements of the concentration of the active drug ingredient

o its therapeutic moiety

o its metabolite(s) in the blood or urine

pharmacological effects

Question 22

• contain the same therapeutic moiety but are different salts, esters, or complexes of that moiety
• different dosage forms or strengths
• Different dosage forms and strengths within a product line by a single manufacturer
• extended-release products when compared with immediate- or standard-release formulations of the same active ingredient
• Ex. Tetracycline hydrochloride vs tetracycline phosphate complex)
• Ex. Quinidine sulfate tablets vs Quinidine sulfate capsules

Answer 22

Pharmaceutical Alternatives

Question 23

• are pharmaceutical equivalents or pharmaceutical alternatives whose rate and extent of absorption do not show a significant difference when administered at the same molar dose of the therapeutic moiety under similar experimental conditions, either single dose or multiple dose.

Some PE and PA may be equivalent in the extent of their absorption but not in their rate of absorption and yet may be considered bioequivalent because such differences in the rate of absorption are intentional and are reflected in the labeling, are not essential to the attainment of effective body drug concentrations on chronic us

Answer 23

Bioequivalent Drug Products

Question 24

• have the SAME pharmacokinetic and pharmacodynamic properties.
• have been proven bioequivalent and the FDA believes they can be expected to have the same clinical effect and adverse-events profile.
• generally, are considered most appropriate for substitution.

Answer 24

Therapeuic Equivalents

Question 25

• are achieved by direct application of the drug to the desired site of action, such as the eye, nose, or skin.

Answer 25

Local effects

Question 26

• result from the entrance of the drug into the circulatory system and transport to the cellular site of its action.

Answer 26

Systemic effects

Question 27

● Drugs are most frequently taken by oral administration

● Most are taken for the systemic drug effects

● ADVANTAGE

o Most natural

o Uncomplicated

o Convenient

o Safe

● DISADVANTAGE

o slow drug response (compared with parenterals)

o chance of irregular absorption of drugs (type of food in GI)

o Destruction of certain drugs by the acid reaction of the stomach or by gastrointestinal enzymes

Answer 27

ORAL ROUTE

Question 28

● Some drugs are administered rectally for their local effects and others for their systemic effects.

● The rectum and the colon can absorb many soluble drugs

● Rectal administration for systemic action may be preferred for drugs destroyed or inactivated by the environments of the stomach and intestines.

● may also be indicated when the oral route is precluded because of vomiting or when the patient is unconscious or incapable of swallowing drugs safely without choking

Answer 28

RECTAL ROUTE

Question 29

● parenteral is derived from the Greek words—

o para : meaning beside

o Enteron : meaning intestine

● which together indicate something done outside of the intestine and not by way of the alimentary tract

Answer 29

PARENTERAL ROUTE

Question 30

Three primary routes

Answer 30

o Subcutaneous

o Intramuscular

o Intravenous

Question 31

OTHER ROUTES

Answer 31

● Ocular

● Otic

● Nasal

● Lungs

● Vagina

● Urethra