S3M1 Pharmacology Babbini Drug Absorption

Front 1

Pharmacokinetics is what the body does to the drug. It deals with the study of the temporal pattern of what three pharmacological processes?

Back 1

Absorption, distribution and elimination

Front 2

Describe the difference between a drugs pharmacological action, its mechanism of action and its pharmacological effect. (give an example for each).

Back 2

Pharmacological action: the modification a drug makes (increased SA node depolarization)

Mechanism of action: (activation of cardiac beta-receptors)

Pharmacological effect: The observed event which has been produced by the drug (tachycardia)

Front 3

Which diffusion type is more frequent, occurs across the cell membrane , is passive and nonselective?

Back 3

Lipid diffusion
Aqueous diffusion occurs through aquaporins, not directly across cell membranes.

Front 4

This type of diffusion occurs through protein channels of cell membranes, is passive and nonselective?

Back 4

Aqueous diffusion

Front 5

Lipid diffusion is determined mainly by...

Back 5

Oil/water partition coefficient, lipid solubility and molecular size.

Front 6

Ionized molecules are ______ soluble?

Nonionized molecules are _______ soluble?

Back 6

Ionized = water soluble

Non ionized= lipid soluble

Front 7

If the pKa of an acidic drug is greater than the pH , what is its solubility?

Back 7

It is mainly non-ionized (lipid soluble)

Front 8

If the pKa of an acidic drug is less than the pH, what is its solubility?

Back 8

It is mainly ionized (water soluble).

Front 9

The pKa of aspirin (acidic drug) is around 3.5. If aspirin is in the gastric lumen, what form will the drug be in?

What happens when the drug is absorbed by the mucosal cell?

Back 9

Since the gastric lumen pH is around 1.5, the pKa of the acidic drug aspirin is higher than the pH. This means the drug will be in a nonionized (lipid soluble) form. However, once absorbed by the mucosal cell, the pH increases and exceeds the pKa of the drug, thereby ionizing the drug and effectively "trapping" it intracellularly.

Front 10

What is the consequence of ion trapping regarding drug absorption?

Describe the concentration gradient formed?

Back 10

Ion trapping occurs when a drug is absorbed by a cell and then immediately ionized due to a fluctuation in the pH. The example given was the acidic drug aspirin which has a pKa of 3.5. Once absorbed, the pH becomes higher than the pKa which immediately ionizes the drug making it water soluble.

As a consequence, the cencentration gradient of the nonionized form will remain high and this will further encourage aspirin to continue crossing the cell membranes

Front 11

What is bulk flow transfer?

Back 11

Drugs that can move across cell barriers through intercellular pores, like maculae or fenestrae of capillaries. This allows for passage of large molecules (up to MW 40,000)

Front 12

Describe first order kinetics in pharmacology.

Back 12

When a constant fraction (or %) of the drug is absorbed, distributed or eliminated per unit of time.

Front 13

Describe zero order kinetics.

Back 13

When a constant amount of the drug is absorbed, distributed or eliminated.
-occurs when the biological system is a saturable process.

Front 14

Definition: " the fraction (F) of a drug dose reaching unchanged to systemic circulation when administered by any route."

Back 14

Bioavailability

Front 15

What two things affect bioavailability?

Back 15

1.) the route of administration (oral vs. intramuscular)

2.) Factors that influence absorption

Front 16

If you double the dose of a drug, what would happen to bioavailability?

Back 16

Nothing, bioavailability of a drug is constant (remember that it is first order and is based on the FRACTION that is absorbed).

Front 17

Describe the time-concentration curve of a drug and describe :
MEC,MTC, Cmax and AUC

Back 17

This is a basic curve representing the drug plasma concentration over time. Initially, absorption of the drug exceeds elimination so plasma concentration increases.

MEC= minimum effective concentration

MTC= maximum (toxic)

Cmax= the point at which there is a balance b/t absorption and elimination of the drug.

AUC= (area under curve) represents the amount of the drug that is absorbed and can be used to assess bioavailability.

Front 18

how do you calculate bioavailability?

If a drug is administered intravenously, what is bioavailability?

Back 18

F= AUC other/ AUC IV

Ex: oral bioavailability=
AUC oral/ AUC IV

bioavailability for IV: F=1

Front 19

Oral drug administration occurs mainly via lipid diffusion and usually absorbed where?

Back 19

The small intestine due to the HUGE surface area available for absorption.

TECHNICALLY, a drug is not "absorbed" until it reaches systemic circulation; which would be once it is processed by the liver and enters the Vena Cava. However, the physical act of absorption of an oral drug does take place in the small intestine.

Front 20

Are oral drugs absorbed fast or slow?

How can we delay oral drug absorption?

Hasten?

Back 20

usually slow

Oral drugs can be delayed when the drug is given as a controlled-release preparation

Oral drugs can be more quickly absorbed when given as an aqueous solution.

Front 21

What is first pass elimination and how does it relate to oral bioavailability?

Back 21

Once a drug passes through the GI the drug must go to the liver; the first pass describes the first time the drug interacts with the liver and how much of the drug is eliminated at first.

Therefore, low systemic bioavailability of drugs given by oral route often indicates a large first pass effect.

Front 22

What is the greatest advantage of sublingual drugs? Is it the same as oral drugs?

Back 22

VERY rapidly absorbed and the first-pass effect is avoided.

The two are distinct. Oral drugs are actually ingested and processed by the GI system while the sublingual drug is absorbed immediately into the bloodstream.

Front 23

Regarding cutaneous drug administration, how does topical compare to transdermal?

Back 23

Topical is local and not absorbed

Transdermal is systemic and absorbed slow and uniformly (also avoids first-pass effect). However, very few drugs can be effectively absorbed through the skin.

Front 24

This type of drug administration if usually local (rarely systemic) and absorbed rapidly.Preparations include eye, nose, ear drops and also solutions or creams for the throat, rectum, and vagina.

Back 24

Mucous membrane drug administration

Front 25

Parenteral administration can be achieved via what two routes?

Which has a quicker absorption?

Back 25

Subcutaneous or intramuscular.

Intramuscular is generally more rapid.

Front 26

This type of drug administration eliminates problems of absorption and is most rapid. However, the speed at which the drug is absorbed may be problematic and evoke negative effects on certain body systems.

Back 26

Intravenous (IV)
Be careful!! Must be slow and cautiously administered.

Front 27

What type of diffusion has the following characteristics:
1.) uses a protein-carrier
2.) passive
3.) specific carrier for the drug
4.) saturable
5.)can be inhibited

Back 27

Facilitated diffusion

Active transport is exactly the same except it is active (uses ATP).

Front 28

Describe transport by endo/exo cytosis.

Give an 3 examples.

Back 28

Very large transport (2000-100000), active process, can be either specific or non-specific.

Ex: bacterial toxins, Ab or protein hormones

Front 29

Is aqueous diffusion passive or active?

How about Lipid diffusion?

Back 29

They are both passive and nonselective.

Both depend on molecular size but differ in how they cross the membrane.