Pharmacology - chapter 1 - Pharmacokinetics

Question 0

what four pharmacokinetic properties determine the speed of onset of a drug?

Answer 0

Absorption - drug absorption from the site of administration
Distribution - drug leave blood stream and enter ECF and ICF
Metabolism - biotransformation by liver or other tissues
Elimination - by urine, bile or feces

Question 1

Pharmacokinetics =

Answer 1

What the body does to a drug

Question 2

what are the two ways of enteral drug administration, and what are their benefits?

Answer 2

Swallowed or sublingual.

The benefits are that they are safe, cheap, convenient and common

Question 3

enteric coated preparations vs. extended-release preparatioins?

Answer 3

Enteric-coated - chemical envelope that protects from stomach acid, but is absorbed in upper intestine.

Extended-release - medication does not have to be taken as often. Longer duration.

Question 4

The three major parenteral routes are?

Answer 4

IV, IM and SC

Question 5

IV injection. Pro’s & Con’s?

Answer 5

Pro - rapid effect and maximum degree of control. Almost emmidiate systemic delivery.

Con - cannot be recalled. Introduce bacteria and infective particles. May precipitate blood constituents, induce hemolysis.

Question 6

IM injections, two different types?

Answer 6

aqueous soulutions - rapid absorption.

depot preparations - slow absortion due to nonaqueous vechile(polyethylene glycol)

Question 7

SC injection, two characteristics?

Answer 7

Require absorption via simple diffusion. Minimizes risk of hemolysis or thromobosis associated with IV.

Question 8

Six “less common”routes of administration?

Answer 8

Oral inhalation, nasal inhalation, intrathecal/intraventricular, topical, transdermal & rectal

Question 9

what is drug absorption?

Answer 9

the transfer of a drug from its site of administration into the bloodstream

Question 10

name four mechanisms of drug absorption in the GI tract?

Answer 10

passive diffusion(most common)
faciliitated diffusion
active transport
endocytosis and exocytosis

Question 11

name five factors that influence drug absorption?

Answer 11

pH - most drugs are either weak acids or weak bases
Blood flow to absorption site - intestine favored over stomack
Total surface area available for absorption - again intestines
Contact time at absorption surface - e.g. transport and food influence.
Expression of P-glycoprotein

Question 12

what is P-glycoprotein, and what is its function in different tissues?

Answer 12

P-glycoprotein is a multidrug membrane transporter protein that transport various molecules, including drugs, across membranes.

Liver - transport drugs into bile
Kidney - pump drugs into urine
Placenta - transport drugs back into maternal blood
Intestines - transport drugs into intestinal lumen, reducing absorption.
Brain capillaries - pump drug into blood, limiting drug access to brain.

Question 13

what is bioavilability?

Answer 13

Fraction of administered drug that reaches the systemic circulation.
By definition this is 100% for drugs that are delivered intravenously.

Question 14

Four factors that influence bioavailability?

Answer 14

1 First-pass hepatic metabolism
2 Solubility of drug - should be largely hydrophobic with aqueous some solunility
3 Chemical stability - e.g. penicilin G is unstable in the gastric juices
4 Nature of the drug formulation - size, salt form, crystal polymorphisms, enteric coatings and the presence of binders & dispersing agents.

Question 15

bioequivalence vs therapeutical equivalence, co jest the difference?

Answer 15

bioequivalence - two related drug preparations show similar bioavailability and similar time to achieve peak blood concentrations

therapeutical equivalence - two similar products are pharmaceutically equivalent with similar clinical and safety profiles.

Question 16

What is drug distribution?

Answer 16

the process by which a drug reversibly leaves the blood stream and enters the interstitium and then the cells of tissues.

Question 17

Name five facors that influece drug distribution? Come on nah!

Answer 17

1 cariac output
2 blood flow(brain, kidney & liver recieve the most blødd)
3 capillary permeability( spleen and liver have fenestrated capillaries whereas the brain got the BBB)
4 the tissue volume
5 binding of drugs to plasma proteins and tissues( albumin, lipids, proteins, nucleic acids etc.)

Question 18

Three major routes of drug metabolism?

Answer 18

1 hepatic metabolism
2 elimination in bile
3 elimination in urine

Question 19

Kinetics of metabolism:

The two main types: name them and their differences.

Answer 19

First-order kinetics: more enzyme precent than free drug, therefore the rate of drug metabolism is directly proportional to the concentration of free drug.

Zero-order kinetics: enzyme is saturated by high free drug concentration. E.g aspirin, ethanol and phenytoin, where does are large.

Question 20

Two general sets of drug metabolism?

Answer 20

Phase I: convert lipophilic molecules into more polar molecules by introducing or unmasking a polar functional group, such as -OH or -NH2. This is most frequently done på P450 system

Phase II: Conjugation reactions that convert too lipophilic metabolites into sufficiently polar molecules that can be excreted.

Question 21

Four major P450 isozymes?

Answer 21

CYP3A4/5

CYP2D6

CYP2C8/9

CYP1A2

Question 22

P450 and grapefruit??

Answer 22

bergamottin, dihydroxybergamotin and paradicin-A, found in grapefruit juice, inhibit CYP3A4/5. Thus, drugs such as nifedipine, clarythroycin and simvastatin, which are metabolized by this system, persist in greater amount in the blood. This can potentially increase the drugs therapeutic and/or toxic effects.

Question 23

Drug clearance by the kidney:

Name the three processes.

Answer 23

1 glomerular filtration
2 proximal active tubular secretion
3 distal passive tubular absorption

Question 24

What is ion trapping?

Answer 24

making a drug polar by changing the pH of the urine, this traps the molecule in the renal tubule where it is excreted. Weak acids can be eliminated by alkalinization of the urine, whereas weak bases can be eliminated by acidification of the urine.

Question 25

Liver and kidney… name four other routes by which drugs can be cleared

Answer 25

bile, intestines, the lungs and milk in nursing mommas

Question 26

CL total =

Answer 26

CLhepatic + CLrenal + CLpulmonary + CLother

Question 27

3 clinical situations where half life is increased and 3 where it is decreased?

Answer 27

Increased: low renal plasma flow or hepatic blood flow, decreased bility to etract drug from plasma(renal failure), decreased metabolism

Decreased: increased hepatic blood flow, decreased protein binding, increased metabolism

Question 28

How long does it usually take a drug to reach the steady state(state where drugs is absorbed and excreted at the same rate)?

Answer 28

Approx 4 x half life

Question 29

Vd = ?

Answer 29

drug in body:drug in plasma ratio

Question 30

Drug clearance =?

Answer 30

ratio of the rate of elimination: concetration in plasma

Question 31

What is first-pass effect?

Answer 31

the elimination of a drug that occurs after administration but before it reaches the systemic circulation.

Question 32

What is steady state?

Answer 32

condition where the total amount of drug in the body does not change over multiple dosing.

rate of drug input = rate of elimination

Question 33

What is extraction?

Answer 33

The fraction of drug in the plasma that is removed by an organ as the drug passes through that organ.