Pharmacokinetics

Question 0

What are the factors affecting drug absorption? (11)

Answer 0

Route of administration
Drug formulation
Drug dosage
Digestive motility
Digestive tract enzymes 
Blood flow at administration site
Degree of ionization of drug
pH of surrounding environment
Drug-drug interactions
Food-drug interactions
Dietary supplement/herbal product-drug interactions

Question 1

What are the 4 components of pharmacokinetics?

Answer 1

Absorption - how does it get into the body
Distribution - how is it transported throughout the body
Metabolism - how do we break it down
Excretion - how do we get rid of it

Question 2

What is metabolism?

Answer 2

Aka biotransformation
converts a drug to a form that can be more easily removed from the body
involves biochemical reactions
mostly takes place in the liver

Question 3

What is the first-pass effect?

Answer 3

Oral drugs (drugs that go into the stomach) follow the following path:
they are absorbed, enter the hepatic circulation, are metabolized to an inactive form, conjugate and then leave the liver, are distributed to general circulation

Question 4

What is distribution?

Answer 4

Involves how drugs are transported in the body.
Occurs in the blood - the greater the blood flow to the area, the higher concentration of drug is delivered.
Lipid-soluble agents are not limited by barriers therefore are completely distributed to body tisses

Question 5

What is drug distribution?

Answer 5

Initially drugs are carried in largest amounts to the most richly perfused tissues (e.g., adrenals, brain, heart, lungs, kidneys, muscles)
Later drugs undergo redistribution within the body being retained in tissues for which they have affinity (e.g., fat for lipophilic drugs)

Question 6

Plasma protein binding

Answer 6

Drug molecules may be bound to plasma proteins
while bound to plasma proteins - drugs are inactivated because they cannot leave vascular system and enter tissues
Once free level of drug falls, drug molecules diffuse off the plasma proteins to maintain a constant bound/free ratio

Question 7

What is affinity?

Answer 7

How much the drug likes the receptor

Question 8

What is excretion?

Answer 8

Primary site of excretion is the kidneys
Ionized and water-soluble drugs are filtered
Drug-protein complexes are secreted into distal tubule
Secretion mechanism is less active in infants and older adults
pH of filtrate can increase excretion

Question 9

How are drugs eliminated? Renal excretion

Answer 9

Drugs are filtered, secreted and reabsorbed

Question 10

Filtration

Answer 10

All drugs not bound to plasma proteins are filtered.

Question 11

Secretion

Answer 11

Some acidic and basic drugs are secreted.
This is an active process with transport maxima.
Drugs that are secreted usually have short half-lives.

Question 12

Reabsorption

Answer 12

Drug reabsorption from the renal tubules depends on the percentage of the drug in the non-ionized form.
Non-ionized drug molecules are usually reabsorbed into the systemic circulation
Ionized molecules are not reabsorbed

Question 13

Renal failure and excretion

Answer 13

Renal failure diminishes the excretion of medication
drugs are retained for extended times
dosages must be reduced

Question 14

What other organs can be sites of excretion?

Answer 14

respiratory system
glands
biliary system

Question 15

Enterohepatic recirculation of drugs

Answer 15

Drugs excreted in bile
Bile recirculates to liver
Percentage of drug recirculated numerous times
Prolongs activity of drug - activity of drug may last after discontinuation

Question 16

What is half-life?

Answer 16

Length of time needed to decrease drug plasma concentration by one half
The greater the half-life the longer it takes to excrete
Determines frequency and dosages

Question 17

What is steady state?

Answer 17

3-5 half lifes
amount of drug in = amount of drug out
The amount of drug being absorbed is equal to the amount being eliminated.

Question 18

How drug reaches and maintains therapeutic range

Answer 18

Repeated doses of drug given
Drug accumulates in bloodstream
Plateau reached
Amount administered equals amount eliminated

Question 19

What is loading dose?

Answer 19

Higher amount of drug is given
Plateau is reached faster
Quickly produces therapeutic response
Sometimes called bolus dosing
Helps to get to therapeutic range or steady state faster
Not everything gets a loading dose. Designed to by-pass the 3-5 half-lifes of steady state.

Question 20

What is maintenance dose?

Answer 20

Keeps plasma drug concentration in therapeutic range
Keeps person at steady state
Not for life and death situation, if first dose.

Question 21

What are the routes of drug administration?

Answer 21

Sublingual - (SL)
Oral - (PO, enteral)
Rectal - (Supp, PR)
Parenteral - injections 
   - Intravenous (IV)
   - Intramuscular (IM)
   - Subcutaneous (SC)
   - Intra-articular (IA)
Inhalation 
Topical

Question 22

What is sublingual?

Answer 22

Under the tongue
Used for drugs that: 
1. irritate the stomach
2. are destroyed in the stomach
3. are destroyed during the first pass through the liver
Use for drugs that:
1. rapidly dissolve in saliva
2. are to irritating to the oral mucosa, and
3. are lipophile

Question 23

what is oral?

Answer 23

1. drugs are absorbed from the stomach and the duodenum
2. drug absorption is better from the duodenum because of the larger absorbing surface
3. the stomach can absorb acidic drugs and weakly basic drugs
4. the duodenum can absorb the same drugs as the stomach plus most basic drugs
   For a drug to be absorbed from the stomach and/or duodenum, it must: be dissolved in the GI tract, have sufficient non-ionized drug molecules, and have non-ionized molecules with sufficient lipid solubility to pass through the GI mucosa

Question 24

What is rectal?

Answer 24

Drugs are administered rectally for a systemic effect if:
1. they are irritating to the stomach
2. the patient is nauseated
3. the patent is an infant or cannot take the drug orally, or
4. a sustained effect is desired
Drugs are also administered rectally for a local effect
The rate limiting factor controlling rectal absorption is extraction of the drug from the suppository mass. - After this step, drugs are absorbed in relation to the lipid solubility of the non-ionized molecule

Question 25

what is IV injection?

Answer 25

Intravenous - into the vein

Immediate effect, danger of overdose

Question 26

What is IM injection?

Answer 26

Intramuscular - into the muscle
If the drug is soluble in aqueous media, absorption occurs rapidly; if the drug is administered in suspension, absorption is prolonged.

Question 27

What is SC injection?

Answer 27

Subcutaneous - beneath the skin

absorption almost as rapid as intramuscular

Question 28

What is IA injection?

Answer 28

Intra-articular - injection into a joint

Question 29

What is inhalation?

Answer 29

puffs, inh
For systemic effect - actions start immediately
For local effect - on the bronchioles

Question 30

What is topical?

Answer 30

topical - applied to the skin, creams, ointments, lotions, patches
For a systemic effect - drug must be able to pass through the stratum corneum; drug must be lipophilic; occlusion (covering an area) facilitates drug penetration. This method of drug administartion provides for a slow, continuous absorption of the drug over a period of many hours
For a local effect - to treat inflammation or localized infections

Question 31

What is blood brain barrier?

Answer 31

Brain capillary endothelial cells have no pores
In addition, glial connective tissue is attached to the basement membrane of capillary endothelium
Together, these structural modifications are called the blood-brain barrier.
Ionized molecules cannot enter the brain - water soluble
Non-ionized molecules, not bound to plasma proteins enter the brain easily - fat soluble.

Question 32

Placental transfer of drugs

Answer 32

The mature placenta contains a network of maternal blood sinuses that interface with villi that carry the fetal capillaries
Drugs cross the placenta by simple diffusion
Lipid-soluble, non-ionized drugs readily enter the fetal blood from the maternal circulation
Placental transfer occurs less readily with drugs possessing a high degree of dissociation or low lipid solubility
The view that the placenta is a barrier to drugs is not correct
The fetus is, to at least some extent, exposed to essentially all drugs taken by the mother.