Lecture 2 Flashcards
Pharmacokinetics - Absorption (47 cards)
1
Q
What is pharmacokinetics?
A
- study of drug movement in the body
- what the body does to the drug, composed of 4 basic processes: absorption, distribution, metabolism, excretion
2
Q
What is absorption?
A
- the movement of the drug from the site of administration into the blood
3
Q
What does the rate of absorption tell us?
A
how quickly the drug effect will occur
4
Q
what does the amount of drug absorption determine?
A
how intense the effect of the drug will be
5
Q
what are 6 factors affecting absorption?
A
- rate of dissolution
- surface area
- blood flow
- lipid solubility
- pH partitioning
- activity of drug transport proteins
(SPARBL)
6
Q
How does the rate of dissolution affect absorption?
A
- drugs must dissolve before they are absorbed
- fate rate of dissolution = faster onset of action
7
Q
How does surface area affect absorption?
A
- larger SA = faster absorption
- intestine has thousands of finger like projections called villi that line the intestine and make its surface area larger than that of the stomach
8
Q
How does blood flow affect absorption?
A
- high blood flow = faster absorption bc they maintain a concentration gradient which drives absorption
- i.e exercise can increase drug absorption while heart failure, hypotension, hypothermia etc decrease it
9
Q
How does lipid solubility affect absorption?
A
- high lipid solubility = faster absorption (compared to water soluble drugs) bc they can cross the cell membrane
10
Q
How does pH partitioning affect absorption?
A
- absorption increases when there is a difference between the pH at the administration site vs the blood, such that the drug becomes ionized and trapped in the blood
11
Q
How does drug transport protein activity affect absorption?
A
- uptake transports = increased absorption
- efflux transporters = decreased absorption
12
Q
What are the 8 major routes of administration?
A
- oral
- sublingual
- transdermal
- rectal
- intravenous (IV)
- subcutaneous
- intramuscular (IM)
- Pulmonary
13
Q
What are enteral routes of administration and which major routes are enteral?
A
- involve the gastrointestinal tract
- oral and rectal routes
14
Q
What are parenteral routes of administration and which major routes are parenteral?
A
- do not involve the gastrointestinal tract
- intravenous, intramuscular, subcutaneous
- mostly only consider the injections parenteral
15
Q
Why do orally administered drugs absorb faster in the small intestine than the stomach?
A
- SA of the stomach is small and covered with a thick layer of mucous, so even though the pH environment of the stomach is better, it still has decreased absorption
16
Q
Advantages of oral administration
A
safe, convenient, economical
17
Q
Disadvantages of oral administration
A
dissolution not always complete, varies between patients
18
Q
What is the pharmaceutical phase of orally administered drugs?
A
- occurs after the patient swallows a tablet; involves the disintegration and dissolution
- less complete disintegration = less dissolution = less absorption
19
Q
What is gastric emptying?
A
- movement of the stomach contents into the intestine
- things that increase gastric emptying also increase rate of absorption
20
Q
Factors that increase gastric emptying?
A
- taking meds on an empty stomach
- taking meds with cold water
- lying down on the right ride
- high osmolality feeding (tube feeding)
- taking a pro-kinetic drug (one that increases GI motility)
21
Q
Factors that decrease gastric emptying?
A
- high fat meal
- heavy exercise
- lying down on the left side
- taking a drug that inhibits the vagus nerve (i.e anticholinergic drugs)
22
Q
What is enteric coating and how does it effect absorption?
A
- special drug coating that prevents dissolution in the acidic environment of the stomach
- once its in the more alkaline duodenum it dissolves
23
Q
What is bioavailability?
A
- fraction of a dose of a drug that reaches the systemic circulation unchanged
24
Q
What is bioavailability influenced by?
A
- drug formulation
- route of administration
- degree of metabolism
25
Lowest to highest bioavailability of different drug types
1. time release capsules
2. enteric coated tablets
3. compressed tablets
4. capsules
5. granules
6. chewable tablets (eliminates disintegration phase)
7. suspension
8. syrup
9. aqueous solution
26
What is sublingual administration?
- involves placing drug under tongue where it is dissolved and absorbed across oral mucosa
- venous drainage from there to the superior vena cava, which takes blood to the heart
- this administration route avoids first pass metabolism through the liver
- drugs administered this way must be lipophilic and uncharged
27
What is transdermal administration?
- drugs absorbed through the skin
- must be lipophilic and relatively hydrophilic in order to dissolve in the extracellular fluid
- are also usually small (< 600 Da)
- typically administered as patches, ointments, sprays, or lotions
28
Transdermal preparations
- provide constant plasma drug levels with minimal peaks and troughs
- tolerance may develop without drug-free period
- are usually not used for 6-10 hrs a day to avoid tolerance
29
What are the factors affecting transdermal absorption?
- thickness of the skin
- hydration
- hair follicles
- application area
- integrity of the barrier
30
How does thickness of the skin affect transdermal absorption?
- TA is inversely proportional to skin thickness
31
hydration and TA
- TA is increased when the skin is well hydrated
32
hair follicles and TA
- provides route for drugs to bypass the barrier function of the epidermis
- the more hair follicles, the greater the TA
33
Application area and TA
- greater the application area, the greater the TA
34
Integrity of the barrier in TA
-conditions like psoriasis, burned or abraded skin TA is increased
35
What is rectal administration?
- drug inserted into the rectum as suppository
- drug dissolves and crosses the rectal mucosa into the blood
- ~50% of rectally administered drugs bypass the liver
36
When is rectal administration useful?
- when patient is unconscious or vomitting
37
Disadvantage of rectal admin
- incomplete absorption
| - irritation of the rectal mucosa
38
What is Intravenous (IV) administration?
- injected directly into a peripheral vein
- can be given as bolus or IV drip
- bolus is a single dose over a short period of time, drip is continuous infusion over a prolonged period
- IV drip drugs usually diluted in a "vehicle" like saline
39
What veins are commonly used for IV?
- back of the hand
- median cubital vein at the elbow
- but any visible vein can be used
40
Advantages of IV admin
- no barriers to absorption, bioavailability 100%
- precise control of dosage and duration
- admin of poorly soluble drugs
- allows the injection of irritants
41
Disadvantages of IV admin
- expensive, invasive, inconvenient
- drug cannot be removed once injected
- risk of infection and fluid overload
- risk of injecting wrong formulation
42
What is subcutaneous administration?
- injected beneath the skin into subcutaneous tissue
- capillary wall only barrier to absorption
- blood flow and water solubility primary determinants of rate of absorption
- irritant drugs must not be injected this way
43
What is intramuscular (IM) administration?
- injected directly into muscle tissue
- absorption determined by ability of the drug to pass through fenestrations in the capillary wall
- primary determinants of rate of absorption = blood flow and water solubility
44
Advantages of IM admin
- can be used for poorly soluble drugs
| - can use it to admin depot preparations (drug is absorbed slowly over time)
45
Disadvantages of IM admin
- pain/discomfort
| - may cause local tissue or nerve damage
46
Factors affecting IM absorption
- blood flow level depends on muscle; i.e deltoid > vastus lateralis (thigh) > gluteal
- exercise increase blood flow and therefore absorption
- blood flow decreased by heart failure, hypotension, hypothermia
47
What is pulmonary administration?
- gaseous and volatile drugs inhaled and absorbed into blood through pulmonary epithelium
- absorption very rapid (almost instantaneous) bc lung = large SA
- drug can be delivered right to site of action in case of pulmonary disease
