lecture 3 absorption Flashcards
(70 cards)
1
Q
define bioaccessibility
A
the availability of a molecule to enter an organism from the environment
2
Q
what is important to know about chemicals in the environment
A
knowing how they go through environment and the cycles it goes through and how bioaccessible it is
3
Q
what is bioaccumulation? what is biomagnification?
A
bioaccumulation - how levels will accumulate over time in an organism
biomagnification - how contaminant levels become magnified through the food chain. this happens particularly in lipophilic molecules that can be stored in fatty acid tissue.
4
Q
what are the two routes of exposure. which is more common?
A
enteral = alimentary routes: through the digestive tract, most common
parenteral = extra-alimentary routes: intra, injections, and other types
5
Q
name the three types of enteral routes
A
- oral
- sublingual & buccal
- rectal
6
Q
name the nine types of parenteral routes
A
- intravenous
- intramuscular
- subcutaneous
- intraperitoneal
- intrathecal
- intra-arterial
- intracardiac
- intra-articular
- intraosseous
7
Q
what are 3 physical factors influencing absorption
A
- substance properties
- matrix properties
- route of exposure / administration
8
Q
what are the three different things to consider for the route of exposure/administration
A
- blood flow available for absorption
- surface area and time available for absorption
- contact time at absorption surface
9
Q
what is the significance of blood flow that is available for absorption and what parts of the body have the most blood flow
A
> blood flow = > absorption
brain and heart get the most, then secondary organisms like the liver, kidney, gi tract, muscles
10
Q
what is the significance of surface area and time that is available for absorption. which part of the body has the highest absorption
A
> surface area = > absorption
time = > absorption
intestines have most absorption
11
Q
what is the significance of contact time that is available for absorption. which part of the body has the highest absorption
A
> contact time = > absorption
12
Q
what are the five functions of the digestive system
A
- Digest - to break molecules into smaller molecules
- Secrete - the active release of a substance
- Absorb - movement of nutrients into from digestive tract into stomach or intestinal cells after digestion
- Excrete – elimination of non-absorbed or metabolic wastes
- Protect
13
Q
what is the gastrointestinal tract? does everything get absorbed in it?
A
The gastrointestinal tract (a.k.a. digestive tract) is a flexible muscular tube extending from the mouth to the anus
no many things pass through without being absorbed
14
Q
where does mechanical digestion begin
A
mouth
15
Q
give the three steps of mechanical digestion
A
- mouth shreds into smaller pieces; increase surface area
- adds water (saliva - enzymes)
- peristalsis liquifies and mixes (slows down in intestine)
16
Q
describe the 5 digestive juices and their functions
A
- saliva (mouth): amylase, lipase, neutralizes acid
- gastric juice (stomach): water, enzymes (mostly proteases), HCl. gastric mucosa provides protection
- bile (intestine): emulsifier. produced by liver – released by gall bladder
- pancreatic juice (intestine): enzymes, bicarbonate
- epithelial cell secretions: enzymes
17
Q
what is the primary site of absorption and what gets absorbed here
A
small intestine, nutrients, xenobiotics, chemical fragments reach the blood and lymph via intestinal epithelial cells
18
Q
what is the benefit of tight junctions
A
they form an extra barrier
19
Q
what are the 4 methods of chemical absorption
A
- transcellular
- paracellular
- transcytosis
- absorption into lymph
20
Q
explain how transcellular absorption works
A
through epithelial cells
21
Q
explain how paracellular absorption works and what are its limitations
A
sneaks through cracks
limited by size, lipophlicity and surface area
22
Q
explain transcytosis and what is it limited by
A
macromolecules transported through vesicles in the cell
limited by size, lipophlicity and surface area
23
Q
explain how absorption into lymph works
A
via M-cells of Peyer`s patches
24
Q
explain the degrees of surface area in the small instestine
A
small intestine has folds, folds have villi, each villus has microvilli
25
assuming a 24 transit time give the time breakdown in mouth, stomach, small intestine, large instestine
mouth = less than minute
stomach = 1-2 hours
small intestine = 7-8 hours
large intestine = rest
26
what is the secondary site of absorption, what is digested here, what happens to things that are not absorbed
large intestine
unabsorbed materials (fibres, xenobiotics) may be partially or completely digested by microflora
remaining material not absorbed = excreted as feces
27
explain the four steps of the hepatic portal system
1. blood enters general circulation by way of hepatic vein
2. liver monitors blood content
3. nutrient molecules travel in hepatic portal vein to liver
4. small intestine absorbs products of digestion
28
what can first-pass metabolism reduce / effect and how
first-pass metabolism (intestine and liver) can reduce bioavailability and effects of orally ingested bioactive substances
certain proportion is metabolized before they get absorbed
29
what are the 8 advantages to oral routes of exposure
- Most common, convenient, and economical ROA (drugs)
- Non-invasive, does not require sterility
- Used for local and systemic actions
- slow delivery into circulation (avoid spike and reduce toxicity)
- Larger dose can be given
- Large surface area for absorption
- When parenteral admin leads to irritation
- Toxicity can be reduced or reversed (e.g. activated charcoal, emesis)
30
what are 7 disadvantages to oral route of exposure
- Easy access for toxins (food, water)
- Variable rate of absorption
- Unsure patient compliance
- First-pass effects (metabolized before reaching site of action?) (but sometimes taken advantage of- PRODRUGS XXXX)
- Patient must be capable
- Poor absorption of lipophobic agents
- Drugs destroyed by digestive enzymes or gastric acidity
31
what is the enteral - sublingual route of administration
administration under the tongue
32
how do sublingual drugs diffuse
through oral mucosa into the capillary network to enter systematic circulation
33
what is the enteral - buccal route of administration
administration between the cheek and gums
34
how do buccal drugs diffuse
through oral mucosa into the capillary network to enter systemic circulation directly
35
what is the enteral - oral spray route of admin
literally using a mouth spray
36
how does mouth spray diffuse
through oral mucosa into the capillary network to enter systemic circulation directly
37
what are the 8 advantages of sublingual and buccal route of admin
- Rapid absorption
- emergency treatment
- Convenient, economical
- Non-invasive, does not require sterility
- Excess (drug) can be removed from mouth
- Avoids first-pass metabolism
- Avoids GI enzymes and pH
- Stability
38
what are the 10 disadvantages of sublingual and buccal route of admin
- Easy access for toxins (liquids, vapours, volatiles)
- Relatively uncommon
- less specialized transport
- Can’t use for drugs causing vasoconstriction of mucosa
- Cannot administer large doses
- Repeated exposure can damage oral mucosa
- Can irritate oral mucosa
- Can have unpleasant taste
- Advantages lost if swallowed once you swallow, it is not oging to be absrobted in the mouth, its going to go to the intestines for its absorption
- Unsure patient compliance
39
what are the 4 main veins/arteries in the rectum
1. superior rectal vein
2. inferior rectal vein
3. middle rectal artery
4. inferior rectal artery
40
is there a high or low abundance of blood and lymphatic vessels in the rectal wall
high, in sub-mucosal regions
41
where does the superior rectal vein drain into
portal circulation
42
where do the middle and lower rectal veins drain into
inferior vena cava
43
what are the 10 advantages of rectal route of admin
- Useful when oral administration is impractical
- unable to swallow
- coma / unconscious
- prior to x-rays
- children, elderly, uncooperative patients
- Useful when drug induces vomiting or irritates stomach
- delivery of antiemetics
- Excess (drug) can be removed
- Can partially avoid first-pass metabolism
- Avoids GI enzymes and pH
44
what are the 7 disadvantages of rectal route of admin
- Patient preferences
- Absorption is imperfect and unpredictable
- Degree of metabolism variable
- Cannot be used frequently
- repeated exposure can damage rectal mucosa
- Many drugs irritate the rectal mucosa
- Unsure patient compliance
45
what is parenteral admin
route of administration beside the intestine
46
what is parenteral route of admin used for
Used for substances that are unstable in (e.g. insulin) or poorly absorbed from the GI tract (e.g. heparin, anticoagulant)
47
how are parenteral drugs common administered
Often by injection (drugs, poisons) and inhalation or transdermal exposure (toxins, drugs) targeting local vs systemic effects
48
what is the most common parenteral route of drug admin
iv
49
what are some advantages of parenteral injections
- bypass first pass effect
- bypass all the barriers
- bioavailblity is much more predictable
- able to specifically target a location
- different angles you can inject it
50
give the angles for: intradermal, subcutaneous, and intramuscular iv injections
dermal = 10-15
sub = 45
intramusc = 90
51
what is the difference between injection and infusion
injection = one time thing. start at low rate then reach desired concentration slowly
infusion = constant amount being delivered, bypass the absorption phase. start at max concentration, then proceed to elimination stage.
52
how does iv represent 100% bioavailability
you get the highest value as soon as you inject, and then from there its just going to be in the elimination phase. you put the whole dose right into circulation. bypass adsorption and first-pass
53
what are the 8 advantages to iv route of admin
- Precise and accurate
- Immediate onset of action
- Can be controlled and adjusted for desired effects (infusion)
- large quantities over time
- Useful for comatose or unconscious organisms
- When substance induces vomiting or irritates stomach
- Avoids first-pass & GI tract
- Assures patient compliance (when not self-administered)
54
what are the 12 disadvantages to iv route of admin
- Greater risk of adverse effects and discomfort or fear
- High concentrations attained rapidly
- Irreversible
- Must be sterile – risk of infection
- Elevated risk of addiction
- Local irritation
- Risk or air emboli or particulate materials (e.g. glass)
- pH must match body fluids
- Limited volume to avoid phlebitis, pain and necrosis
- Need for skilled personnel, new sterile materials
- Higher costs
- Limited types of formulations
55
where is the intramuscular injection injected and why
Substance is injected deep between the layers of large skeletal muscles in vicinity of capillaries
because this area has a rich blood supply, fewer nerves
56
how does absorption from aqueous solutions work with intramuscular injections
Rapid diffusion through extracellular fluids and capillary endothelium to circulation
57
how does adsorption from depot preparations work with intramuscular injections
- nonaqueous vehicle (e.g. polyethylene glycol) diffuses out of muscle, leaving drug to precipitate at site of injection
- drug dissolves slowly – sustained dose
- sustained-release formulations
- emerging approaches (e.g. microspheres, liposomes)
58
what are common IM injection sites for children
- B) vastus lateralis muscle
- C) deltoid muscle
59
what are common IM injection sites for adults
- C) deltoid muscle
- D) buttock (dorsogluteal site)
- E) anterolateral thigh
60
what are the 11 advantages to IM route of admin
- Rapid onset of action (but not compared to iv)
- More predictable than po route (less predictable than iv)
- More convenient than IV route
- slower onset – longer duration
- practical outside clinical setting
- Can rotate between injection sites to reduce irritation
- When substance induces vomiting or irritates stomach
- Avoids first-pass & GI tract
- Assures patient compliance (when not self-administered)
- Route of choice in animals
- most suitable for excitable or difficult to restrain wild and zoo animals
61
what are 9 disadvantages of IM route of admin
- Only small volumes
- Risk of improper disposition in nerve, vasculature, fat, or connective tissue
- Not suitable for emergency situations restricting absorption and distribution
- Must be sterile – risk of infection or clot formation
- Local irritation
- Risk or air emboli or particulate materials (e.g. glass)
- pH must match body fluids
- Need for skilled personnel, new sterile materials
- Higher costs
62
how are subcutaneous drugs administered and why
Substance is injected into fatty tissue below the skin
because, rich blood supply, fewer nerves
63
what are some pros and cons to subcutaneous routes of admin
- Similar pros & cons to IM route
- slower absorption and distribution
- requires absorption but less blood supply and greater innervation (more painful)
- Limited to smaller volumes (<1.5 mL)
- Minimizes risks associated with IV
- Suitable for depot preparations
- especially with having air bubbles
- Not always injections
- implantation, programmable pumps
- Systemic (sometimes local)
- For local effects – co-administration with *epinephrine*
64
how are intraperitonial drugs administered and why
- Injection into peritoneum (body cavity)
- More often applied to animals than humans
- Useful when blood or fluid replacement is needed
- low blood pressure or other problems impeding IV
65
what are the advantages (5) and disadvantages (3) to intraperitonial route of admin
- Advantages
- Rapid absorption and onset of action
- Large volume may be injected
- When substance induces vomiting or irritates stomach
- Avoids first-pass & GI tract
- Route of choice in research animals (convenience)
- Disadvantages
- Irritant substances can cause peritonitis
- Risk of improper disposition into or puncturing of GI and abdominal organs
- Other risks associated with needles
66
what is intra-articular injections used for and why
used for carpal tunnel, inflammation, arthritis since the 1950s
because the drug is delivered straight to the joint
67
what are some advantages and disadvantages to intra-articular injections
- Advantages
- Direct local administration (highest concentration in the local area)
- Avoids first-pass & GI tract
- Well-established with low risk of serious adverse effects
- Disadvantages
- Required advanced technical skill
- Risk of damage to articular cartilage and joint
- Other risks associated with needles
68
what are intracardiac route of admin and an example of them
injection right to the heart
example = adrenaline for heroin overdoses
69
what is epidiural route of admin and what is it used for
injection into the epidural space (located in the spine between the vertebrae and the dural sac, which surrounds the spinal cord
used for childbirth, surgery, back, legs, palliative care
70
what are some advantages and disadvantages to the epidural route of admin
adv: passing all the biological barriers except the blood brain barrier, giving directly into a space that has access to the nerves around your spinal cord
dis: hurts, very invasive, may be put in the wrong place, requires lots of training
