unit two: general principals ll Flashcards
1
Q
what are the 3 divisions of pharmacology
A
- pharmacokinetics (what the body does to the drugs)
- pharmacodynamics
- toxicology
2
Q
what 4 factors are included in pharmacokinetics
A
- absorption
- distribution
- biotransformation (metabolism)
- elimination/excretion
3
Q
define pharmacodynamics:
A
- the study of the actions and effects of drugs on living organisms
- ‘what the drug does to the animal’
(main focus of this course)
4
Q
describe toxicology:
A
- the aspects that deal with adverse reactions to drugs
(not described in detail in this course)
5
Q
what might happen to the parts of the drug that do not reach the site of action?
A
- diverted to tissues
- broken down (metabolized)
- excreted before arriving at the site of action
6
Q
describe bioavailability
A
- the rate and relative amount of the administered drug that reaches systemic circulation UNCHANGED
7
Q
describe the cell membrane
A
- lipid-protein structure
- permeable to lipid-soluble materials
- watersoluble materials enter through pores in the cell membrane
8
Q
describe passive transport
A
- aka passive transfer
- the membrane is inert
- follows the concentration gradient
- no energy is expended
- 2 types (simple diffusion (fats), filtration through pores (water))
9
Q
describe specialized transfer
A
- the cell membrane plays an active part in the transfer of the substances through it
- 3 types: active transport, exchange diffusion, pinocytosis/phagocytosis
10
Q
describe active transport
A
- transport of a lipid-soluble drug from an area of low concentration to an area of high concentration (against the concentration gradient)
- requires energy
- is SELECTIVE
- may be inhibited by low body temperature
- may be competitively inhibited by chemically similar compounds
- may be saturated by high concentrations
11
Q
describe exchange diffusion
A
- the movement of WATER-SOLUBLE drugs through pores in cell membranes from an area of low concentration to an area of higher concentration
- the body pushes it in (like ringing out a sponge)
12
Q
describe pinocytosis/phagocytosis
A
- the process by which some cells are able to integrate new material by engulfing the drug molecule
- engulfing a solution: pinocytosis
- engulfing a solid: phagocytosis
13
Q
what are the 2 major factors that determine the rate and extent to which a drug is absorbed into the systemic bloodstream?
A
- ROA
- characteristics of the drug
14
Q
consequences of greater barriers (3)
A
- longer latent period
- less drug enters systemic circulation overall
- effects on the plasma drug concentration over time
15
Q
latent period
A
- delay between drug administration and effect
16
Q
the absorption of aqueous solutions injected IM or SQ depends on: (4)
A
- vascularity at the injection site
- vasoconstriction of vasodilation at the injection site
- the degree of ionization and lipid-solubility of the drug (fat or water-soluble)
- the area over which the injected solution has spread
17
Q
what helps increase blood flow to increase IM absorption? (4)
A
- fear and rage (increases endogenous epinephrine)
- epinephrine-like drugs
- heat
- massage
18
Q
what will decrease blood flow to decrease IM absorption
A
a drop in blood pressure
19
Q
why would we want to decrease the absorption rate?
A
- when a prolonged effect is desired
- to maintain an effective concentration in the blood (reducing the frequency of administration)
20
Q
how can we decrease the absorption rate of a drug? (4)
A
- adding a vasoconstrictor
- use a less soluble, salt form
- formulation in a water-repellant vehicle (makes the body work more)
- formulation for implantation under the skin
21
Q
how to increase the absorption of a drug?
A
- spread the drug over a larger area (massage, heat, pairing with an enzyme)
22
Q
what are the 2 steps needed for the absorption of a non-solution drug administered PO
A
- the release of the drug from its dosage form
- access and transfer across the gut wall into the hepatic portal system (first pass effect)
23
Q
where are oral drugs absorbed?
A
- the entire length of the GIT has absorptive capacity
- the stomach and SI are the most important sites of the absorption of drugs and nutrients
24
Q
what biological factors may affect the absorption of PO drugs
A
- status of the GIT (increased or decreased mobility?)
- interaction between the drug and other substances (chelation, mineral oil, food)
- decreased blood flow to the intestines (from shock or epinephrine)
- low pH
- ionization of the drug (non-ionized vs ionized)
- biological variation (animal-to-animal variation)
25
describe chelation
- a strong binding effect
- happens between tetracycline drugs and positively charged ions (Ca, Al, Mg) and minimizes its absorption
26
what effect does mineral oil have on drugs administered PO?
- decreases the absorption of highly fat-soluble drugs
27
what effect may food have on drugs administered PO?
- may increase the protein-binding of many drugs in the gut
28
what effect may a low pH of the stomach have on drugs administered PO?
the drug may precipitate (which is why some drugs say to give with food)
29
describe ionized and non-ionized drugs
Non-ionized drugs: are neutral and lipophilic and will pass through cell membranes
Ionized drugs: hydrophilic, will dissolve in tissue fluid
30
how is the drug absorbed if administered in the rectum
- absorption through the rectal mucosa
- this by-passes the liver
- the drug gets absorbed directly into circulation via the caudal vena cava
31
describe inhalation administration
- in healthy lungs, there is a very thin barrier between air and blood
- absorption is generally very fast because of the large SA of the alveoli and because of the extensive capillary network surrounding the alveoli
- excretion is also very rapid
32
describe the species variation of asprin
- is WELL absorbed by dogs and ponies
- POORLY absorbed by goats
33
describe the species variation of xylazine
- is more potent in cattle
- must be used with caution
34
what drug characteristic has the most impact on its ability to move through barriers?
its solubility
35
lipid-soluble drugs are well absorbed following which ROA?
oral administration (movement through the gut wall)
36
water-soluble drugs are well absorbed following which ROA?
IM or SC (moves readily through tissue fluid, can reach capillaries quickly)
37
what does drug distribution refer to?
- the movement of a drug from absorption into the bloodstream until reaching the site of action
- describes what happens to the drug once it enters circulation
38
what factors may affect the distribution of a drug once it has reached systemic circulation?
- plasma protein binding
- cell storage
- tissue storage (large storage, slow release)
- drug dilution
- barriers within the body (blood-brain barrier, placental barrier)
39
describe plasma protein binding
- once the drug reaches circulation, a portion of the drug becomes bound to plasma proteins (usually albumin)
- the amount varies with the drug
- be cautious if the animal has low protein levels
40
what are the characteristics of bound drugs?
- the drug cannot leave circulation (can't reach the site of action)
- not active (will not be metabolized)
41
what are the characteristics of free drugs?
- can leave circulation
- is active at the site of action
- reaches a dynamic equilibrium with a bound drug (when the free drug leaves the circulation, the bound drug is released from its binding site, and as binding sites on plasma proteins become ocupoied, the level of free drugs in circulation increases)
42
describe how cells store the drugs
- some drugs may become bound to protein cytoplasm constituents within tissue cells (dynamic equilibrium)
43
which tissues have an affinity for becoming storage depots?
- fat (#1)
- liver
- kidney
- connective tissue
- bone
- muscle
44
describe the blood-brain barrier
- barrier between the plasma and extracellular fluid of the brain
- highly protective
- allows nutrients to pass with ease
- highly lipid soluble
45
what may increase the permeability of the blood-brain barrier
- traumatic injury
- inflammation
- allergic reaction
- decreased blood pressure
- lack of oxygen
46
describe the placental barrier
- not as protective as the blood-brain barrier
- nutrients and drugs move primarily by simple diffusion from maternal to fetal blood
- highly lipid-soluble drugs move rapidly into fetal circulation
- highly ionized
47
describe the redistribution of drugs within the body
- describes the movement of a drug from systemic circulation into storage (and out of it)
48
what diseases may interfere with the redistribution of drugs
- heart failure
- shock
- kidney failure
- liver failure
49
what is biotransformation also known as?
drug metabolism
drug detoxification
drug inactivation
50
define biotransformation
- an enzyme-mediated chemical alteration of a drug molecule by the cells of an animal
51
what may biotransformation aid with
- may be necessary for excretion
- prevents accumulation of the drug and possible toxicity
52
how do lipid-soluble drugs get excreted (briefly)
- they are not readily excreted in the lipid-soluble state
- they get re-absorbed into circulation via the kidney
- metabolism results in a more ionized, water-soluble form of the drug which remains in, and is excreted with, the urine
53
what are the 2 major results of biotransformation
1. the metabolites formed are more polar and water-soluble.
* the metabolites are less likely to become bound to plasma or cell protein, and less likely to be stored in body tissue (eg. fat). results in the metabolites being less capable of passing through membranes and get filtered through the glomerulus and get excreted with urine
2. a change in the activity of the drug
54
where is the principal site of biotransformation?
the liver
55
where in the liver are the enzymes that aid with biotransformation reside?
smooth endoplasmic reticulum
56
which ROA required the drug to pass through the liver?
-PO
- intraparitoneal
57
besides the liver, where else may biotransformation occur (to a lesser degree)?
- kidneys
- lungs
- blood
- gut wall
- gut content (normal flora)
58
what may occur if a dog is fed too many liver treats?
overdose of vitamin A
59
describe phase one of drug biotransformation
- non-synthetic reaction
- involves natural biochemical reactions (oxidation, reduction, hydrolysis)
60
describe phase two of drug biotransformation
- is a synthetic reaction called conjugation
- the enzymes in the liver facilitate the attachment of an endogenous substance to lipophilic drug molecules. Glucuronic acid increases water solubility of lipophilic drug
61
what factors affect drug biotransformation (11)
1. age
2. gender (eg. hormones)
3. species differences
4. body temperature
5. liver pathology
6. nutritional status
7. plasma protein binding
8. localization of the drug in tissue sites (get stuck)
9. ROA
10. other drugs
11. previous exposure to the drug
62
how may age affect drug biotransformation
- if they are too YOUNG they may be deficient in drug-metabolizing enzymes
- if too OLD they may have a decreased ability to synthesize the appropriate enzymes to metabolize the drug
63
What is the component of chocolate that dogs cannot break down?
theobromine
64
what 2 situations could occur when more than one drug is present?
- drug B may inhibit the enzymes needed to break down drug A which increases the duration drug A stays in the body
- Drug B stimulates the enzymes needed to break down drug A decreasing the amount of time it spends in the body
65
what effects may constant exposure to a drug have
- the liver may get better at metabolising the drug
- the enzyme required to metabolize the drug may have a higher resting concentration
- may become tolerant or resistant to the drug
66
define tolerance
- a decreased response to a drug resulting from repeated use
- tolerant animals require larger doses
- 2 types, metabolic and cellular
67
describe metabolic tolerance
the drug gets metabolized more quickly
68
describe cellular tolerance
decreased cellular receptors with repeated use
69
for most drugs, what is the most important factor for regulating drug levels in the blood?
biotransformation
70
what are the main organs of drug excretion?
- liver
- kidney
- lungs, milk, semen, sweat, and saliva
71
describe excretion by the liver
- eliminates both fat and water-soluble drugs and their metabolites via the bile (therefore gets excreted with fecal matter)
72
describe the excretion by the kidney
- eliminates water-soluble material
- excreted either by glomerular filtration or tubular secretion `
73
describe glomerular filtration
- most drugs are filtered from the blood capillaries of the glomerulus through pores in the glomerular membrane
- gets into the filtrate and passes into the tubules
- IF water soluble they will remain in the filtrate and will be passed out in the urine
- IF lipid-soluble, will be re-absorbed through the cells lining the tubule, and re-entry into the blood may occur (the drug will get re-broken down until it can be excreted)
74
what effects kidney filtration rate>
- the rate of blood flow through the kidney
- the extent of plasma protein binding of the drug
75
can protein-bound molecules be filtered through the glomerulus?
no
76
describe tubular secretion
- some drugs (eg. penicillin) bypass glomerular filtration
- gets actively secreted by the tubular cells from the blood into the urinary filtrate
- is an active transport system (uses enzymes and energy)
77
what is the danger of biotransformation resulting in a less soluble form than the original?
- the increased danger of drug precipitation in the kidney tubules
- is also why water is important during treatment
- kidney/bladder stones
- this is one of the dangers of taking vitamins
78
describe excretion by the liver
- liver cells excrete some drugs and metabolites into bile (subsequently the intestines). The drug could be changed or unchanged
- more commonly an entero-hepatic cycle will be established and the drug is metabolized
79
describe an entero-hepatic cycle
1. the liver cells change the drug into a metabolite
2. the metabolite is either: returned to the blood and excreted by the kidney
OR secreted into the bile
OR lipid-soluble drugs transported via bile into the SI may be reabsorbed into the venous system and returned to the liver
3. once back in the liver the drug/metabolite may then be:
- acted on by liver cells
- passed to the kidney in blood for excretion
- secreted by bile into the intestine for further reabsorption or excretion in the feces
80
why may drugs appear in the feces
- result of entero-hepatic process
- PO drugs that aren't absorbed and remain in the GIT for excretion
- drugs intended to act in the gut
- drugs that are secreted from the plasma across the intestinal wall
81
how do the lungs excrete drugs?
- rapid absorption and excretion
- oxygen is the carrier
82
describe excretion by milk
- many drugs readily form circulation into the milk of lactating females
- of particular importance when antibiotics are used (must adhere to withdrawal time)
- may lead to drugs accumulating in the newborn because their drug-metabolizing enzymes are not fully developed
83
describe excretion by semen
- limited information \
- drugs can penetrate the seminiferous tubules of the testes and have an effect on stored sperm
84
how are drugs transmitted via sweat and saliva
- not of great significance
- important for forensics
85
in what circumstances is drug activity terminated?
- drug stored in any site other than the site of action
- biotransformation
- excretion from the body
86
what are the mechanisms of drug action
- drug action
- drug effect
- clinical response
87
describe drug action
- the METHOD by which a drug influences cell function
- does not have to be a body cell (eg. antibiotic)
88
describe drug effect
- the RESPONSE to the drug action
- is a detectable change following an alteration in cell function
- a change due to the interaction between drug molecules and the components or contents of tissue cell
89
describe clinical response
- the observable or measurable change in the condition of the animal as a result of drug effect
- can have multiple
- not just visual (holistic)
90
describe drug receptors
- specific sites within the tissue cells of target organs upon which the drug molecules react
- they are: 3-D molecules
- usually protein in nature
- are enzymes or enzyme- like
- they are cell and drug specific
91
describe the lock-and-key method
- when a drug molecule fits into a receptor site and interacts with the cellular components
- a biological effect is produced (eg, secretion, contraction, depolarization)
92
describe drug molecules
- are 3-D
consist of 2 parts
1. the part that attaches to the drug receptor area suggesting the drug has an affinity for that receptor
2. the part that results in an exact fit between the molecule and the receptor
'lock and key'
93
what does the action of a drug depend on (2)
- its affinity for a drug receptor(the drug can fit but not perfectly, blocking the receptor)
- its efficacy for a drug receptor (the drug is a perfect fit and will cause a biological effect)
94
describe an agonist when referring to the lock and key method
- a drug with both affinity and efficacy for the drug-receptor (a perfect fit)
- positive drug action when it reaches a receptor
95
describe a partial agonist when referring to the lock and key method
- a drug that can complex with a receptor but produces only a weak response (good affinity, partial efficacy)
- (can be seen as a secondary effect of the drug)
96
describe competitive antagonist
- a drug that reacts with and fills a receptor site but does not elicit a response (high affinity but no efficacy)
- they take the place of an agonist on a receptor and block the attachment of the agonist
- reversal agents and poison antidotes are often based on this drug action
97
what is Vodca used for?
ethylene glycol
98
what are the 2 types of outcomes for potential drug action
enhancement or interference
99
what are the 8 types of drug action
1. interferes with the way cells are maintained
2. may influence the bound forms of physiologically active substances
3. chelation
4. influence biological control systems
5. be an antagonist
6. cause a biological antagonist
7. may be a replacement for inadequate levels (eg. hormones, vitamins)
8. may act on the NS
100
how may drugs interfere with the way cells are maintained, affecting drug action
- the drug may change enzyme activity or metabolism within the cell
- may alter the movement of substances into or out of the cell
101
how may influence the bound forms of physiologically active substances, affecting drug action?
- the drug may displace a hormone bound to plasma protein or attached to tissue sites, thus making the hormone more active (bound vs non-bound)
- can knock molecules off leading to toxic levels
102
describe chelation
the drug binds the a substance without chemically altering either
103
how may drugs influence biological control systems, thereby affecting drug action
- by activating enzymes or causing the release of chemical messengers
(catalyst)
104
how may a biological antagonist be used to affect drug action?
- the drug will enter the metabolic process of a cell and inhibit the process
- this changes the function of the cell
105
how may drugs act on the NS to affect drug action?
- influence neurotransmitters in a number of ways
*mimicking the action of the neurotransmitter
*blocking the action of the neurotransmitter
* inhibiting neurotransmission production
*accelerating neurotransmission production
106
describe adverse drug reactions
- an undesirable response to a drug
107
what does the type of adverse reaction depend on?
- characteristic of the drug
- quality or purity of the drug
- the amount of drug used
108
describe synergistic effect
- 2 drugs are given together and work together
- can allow you to administer less of the drug therefore the patient will have less severe side effects
109
describe drug interactions
- an altered pharmacological response to a drug caused by the presence of a second drug
- can be beneficial or have no impact
110
describe the therapeutic index
- the relationship between the drug's ability to achieve the desired effects and its tendency to produce toxic effects
- expressed as a ratio between LD50 and ED50
LD50/ED50
- the larger the index, the greater the margin of safety
111
LD50
lethal dose 50
- the dose that is lethal to 50% of animals when administered in a dose-related trial (everything has an LD50)
112
ED50
effective dose 50
- the dose of the drug that produces the desired effect in 50% of animals when administered in a dose-related trial
