Unit 1 Flashcards
(187 cards)
1
Q
Name two ways drugs are excreted from the body
A
Excretion (drug eliminated intact)
Biotransformation (elimination of metabolite)
2
Q
What are the possible results of biotransformation of a drug?
A
Inactive metabolites
Active metabolites
Toxic metabolites
3
Q
What (generally) is Phase I Biotransformation?
A
Change in structure of a drug to form more polar metabolites, which can be active, toxic, or inactive.
4
Q
What is (generally) Phase II Biotransformation?
A
Conjugation of endogenous structure to a drug to form a larger, polar, almost always inactive metabolites.
5
Q
What (specifically) is Phase I Biotransformation?
A
Reduction
Oxidation
Hydrolysis
6
Q
What (specifically) is Phase II Biotransformation?
A
Glucuronidation Acetylation Methylation Sulfation Conjugation to amino acid (glycine) Conjugation to glutathione
7
Q
Why are drugs metabolized differently by different species?
A
Variations in the types of CYP enzymes (cytochrome p450) that the animal expresses.
8
Q
Where does drug biotransformation occur? (6 sites)
A
LIVER Plasma/Blood Kidney Lung Intestinal mucosa GI flora
9
Q
What is a first order process?
A
When drug ADME increases proportionally with drug concentration (linear process on a log scale graph).
Seen before a biological system (transporter, enzyme) is saturated.
10
Q
What is a zero order process?
A
When drug ADME does not increase proportionally with drug concentration (non-linear process on a log scale graph).
Seen after a biological system (transporter, enzyme) is saturated.
11
Q
Name two differences that could result in differing drug metabolism between species or groups.
A
Enzyme structures (mutations, etc) Enzyme availability at site of biotransformation
12
Q
Why is acetaminophen dangerous for cats?
A
Slow rate of acetaminophen glucuronidation = greater saturation of enzymes = greater plasma drug concentrations = methemoglobinemia
13
Q
Why is piroxicam longer lasting in dogs than in cats?
A
Cats oxidize drug more quickly than dogs.
14
Q
Why do dogs eliminated sulfonamide antibiotics by alternative routes?
A
They lack N-acetyl transferase.
15
Q
Why do cats have low elimination rates of sulfa drugs?
A
They lack N-acetyl transferase 2 and so have lower acetylation rates.
16
Q
Why does azathioprine lead to myelotoxicity in cats?
A
They have low thiopurine methyltransferase activity.
17
Q
What group exhibits slow propofol elimination?
A
Greyhounds
18
Q
What group exhibits neurotoxicity with ivermectin?
A
White feet don’t treat
MDR-1 mutants, often seen in collies, aussies, long-haired whippets, border collies, etc.
19
Q
What is enzyme induction?
A
When a drug increases the rate of transformation of another drug.
20
Q
What is enzyme inhibition?
A
When another drug or a systemic process decreases the rate of transformation of a drug.
21
Q
What is first pass loss?
A
Biotransformation of the drug before it reaches systemic circulation. Mainly from the liver but also can be seen in GI tract, with flora, through kidneys in some species, etc. Also will be affected by induction or inhibition of biotransformation.
22
Q
What reaction do CYP enzymes facilitate?
A
Microsomal oxidation.
23
Q
What transport mechanism is severely inhibited by chemotherapeutic drugs?
A
P-glycoprotein mediated excretion of conjugated drugs into the biliary system.
24
Q
What are the three processes of excretion in the kidney and which is the most important?
A
SECRETION
Filtration
Reabsorption
25
What type of molecules are secreted by the kidney?
small, polar, unbound
26
What type of molecules are filtered by the kidney?
small, polar, unbound
27
What type of molecules are reabsorbed by the kidney?
small, non-polar, unbound
28
What are the body's routes of excretion? (6)
```
Renal
Gastrointestinal (biliary)
Pulmonary
Mammary
Sweat
Saliva
```
29
Does milk trap acids or bases?
Bases. Milk has a significantly lower pH than plasma.
30
To produce a pharmacological effect, what three things must a drug be in the body?
Present at site of action
At a sufficient concentration
For a specific period of time
31
What does a pharmacokinetic study of a drug entail? (4)
Drug administration route
Blood sampling over set periods of time
Determination of drug concentration in each sample
PK analysis
32
What is a pharmacokinetic parameter?
A mathematical model of drug in the body over time.
33
What are the dose dependent PK parameters?
Cmax
| AUC
34
What are the dose independent PK parameters?
```
Tmax
Bioavailability
Clearance
Volume of drug distribution (Vd)
Half-life
```
35
What does Cmax represent?
Maximal concentration of the drug in the plasma, directly proportional to dose. With a larger Cmax, should see a larger intensity of pharmacological effect.
36
What does AUC represent?
Area under the curve - reflects exposure to drug and duration of drug. Will also be affected by formulation and route of drug administration.
Directly proportional to dose and bioavailability.
Inversely proportional to drug clearance.
37
By increasing the dose of a drug, what will you see in the patient?
Increased intensity, duration, and exposure to the drug.
38
What does Tmax represent?
Time to Cmax. May be close to time of drug onset, but not always.
39
How much drug will be eliminated after 5 half lives?
97%
40
How much drug will be eliminated after 10 half lives?
99.9% - effectively all, drug considered to be gone from the body.
41
How can drug bioavailability be used to calculate extravascular doses?
EV dose = IV dose / F
42
What is F defined as?
Bioavailability: the rate and extent of drug absorption after extravascular drug administration.
F = AUC EV / AUC IV
43
Name some factors that will affect F.
```
Liver disease
Concurrent drugs acting as liver enzyme inducers/inhibitors
Compounded formulations
GI disease (oral administration)
Dehydration
```
44
What is the formal definition of clearance?
The rate of drug elimination scaled by plasma drug concentration.
45
What is the operational definition of clearance?
The volume of plasma cleared of drug per unit time.
46
What is Vd?
Volume of distribution - reflects the dilution of drug in the body. Value is proportional to the amount of drug in the target tissue vs amount of drug in the blood.
47
What are the consequences of a low Vd?
Most of drug in blood rather than target tissue, leading to slow or limited intensity of effect.
48
What are the consequences of a high Vd?
Most of drug in target tissue rather than blood, faster or greater intensity of effect.
49
What may cause a low Vd?
Extensive binding of drug to plasma proteins
| Physical barrier that does not allow much drug passage (like blood brain barrier)
50
What may cause a high Vd?
High numbers of binding sites in tissues
Lipid soluble
Ion trapped in non-plasma compartments
51
Is a drug with a low or high Vd more likely to be reabsorbed by the kidney?
High Vd. Low Vd is likely to be protein bound and so not filtered in the first place. High Vd is more likely to be lipid soluble and so passively is reabsorbed from the renal tubules due to concentration gradient.
52
What physiologic conditions can affect Vd and how? (4)
Pregnancy - increase Vd of water soluble drugs
Neonatal animals - increase Vd due to lower extent of plasma protein drug binding
Ruminants - increase Vd of water soluble drugs
Excitement/Exercise - increase Vd by increasing blood flow to organs and thus speeding up distribution.
53
What pathologic conditions can affect Vd and how? (3)
Shock - decrease Vd by slowing blood flow to organs and thus slowing distribution.
Obesity - increase Vd of fat soluble drugs
Ascites - increase Vd of water soluble drugs
54
What is t1/2?
Drug half life: the time it takes to decrease the plasma drug concentration by one half.
55
Give the equation to calculate half-life
T1/2 = (0.693 x Vd) / CL
Directly proportional to Vd (more drug in plasma, faster elimination)
Inversely proportional to clearance (less drug being cleared, longer life of drug in plasma).
56
What is the therapeutic window?
The dose range between the maximum tolerated drug concentration and minimum effective drug concentration. In this range the drug should be both safe and effective.
57
What is the MOS?
The size of the therapeutic window (maximum tolerated drug concentration - minimum effective drug concentration).
58
What does a non-linear PK mean clinically?
You cannot predict how fast the plasma drug concentration will increase or decrease in the body, or exactly what final plasma concentration will be reached.
It doesn't mean you CAN'T safely increase the dose, but you just don't know.
59
When can you increase the dosage of a drug safely in a patient?
When the MOS is large and the drug has LK.
60
When is it unsafe to increase the dosage of a drug in a patient?
When the MOS is small or the drug has NLK.
61
When might you consider a CRI clinically?
When half life of drug is very short
| When drug is dangerous (so you can avoid peaks in Cp)
62
How long does it take you to reach Cplat when giving a CRI?
5HL (only 97% technically, but functionally this is going to work well)
63
What should your CRI loading bolus be?
Double the desired Cplat for one half life of the drug, then reduced.
64
What is the danger of a loading dose?
If adverse reactions are seen with the drug, there is no way to stop the drug before Cplat is reached, so it will take longer for drug amount to be eliminated to safe amounts in the body (i.e. if drug started causing harmful side effects at 0.5 Cplat it will take one more half life for drug to be eliminated to non-toxic doses)
65
How long does it take to reach a new Cplat when adjusting the rate of a CRI?
5HL
66
What is infusion rate?
Amount of drug per unit time given in a CRI (mg/ml)
67
What is flow rate?
Volume of solution per unit time given in a CRI.
68
What is the physiological meaning of the Cplat?
A point at which rate of infusion = rate of elimination.
69
With intermittent dosing, what is Cp max?
Maximal concentration of drug reached after first administration
70
With intermittent dosing, what are Css min and Css max?
Concentrations of drugs reached at plateau / steady state.
71
With intermittent dosing, what is Css ave proportional too?
Directly proportional to dose.
| Inversely proportional to dose interval.
72
When will a drug accumulate in the body during intermittent dosing?
When the dosing interval is less than 3 half lives.
73
With intermittent dosing, what is the RDI and what does it mean?
Relative Dosing Interval
| Predicts the rate of drug accumulation in the body due to drug half life and dosing interval.
74
What is the mathematical formula for RDI?
RDI = DI / HL
75
Predict the rate of drug accumulation with a small RDI.
Fast (especially if fractional)
76
Predict the rate of drug accumulation with a large RDI.
Slow (or none if greater than 3)
77
What does the Accumulation Factor (FAC) represent?
Inverse of the fraction of drug lost during the dosage interval.
78
What is the relationship between the RDI and the FAC?
Inversely proportional.
79
How do you calculate a loading dose with intermittent dosing?
Loading dose = maintenance dose x FAC
80
How many doses does it take to reach steady state with intermittent dosing?
5HL / dosing interval
81
How is RDI related to fluctuation?
Css max / Css min = 2 RDI
82
How can amount of fluctuation be reduced with intermittent dosing?
Smaller doses of drug more at smaller dosing intervals.
83
Define pharmacology.
The study of how drugs are handled by the body and why they produce an effect.
84
Define pharmacy.
The study of dispensing or delivering drugs to a patient.
85
Define toxicology.
The study of undesired effects of an agent on the body.
86
Explain the difference between a targeted and non-targeted drug mechanism.
Most drugs bind to a specific target, either activating or inactivating that target. This allows for drugs to be selective in their effects. Non-targeted drugs change the environment instead - change pH, ion concentration, osmolarity, etc. These drugs include salves, chelators, and antacids and have no specific targets.
87
Name the five most common examples of drug targets.
```
Receptors
Ion channels
Enzymes
Nucleic acids (DNA/RNA)
Membrane transport proteins
```
88
What determines the speed of onset of a drug?
Pharmacokinetics
| Type of receptor the drug binds (pharmacodynamics)
89
What is a receptors normal role?
Monitor and respond to cell external environment.
90
Name four categories of receptors and how fast each can respond to stimulation
Ligand gated ion channels (msec)
G-coupled protein receptors (sec to mins)
Receptor regulated enzymes (mins to hours)
Intracellular receptors (hours to days)
91
Name one example of a receptor in each class.
Ligand gated: Nicotinic acetylcholine receptor, glutamate or GABA receptors, serotonin receptors.
GPCR: Muscarinic acetylcholine receptor, histamine receptors, opioid receptors.
Receptor-regulated enzymes: Tyrosine kinase receptors for insulin or growth factors, guanylyl cyclase.
Intracellular: Steroid receptors, thyroid hormone receptor, Vitamin D receptor.
92
Name one drug example for a receptor in each class.
Ligand gated: Ketamine
GPCR: Epinephrine, opioids
Receptor regulated: Insulin
Intracellular: Corticosteroids
93
Name one drug example that binds a non-ligand gated ion-channel.
Lidocaine (and other local anesthetics) - binds and inhibits voltage-gated Na+ channels.
94
Name one drug example that binds an enzyme.
NSAIDs (Inhibit COX enzymes)
95
Name three ways that drugs that bind enzymes may work to produce an effect.
Inhibit production of transmitter/hormone - onset of action as endogenous protein breaks down.
Inhibit breakdown of transmitter/hormone - onset of action is as more endogenous protein is created.
Inhibiting intracellular enzymes to change cell signaling pathways.
96
Name one drug that binds a membrane transport protein.
SSRI - prevents the reuptake of serotonin by presynaptic neurons.
97
Name one drug that binds DNA or RNA.
Antineoplastics (doxorubicin) and antivirals (pyrimidine nucleoside analogs)
98
Name some examples of non-targeted drugs
```
Chelators
Salves
Pore-forming antibiotics
Antacids
IV fluids (electrolytes)
Osmotic agents (mannitol)
```
99
Name a drug with an unknown mechanism
Anesthetic agents (isoflurane, propofol). Not known if these are targeted or non-targeted. Act at least in part by binding to glycine and GABA receptors, but more is going on.
100
What does a drug do when it binds to a receptor?
Stabilizes either the active (signaling) state or inactive (non-signaling) state.
101
What is drug affinity?
The ability of a drug to bind a receptor.
102
What is drug efficacy?
The ability of a drug to produce a response.
103
Name three types of efficacy
```
Receptor efficacy (molecular)
Cellular efficacy
Clinical efficacy (response in whole animal)
```
104
What is an agonist?
Ligand that activates a receptor. Can be full or partial.
105
What is an antagonist?
Ligand that stabilizes inactive state of a receptor.
106
What determines the efficacy of an antagonist?
Concentration/tone of the endogenous agonist that the antagonist is blocking.
107
What does Kd define?
The concentration of a drug required to occupy 50% of receptors at equilibrium.
108
What is the relationship between Kd and affinity?
Inversely proportional.
109
What is the relationship between Kd and receptor efficacy?
There is none. Kd tells us that a drug can bind, but does not tell us if it produces an effect.
110
How do you measure cellular efficacy of a drug?
A biological assay - example given is piece of ileum in a physiological bath that includes drug, where force of contraction of the tissue is measured.
111
What type of graph is created while measuring cellular efficacy?
Dose-response curve.
112
What is the EC50?
The concentration of drug required to produce 50% of the maximal effect of the drug.
113
How is EC50 related to efficacy?
Inversely proportional.
114
How is EC50 related to affinity?
It is not related. Drugs with low affinity for receptors can still be efficacious.
115
How do Kd and EC50 compare for an agonist at a clinical or cellular level? What is the name of this effect?
Kd > EC50
This indicates the presence of SPARE RECEPTORS - a large effect is being produced with only a small percent of receptors bound.
116
How do Kd and EC50 compare for an antagonist at a clinical or cellular level? What is the name of this effect?
Kd < EC50
This indicates a THRESHOLD EFFECT - a smaller effect is being produced with a large percentage of receptors bound - generally antagonists must bind a large percentage of receptors in order to block endogenous agonist (consider the endogenous agonist to usually have a spare receptor effect).
117
How do EC50 and Kd relate at the molecular level?
Generally at a molecular level, Kd50 and EC50 are very well correlated.
118
What does potency mean?
The concentration of a drug needed to produce a CLINICAL effect. Highly potent drugs require only a small concentration of drug to be effective.
119
How do low potency drugs relate to high potency drugs in terms of ability to produce a clinical effect?
They both can create the same effect, but the low potency drug will need to be at a higher concentration.
120
How might a high affinity drug have a low potency?
Drug has low efficacy
Drug does not gain access to site of action
Drug is rapidly metabolized or excreted.
121
Relate stereoisomers to drug affinity.
Different stereoisomers of the same drug have different binding affinities, as receptors are proteins which have chiral amino acids.
122
Name the four most common forces involved in drug-receptor binding from strongest to weakest.
Ionic interactions
Hydrogen bonds
Hydrophobic interactions
Van der Waal's forces
123
Most drugs bind (BLANK) with (BLANK) interactions.
Reversibly
| Non-covalent
124
Name one notable drug that binds irreversibly
Aspirin - forms a covalent interaction with cyclooxygenase.
125
Name one advantage of high potency drugs
Only need a small volume (good for darts or if drug is expensive)
126
Name one disadvantage of high potency drugs
Easy to overdose.
127
How is a partial agonist defined?
Produces only partial activation of receptors even if high proportion of receptors are bound.
128
What determines the effect of an agonist?
The ABSOLUTE NUMBER of receptors bound.
129
Name and define the three classes of antagonists.
Pharmacological antagonists - bind to the same receptors as agonists and stabilizes their inactive state.
Physiological antagonists - oppose action of agonist by binding another receptor that activates an opposing signaling pathway. This may be on the same cell or in an entirely different system.
Pharmacokinetic antagonists - Removes the agonist from the system by binding to the agonist directly or reducing the absorption of the agonist.
130
What are the two types of interactions that pharmacological antagonists can have with agonists?
Simple competitive interactions: Binds reversibly at the same site of the agonist - can be overwhelmed by high concentrations of the agonist so generally must be used at high concentrations.
Noncompetitive interactions: Either binds irreversibly at the same site as the agonist or binds at another site that prevents receptor activation even if the agonist is bound. Can be used at lower concentrations.
131
Which class of antagonists is the safest?
Pharmacological antagonists - these have the most predictable effects.
132
What is an inverse agonist?
Ligand that binds to a receptor that is NORMALLY in a signaling state and causes inactivation of that receptor. Relatively rare.
133
Why does an anti-histamine do nothing if you are not having an allergic reaction?
Basal histamine tone (concentration) is very low. Anti-histamines are antagonists of histamine receptors, and if they block histamine receptors when there is no histamine present there is no observed clinical effect.
134
What is a Quantal Dose-Response Curve?
A cumulative frequency curve that allows for comparison between individual responses in a population of animals.
135
What is a therapeutic index?
An ARBITRARY ratio between dose that is effective for some percentage of the population and dose that is toxic or lethal to some percentage of the population.
136
What is a safety factor?
Same as therapeutic index.
137
What is ED50?
Dose that is effective for 50% of the population.
138
What is TD50?
Dose that is toxic for 50% of the population.
139
What is LD50?
Dose that is lethal for 50% of the population.
140
How is therapeutic index calculated?
BAD % / Good %
So, LD50 / ED50
Or, TD3 / ED97
Or any combination of bad/good
141
What are some major problems with using the therapeutic index as a reference?
Often the % values used are not defined
Varies greatly between species
What severity of problem is considered "toxic?"
What type of therapeutic effect is considered "effective?"
How steep is the quantal curve for toxicity?
Are the effects of chronic toxicity accounted for or only acute toxicities?
142
What are two better measures of drug safety?
LOAEL: lowest observed adverse effect level
NOAEL: (greatest) no observed adverse effect level
143
What are the two types of adverse reactions?
Type 1/A: Dose-related, predictable toxicity. Will occur in all individuals with high enough dose.
Type 2/B: Idiosyncratic toxicity, due to some abnormality of the individual - often allergic.
144
What are the causes of Type 1 toxicity?
Over activation of normal target
Activation of lower-affinity non-target receptors at higher dose
Cytotoxicity/organ toxicity
Pharmacogenetics - when an individual has some sensitivity to a drug but effects are still dose related (white feet and ivermectin)
145
What are the causes of Type 2 toxicity (types of immune reactions)?
Type I - anaphylaxis due to release of histamine. Requires previous exposure.
Type II - cytolysis due to formation of antigens on cells
Type III - creation of immune complexes
Type IV - delayed hypersensitivity/cell-mediated
146
Define pharmacokinetics
The study of the time course of a drug in the body.
147
Name the four physiologic processes that pharmacokinetics examines
Absorption
Distribution
Metabolism
Excretion
148
What are the two phases of absorption?
Introduction of the drug into the body
| Movement across several semipermeable membranes into systemic circulation (if IV, no absorption necessary)
149
What 5 factors affect drug absorption?
Route of drug administration
Availability of drug at site of absorption
Local blood flow to site of administration
Physical barriers
Drug physicochemical properties
150
Name 3 ways a drug can pass through the endothelium
Transcellular (passive diffusion through membrane)
Paracellular (between cells)
Facilitated transport
151
When is drug influx rate by transporters directly proportional to drug concentration?
When transporters are not yet saturated.
152
What are the physicochemical properties of a drug that is rapidly absorbed?
Lipid soluble (non-polar)
Small (low molecular weight)
Non-ionized
153
What is the general mechanism of ion trapping?
Only uncharged molecules can pass through lipid membranes.
If a basic molecule passes into an acidic environment, it will become ionized and thus be trapped in tissues, and the same will happen with an acid in a basic environment.
Remember, acids and bases are at an ionized/non-ionized equilibrium, so may not trap all drug but will trap some.
154
What are the advantages and disadvantages of oral drug administration?
A: easy
D: slow
155
What are the advantages and disadvantages of topical drug administration?
A: easy, non-invasive
D: May cause unwanted effects if animal licks or damaged skin allows systemic access
156
What are the advantages and disadvantages of mucosal drug administration?
A: Fast, good for local effects
D: May gain access to systemic circulation
157
What are the advantages and disadvantages of parenteral (IV, IM, SQ, IP) drug administration?
A: Fast
D: May cause local tissue damage, harder to administer
158
What are the advantages and disadvantages of aerosol drug administration?
A: VERY fast
D: Airway irritation
159
What variables affect enteric drug absorption time?
Presence of food in stomach
pH of stomach/intestines
Intestinal flora loads
Gastric/intestinal transit time
Potential drug interactions/precipitation of drug
First pass effect
Formulation (must be in aqueous solution to be absorbed)
160
What are the various oral drug formulations?
```
Tablets
Capsules
Aqueous solution
Aqueous suspension (particles settle)
Carriers
Implants
```
161
What is distribution?
The reversible process of drug moving out of blood into the tissues. Again must pass through endothelium.
162
What four factors does drug distribution influence?
Onset of action
Intensity of effect
Extent of effect
Adverse reaction
163
What four factors influence drug distribution?
Blood flow to organs
Tissue barriers (ie BBB)
Drug physicochemical properties
Plasma protein binding
164
What is the difference between a physical and functional barrier?
Physical - drug cannot pass due to physicochemical properties
Functional - drug can pass through membrane but is rapidly excreted by efflux transporters.
165
Which tissues have greatest blood flow (and thus most rapid absorption/distribution)?
```
CNS
Liver
Lung
Gut
Kidney
Heart
Exercising muscle
```
166
Which tissues have least blood flow (and thus least rapid absorption/distribution)?
Skin
Fat
Bone
Resting muscle
167
When is a drug considered highly bound in the plasma?
If >80% drug is protein bound at equilibrium.
168
Name the 7 physiologic/pathogenic conditions that affect distribution.
```
Ascites
Shock
Obesity
Pregnancy
Excitement/Exercise
Ruminants
Neonates
```
169
Define tolerance.
Repeated administration of the same dose of drug fails to produce the same magnitude of response.
170
What are the three general mechanisms for tolerance?
Pharmacokinetic
Pharmacodynamic
Physiologic
171
What is pharmacokinetic tolerance?
The change in the metabolism rate of a drug, usually by the drug inducing liver enzyme functions.
172
What is pharmacodynamic tolerance?
Change in receptor number or desensitization (conformation change) of a receptor.
173
What is physiologic tolerance?
Loss/exhaustion of an endogenous mediator the drug releases or physiological adaptations of another system to compensate for changes due to drug.
174
Why is it dangerous to stop beta adrenergic antagonists quickly?
The antagonist causes pharmacodynamic tolerance of the drug by increase in production of receptors so that the endogenous agonist is able to produce a large enough absolute number of bound receptors to produce an effect. Then if the drug is withdrawn the endogenous agonist produces a huge effect which can be dangerous.
175
How can cross-tolerance be produced?
Can see cross-tolerance when drugs have very similar mechanisms of action or drugs act on the same receptor.
176
What is tachyphylaxis?
Aka desensitization. The very rapid onset of (and very rapid recovery from) tolerance.
177
What is refractoriness?
A loss of drug therapeutic effectiveness.
178
What is drug resistance?
Generally used with microbial resistance.
179
What is sensitization?
The opposite of tolerance - when repeated administration of a drug produces increased effects. Thought to be important with drug abuse.
180
What are the three major mechanisms of drug-drug interactions?
Pharmacodynamic: Drugs act at the same receptor.
Physiologic: One drug changes target receptor expression of another drug or changes physiologic parameters like osmolarity in the body that changes the action of another drug.
Pharmacodynamic: one drug changes the ADME of another drug.
181
What will be the pharmacodynamic action of two agonists?
Generally will not see any change in effect, especially as cross tolerance is prone to develop.
182
What will be the pharmacodynamic action of an agonist and an antagonist?
Generally the agonist will be ineffective, though some change might be seen at high concentrations if the antagonist is competitive rather noncompetitive.
183
What will be the pharmacodynamic action of two antagonists?
Generally will not see any change in effect (remember that antagonists already must be present at a very large percentage of receptors to be effective).
184
How can pharmacokinetic drug-drug interactions change absorption? Give one example.
They can change the amount of drug available to be absorbed (GI chelators or activated charcoal) or alter the pH state of the drug (antacids in GI)
185
How can pharmacokinetic drug-drug interactions change distribution? Give one example.
They can competitively displace drug from plasma or tissue proteins (aspirin and thyroxine) or cause increased sequestration in tissues (diuretics and ahminoglycosides causing ototoxicity).
186
How can pharmacokinetic drug-drug interactions change metabolism? Give one example.
Induction or inhibition of metabolic enzymes. Important example: Phenobarbital inducing enzyme for itself and for warfarin/cortisone.
187
How can pharmacokinetic drug-drug interactions change excretion? Give one example.
Generally, see changes in renal excretion. Seen with agents that alter urine pH (NaCHO3) or diuretics.
