Drug Interactions

Question 1

A ___ ___ is a situation in which a substance (usually another drug) affects the activity of a drug when both are administered together.

Answer 1

drug interactions

Question 2

What is the term used to describe when a drug’s effect is increased?

Answer 2

synergistic

Question 3

What term is used to describe when a drug’s effect is decreased?

Answer 3

antagonistic

Question 4

When drugs interact, what types of effects can happen?

Answer 4

1. synergistic
2. antagonistic
3. new effect can be produced that neither drug produces on its own

Question 5

T/F. Antagonism is when the biologic or clinical response to a drug is reduced by administration of a second drug.

Answer 5

True.

Question 6

Explain how penicillin and tetracycline are antagonistic because they oppose each others mechanism of action.

Answer 6

Penicillin inhibits new cell wall synthesis, which requires that bacteria are actively dividing and synthesizing proteins. Tetracycline inhibits protein synthesis. Therefore, tetracycline attenuates the effectiveness of penicillin.

Question 7

Tetracycline chelates divalent metal ions. What is chelation?

Answer 7

when an organic compound will grab metal ions and form a relatively stable structure.

Question 8

Give an example of chemical antagonism.

Answer 8

Chelation by tetracycline interferes with its absorption and its microbial activity. Therefore someone taking Tums - Ca(CO3) -, which contains a ton of calcium, will diminish the effectiveness of tetracycline. It won’t get absorbed or what does will not be as effective.

Question 9

P450 is an example of how antagonistic drug interactions alter drug ___.

Answer 9

metabolism

One drug stimulates metabolism of another.

Question 10

T/F. The induction of P450 enzymes by one drug will affect the metabolism of all the drugs that are metabolized by P450.

Answer 10

True, if taking one drug which increases the activity of P450 then when you take another drug that is metabolized by P450 it will be metabolized and cleared more rapidly.

Question 11

Another example of antagonistic drug interactions is when drugs compete at the same ___ and one is a partial agonist it will act as an ___ of the full agonist.

Answer 11

receptor; inhibitor

Question 12

T/F. Drugs create unopposing actions through signaling at different receptors.

Answer 12

False, Drugs create opposing actions through signaling at different receptors.

Activating GPCR causes Galpha-S proteins that activate AC and Galpha-I proteins that inactivate AC. Therefore, if two drugs acting on the same cell activate diff Galpha subunits, the AC effect would be opposed and this would alter the downstream events.

Question 13

___ occurs when a second drug with a different activity enhances the activity of the first drug.

Answer 13

Potentiation

Question 14

Explain how drug B can alter the pharmacodynamics of drug A.

Answer 14

Drug B enhances the absorption, alters distribution or inhibits the elimination of Drug A.

Question 15

___ acts at nicotinic acetylcholine receptors to produce ___ block. It is hydrolyzed by ___. Inhibition of this enzyme by ___ will increase the plasma half life of succinylcholine.

Answer 15

Succinylcholine; neuromuscular; pseudocholinesterase; neostigmine

Question 16

How does ethanol become acetate?

Answer 16

ethanol (alcohol) is converted to acetaldehyde by alcohol dehydrogenase. Acetaldehyde is converted to acetate by aldehyde dehdrogenase.

Question 17

What would happen if acetaldehyde was allowed to accumulate?

Answer 17

acetaldehyde produces serious headache and other undesirable symptoms

Question 18

What is given to treat alcoholism? How does it work?

Answer 18

Disulfiram inhibits aldehyde dehydrogenase, thus producing undesirable side effects if taken with alcohol due to the accumulation of acetaldehyde.

Question 19

What is the combined activity of two drugs acting at the same or similar sites?

Answer 19

summation

Question 20

Match the following with its definition:

A. Additive
B. Infra-additive
C. Supra-additive

1. drug action is interchangable when dosed at fractions of their EC50’s
2. yield more than additive response when dosed as above
3. yield less than additive response when dosed as above

Answer 20

A - 1
B - 3
C - 2

Question 21

Give an example of summation acting at the same site? different site?

Answer 21

same - opioids, morphine, and meperidine

different - general anesthetics midazolam (potentiates GABA receptor mediated hyperpolarization) and sevoflurane (traditional inhalational anesthetic)

Question 22

What term is used when the combined activity of two drugs produces an effect greater than the maximal effect produced by either drug alone?

Answer 22

synergism

examples
1 - carbon tetrachloride is hepatotoxic and its toxicity is substantially enhanced by ethyl alcohol
2. HAART (highly active anti-retrovirus treatment) therapy involves the treatment of AIDS using multiple drugs from different classes

Question 23

What are the 5 types of drug interactions?

Answer 23

1. Antagonism
2. Potentiation
3. Unexpected Drug Effect
4. Summation
5. Synergism

Question 24

___ interactions is a drugs incompatibility of a physical or chemical nature.

Answer 24

Pharmaceutical

Question 25

Pharmaceutical interactions of relevance to dentistry tend to involve drugs given ___ for intravenous sedation.

Answer 25

parenterally

bottom line: drugs should not be mixed within the same syringe

Question 26

T/F. Pharmocokinetic interactions that affect dstribution is an interaction that can affect the rate or extent of effective absorption of the drug into the circulation, causing an increase or decrease in the drug’s effect.

Answer 26

False, Pharmocokinetic interactions that affect ABSORPTION is an interaction that can affect the rate or extent of effective absorption of the drug into the circulation, causing an increase or decrease in the drug’s effect.

Question 27

What factors affect absorption?

Answer 27

pH of lumen fluids, enzyme activity, intestinal motility

Question 28

Give two examples of absorption pharmacokinetic interactions.

Answer 28

1. Chelation of tetracycline diminishes its absorption

2. Penicillin G is hydrolyzed at acid pH, there may not want to eat when administering this drug

Question 29

What type of pharmacokinetic interaction can occur after a drug is absorbed?

Answer 29

Distribution. An interaction may alter the drugs distribution or it’s rate of transfer from one site to another

Question 30

Most drugs (especially if in pill form) have a ___ component so that they can enter the body via passive ___. These drug are more likely to bound to ___ ___ in the blood.

Answer 30

hydrophobic; diffusion; plasma proteins;

Question 31

Give an example of how distribution of drug A is affected by drug B through the interaction of plasma proteins.

Answer 31

Drugs A and B interact with plasma proteins and the availability of “free” drug A for distribution, metabolism, and excretion is affected by the presence of drug B.

Question 32

Drug A can create respiratory ___ causing too much CO2 to be in the blood. This ___ in pH will alter the distribution of drug B.

Answer 32

acidosis; drop

Question 33

Drug A can alter ___ cell structure and disrupt the ___-___ barrier. This will allow drug B to penetrate the CNS.

Answer 33

endothelial; blood-brain

Question 34

Inhibition of microsomal enzymes (P450) keeps drugs around ___ and the activation of these same enzymes keeps drugs around ___.

Answer 34

longer; shorter

Question 35

What does erythromycin do to CYP3A4?

Answer 35

it irreversibly inhibits CYP3A4 and this will affect any drug metabolized by CYP3A4

Question 36

Some drugs induce microsomal enzymes and will increase the metabolism of other drugs. List those drugs given in class.

Answer 36

phenobarbital; phenytoin; carbamazepine

Question 37

Drugs that reduce ___ blood flow may also affect the metabolism of other drugs. Give an example.

Answer 37

hepatic

Propranolol reduces cardiac output, which causes a reduction in blood flow to the liver and any drugs metabolized in the liver get altered (such as the inhibition of clearance of lidocaine by the liver, therefore, it would last longer)

Question 38

Urinary pH does not alter excretion.

Answer 38

False, Urinary pH DOES alter excretion.

Question 39

The weak acid aspirin is more rapidly excreted in alkaline urine therefore, aspirin clearance is increased by the administration of what?

Answer 39

Na+HCO3- (sodium bicarb)

Question 40

The weak base, ___, is more rapidly excreted in basic urine therefore, its clearance is increased by the administration of NH4+CL- (ammonium chloride).

Answer 40

amphetamine

Question 41

What competes with penicillin’s transport mechanism to be cleared from the blood?

Answer 41

Penicillin is cleared from blood via transport into renal tubules. Probenacid competes with penicillin for this transport, thereby increasing the duration of action of penicillin.

Question 42

Explain the pharmoDYNAMIC interactions when a drug, A, blocks a transmitters reuptake while drug B stimulates its release.

Answer 42

Drug B will be less effective after administration of drug A because the transmitter stores get depleted.

Question 43

In pharmodynamic interactions in the CNS, there are ___ (caffeine, amphetamine) and ___ (benzodiazapine) that compete with each other. Or two drugs can compete at the same receptor site.

Answer 43

stimulants; depressants