Pharmacotheraputics - Lecture 6

Question 1

What are the two primary factors that influence drug effects?

Answer 1

Pharmacokinetic differences

Pharmacodynamic differences

Question 2

Pharmacokinetic differences

Answer 2

When people take the same thing, the drug reaches different plasma concentrations in different people

Question 3

Pharmacodynamic differences

Answer 3

When a drug has the same concentration in the plasma, it can have different effects on different people

Question 4

What is a secondary factor effecting drug effects?

Answer 4

Patient compliance

Question 5

What is the drug theraputic complex?

Answer 5

The difference between what concentration help alleviate the problem, and at what level it becomes harmful
The larger the number, the larger the difference

Question 6

What patient factors can influence drug effects?

Answer 6

Body weight and composition
Age
Sex
Pregnancy and lactation
Environmental factors
Physiological factors
Pathologic conditions
Genetic factors

Question 7

How does body weight and composition effect drugs?

Answer 7

Smaller people take a lower dose

Question 8

What should you base dosing children on?

Answer 8

Clinical data is best, because complexities and uncertainties make prediction difficult
Children are not just “small adults”

Question 9

What can drugs do to geriatric patients?

Answer 9

Geriatric patients can be hyper-reactive to drugs

Question 10

Why does sex need to be taken into mind when prescribing drugs?

Answer 10

Women have only been adequately used in clinical trials starting in the 1990s
Does adjustments need to be made for women (generally smaller, higher % body fat)

Question 11

Why does pregnancy and lactation need to be taken into account when prescribing drugs?

Answer 11

There can be alterations in liver functions
Drugs can have effect on the fetus
Drugs can be excreted in teh breast milk

Question 12

What environmental factors need to be taken into account when prescribing drugs?

Answer 12

Temperature
Sunlight
Altitude
Diet

Question 13

What can occur to a patient taking atropine on a warm day?

Answer 13

Atropine-induced hyperthermia
If someone is taking atropine, it can reduce blood flow to the skin, and the body won’t deal with heat exchange well, leading to hyperthermia (too hot)

Question 14

What is the connection between sunlight and sulfonamides?

Answer 14

Patients can have toxic skin reactions when using sulfonamides on a sunny day

Question 15

The “cheese effect”

Answer 15

Monoamine oxidase (MAO) inhibitors are used to treat depression
Tyramine (in cheese and red wine) can cause a hypertensive crisis, but it is normally metabolized by MAOs
If MAO inhibitors are used, there isn’t any MAO to metabolize tyramine, it can cause a hypertensive crisis

Question 16

How can grapefruit juice effect drug metabolism?

Answer 16

CYP3A4 is responsible for the metabolism of 60% of all drugs
CYP3A4 makes up 28% of hepatic cytochrome P450
Ingestion of grapefruit reduces the expression of CYP3A4
So it you drink grapefruit juice, it reduces the ability to metabolize drugs

Question 17

What effect can the bacteria in the gut on drugs?

Answer 17

They can have a significant effect on the metabolism of some drugs
There can be significant effects on the pharmacokinetics of a drug if the patient is taking antibiotics

Question 18

What physiologic factors can effect drugs?

Answer 18

pH variations in the plasma, gut, and stomach

Circadian rhythms

Question 19

What pathologic conditions can effect drugs?

Answer 19

Diseased organs of drug absorption, metabolism, and/or excretion can have a profound effect
Disturbances in blood and circulation

Question 20

What is drug tolerance?

Answer 20

Decreased responsiveness to drug upon repeated or continuous administration

Question 21

What is pharmacokinetic tolerance?

Answer 21

Effect of drug concentration is diminished

Question 22

What is pharmacodynamic tolerance?

Answer 22

Response is diminshed

Question 23

Tachyphylaxis

Answer 23

Rapid loss of response

Question 24

Tyramine and its association with Tachyphylaxis

Answer 24

Tyramine increases heart rate and BP by promoting the release of norepinephrine
Tachyphylaxis develops because norepinephrine stores are depleted

Question 25

How does tolerance occur?

Answer 25

Drug-induced changes in cellular distribution

There’s a pump that uses ATP to get rid of stuff

Question 26

What is sensitization?

Answer 26

Usually seen in CNS drugs

Pathways in the brain can make it more responsive to the drug when it is administered chronically

Question 27

What are extension effects?

Answer 27

When the mechanism of action does too much

Question 28

What is the extension effect of Warfarin?

Answer 28

Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors
Approx. 2-4% of the time, warfarin treatment can lead to hemorrhaging

Question 29

What are the two different ways a side effect can occur?

Answer 29

1) A drug can act on two different receptors in the same tissue - one receptor does what we want, the other does a side effect
2) A receptor can be present in two different tissues - in one tissue it does what we want, and in the other it does a deliterious effect
The more selective the drug, the better

Question 30

What are idiosyncratic reactions?

Answer 30

Effects that occur rarely and unpredictably amongst the population
They often happen because the patient metabolizes something differently, they have different receptors, etc

Question 31

How common are drug allergies?

Answer 31

10% of all adverse effects

Occur in 1/20 people (5%)

Question 32

How many types of drug allergies are there?

Answer 32

4

Question 33

Type I drug allergy

Answer 33

Immediate
Mast cells spew out contents that are nasty to the organism/patient
Occur very quickly

Question 34

Type II drug allergy

Answer 34

Cytotoxic

A drug is attached to the plasma membrane, and this signals compliment fixation and lysis of that cell

Question 35

Type III allergy

Answer 35

Immune complex

An antigen-antibody complex forms

Question 36

Type IV allergy

Answer 36

Cell-mediated
T cells are activated and this activates cytokines and other things to a site
An example is contact dermatitis to procain

Question 37

How can you minimize the occurrence of allergic drug response?

Answer 37

1) Take med history
2) Avoid offending drugs and their relatives
3) Avoid inappropriate drug administration
4) Drugs taken orally are less allergenic than drugs taken topically
5) Request allergy testing if appropriate

Question 38

What are pseudo-allergies and how do they work?

Answer 38

They are an adverse effect that mimics an allergy, but is not a true allergic reaction.
They mimic the effects downstream, such as release histamine from mast cells

Question 39

Carcinogenesis

Answer 39

Drugs that can cause cancer
More of an issue for drug developers than prescribers.
However, you should be aware of clinical data of things you’re prescribing

Question 40

What are the effects of Category A drugs on pregnant women?

Answer 40

Studies failed to show risks in 1st trimester and there’s no evidence of problems later

Question 41

What are the effects of Category B drugs on pregnant women?

Answer 41

1) Studies failed to show risk in 1st trimester and later, BUT animal studies have shown adverse effects on fetus
or
2)Human studies are lacking, but animal studies failed to show risk

Question 42

What are the effects of Category C drugs on pregnant women?

Answer 42

No adequate human studies and animal studies are either lacking or have shown adverse effects on the fetus
Benefit ma warrant issue

Question 43

What are the effects of Category D drugs on pregnant women?

Answer 43

Positive evidence of human fetal risk

Benefit of the drug may warrant use

Question 44

What are the effects of Category X drugs on pregnant women?

Answer 44

Studies in humans or animals have shown fetal abnormalitites, or there is positive evidence of human fetal risk, or both.
The potential risk of the drug to the fetus outweighs the potential benefit.