Pharmacotheraputics - Lecture 6 Flashcards
What are the two primary factors that influence drug effects?
Pharmacokinetic differences
Pharmacodynamic differences
Pharmacokinetic differences
When people take the same thing, the drug reaches different plasma concentrations in different people
Pharmacodynamic differences
When a drug has the same concentration in the plasma, it can have different effects on different people
What is a secondary factor effecting drug effects?
Patient compliance
What is the drug theraputic complex?
The difference between what concentration help alleviate the problem, and at what level it becomes harmful
The larger the number, the larger the difference
What patient factors can influence drug effects?
Body weight and composition Age Sex Pregnancy and lactation Environmental factors Physiological factors Pathologic conditions Genetic factors
How does body weight and composition effect drugs?
Smaller people take a lower dose
What should you base dosing children on?
Clinical data is best, because complexities and uncertainties make prediction difficult
Children are not just “small adults”
What can drugs do to geriatric patients?
Geriatric patients can be hyper-reactive to drugs
Why does sex need to be taken into mind when prescribing drugs?
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)
Why does pregnancy and lactation need to be taken into account when prescribing drugs?
There can be alterations in liver functions
Drugs can have effect on the fetus
Drugs can be excreted in teh breast milk
What environmental factors need to be taken into account when prescribing drugs?
Temperature
Sunlight
Altitude
Diet
What can occur to a patient taking atropine on a warm day?
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)
What is the connection between sunlight and sulfonamides?
Patients can have toxic skin reactions when using sulfonamides on a sunny day
The “cheese effect”
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
How can grapefruit juice effect drug metabolism?
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
What effect can the bacteria in the gut on drugs?
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
What physiologic factors can effect drugs?
pH variations in the plasma, gut, and stomach
Circadian rhythms
What pathologic conditions can effect drugs?
Diseased organs of drug absorption, metabolism, and/or excretion can have a profound effect
Disturbances in blood and circulation
What is drug tolerance?
Decreased responsiveness to drug upon repeated or continuous administration
What is pharmacokinetic tolerance?
Effect of drug concentration is diminished
What is pharmacodynamic tolerance?
Response is diminshed
Tachyphylaxis
Rapid loss of response
Tyramine and its association with Tachyphylaxis
Tyramine increases heart rate and BP by promoting the release of norepinephrine
Tachyphylaxis develops because norepinephrine stores are depleted
How does tolerance occur?
Drug-induced changes in cellular distribution
There’s a pump that uses ATP to get rid of stuff
What is sensitization?
Usually seen in CNS drugs
Pathways in the brain can make it more responsive to the drug when it is administered chronically
What are extension effects?
When the mechanism of action does too much
What is the extension effect of Warfarin?
Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors
Approx. 2-4% of the time, warfarin treatment can lead to hemorrhaging
What are the two different ways a side effect can occur?
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
What are idiosyncratic reactions?
Effects that occur rarely and unpredictably amongst the population
They often happen because the patient metabolizes something differently, they have different receptors, etc
How common are drug allergies?
10% of all adverse effects
Occur in 1/20 people (5%)
How many types of drug allergies are there?
4
Type I drug allergy
Immediate
Mast cells spew out contents that are nasty to the organism/patient
Occur very quickly
Type II drug allergy
Cytotoxic
A drug is attached to the plasma membrane, and this signals compliment fixation and lysis of that cell
Type III allergy
Immune complex
An antigen-antibody complex forms
Type IV allergy
Cell-mediated
T cells are activated and this activates cytokines and other things to a site
An example is contact dermatitis to procain
How can you minimize the occurrence of allergic drug response?
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
What are pseudo-allergies and how do they work?
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
Carcinogenesis
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
What are the effects of Category A drugs on pregnant women?
Studies failed to show risks in 1st trimester and there’s no evidence of problems later
What are the effects of Category B drugs on pregnant women?
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
What are the effects of Category C drugs on pregnant women?
No adequate human studies and animal studies are either lacking or have shown adverse effects on the fetus
Benefit ma warrant issue
What are the effects of Category D drugs on pregnant women?
Positive evidence of human fetal risk
Benefit of the drug may warrant use
What are the effects of Category X drugs on pregnant women?
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.
