Basic Pharmacology and Drug-Nutrient Interactions

Why do we study pharmacology?

What is the difference between food dose response curves and pharma dose response curves?

drugs

• sigmoid dose-response curve

nutrients

• have a U-shaped dose-response curves

What is the connection between nutrients and oral drugs?

nutrients and oral drugs share same metabolic processes and can have overlapping molecular targets

Describe characteristics associated w/ the sigmoid dose response curve.

have a drug receptor interaction model; have a specific defined chemical structure and metabolic effects

• may act at single site or multiple tissues

Describe characteristics associated w/ the U-shaped dose-response curve.

don’t function in isolation, act on multiple tissues and organ systems

• typically consumed in various forms in mixed meals, multiple nutrients contained within a specific food and mixed meals, and nutrient effects are usually subtle compared to drugs

• nutrients at high doses can have pharmacologic type of effects sand toxicity

What are xenobiotics?

a compound from outside the body

• could be a nutrient, drug, environmental toxins, etc.

• seen as foreign and thus our body tries to metabolize it

What is the issue w/ drug-nutrient interactions of clinical significance?

can lead to treatment failure, adverse side effects, and possible changes in nutritional status and malnutrition

• potential for drug-nutrient interaction exists with all drugs

• interactions are bi-directional

What are two things that indicate a drug-nutrient interaction is clinically significant?

1. alters the therapeutic drug response

2. compromises nutrition status

What are the four processes under pharmacokinetics?

ADME

• absorption

• distribution

• metabolism

• excretion

What are pharmacodynamics?

the goal for the medication, what you want to see in terms of effect aka the body’s physiologic response to a drug or combination of drugs

What is the role of membrane transport proteins present in intestinal epithelial cells?

facilitate absorption of polar drug compounds and function through numerous mechanisms

• they act as gatekeepers to regulate uptake and efflux of nutrients and drugs

What are five examples of transporters for drugs, nutrients, and endogenous substrates?

1. ATP Binding Cassette transporter family (ABC transporters)

2. Solute Carrier Proteins (SLC) transporters

3. Organic anion transporting polypeptide (OATP) family of drug transporters

4. Peptide transport protein (PEPT) transporters

5. multidrug resistance protein (MRP)

General characteristics associated w/ membrane transport proteins.

• found in many tissues, at apical and basolateral sides of cells

• have many different isoforms

• transport a wide range of substances

• are capable of transporting large array of structurally divergent drugs

Describe first pass metabolism in terms of drugs?

oral medication come into the GI tract, taken across into the enterocyte where some metabolism occurs, then it goes out the basolateral side into the portal vein

• from the portal vein it gets transported to the liver for further metabolism before it reaches systemic circulation

• changes bioavailability (would be different if we give the drug via iv)

During first pass metabolism, what do we find in the enterocytes and hepatocytes?

biotransformation enzymes

What can biotransformation enzymes do? (2)

1. turn an active drug into less active/inactive

2. turn a pro drug (inactive/less active) into a more active drug

What are two phases that occur through biotransformation reactions carried out by biotransformation enzymes.

1. phase I reactions (non-synthetic)

2. phase II reactions (synthetic)

helps to make them be more polar so that they can circulate in the blood and be excreted from the kidney

What occurs during phase I reactions (non-synthetic)?

drugs are oxidized or reduced to a more polar form

What enzymes carry out phase I reactions?

cytochrome P45- enzymes (CYP P450)

What occurs during phase II reactions (synthetic)?

a polar group is conjugated to the drug

What enzymes carry out phase II?

GST, QR, etc.

What are 7 drug excretion routes?

1. urine

2. feces

3. exhaled air

4. sweat

5. saliva

6. tears

7. breast milk

What are 7 factors that can alter drug pharmokinetics and thus alter the physiological drug effects?

1. age and body weight

2. pregnancy status

3. smoking and drinking habits

4. GI physiology

5. liver or kidney disease

6. pharmacogenetics

7. drug-drug and drug-nutrient interactions

In general, what are two different ways that food and nutrition status can affect drug therapy?

1. alter drug absorption/availability

2. alter drug distribution and metabolism

How does food impact drug absorption and availability?

absorption can be decreased, delayed, increased, or unaffected by physiologic changes occurring in the GI tract when food is present

What are five things drug absorption is influenced by?

1. stomach and intestinal pH

2. gastric emptying/GI tract motility

3. absorptive capacity of cells

4. presence of food

5. presence of certain nutrients

How does stomach and intestinal pH influence drug absorption?

achlorhydria (decreased gastric acid secretion) w/ aging decreases drug absorption

How does gastric emptying/GI tract motility influence drug absorption?

• high fat meals slow down gastric emptying rate

• vomiting and diarrhea will alter absorption

both alter absorption

How does the absorptive capacity of the cells influence drug absorption?

malnutrition can damage the integrity of GI enterocytes and decrease absorption

How does the presence of food influence drug absorption?

some foods decrease and increase absorption

What are examples of drugs that have decreased and increased absorption as a result of the presence of food?

• Fosamax (used to prevent osteoporosis and influence rebuilding of bone): if food is present then it decreases absorption of this drug

• Levodopa (used for those w/ Parkinson’s): taken w/ proteins w/ neutral aas, absorption is decreased

• some medication have increased absorption w/ CHO or fats

How does the presence of certain nutrients influence drug absorption?

• calcium can chelate tetracycline (antibiotic) and decrease absorption

• citrus juice can increase plant based Fe absorption

What are four examples of how food and nutrition can impact drug distribution and metabolism?

1. John’s Wort

2. Tyramine (pressor agents in food) + MAO inhibitor drugs

3. Vitamin K and Coumadin

4. Grapefruit

How does St. John’s Wort impact drug distribution and metabolism?

it is a herbal supplement that decreases the effectiveness of many drugs

How do Tyramine (pressor agents in food) + MAO inhibitor drugs impact drug distribution and metabolism?

when paired together, a hypertensive crisis is possible

What foods do people on MAO inhibitor drugs need to avoid?

foods high in tyramine

• red wines

• cured meats (salami)

• aged cheeses

• fermented foods

What is coumadin?

blood thinner medication to help reduce the rate at which blood clots form

• import for conditions such as atrial fibrillation

• blocks a vit K dependent step in clotting factor production, decreasing the amount of vit K that is recycled, inhibits bleeding a little bit

  • not all blood thinners interact w/ vit K, some newer ones have different mechanisms

What are 7 sources of foods high in vitamin K?

1. kale

2. spinach

3. turnip greens

4. collards

5. swiss chard

6. broccoli

7. brussel sprouts

What do we want to keep in mind for individuals who take coumadin?

want a consistent vitamin K intake, don’t want to avoid it all together

• goal is to keep a balance between the amounts of vit K and the medication

How does grapefruit juice impact drug distribution/metabolism?

impacts at the level of biotransformation enzymes in phase I, aka CYP P450s

• furanocumarins in grapefruit juice inhibit CYP3A4 enzymes (within cytochrome family) which affect the rate of Phase I drug biotransformation, slowing down the metabolism of the drug

What are examples of drugs affected by grapefruit juice? (3)

1. statin drugs (but not all)

2. calcium channel blocker drugs

3. immunosuppressant drugs

What are statin drugs used for?

used to lower cholesterol

• ex: Lovastatin, Simvastatin, etc.

What are calcium channel blocker drugs used for?

used to decrease BP

• ex: Nifedipine

What is an example of an immunosuppressant drug?

Cyclosporine

What are five ways that drugs can affect nutrient ingestion/appetite?

1. Changes in GI function

2. Decreased appetite via anorexic agents

3. Increased appetite

4. Alter or diminish taste perception or saliva production

5. Drugs w/ high caloric content

How does changes in GI function impact nutrient ingestion/appetite?

can cause nausea, vomiting, diarrhea, constipation

• decreases want to eat

What are two types of unintended drugs that decrease appetite?

1. drugs that act on CNS

2. drugs for cancer treatment

What class of drugs intentionally decrease appetite?

anorexic agents

• often used for weight management

What are three groups of anorexic agents for weight management?

1. adrenergic agents (amphetamines)

2. serotoninergic agents (phentermine, Lorcaserin)

3. GLP-1 receptor agonists (Ozempic, Wegovy)

What is the mechanism behind adrenergic agents (amphetamines)?

stimulates the secretion of norepinephrine

What is the mechanism behind serotoninergic agents (phentermine, Lorcaserin) ?

inhibit the reuptake of serotonin, and or norepinephrine

What is the mechanism behind GLP-1 receptor agonists (Ozempic, Wegovy) ?

slow GI motility and act on brain and other tissues

What is an example of a drug that unintentionally increases appetite?

corticosteroids

What is a drug that intentionally increase appetite?

Megestrol acetate

• used in individuals w/ AIDS-related wasting syndrome or in treatment of cancer-related cachexia

What are two ways that taste perception are altered or diminished?

1. dysgeusia: altered in tate perception

2. hypogeusia: reduced acuity of taste perception

What is an example of a drug w/ high caloric content and thus alters nutrient ingestion/appetite?

propofal

• sedative w/ 10% soybean oil, 1663 kcal/day