Week 1 Pharm Principles

Question 1

Pharmaceutic Phase

Answer 1

Dissolution

All oral drugs must go through dissolution in order to be absorbed.

Question 2

Pharmacokinetic Phase

Answer 2

Drug moving through the body and what the body does to the drug

Four processes
• Absorption, Distribution, Metabolism, Excretion

THINK –> GI tract -> blood -> liver -> bile
kidney -> urine

Question 3

Pharmacodynamic Phase

Answer 3

• What the drug does to the body
  
  • The action of the drug or mechanism of action (MOA)
  • The intended effect of the drug
  • The therapeutic action

Question 4

The Phospholipid Layer

Answer 4

• Cell membranes are composed of layers of cells
• These cells are close together, drugs must pass to get to blood and site of action
• Membrane structure is phospholipid
• Drugs must be lipid soluble to pass membrane MOST COMMON
• Water soluble drugs require passage through channels or pores

Question 5

First Pass Effect

Answer 5

• Metabolism of drug before systemic circulation
• % of drug broken down in liver
• Bioavailability is the amount of drug left after first pass
  * Bioavailability of PO varies (liver has to take some)
  * Bioavailability of IV is 100%

Question 6

Enteral route

Answer 6

• By way of GI tract (oral/gastric mucosa, small intestine, rectum)
  * EC intended to break down in small intestine NOT stomach
  * First pass effect
  * PO break down starts in stomach, absorbed in small intestine
  * First pass effect
  * SL, Buccal, Rectal all highly vascularized tissue
  * No first pass effect, by-passes liver

CANNOT MAKE PO DRUG RECTAL

Question 7

Parenteral route

Answer 7

• SQ, IM, IV, intrathecal (into spinal canal), epidural (the space around the spinal cord)
• IV is the fastest (no barriers to absorption, often irreversible)
• Does not go through first-pass effect

Question 8

Topical (transdermal) route

Answer 8

• Application of meds to body surfaces
  * Eyes, skin, ears, nose, lungs

Onset slower, don’t worry about first pass effect

Question 9

Blood Brain Barrier (BBB)

Answer 9

• Cells in the capillary wall in the brain with very tight junctions that prevent drug passages
• Only drugs that have a transport system or are lipid-soluble can cross the BBB

Question 10

What can cross the BBB?

Answer 10

Alcohol
Glucose

• THIS IS NOT FULLY DEVELOPED IN INFANTS

Question 11

Protein-Binding Effect

Answer 11

• Temp storage of drug molecule that allows drug to be available for a longer period
of time
• Drug ratio of bound to unbound (free) molecules varies
• Binding is reversible (a rapid process)

• Goal: maintain a steady free drug concentration aka Steady State
• Remember only unbound drug is active and free to exert effects
• Albumin is the primary plasma protein
• Drugs bind to protein [albumin]
• Hypoalbuminemia (ie, malnutrition or liver disease)
  * More free drug is available for distribution to tissue site
  * Possibility of overdose and toxicity

Question 12

Example: Protein-Binding

Answer 12

• warfarin/Coumadin
  * Drug used to decrease coagulation (blood thinner)
  * Very highly protein bound (97 – 99%), leaves 1 – 3% free to exert effect

• A client with low albumin = less bound Coumadin (inactive) and more free
Coumadin (active)

• More free Coumadin can exert effect
• Increased risk of toxicity –> Increased bleeding

Question 13

Metabolism

Answer 13

• Method by which drugs are INACTIVATED or biotransformed
  * The new structure is called a metabolite
• Liver is the major site for drug metabolism
  * Converts lipid-soluble drugs into water-soluble metabolites
  * Kidney can excrete these metabolites
  * Cytochrome P-450 enzymes
• If liver isn’t working, drug can build up, increasing toxicity

Question 14

Metabolism: CYP450

Answer 14

Clinical Significance
• Substrate – if a drug uses the CYP450 system for metabolism
• Pro-drug is a substrate that uses CYP450 to convert to an active form

 * Inducer – speeds up metabolism of the CYP450 system
      * Reduces the amount of drug in the body
      * Reduces therapeutic effect

 * Inhibitor – slows down metabolism of the CYP450 system
      * Increases the amount of drug in the body
      * Increases risk of toxicity

Question 15

CYP450 Inhibitor Example

Answer 15

Grapefruit juice is a known CYP450 inhibitor
“It will stop breakdown of other meds”

 • Taking grapefruit juice with another drug that uses this system increases the 
    amount of drug in body
 • Can lead to toxicity

Teaching point
• Don’t take medications with grapefruit juice
• Avoid eating grapefruit or drinking the juice for 2-4 hours after taking meds

Question 16

Excretion

Answer 16

• Elimination of drug from the body
  
  • Generally only hydrophilic (water soluble) drugs can be excreted effectively
• Kidney is the major site of excretion
  
  • Through glomerular filtration
  • Tubular secretion
  • Tubular reabsorption
• Reabsorption and Secretion
  
  • Some of the drug is secreted, some is reabsorbed

• Important in maintaining a steady state
• Example: 90% of Penicillin G is excreted through the kidney so very little is
reabsorbed so the drug would need to be given more frequently to maintain
steady state

Question 17

Excretion LABS

Answer 17

Renal labs

- blood urea nitrogen (BUN) 
- creatinine

Question 18

glomerular filtration rate (GFR)

Answer 18

• Best measure of kidney function
• Calculated from the creatinine level, age, body size, and gender
• GFR of drugs is related to free drug concentration in plasma

“Want to look at this first”

Question 19

Half-Life

Answer 19

• Serum half-life (T ½) is time required for the serum concentration of a drug to
decrease by 50%

• Takes 5 half-lives for 97% of drug to be eliminated

• T ½ varies from drug to drug
  * Can be minutes, hours, days, weeks or more
• Example:
  • Patient is taking a drug with T ½ of 1 week and stops taking
  • It will take about 5 weeks for drug to be gone from system

Question 20

Half-Life: Steady State

Answer 20

• Takes about 4-5 half-lives for “steady state” to occur
  
  • Goal is steady state
• Steady state occurs when intake of drug equals amount metabolized/excreted
• T ½ determines dosing interval, ie QD, QID

Question 21

Half-Life Example

Answer 21

• A one time dose of morphine 10 mg is given at 12:00

• T ½ of morphine is 3 hours
  
  • At 15:00, 5 mg of morphine is left in body
  • At 18:00, 2.5 mg is left
  • At 21:00, 1.25 mg is left
  • At 24:00, 0.625 mg is left
  • At 03:00, 0.313 mg is left
• Note after 5 half-lives most of the drug has been eliminated
• Patient will start feeling pain again about 18:00

Question 22

Around the Clock Dosing (ATC)

Answer 22

• Goal is to maintain 50% concentration in body

• Example: Morphine 10 mg given every 3 hours (ATC)
• After about 4 doses there would be a constant level or “steady state” of 5 mg at
all times
• Serum concentration maintained at 50%

• Used to treat chronic pain
• PRN ordered for “break through” pain

Question 23

Onset, Peak & Duration definitions

Answer 23

Onset – time it takes for drug to elicit therapeutic response (latent period)

Peak – time it takes for drug to reach its maximum therapeutic effect

Duration – time drug concentration is sufficient to elicit a therapeutic response

Question 24

Multiple Effects: Example

Answer 24

• Drug name: metaproterenol
• MOA: broncho dilator
• Uses: Acute asthma attack or COPD
• Adverse Effects: Tachycardia and/or palpitations
• Multiple Effects:
  
  • Desired: dilates bronchial passage
  • Not Desired: tachycardia or palpitations

Question 25

Receptors

Answer 25

Proteins located on cell surfaces Chemicals in the body interact with drugs to produce effects Ex. Hormones, neurotransmitters These chemicals BIND with the drug = drug-receptor complex Complex initiates a physiochemical reaction AGONIST= stimulates/activates ANTAGONIST= inhibits/blocks

Answer 26

• A drug that has the ability to INITIATE a desired therapeutic effect by BINDING to a receptor. • Example: isoproterenol= beta1 adrenergic AGONIST • Binds to beta receptors and causes vasodilation lowering peripheral vascular resistance

Answer 27

• A drug that has the ability to INITIATE a desired therapeutic effect by BINDING to a receptor. • Example: isoproterenol= beta1 adrenergic AGONIST • Binds to beta receptors and causes vasodilation lowering peripheral vascular resistance *WHAT WE WANT TO HAPPEN*

Question 28

Antagonist

Answer 28

• A drug that produces its action NOT by stimulating receptors but PREVENTING or BLOCKING or INHIBITING other natural substances (ligands) from binding and causing a response * Examples: * ranitidine/Zantac, an H2 ANTAGONIST * Blocks release of gastric acid * diphenhydramine/Benadryl, an H1 ANTAGONIST * Blocks action of histamine * propanolol/Inderal, a Beta 1 adrenergic ANTAGONIST * Blocks action of epinephrine *BLOCKS*

Question 29

Receptor-Less Activation

Answer 29

• Not all drug responses involve receptors • Some drugs act through simple physical or chemical interactions with small molecules • Examples: • Antacids work by neutralizing gastric acidity through DIRECT chemical interaction • Magnesium Sulfate works as a powerful laxative by retaining water in the intestinal lumen through the osmotic effect

Question 30

Narrow therapeutic index [NTI]

Answer 30

• NTI have a ratio of lowest concentration at which clinical toxicity commonly occurs • Therapeutic levels checked to ensure the medication is dosed effectively but avoid toxicity • Examples: theophyllin, digoxin, phenobarbital, lithium, coumadin

Question 31

What is a Black Box Warning?

Answer 31

* Required by the FDA for drugs that are especially DANGEROUS * Is the strongest safety warning a drug can carry and still remain on the market * The boxed warning must appear prominently: * On the package insert * On the product label * On any magazine or other advertising

Question 32

JUST THE FACTS

Answer 32

Med errors are the 3rd leading cause of death

Question 33

Processes to Prevent Errors

Answer 33

1. Restrict high-alert drugs and medication routes 2. Practice drug differentiation. Use of “tall-man” lettering for look-alike drug names. Ex. “HePARin” 3. Use computerized systems for adm meds 4. Make patient information readily accesible 5. Standardize and simplify 6. Apply reminders 7. Include the patient in therapy 8. Don’t use trailing zeros (1 mg) 9. Use leading zeros (0.25 mg)

Question 34

High Alert Medications

Answer 34

In 1995 the Institute for Safe Medication Practices (ISMP) identified these drugs to most likely cause serious harm and death • Insulin (antidiabetic) • Heparin (anticoagulant) • Opioids (pain mgt) • Injectable potassium chloride (IV KCL) • Neuromuscular blocking agents • Chemotherapy drugs

Question 35

How do drug interactions occur?

Answer 35

- Drug- DRUG (CYP450) - May be intended - May be unintended - Increased risk w/ polypharm & NARROW THERAPEUTIC INDEX DRUGS (NTI) - Drug- FOOD (grapefruit juice) - Drug- HERB - Drug- DISEASE (kidneys or liver not working)

Question 36

Drug Interactions that INCREASE Therapeutic Effects

Answer 36

* Additive effects: 2 drugs taken with similar MOA * Ex. 2 antibiotics given to treat a complicated infection • Synergism/Potentiation: 2 drugs with DIFFERENT MOA but result in a combined drug effect greater than that of either drug alone • Ex. Coumadin and Aspirin • Activation of drug-metabolizing enzymes in the liver --> decreases metabolism rate of the drug (CYP450 system) • Displacement: Displacement of one drug from plasma protein-binding sties by a second drug --> increases effect of displaced drug

Question 37

Drug Interactions that DECREASE Therapeutic Effects

Answer 37

* Antidote: drug given to ANTAGONIZE the toxic effects of another drug * Ex. naloxone antidote for opioid overdoses • Intestinal Absorption -> applied to PO medications * Activation of drug-metabolizing enzymes in the liver --> enzyme inducers * Increased metabolism rate of the drug [quicker out of system] * CYP450 system

Question 38

Older Adults and Pharmacokinetic Consequences

Answer 38

HEPATIC CHANGES: drugs metabolized more slowly CARDIAC & CIRCULATORY CHANGES: impaired circulation = decrease distribution of drugs Decreased Production of CYP 450 enzymes increased risk for drug interactions can decrease up to 30% in elderly! RENAL CHANGES: drugs excreted less completely GASTROINTESTINAL CHANGES: decreased absorption of oral drugs