Lecture 3

Question 1

What is Pharmacokinetics?

Answer 1

What the body does with the drug

Question 2

What is Pharmacodynamics?

Answer 2

What the drug does to the body

Question 3

What are the 4 processes of Pharamcokinetics (ADME)?

Answer 3

1. Absorption
2. Distribution
   3.Metabolism
   4.Excretion

Question 4

How is the route of administration determined (2 things)?

Answer 4

1. properties of the drug
2. the therapeutic objective

Question 5

What are the TWO major routes of administering?

Answer 5

1. Enteral
2. Parental

Question 6

What routes make up the enteral section?

Answer 6

• oral (has first pass metabolism in intestine and liver)
  -sublingual (DIRECT systemic absorption)
  -rectal (DIRECT systemic absorption)

Question 7

What routes make up the parenteral section?

Answer 7

• IV (avoids first pass, once given difficult to remove)
  -IM (intramuscular, abosrbs aq solutions quick so prepared as a “depot” to promote slow absorption)
  -subcutaneous (like IM, rapid or slow, localize drug effect)

Question 8

how do they move molecules across the membrane?

Answer 8

1. diffusion
2. active transport

Question 9

What is drug ABSORPTION?

Answer 9

• from the site of administration that allows the agent access to the plasma
• depends on drug’s ability to cross cell membrane and resist presystemic metabolism
• bioavailibility involved

Question 10

What is bioavailibility?

Answer 10

amount of drug that reaches systemic circulation intact

if anything goes wrong in absorption, you can get MORE drug than anticipated

Question 11

What factors affect absorption?

Answer 11

1. acidity of stomach (*do NOT take an antacid before)
2. physiochemical properties
3. route of administration (100% bioavailibity for IV)
4. lipid solubility
5. blood flow
6. surface area

Question 12

What is drug DISTRIBUTION?

Answer 12

passage of agent through blood or lymph to various body sites and into interstitial tissue and intracellular fluids

Question 13

What factors affect drug DISTRIBUTION?

Answer 13

1. Blood flow –> want HIGH flow tissues
   - (brain, liver, kidney) = handle LARGE volumes of drugs
2. Capillary permeability –> based on structure
   - CNS blood brain barrier –> stops drug penetration if they are not lipid soluble or have a specific transport mechanism
3. drug structure
   -hydrophobic, non polar, uniform electron distribution, no net charge = move DIRECTLY through endothelial membrane
   - the opposite of above = pass through endothelial slit junctions
4. binding to plasma proteins
   - talk later

Question 14

When is a drug active or inactive?

Answer 14

Drugs are only ACTIVE when they are FREE!

Therefore, when bound to plasma proteins , they are INACTIVE

Question 15

What is the binding and binding capacity of albumin like?

Answer 15

• low (1:1) or high
• bind REVERSIBLY
• 2 categories:
  1. Class 1 –> low dose/albumin binding ratio
  2. Class 2 –> high dose/albumin capacity ratio , majority of drug exists in its FREE state, can displace Class 1 from albumin (competition for binding sites!!!)

Question 16

What is drug METABOLISM?

Answer 16

• mostly occurs in LIVER
  -consists of “first pass-effect”
• involves the “hepatic portal circulation”
• P450 enzymes
• biotransformation occurs

Question 17

What are the Phases of metabolism reactions?

Answer 17

Phase 1:
- modify chemical by adding a functional group
- helps substrate to “fit” into phase 2 enzyme
- consists of Oxidation, Reduction, and Hydrolysis

Phase 2:
- conguation occurs –> adding a group (glucuronic or sulfuric acid) to make it water soluble

Question 18

What are P450 enzymes?

Answer 18

-isoenzymes
- in GI and liver
- helps with metabolism

Question 19

What is Biotransformation?

Answer 19

conversion of drug into 4 stages
Phase 1:
- oxidation
- reduction
- hydrolysis

Phase 2 :
- conjugation –> adding a group (glucuronic or sulfuric acid) to make it water soluble

Question 20

What can modify biotransformation?

Answer 20

• age
  -body weight
  -gender
• race
  -genetic variability
• body rhythms
• poor nutrition
• acid-base, fluid, electrolyte balance
  -enzyme deduction
  -dose level
• diseases (liver and kidneys)
• immunoolgy –> drug allergies
• psychology –> placebo affect
• Environment
• tolerance

Question 21

What is drug EXCRETION ?

Answer 21

• occurs in the kidneys (spaghetti and meatballs organs)
  -elimination of drugs and toxicants

Question 22

What is the process of renal excretion?

Answer 22

1. Passive glomerular filtration
2. active tubular secretion in the proximal tubules
3. passive distal tubular reabsorption

Question 23

What can affect renal excretion? (2 things)

Answer 23

1. golumerular filtration rate
2. change in urinary pH after excretion of weak acid and base drugs

Question 24

What is a Drug half-life and how can it be affected?

Answer 24

• time taken for the drug’s blood or plasme concentration to decrease from full to one-half
• LONGER the half-life, the LONGER the drug remains in your body
• if you cant metabolize or excrete drug properly, the half life INCREASES

Question 25

What does plasma concentration of a drug vs time conisist of?

Answer 25

1 .Toxic concentration
- range that will cause harm to the body

2. therapeutic range
   - causes desired effect of drug
   - can be quite narrow
   - consists of peak plasma concentration
3. minimum effect concentration
   - just below therapeutic range
   - when you want to take your next dose of drugs
4. onset of action = 2 hours
5. duration of action = 6 hours
6. termination of action = 8 hours mark

Question 26

What is PHARMACODYNAMICS?

Answer 26

talks about
- describes how a medication changes the body

Question 27

What are 4 main drug actions?

Answer 27

1. depressing
2. stimulating
3. destroying cells
4. replacing substances

Question 28

What 2 things to majority of drugs do?

Answer 28

1. mimic
2. inhibit

Question 29

What is the “DOSE-EFFECT relationship”?

Answer 29

relationship between the dose of a drug that produces therapeutic effects and the potency of the effects on the individual

Question 30

What is the “FREQUENCY DISTRIBUTION CURVE”?

Answer 30

number of patients that respond to a drug’s action at different doses

median effective dose = drug needed to produce a specific response in 50% patients

Question 31

What is the “Therapeutic index and drug safety”?

Answer 31

predicts whether a certain dosage is safe for a specific patient

Question 32

What is “cellular receptors and drug action”?

Answer 32

• each drug has a specific AFFINITY for its target
• the receptors are often proteins on surface and require an interaction to cause a cascade of events (second messenger effects)

Question 33

What are the two basic receptor types for drugs?

Answer 33

1. alpha
2. beta

Question 34

What are some “non-specific cellular responses” that drugs produce independently?

Answer 34

change in….
1. cell permeability
2. function of cellular pumps
3. DEPRESS membrane excitability

Question 35

What are some examples of drug receptors?

Answer 35

1. ligand gated ion channels
2. GPCRs
3. Transcription factors

Question 36

What are some “drug-receptor interactions”?

Answer 36

1. agonist—> binds to receptor = stimulatory repsonse
2. agonist-antagonist –> acts alone or competes with other drug
3. anatagonist –> blocks or anatagonizes effects of another drug, competitive or non-comp., NO activity

Question 37

What is the difference between competitive and non-competitive binding?

Answer 37

Comp = compete for binding site

Non-comp = Bind elsewhere in the receptor