Lect 1

Question 0

what is pharmacokinetics?

Answer 0

refers to way the body handles the drug absorption, distribution, biotransformation, and excretion. Once pharmacokinetics is determined, rational dosage regime can be initiated

Question 1

what is definition of pharmacology?

Answer 1

study of biochemical and physiological aspects of drug effects, including absorption, distribution, metabolism, elimination, toxicity, and specific mechanisms of drug action.
ADME

Question 2

what is pharmacodynamics?

Answer 2

the study of biochemical and physiologic effects of drugs and their mechanism of action

Question 3

what are Enteral routes of drug administration?

Answer 3

Oral - most common
Sublingual - doesn’t go into intestines, but mouth is part of digestive system, so it is under enteral
Rectal

Question 4

what are Parental routes of drug administration?

Answer 4

Intravenous - IV
Intramuscular - IM / usu in deltoid or gluteus or quadriceps muscle
Subcutaneous - SC
Intradermal - within skin, ex PPD

Question 5

what are OTHER (other than Enteral and Parental) types of drug administration?

Answer 5

inhalation - meant to go to LU
Intranasal - calcitonin, osteoporosis (goes to nasal mucosa)
Intrathecal / Intraventricular - subarachnoid space in spine where cerebrospinal fluids is (ex AIDs patients with fungal meningitis - goes to brain)
Topical - local action
Transdermal - patch on skin (drug goes to blood so systemic action)

Question 6

what is the First Pass Effect?

Answer 6

the effect of liver metabolism of drug prior to reaching systemic circulation

*administration by IV, IM, and sublingual routes allow drug to attain concentrations in the systemic circulation and to be distributed throughout the body prior to hepatic metabolism

• *when drug administered rectally - 50% goes to Liver and 50% goes to inferior vena cava and to heart to be distributed systemically
• **Orally - 100% goes to Liver first, what is not metabolizes in the liver (a small portion) will go to blood

Question 7

a drug passes through the membranes more readily if it is __________?

Answer 7

uncharged

thus the affects the absorption and excretion of passively diffused drug

Question 8

weak acids are hydrogen ion _______

Answer 8

donors

at high pH they donate H+ and become negatively charged, but at low pH they become protonated and carry a neutral charge

Question 9

weak bases are hydrogen ion _________

Answer 9

acceptors

at low pH, weak bases accept H+ and become positively charged, but at a high pH they are neutral because they dissociate their protons

Question 10

Acid drugs, such as aspirin, are better absorbed in what types of environments?

Answer 10

in acidic environment such as the ST with pH of 2

Question 11

Alkaline drugs are best absorbed in what types of environment?

Answer 11

in alkaline environment such as the small intestine which has pH of 8

Question 12

what is ion-trapping? and in what conditions is it helpful to use this method?

Answer 12

since the pH of urine is acidic, a weakly acidic drug can be extensively reabsorbed into the body from urine.

if pH of the urine is increased, the excretion of drug can be increased.

in cases of aspirin poisoning, the excretion of drug through the urine can be increased by increasing the urinary pH, ideally to higher or equal to pH 8, by injecting sodium bicarbonate

Question 13

what are factors that influence absorption of drugs?

Answer 13

1. more blood flow –> more absorption
2. more surface area –> more efficient absorption
3. quick movt of drug through GI tract –> less absorption

Question 14

what is Bioavailability?

Answer 14

the fraction of administered drug that reaches the systemic circulation unchanged

Question 15

how do you determine the bioavailability of a drug?

Answer 15

by plotting plasma concentration of drug versus time, area under the curve (AUC) is measured

AUC oral / AUC injected IV x 100

Question 16

what affects Bioavailability of drug?

Answer 16

1. first pass hepatic metabolism: rapid metabolism –> decreased amount of drug gaining access to blood
2. solubility of drug: extreme hydrophilic or hydrophobic results in poor absorption, so need some lipid and some liquid solubility for best absorption
3. chemical instability
4. nature of drug formulation

Question 17

what is drug distribution?

Answer 17

process by which drug reversibly leaves bloodstream and enters the intersitium and or cells

Question 18

what factors affect drug distribution?

Answer 18

1. blood flow
2. capillary permeability: the capillaries of liver and spleen have large fenestrations allowing drugs to pass. in the brain, capillaries are continuous forming the blood-brain barrier preventing many substances from entering the brain
3. drug structure: hydrophobic/philic, charged/uncharged
4. plasma protein binding of drugs mostly with albumin which acts as a drug reservoir

Question 19

what is definition of Volume of Distribution (Vd)

Answer 19

calculation of the apparent volume in which drug is disseminated

Vd gives a rough accounting of where the drug goes in the body. it can also be used to calculate the dose of a drug needed to achieve a desired plasma concentration

Question 20

what is equation for Vd?

Answer 20

VD = Dose (mg) / plasma concentration (mg/L)

Question 21

total volume of fluid in the body is?

Answer 21

Male:
total body water is 60% of body weight / 42 Liters
- 20% extracellular (plasma & interstitial fluid) 14 L
- 40% intracellular 28L

Drug –> plasma 4L –> interstitial 10L –> intercellular 28L

Question 22

what is half-life of a drug?

Answer 22

(t 1/2) is the period of time required for the concentration of a drug to decrease by one-half

Question 23

what is the binding of drugs to plasma proteins?

Answer 23

drugs may bind to plasma proteins (usu albumin)

Bound drugs are - INACTIVE
Unbounded drugs - ACTIVE

Question 24

what is binding capacity of albumin?

Answer 24

strongest affinity for anionic and hydrophobic drugs; less affinity for hydrophilic drugs

Question 25

in which class of drugs is the dose small, so the binding sites of albumin are in excess of available drug (bound-drug fraction is high)?

Answer 25

Class I drugs

Question 26

in which class of drugs is the dose large and thus greatly exceed the number of albumin binding sites (and high proportion of drugs exists in free state)?

Answer 26

Class 2 drugs

Question 27

what is the goal of metabolism? where is the major site of metabolism? what are some other sites?

Answer 27

goal is to produce metabolites that are polar or charged, and can be eliminated by the KD.

major site is LIVER

other sites are LU, KD, adrenals, etc.

*metabolism can also transform active drug into less active or inactive forms, or a prodrug (inactive or less active drug) into a more active drug

Question 28

in which phase of drug metabolism is the drug oxidized or reduced to a more polar form?

and most of this phase uses what system of enzymes?

Answer 28

Phase 1 reactions

most phase 1 reactions utilize cytochrome P450 system of enzymes

Question 29

in which phase of metabolism does a polar group such as glutathione is conjugated to the drug? what does this process do?

Answer 29

in Phase II reactions

this substantially increases the polarity of the drug. the highly polar drugs can then be excreted by the KD. Drugs undergoing Phase II reaction may have already phase 1 transformations.

Question 30

where is Cytochrome P450 system of enzymes?

Answer 30

in Smooth Endoplasmic Reticulum of cells in many organs esp in Liver.

through an electron transport chain which uses NADPH as proton carrier, a drug bound to cytochrome P450 can be oxidized or reduced within (phase 1 reaction)