Module 10- Pharm Basics

Question 1

Pharmacology

Answer 1

Study of interactions between a drug and an organism

Question 2

Definition, Includes, Affected by

Pharmacodynamics

Answer 2

Study of biochemical, physiological, and molecular effects of drugs on the body

Includes:
-Site of action
-MOA
-Receptor Binding
-Postreceptor effects
-Chemical Interactions

Affected by:
-Disease or disorder
-Age
-Drug-drug interactions

Question 3

Receptor Subtypes Include:

Answer 3

Enzymes
Ion Channels
Membrane receptors

Question 4

Drugs bind due to chemical interactions: Which kind?

4 of them

Answer 4

Electrostatic interactions (intermolecular forces)
Hydrophobic interactions
Covalent bonds (INTRAmolecular)
Stereospecific interactions (enantiomers)

Question 5

Properties; Affinity, Efficacy, Potency

Drugs Act as…

Drug Categories

Answer 5

Act as a ligand that bind to the receptor

Affinity: How well the drug binds to te receptor
Efficacy: How well the drug produces its desired effect
Potency: Term used to compare the relative affinity of competing drugs

Categories:
Agonists: Bind to and activate receptors
Antagonists: Bind to, but do not activate
-Competitive: Bind reversibly, can be out-competef
-Non-competitive: Either binds irreversibly or binds to an allosteric site

Question 6

Definition

Pharmacokinetics

Concentration affects what? Helps us to understand what better (4)?

Answer 6

The study of absorpion, distribution, metabolism, and excretion of drugs from the body
Concentration affects the ability of the drug to produce its desired effect

Helps us to understand:
Drug administration
Therapeutic dosing
Time intervals between dosing
Toxic dosing

Question 7

Factors that affect, absorption rate determines..

Absorption

Answer 7

Route:
PO: must travel through intestine
Parenteral: Intramuscular, Sub-Q, IV, Inhalation

Absorption rate determins time to maximal concentraation at the receptor to produce peak effect

Question 8

Definition, factors that affect (8)

Bioavailibilty

Answer 8

How much of the administered drug is actually absorbed; typically used for PO

Factors:
Molecular weight of the drug
Drug formulation
Drug stability (especially pH sensitivity)
First pass metabolism (liver)
Blood flow
Gastric emptying
Intestinal motility
Drug interactions

Question 9

Definition, influenced by…

Distribution

Drug solubility properties do what?

Answer 9

Effectiveness of the movement of the drug throughout the body

Influenced by:
Blood
Total body water
ECF
Lymphatic fluids
CSF
Protein-binding

Drug solubility properties help determine ability of drug to be distributed to the desired receptor

Question 10

Definition, common processes

Metabolism

Has the potential to…

Answer 10

Breakdown of drugs into metabolites
-Prodrugs: Converted from inactive form to active
-Typically inactivates the drug ahead of excretion

Common processes include:
Hydrolysis (Pancreas)- converted to esters, amides, and nitriles
REDOX: Cytochrome P450

Has the potential to lead to the formation of toxic metabolites

Question 11

Definition

Excretion

Main routes?

Answer 11

-Removal of the drug and it’s metabolites from the body
-Helps to prevent toxic buildup of drug in the body

Main Routes:
Kidneys (majority of drugs)
Feces (unabsorbed drug or metabolites from bile)
Lungs (inhaled anesthetics)
Sweat (not very common)

Question 12

Most drugs fail when? Percentage of drugs that fail in clinical?

Drug Development

Answer 12

-Most drugs fail in the discovery phase
- 90% of all drugs fail in clinical testing
- 39% Pharmacokinetics
- 30% lack of efficacy

Question 13

Lipinski Rule of 5

Answer 13

Lipinski Rule of 5:
The Lipinski Rule of 5 helps predict if a molecule (NCE) is likely to be an orally active drug. It checks for specific criteria like size and solubility

no more than 10 total hydrogen bond donors or hydrogen bond acceptors (Count N and O)
molecular weight under 500 daltons
and a logP (octanol-water partition coefficient) under 5
Contains no more than 1 toxicophore (functional groups prone to toxic metabolites)

Violation of more than two+ rules predicts a NCE is “not a good drug”

Question 14

Lipophillic Moiety

Lipophillic Moiety

Answer 14

Lipophillic Moeity: Dissolve in the fatty cell membrane, allowing it to cross the membrane easier. Typically uncharged. Need to look for nonpolar areas (long carbon chains & rings)
Ex: Steroids, antidepressants, antifungal

Question 15

Ester Linkage

Answer 15

Interaction between an acid and an alcohol.

An ester linkage has a dipole because of the oxygen atoms, which are more electronegative than carbon. This creates a partial charge difference, allowing dipole interactions.

Look for a bond between a carbon double-bonded to oxygen (C=O) and single-bonded to another oxygen (O). This structure is typical of esters.
Ex: ASA

Question 16

Hydrophillic Moiety

Answer 16

Hydrogen bonding: Look for hydroxyl (-OH), amino (-NH), or carbonyl (C=O) groups. These polar groups can form hydrogen bonds

Hydrogen Acceptors: NOF (F is added to prevent drugs from breaking down)

   Ex: Penicillin, Acetaminophen

Question 17

Low MW with low cLogP does what?

Potential drug compounds must have a mix of…

Answer 17

-Low MW drugs with a low cLogP can easily cross membranes
-Potential drug compounds must have a mix of hydrophilic and lipophilic groups

Question 18

Functional Groups Linked To Increased Toxicity

Answer 18

-Aromatic anilines: An aromatic aniline is an amino group attached to a benzene ring(NH2 attached to a benzene ring).

-Nitroaromatics: compound with a nitro group (NO2) attached to an aromatic ring like benzene.

CypP450 metabolize ^

-Aliphatic halides: CH2 compound where a halogen (like chlorine or bromine) is attached to a straight or branched carbon chain.

-Polycyclic aromatic hydrocarbons: Compounds with multiple (3+) fused benzene rings.
Ex: Napthalene is okay, fullerene

-Thiopenes: A five-membered ring containing four carbon atoms and one sulfur atom.

Question 19

Drug efficacy is directly related to..

Pharmacokinetics of Transport

Drug concentration must be high enough..

Answer 19

-Drug efficacy is directly related to the concentration of the drug at it’s site of action
-Drug concentration must be high enough to elicit the desired effect, but not too high to cause negative effects

Question 20

How do drugs cross membranes throughout this entire process?

ADME & Drug Transport

Answer 20

Absorption: Enter into the bloodstream
Distribution: Contact with the receptor
Metabolism- Leave receptor and move to the liver or other metabolism site
Excretion: Passage to kidneys for removal

Question 21

Low MW drugs have an easier time…

Passive Diffusion

Absorption of drugs into the bloodstream is dependent on…

Answer 21

-Transport across a membrane from area of high concentration to area of low concentration

-Low MW drugs have an easier time crossing membranes

-Absorption of drugs into the bloodsteam is dependent on the acid/base properties of the drug and the pH at the site of absorption

Question 22

Requires what?

Active Transport

Why does transport plateau?

Answer 22

-Requires the aid of membrane-bound proteins to recognize the drug for transport
-Requires energy
-At high drug concentrations, transport plateaus due to limitd number of transport proteins
-Can lead to competition with structurally similar compounds

Question 23

Drug Sizes

Transport & Drug Distribution

Is affected by what?

Answer 23

Affected by size and charge of the drug molecule

Small drugs: <50 Da–> Bulk flow

Lipophilic drugs (considered small drugs): 50-500 Da –> Passive transport

Drug Charge: >50 Da –> Active transport

Question 24

Daltons

Answer 24

g/mol

Question 25

Increased specifity does what?

Answer 25

Binds to specific receptors; less adverse affects

Question 26

Van Der Waals

Answer 26

Non polar atoms bound together. C-C

Common examples include interactions between noble gases, lipid tails in cell membranes, and nonpolar molecules like alkanes.