Module 10- Pharm Basics Flashcards
Pharmacology
Study of interactions between a drug and an organism
Definition, Includes, Affected by
Pharmacodynamics
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
Receptor Subtypes Include:
Enzymes
Ion Channels
Membrane receptors
Drugs bind due to chemical interactions: Which kind?
4 of them
Electrostatic interactions (intermolecular forces)
Hydrophobic interactions
Covalent bonds (INTRAmolecular)
Stereospecific interactions (enantiomers)
Properties; Affinity, Efficacy, Potency
Drugs Act as…
Drug Categories
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
Definition
Pharmacokinetics
Concentration affects what? Helps us to understand what better (4)?
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
Factors that affect, absorption rate determines..
Absorption
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
Definition, factors that affect (8)
Bioavailibilty
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
Definition, influenced by…
Distribution
Drug solubility properties do what?
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
Definition, common processes
Metabolism
Has the potential to…
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
Definition
Excretion
Main routes?
-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)
Most drugs fail when? Percentage of drugs that fail in clinical?
Drug Development
-Most drugs fail in the discovery phase
- 90% of all drugs fail in clinical testing
- 39% Pharmacokinetics
- 30% lack of efficacy
Lipinski Rule of 5
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”
Lipophillic Moiety
Lipophillic Moiety
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
Ester Linkage
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
Hydrophillic Moiety
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
Low MW with low cLogP does what?
Potential drug compounds must have a mix of…
-Low MW drugs with a low cLogP can easily cross membranes
-Potential drug compounds must have a mix of hydrophilic and lipophilic groups
Functional Groups Linked To Increased Toxicity
-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.
Drug efficacy is directly related to..
Pharmacokinetics of Transport
Drug concentration must be high enough..
-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
How do drugs cross membranes throughout this entire process?
ADME & Drug Transport
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
Low MW drugs have an easier time…
Passive Diffusion
Absorption of drugs into the bloodstream is dependent on…
-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
Requires what?
Active Transport
Why does transport plateau?
-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
Drug Sizes
Transport & Drug Distribution
Is affected by what?
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
Daltons
g/mol
Increased specifity does what?
Binds to specific receptors; less adverse affects
Van Der Waals
Non polar atoms bound together. C-C
Common examples include interactions between noble gases, lipid tails in cell membranes, and nonpolar molecules like alkanes.
