Midterm Part 1 Flashcards
Bioavailability is dependent on what?
Route of administration
Chemical form of the drug
Patient factors such as
- Gastrointestinal enzymes and PH,
and Hepatic Metabolism
Drugs occur in two forms in the blood
- Bound to plasma proteins, most
commonly albumin - “Free” or unbound drug
-This is the active part of the drug
The processes by which biochemical (enzymatic) reactions alter within the body are collectively called
drug metabolism or drug biotransformation
Biotransformation reactions are classified as
Oxidation/Reduction or Phase I
Conjugation/Hydrolysis or Phase II reactions
Drug metabolism reactions convert ________ _________ drugs to _________ __________ metabolites so that the drugs can be more easily excreted by the kidneys
These reactions convert lipid soluble drugs to water soluble metabolites so that the drugs can be more easily excreted by the kidneys
The majority of drug metabolism occurs in the______
Drug metabolism also occurs in ______, ________, ______, ______,_______ and _________
The liver contains the greatest quantity and diversity of metabolic enzymes
The majority of drug metabolism occurs in the liver
Drug metabolism also occurs in kidneys, lungs, nerves, skin, plasma, and GI tract
_______ is First part of metabolism of the drug in the liver. Occurs after the drug has excreted its affect on its organ. occurs for all Medication routes
Phase 1
Oxidation/Reduction or Phase I
________ Before the drug goes to the blood stream and only occurs for the oral administration detoxification of medication.
Fast - Pass Metabolism Before the drug goes to the blood stream and only occurs for the oral administration detoxification of medication.
Function & time is different of the location is the same (liver)
_________ system protects individuals from the effect of ingested toxins, which are detoxified in the liver. It Detoxifies oral medications and occurs in liver before it goes into the blood stream.
Fast - Pass Metabolism
______ metabolism of the drug happens after the drug has exerted its effect. Occurs for all drugs (topical, oral, all administration)
Phase 1 metabolism of the drug happens after the drug has exerted its effect. Occurs for all drugs (topical, oral, all administration)
Function & time is different of the location is the same (liver)
What is Forming a compound by the joining two or more chemical compounds
Conjugation is
Forming a compound by the joining two or more chemical compounds
Define Conjugation
Forming a compound by the joining two or more chemical compounds
A reaction involving the breaking of a bond in a molecule using water is known as
Hydrolysis
A reaction involving the breaking of a bond in a molecule using water
Define Hydrolysis
Hydrolysis
A reaction involving the breaking of a bond in a molecule using water
The function of Phase I and II biotransformation is to
The function of Phase I and II biotransformation is to enhance the hydrophilic nature of a hydrophobic drug so that it can be excreted easily out of the body
_____ is the movement of a drug and/or its metabolites out of the body
Drug Excretion
It is the movement of a drug and/or its metabolites out of the body
True or False
If a drug is still fat soluble when it reaches the kidney, it will be reabsorbed by the kidneys and placed back into the bloodstream
TRUE
If a drug is still fat soluble when it reaches the kidney, it will be reabsorbed by the kidneys and placed back into the bloodstream
Kidney function is affected by many conditions including what?
Kidney function is affected by many conditions including
- Age (kidney function declines with age)
- Drug toxicity
- Altered kidney function from disease such as
- Diabetes (impaired renal blood supply)
- Hypertension
- Renal disease such as polycystic kidneys and
Glomerulonephritis
- Cancers
What does ADME stand for
Absorption
Distribution
Metabolism (biotransformation)
Excretion (elimination)
What is Pharmacodynamics
Pharmacodynamics describes the effects of a drug on the body
What medications do to our body and how they do it!!!
Pharmacodynamics effects are described in quantitative terms in order to what?
To determine appropriate dose ranges
To compare potency, efficacy and safety of one drug to another
Drugs Do not impart new function they either …..
Produce the same action as the body’s own chemicals or
Block the action of the body’s own chemicals
True or False
Drugs or ligands bind to receptors at a cellular level to bring about a drug action
TRUE
Receptors can be present where?
Receptors can be present either
- On the outside of the cell membrane
- Inside of the cell membrane
- Span both sides of the cell membrane
How do drugs attach to or interact with receptor sites
Covalent, ionic, hydrogen, hydrophobic, or Van der Waals bonding to produce a definable pharmacological response
True or False
Covalent and ionic bonding are the most common
FALSE
Hydrogen and ionic bonding are the most common
These interactions require little energy and may be easily broken
The pharmacological properties of drugs are based on the effects they have on the state of their ________ __________
The pharmacological properties of drugs are based on the effects they have on the state of their COGNATE RECEPTORS
- Cognates are two biomolecules that typically interact
A drug that after binding to its receptor site results in an active conformation is called an what?
agonist
A drug that after binding to its receptor site results in an active conformation is called an agonist
A drug that favors an inactive conformation after receptor binding is called an what?
antagonist or inhibitors
A drug that favors an inactive conformation after receptor binding is called an antagonist or inhibitors
What are Agonists
Agonists are ligands that activate receptors
True or false
All neurotransmitters are antagonist at their respective sites
FALSE
All neurotransmitters are AGONISTS at their respective sites
Although all neurotransmitters are agonists at their respective receptor sites, there are drugs that are agonists or antagonists to neurotransmitter actions
What are Antagonists?
Antagonists inhibit the action of natural agonists at receptor site but have no effect in the absence of agonists
Antagonists are classified as what?
Receptor antagonists
Non Receptor antagonist
A receptor antagonist can bind to the what?
A receptor antagonist can bind to the
- Active receptor site, which prevents the binding of an agonist to the receptor
- Allosteric (not active) receptor site, which prevents the conformational change required for receptor activation
Types of receptor antagonist
Reversible, those that bind to the receptor site reversibly
Irreversible, those that bind to the receptor site irreversibly
- Can be a problem if they don’t go away
What is a Competitive Receptor Antagonists
Competes with the agonist for the same receptor site and blocks the agonist from binding, maintaining the receptor in its inactive form
Competitive binding of the antagonist to the active receptor site is reversible or irreversible?
reversible
How does Non-competitive antagonists differ form competitive antagonist in two distinct ways?
Noncompetitive antagonist can bind to either the active or the allosteric (non-active) receptor site
Noncompetitive antagonist bind irreversibly often through covalent bonding
Therapeutic Window
It is the range of doses (concentrations) of a drug that elicit a therapeutic response without unacceptable adverse affects (toxicity)
Therapeutic Index (TI)
The therapeutic window can be quantified by the therapeutic Index (TI), also called the therapeutic ratio
what is the therapeutic ratio
TI = TD50 ÷ ED50
TD50 = Drug dose that causes a toxic response in 50% of the population
ED50 = Drug dose that is therapeutically effective in 50% of the population
what are the two major types of dose- repose relationships?
Graded
Quantal
Graded Dose-Response
A graded dose-response relationship describes the effect of the various drug doses on an individual
- A graded response = change in blood pressure in
one patient
Quantal Dose-Response
A quantal dose-response relationship describes the effect of the various drug doses on a population
Population responses that can be examined using quantal-dose response relationship include
Effectiveness (therapeutic effect)
Toxicity (toxic effects)
Lethality (lethal dose)
The doses that produce these responses in 50% (median) of the population, are known respectively as (quantal dose)
The median Effective dose (ED50)
The median toxic dose (TD50)
The median lethal dose (LD50)
what measures population response to drugs
Quantal-dose response measures population response to drugs
what measures individual responses to drugs
Graded-dose response measures individual responses to drugs
It is the range of doses (concentrations) of a drug that elicit a therapeutic response without unacceptable adverse affects (toxicity)
Therapeutic Window
The therapeutic window can be quantified by
The therapeutic window can be quantified by the therapeutic Index (TI), also called the therapeutic ratio
A large therapeutic Index (TI)
A large therapeutic Index (TI) a large therapeutic widows
meaning a large difference between the therapeutic and toxic dose
A small therapeutic Index (TI)
A small therapeutic Index (TI) a small therapeutic widow
meaning a small difference between the therapeutic and toxic dose
Two important parameters are deduced from Graded dose response relationship
- The potency (EC50) of a drug
- Refers to the concentration at which the drug elicits 50% of its maximal response
Potency is related to affinity of a drug to its receptor
How much a drug likes its receptor ( binds really quickly or binds really well) - The efficacy (ECmax) of a drug
- Refers to the maximal response produced by a drug
- Efficacy is related to receptor occupancy by drug molecules
- It is the state at which all receptors are occupied by the drug.
Refers to the maximal response produced by a drug
efficacy (ECmax) of a drug
Efficacy is related to receptor occupancy by drug molecules
Refers to the concentration at which the drug elicits 50% of its maximal response
potency (EC50) of a drug
Potency is related to affinity of a drug to its receptor
True or False
Drugs (ligands) can only bring about a pharmacological effect on the cells if it can attach to specific receptors that are either on the cell membrane or in the cell
TRUE
refers to the maximal response produced by a drug and is related to receptor occupancy by drug molecules
Efficacy (ECmax)
is related to affinity of a drug to its receptor
Potency (EC50 )
Higher the potency, less amounts of the drug needed to cause action
A drug ______ the body, _______ within the body, is ________ by the body and _______the body
A drug enter the body, circulate within the body, is changed by the body and leaves the body
Method of drug administration greatly affects its _______
absorption
What factors affect a drug’s ability to cross a bilayer membrane?
Lipid solubility
Degree of ionization (charge)
Molecular size
Shape of the drug molecule
extremely selective barrier that separates the circulating blood from the brain extracellular fluid in the CNS
The blood-brain barrier (BBB)
The BBB is a specialized barrier formed by _________ __________ cells connected by ________ _________
The BBB is a specialized barrier formed by capillary endothelial cells connected by tight junctions
an important homeostatic mechanism that protects the inner ear
The blood-labyrinth barrier (BLB)
what are necessary to create the BBB
Astrocytes
Disruption of BLB can
Disruption of BLB can disrupt ion transport system of the lateral cochlear wall, lead to disturbances of inner ear homeostasis, resulting in functional disruption of the auditory system
It serves as a barrier between maternal and fetal circulation and protects the fetus from noxious agents
The blood-placental barrier
What is the Goal of Quantal Dose Response?
The goal is to generalize the results to a population rather than to examine the graded effect of drug doses on an individual!
Active receptor site binding
prevents binding of an agonists to the receptor
prevents binding of an agonists to the receptor
Active receptor site binding
Competitive antagonist
reversible binding (agonist can displace antagonist) to the same active site on the receptor as an agonist; when an antagonist competes with the ligand for agonist site binding
reversible binding (agonist can displace antagonist) to the same active site on the receptor as an agonist; when an antagonist competes with the ligand for agonist site binding
Competitive antagonist
Noncompetitive antagonist
irreversible (cannot be displaced even with high concentrations of agonists),
Differs in 2 ways from competitive: can bind either to active or allosteric receptor site & binds irreversibly by covalent bonding
irreversible (cannot be displaced even with high concentrations of agonists),
- can bind either to active or allosteric receptor site & binds irreversibly by covalent bonding
Noncompetitive antagonist
Receptor Antagonists main types (2)
Active receptor site binding
&
Allosteric binding
Allosteric binding
not active, prevents conformational change needed for receptor binding; antagonists bind to a receptor different from the primary active site; aka the secondary site
not active, prevents conformational change needed for receptor binding; antagonists bind to a receptor different from the primary active site; aka the secondary site
Allosteric binding
________________ is about the drug’s journey through the body, while _____________ is about the drug’s effects on the body.
pharmacokinetics is about the drug’s journey through the body, while pharmacodynamics is about the drug’s effects on the body.
what the drug effect on the body
Pharmacodynamics
what the body does to the drug after it is administered
Pharmacokinetics
How the drug interacts with its target receptor or site of action.
Receptor Binding:
Receptor Binding:
How the drug interacts with its target receptor or site of action.
The relationship between the drug dose and the magnitude of its effect.
Dose-Response Relationship:
Dose-Response Relationship
: The relationship between the drug dose and the magnitude of its effect.
Therapeutic and Adverse Effects:
: The beneficial and harmful effects of the drug, which are influenced by its concentration at the target site.
: The beneficial and harmful effects of the drug, which are influenced by its concentration at the target site.
Therapeutic and Adverse Effects:
How the drug enters the bloodstream from the site of administration (e.g., oral, intravenous).
Absorption:
Absorption:
How the drug enters the bloodstream from the site of administration (e.g., oral, intravenous).
Distribution:
How the drug spreads throughout the body’s tissues and fluids.
How the drug is chemically altered by the body, usually in the liver, to form metabolites.
Metabolism:
How the drug spreads throughout the body’s tissues and fluids.
Distribution:
Metabolism:
How the drug is chemically altered by the body, usually in the liver, to form metabolites.
How the drug and its metabolites are eliminated from the body, often through the kidneys (urine) or liver (bile)
Excretion:
Excretion:
How the drug and its metabolites are eliminated from the body, often through the kidneys (urine) or liver (bile)
What are the four major steps Pharmacokinetics uses for drug movement in the body?
Absorption
Distribution
Metabolism
Excretion
drug ____ will utilize the body’s distribution systems such as blood and lymphatic vessels to reach its target in an appropriate concentration
Drug distribution
Drug distribution
drug will utilize the body’s distribution systems such as blood and lymphatic vessels to reach its target in an appropriate concentration
Drug excretion
After being metabolized, the drug is excreted out of the body
Primarily through the kidneys (urine), liver (bile), and gut (feces)
The body inactivates the drug through enzyme degradation especially in the liver
Drug metabolism
Drug metabolism
The body inactivates the drug through enzyme degradation especially in the liver
After being metabolized, the drug is excreted out of the body
Primarily through the kidneys (urine), liver (bile), and gut (feces)
Drug excretion
True or false
Human body has obstacles to microorganisms to stop invader (including drugs) these barriers must be over come before the drug can reach it intended target
True
Name 4 Physiologic Barriers To Drug Movement in the Body
- The blood-placental barrier The blood-placental barrier
- The blood-labyrinth barrier (BLB)
- The blood-brain barrier (BBB)
- Cell Membrane
