Midterm Part 2 Flashcards
True or false
polar molecule, such as steroids can easily diffuse through the cell membrane
FALSE
Nonpolar molecule, such as steroids can easily diffuse through the cell membrane
True or false
Most drugs and polar molecules are larger and, therefore, simple diffusion through the layers of the cell membrane is not an option
TRUE
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
How does Lipid Solubility affect a drug’s ability to cross a bilayer membrane?
The more lipid soluble the drug the easier it will cross
How does degree of ionization (charge) affect a drug’s ability to cross a bilayer membrane?
- Charged molecules cannot cross (they must used pores/channels)
- Hydrophobic drug molecules can generally pass through easily
- Water hating fat loving
How does molecular size affect a drug’s ability to cross a bilayer membrane?
Small - sized molecules can cross the cell membrane easily
How does shape of the drug molecule affect a drug’s ability to cross a bilayer membrane?
Molecules that can contort to fit through the cell membrane can cross more easily
an extremely selective barrier that separates the circulating blood from the brain extracellular fluid in the CNS
The blood-brain barrier (BBB)
a specialized barrier formed by capillary endothelial cells connected by tight junctions
The blood-brain barrier (BBB)
__________ are necessary to create the BBB
Astrocytes
What Physiologic Barrier allows passage of water, some gases, and lipid soluble molecules by passive diffusion
The blood-brain barrier (BBB)
What Physiologic Barrier allows selective transport of molecules such as glucose and amino acids that are crucial to neural function
The blood-brain barrier (BBB)
What Physiologic Barrier can prevent the entry of potential neurotoxins by way of an active transport (requires energy) mechanism
The blood-brain barrier (BBB)
What Physiologic Barrier prevents passive diffusion of most drugs from systemic to cerebral circulation
The blood-brain barrier (BBB)
an important homeostatic mechanism that protects the inner ear
The blood-labyrinth barrier (BLB)
What Physiologic Barrier Maintains a constant composition of the inner ear fluids and is essential for its function?
The blood-labyrinth barrier (BLB)
What Physiologic Barrier allows for antigens and antibodies to cross both ways
The blood-placental barrier
What Physiologic Barrier is not a strong barrier for drugs as most can cross easily; Non-ionized and lipid-soluble drugs cross most easily
The blood-placental barrier
The blood-placental barrier Small molecules can cross the placental barrier such as & what can it cause ?
Many viruses, including
cytomegalovirus (CMV),
rubella (German measles),
varicella-zoster (chicken pox),
measles,
HIV (AIDS),
Zika, and
poliovirus can cross the placenta
All of these viruses can potentially cause congenital deafness/ hearing loss
what does not typically cross the blood-placental barrier
Bacteria and other protozoa do not ordinarily cross the barrier
what Exceptions can cross the blood-placental barrier
treponema palladium (syphilis) &
toxoplasma gondii (Toxoplasmosis),
- which can cause congenital hearing loss
Disruption of __________ 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
The blood-labyrinth barrier (BLB)
True or false
for the blood-labyrinth barrier (BLB) large molecular weight molecules can enter the perilymph in a dose and time dependent manner
FALSE!
SMALL molecular weight molecules can enter the perilymph in a dose and time dependent manner
Several ototoxic drugs and bacteria can cross the __________ and enter the perilymph
The blood-labyrinth barrier (BLB)
True of false
In the blood-labyrinth barrier The rate of elimination from perilymph is much slower than that from serum
True
Only occur in a women, a pregnant women
The blood-placental barrier
It serves as a barrier between maternal and fetal circulation and protects the fetus from noxious agents
The blood-placental barrier
what are other factors that affect the rate of drug movement across the cell membranes
Solubility of the drug
- The drugs dissolved in solutions are
more rapidly absorbed than insoluble
drugs.
Route of drug administration
- There are many routes of drug
administration, which will affect the
rate of drug absorption
Name the Main Routes of Drug Administration
Enteral route
Topical route
Parenteral route
Oral administration
Rectal administration
Enteral route of Drug Administration
Drugs given by _______ route are placed directly into the gastrointestinal tract
Enteral route of Drug Administration
Name Enteral route of Drug Administration
Oral administration
&
Rectal administration
Drugs given by this route are placed directly into the gastrointestinal tract and includes
Drugs applied to the surface of body (route type)
Topical route of Drug Administration
Name Topical route of Drug Administration
Transdermal administration
- Example skin patches
Otic
nasal
Ophthalmic
Drugs applied to the surface of body and includes
Drugs administered through routes other than enteric or topical is known as what
Parenteral route of Drug Administration
The drug route bypasses the GI tract and its barriers
Parenteral route of Drug Administration
Name Parenteral route of Drug Administration types (9)
- Intramuscular
- Intravenous
- Intrathecal (injected into the spinal
canal/subarachnoid space)
Inhalation
Intradermal
Bypassed the first layer and
interested into the second layer-
some dermal layer
intrarterial
intraosseous
Sublingual (enters venous circulation)
Intraperitoneal (injected in the peritoneum)
Enteral route of Drug Administration Advantages
- Ease of self administration
- Very portable
- Less likely to introduce systemic infection unlike parenteral route
Enteral route of Drug Administration Disadvantages
- E route expose drug to harsh environments
- Food in stomach may or may not alter the rate of absorption
- Presences of drugs in the stomach may cause a drug interaction (in oral route)
_________ drug admin Generally involves injection-able drugs using syringes/needles
Parenteral Drug Administration
Parenteral Drug Administration advantages
- Fast onset of drug action
- One injection can have effects for days or months
-IV administration allows for more controlled delivery - IV route can deliver continuous medication
Parenteral Drug Administration disadvantages
- Greater risk of addiction with drugs that are injected as the onset of action is very rapid
- Not practical for patients who cannot self administer injections
- High risk for hepatitis, HIV, etc., if needles are shared
- Most dangerous route of administration as it bypasses all the body’s natural defenses,
- Potentially fatal air bubbles (especially IV) can be introduced
All orally administered drugs are subjected to a ___________ in the liver
first-pass metabolism
Drugs that are administered orally pass from the __________ to the _______ and enter the __________ before entering the systemic circulation
Drugs that are administered orally pass from the GI tract to the portal veins and enter the liver before entering the systemic circulation
This system protects individuals from the effect of ingested toxins, which are detoxified in the liver
First-Pass Metabolism
True or false
Any drug that exhibits first-pass metabolism must have appropriate dosage to ensure effective concentration on target organs because of some inactivation in the liver
TRUE
True or False
Non-enteral routes of administration do through first-pass metabolism by the liver
FALSEE
Non-enteral routes of administration are not subject to the first-pass metabolism by the liver
ENTERAL ROUTE ONLY
Bioavailability is a subcategory of _______
Drug Absorption
Bioavailability =
Bioavailability = Quantity of drug reaching systemic circulation ÷ Quantity of drug administered
I/V drugs are injected directly into the systemic circulation have a bioavailability of what
Their bioavailability is generally 1 maximum
drugs administered orally have a bioavailability of
drugs administered orally have a bioavailability of < 1 primarily
Their dose than would have to be increased to reach the same amount of drug received via the I/V route
True or False
Drugs soluble in aqueous solutions at physiologic pH often can be administered orally
TRUE
Oil soluble drugs must be administered subcutaneously or Intravenous (IV)
FALSE
Oil soluble drugs must be administered subcutaneously or intramuscular (IM)
After a drug is absorbed from its site of administration, it is distributed to its site of action primarily by the _______ and to a minor degree by the ____________
the circulatory system (the blood plasma,
lymphatic system
Only the ________ ______ form can pass across gaps between ________ ________ to leave plasma and enter interstitial fluids
Only the free drug form can pass across gaps between capillary cells to leave plasma and enter interstitial fluids
Within each compartment of the body, the drug is split between the bound and free forms
- Plasma protein binding reduces the drug’s availability for diffusion (transport) to its target site
- Only the free drug form can pass across gaps between capillary cells to leave plasma and enter interstitial fluids
- As free drug leaves the plasma, the bound drug becomes “unbound”
- Ratio of bound:unbound drug remains the same in the blood
Plasma protein binding reduces the drug’s …
Plasma protein binding reduces the drug’s availability for diffusion (transport) to its target site
As free drug ________ the bound drug becomes ____________
As free drug leaves the plasma, the bound drug becomes “unbound”
True or false
Ratio of bound:unbound drug vary in the blood
FALSE
Ratio of bound:unbound drug remains the same in the blood
Bound form of the drug
- No effect
- Remains in the compartment (vasculature) longer
- A drug that exhibits high level of protein binding requires a higher concentration
Free form of the drug (unbound)
Exerts desired effect on target drug receptor sites in the target organ(s)
Free drug; ___________ → __________ → _________ → __________→ __________
Free drug; Leave plasma membrane → Exert effect → return to Plasma → Bound to proteins → go to liver
The ________ form of drug has no effect and remains in the vasculature longer
Bound form
___________ form of drug will leave the Plasma membrane, exert its effect on target drug receptor sites in the target organs then go back into the plasma membrane and get bound to proteins again because now it has to go to the liver
Free form
The most common pathway in the liver is the ______________________ that mediates oxidative reactions
cytochrome P450 system (CYP )
This prodrug strategy helps to
Facilitate oral bioavailability
Decrease GI toxicity
Prolong the elimination ½ life of the drug
What is prodrug
Some drugs are administered in an inactive prodrug form so that they can be metabolically altered in the liver to the activated form
( they are not active until it goes though metabolism)
in Oxidation/Reduction or Phase I How many CYP enzymes you have a will determine ……
How many CYP enzymes you have a will determine how quickly or slowly the drug will metabolize
More enzymes →Faster metabolism = Decrease drug action
More enzymes →_________ metabolism =__________ drug action
Less enzymes → _________ metabolism = ________ in drug action
Less enzymes → Slower Metabolism = increase in drug action
An individual’s complement of _______ ________ in the liver determines the rate and extent to which individuals can ________ various drugs
An individual’s complement of cytochrome P450 (CYP) enzymes in the liver determines the rate and extent to which individuals can metabolize various drugs
If cytochrome P450 liver enzymes (CYP enzymes) are induced, it would cause what
it would increase the rate of metabolism
Increasing the rate of metabolism would decrease the action of the drug
More enzymes →Faster metabolism = Decrease drug action
If cytochrome P450 liver enzymes are inhibited, it would cause what
it would decrease the rate of metabolism
Decreasing the rate of metabolism would increase the action of the drug
Less enzymes → Slower Metabolism = increase in drug action
What is Conjugation/Hydrolysis or Phase II
Phase II reactions hydrolyze or conjugate a drug to a larger polar molecule by adding other molecular groups such as glutathione, sulfate, and acetate
This reaction inactivates the drug or enhances the drug solubility and excretion rate into urine or bile
Certain classes of drugs such as barbiturates are ____
are powerful inducers of enzymes mediating Phase I reactions
Barbiturates can speed up the metabolic process and decrease the action of drugs being taken concomitantly
True or False
Phase I and II reactions can be effected by a particular drug or dependent on the presence of other drugs taken by the patient at the same time
TRUE
The effect of Phase I and II reactions on a particular drug also are dependent on presence of other drugs taken by the patient at the same time
Liver can Convert an active drug to inactive
Most common outcome
The inactive drug is formed from the active parent drug
Most common outcome
The inactive drug is formed from the active parent drug
Convert an active drug to inactive
Liver can Convert an inactive drug form (prodrug) to active
Inactive parent drug is converted to active drug after metabolism
Inactive parent drug is converted to active drug after metabolism
Convert an inactive drug form (prodrug) to active
Convert an active drug to active
An active parent drug is converted to a second active drug
An active parent drug is converted to a second active drug
Convert an active drug to active
What is the function of phase I and II biotransformation
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
It is the movement of a drug and/or its metabolites out of the body
Drug Excretion or Elimination
Renal flow comprises ______ %of total systemic blood flow
~25%
True or false
As a majority of drugs in the blood stream are filtered and excreted out by the kidneys, therefore, kidney function will affect drug excretion
TRUE
the rate of elimination of a drug from the body relative to the concentration of the drug in the plasma
Drug Clearance
Drug Clearance
Drug clearance is the rate of elimination of a drug from the body relative to the concentration of the drug in the plasma
OR
the rate at which the drug would need too be cleared from the plasma to account for the change sought by the drug in the body
the rate at which the drug would need too be cleared from the plasma to account for the change sought by the drug in the body
Drug Clearance
Drug Clearance equation
Clearance = Metabolism + Excretion ÷ Drug(plasma)
Elimination of a constant quantity per time unit of the drug quantity present in the organism
Zero-order elimination kinetics
Rather rare, mostly occurring when the elimination system is saturated
Constant elimination; the amount leaving isn’t affected on the amount of dose taken;
Zero-order elimination kinetics
Ex: if you take 100mg - 20 will be removed ; if you take 200mg 20 will still be removed. IT DOES NOT change it is constant
Elimination of a constant fraction per time unit of the drug quantity present in the organism
First order elimination kinetics
The elimination is proportional to the drug concentration
First order elimination kinetics
Proportional elimination; the amount of elimination is based on the amount of drug you are taking.
First order elimination kinetics
Ex: if you take 100mg - 20 will be removed; if you take 200mg - 40 mg will be removed (based on the increase in intake there is an increase in elimination)
the time required for the serum drug concentration to decrease by 50% (T½)
Drug Elimination Half-Life
When the half-life of a drug is short, it is removed ________ from the body
When the half-life of a drug is short, it is removed quickly from the body, i.e., short duration of action
Short Half-life = Removed _______ → _______ duration of action
Short Half-life = Removed quick → short duration of action
Long Half-life = Removed ________ →________ duration of action
Long Half-life = Removed slowly → long duration of action
When the half-life is long, the drug is removed _______ from the body,
When the half-life is long, the drug is removed slowly from the body, i.e., long duration of action
A drug is cleared (removed) from the body in ~_____ to ____ half-lives
A drug is cleared (removed) from the body in ~ four to five half-lives
True or false
Renal failure decreases excretion rates and decreases the half-life of drugs
FALSE
Renal failure decreases excretion rates and increases the half-life of drugs
what formula can be used to calculate the elimination half-life of a drug based on the volume of distribution and clearance of the drug
t1/2 = 0.693 x Vd ÷ Clearance (memorize)
t1/2 = Elimination of half - life
Vd = volume of distribution
0.693 = Approximation of inverse of 2
t1/2 =
t1/2 = Elimination of half - life
Vd =
Vd = volume of distribution
0.693 =
0.693 = Approximation of inverse of 2
