Download Polarity and Medications

Polarity and
Medications
Polarity and Medications
 Polarity and the charge of a
medication will determine where it
is absorbed, metabolized, and
eliminated
 pH of the environment will affect
where a medication can be
absorbed based on how the pH
affects the charge of the
medication
 The
cell membrane is made of
phospholipids and is a non-polar
barrier to regulate what can or
cannot enter and leave the cell.
 Non-polar substances like steroidal
hormones and non-polar
medications can move across the
cell membrane easily
SECRETORY
CELL
Hormone
molecule
VIA
BLOOD
TARGET
CELL
Signal
receptor
DNA
Signal
transduction
and response
mRNA
NUCLEUS
Synthesis of
specific proteins
 To
get across most membranes, the
drug must be relatively non
polar/neutrally charged
 To be soluble in water, a drug must
be polar
 If a drug is too nonpolar, it may not
be water soluble, or may bind too
tightly to components in food, or to
proteins in the blood and not be
available for action.
 Polar
substances, such as peptide
hormones, cannot move across the
membrane and bind to surface proteins
on the cell membrane to initiate the signal
transduction pathway or must be
transported through by a membrane
protein.
SECRETORY
CELL
Hormone
molecule
VIA
BLOOD
Signal receptor
TARGET
CELL
Signal
transduction
pathway
OR
Cytoplasmic
response
DNA
Nuclear
response
NUCLEUS
Effect of pH on Drug Absorption

Many molecules can change their charge based
on the environmental pH.

Low pH’s will have higher levels of free H+ ions.

H+ ions will bond to negatively charged portions of
molecules such as a R-COO- or R-NH2, which are
common components on medicines.


R= the rest of the medicine molecule
Acetylsalicylic Acid
and
Lyrica
 Effect
of environmental pH on R-COOH
Basic Conditions
Acidic Conditions
 Effect
of environmental pH on R-COOH
Basic Conditions
Acidic Conditions
 Effect
of environmental pH on R-COOH
Basic Conditions
Acidic Conditions
 In
acidic conditions the R-COO- will
become R-COOH and become
electrically neutral and be able to move
across membranes.
 In basic conditions the R-COOH will lose a
H+ and become R-COO- and be unable
to move across membranes.
Unshared electron
pair are
negatively
charged and will
attract H+ ions
H+
+ H+
H+ = Acidic Conditions
Unshared electron
pair are
negatively
charged and will
attract H+ ions
H+
+ H+
H+ = Acidic Conditions
Unshared electron
pair are
negatively
charged and will
attract H+ ions
H+
+ H+
H+ = Acidic Conditions
 In
acidic conditions, the R-NH2, because
of an unshared electron orbital, will bind
to the H+ and become R-NH3+, and have
an electrical charge. This prevents the
molecule from moving across the
membrane.
 In
basic conditions the R-NH3+ will lose the
H+ and become electrically neutral
permitting movement across membranes.
In low pH environments there is a higher concentration of H+.
These will bind to molecules and either neutralize ionized forms, or
ionize neutral forms.
Here, the R-COO- becomes neutral and moves across the
membrane into the cell and then becomes R-COO- again.
R-NH2 becomes ionized as RNH3+ and can’t move across the
membrane.
Concentration
of molecules
Concentration
of molecules
Blood
Blood
In a higher pH with fewer H+ both the R-COOH and the R-NH3+ will act as acids
and give away their H+ ions. This causes the direction of movement of the
molecules will shift.
R-COOH becomes ionized (R-COO-) and can’t move across the membrane.
R-NH3+ becomes neutral (R-NH2)and can move across the membrane.
Blood
Concentration
of molecules
8
Blood
8
Concentration
of molecules
 pH
stomach = 1 to 3
 pH small intestine = 8
 pH blood = 7.4
 Thus
drugs can exist in different ionic states in
different regions of the body and affect where
they will be absorbed
Drug Administration
 Enteral
= Through or within the intestines or
gastrointestinal tract.
 Parenteral
= Not in or through the
digestive system.
Oral Administration
 Easiest
 Disadvantages



Some drugs (eg proteins) are not stable to
the acidic environment and digestive
enzymes of the stomach
May cause emesis (vomiting)
Drug may not be absorbed properly
 Sublingual:



Under the tongue.
Example: Nitroglycerin
a nitrate used to relieve and prevent chest pain
(angina) that occurs when the heart is deprived of
oxygen
Nitroglycerin relaxes blood vessels allowing more
blood to flow through. This reduces the workload
on the heart and improves blood flow to the heart.
Suppositories
 Rectal:
the substance crosses the rectal
mucosa into the bloodstream
 Vaginal: commonly used to treat
gynecological ailments, including vaginal
infections.
Transdermal: through the skin – patches
applied to skin
Nicotine
Fentanyl
Insulin
Nitroglycerin
Hormones
Parenteral Routes
 Intravascular-
placing a drug directly into the
blood stream
 Intramuscular - drug injected into skeletal
muscle
 Subcutaneous - Absorption of drugs from the
subcutaneous tissues, such as fat
 Inhalation - Absorption through the lungs
Intraosseous
infusion is the process of injection
directly into the marrow of the bone. The
needle is injected through the bone's hard
cortex and into the soft marrow interior.
An
intrathecal injection is an injection into
the spinal canal , as in a spinal anesthesia or
in chemotherapy or pain management
applications.
Intrathecal Injection
 This
route is also used for some infections, particularly
post-neurosurgical. The drug needs to be given this
way to avoid the blood brain barrier. If the drug were
given via other routes of administration where it would
enter the blood stream it would be unable to reach
the brain.
Blood Brain Barrier
 Tightly
packed cells that separate the
blood and the fluid of the central nervous
system (spinal cord and brain).
 Prevents harmful materials, such as
pathogens, from moving to the brain.
 Non-polar materials (O2 and CO2) can
diffuse through, but polar molecules such
as glucose must have special channel
proteins.