1. Polarity and Medications

2. 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

3. 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

4. SECRETORY
CELL
Hormone
molecule
VIA
BLOOD
TARGET
Signal
receptor
transduction
and response
DNA
mRNA
NUCLEUS
Synthesis of
specific proteins

5. 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.

6. 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.

7. SECRETORY
CELL
Hormone
molecule
VIA
BLOOD
Signal receptor
TARGET
Signal
transduction
pathway
Cytoplasmic
response
Nuclear
NUCLEUS
DNA OR

8. 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

9. Effect of environmental pH on R-COOH
Basic Conditions
Acidic Conditions

10. Effect of environmental pH on R-COOH
Basic Conditions
Acidic Conditions

11. Effect of environmental pH on R-COOH
Basic Conditions
Acidic Conditions

12. 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.

13. Unshared electron pair are negatively charged and will attract H+ ions
H+ = Acidic Conditions

14. Unshared electron pair are negatively charged and will attract H+ ions
H+ = Acidic Conditions

15. Unshared electron pair are negatively charged and will attract H+ ions
H+ = Acidic Conditions

16. 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.

17. In basic conditions the R-NH3+ will lose the H+ and become electrically neutral permitting movement across membranes.

18. In low pH environments there is a higher concentration of H+
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
Blood
Concentration of molecules
Blood

19. 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.
Concentration of molecules
Blood 8
Concentration of molecules
Blood 8

20. 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

21. Drug Administration
Enteral = Through or within the intestines or gastrointestinal tract.
Parenteral = Not in or through the digestive system.

22. 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

23. 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.

24. Suppositories
Rectal: the substance crosses the rectal mucosa into the bloodstream
Vaginal: commonly used to treat gynecological ailments, including vaginal infections.

25. Transdermal: through the skin – patches applied to skin
Nicotine
Fentanyl
Insulin
Nitroglycerin
Hormones

26. 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

28. 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.

30. An intrathecal injection is an injection into the spinal canal , as in a spinal anesthesia or in chemotherapy or pain management applications.

31. 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.

32. 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.