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 Signal receptor transduction and response DNA 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 Signal transduction pathway Cytoplasmic response Nuclear NUCLEUS DNA OR

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+ = Acidic Conditions

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

Unshared electron pair are negatively charged and will attract H+ ions 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+ 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

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

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.