Pharmacological Principles on the Physician Assistant Exam
Before getting into nasty medication side effects, drug-drug interactions, and toxic ingestions, you need to review basic pharmacological principles for the Physician Assistant Exam (PANCE). The body processes a medication in four basic ways: absorption, distribution, metabolism, and elimination. If any of these processes is altered in some way, then bad things can happen.
For a medication to work in the body, it has to be absorbed. Medications given orally (the most frequently used route of administration) require an intact gastrointestinal (GI) tract for proper absorption. Such conditions can cause malabsorption of oral medications, too.
Other factors can impact a medication’s absorption as well, one being its bioavailability (how much medication is absorbed in the GI tract). Different medications are made differently and absorbed differently by the intestine; for example, you sometimes see significant differences in bioavailability when comparing a brand name medicine to its generic counterpart.
Certain medications can also affect the absorption of others. For example, many oral iron preparations must be taken separately from other medications because iron can decrease their absorption. Usually, the medication levothyroxine (Synthroid) is taken separately from other meds because the interaction can affect its absorption. Less of it is absorbed when it’s not taken on an empty stomach apart from other medications.
After a medication is absorbed, it has to go somewhere. Different medications have different volumes of distribution. For example, medications that are lipophilic (fat-loving) are found in higher concentrations in adipose tissue than those that are hydrophilic (water-loving). Some medications can achieve a therapeutic blood concentration, and others build up in the body tissues.
For example, fluoroquinolones are used in treating many genitourinary infections because they have good tissue penetration into that area. They’re used for treating lung infections such as bronchitis and pneumonia for the same reason. Although the aminoglycoside antibiotics likewise have good GU penetration, they wouldn’t be good choices for treating a lung infection because they don’t penetrate the lung tissue very well.
If you understand how the body handles a medication or class of medications, you can better understand how to treat a toxic ingestion or a significant drug interaction. Some medications, like digoxin (Lanoxin), bind to plasma proteins such as albumin.
These medications can stick to these proteins like glue, which becomes problematic if they reach a toxic level. For drugs such as this, you need to know how much of a medication is protein-bound and how much is the unbound (active) portion. If a medication is highly protein bound, it cannot be removed by dialysis.
How the body metabolizes a medication is a biggie in terms of drug-drug interactions. The majority of medications are metabolized in the liver (meaning they’re hepatically metabolized), usually via various cytochrome pathways. For example, cytochrome P450 (CYP) is a common metabolic pathway for many medications, including antiseizure meds. As the liver’s metabolic machinery processes the medications, they can act as either enzyme inhibitors or enzyme activators:
Enzyme inhibitors: Inhibit the metabolism of other medications
Enzyme activators: Increase the metabolism of other medications, thus lowering drug levels
A common example of an enzyme inhibitor is cimetidine (Tagamet). This H2 blocker can inhibit the metabolism of many medications processed by the same metabolic pathway so they have a longer half-life in the body.
Increasing or decreasing the half-life of some medications can have dramatic results. One of the most dramatic examples of this is warfarin. Any medication that’s an enzymatic inhibitor can increase the half-life of warfarin. This can thin the blood and increase the risk of bleeding. Too low of a warfarin level can increase the risk of clots. Being on warfarin means following the blood levels and the prothrombin time closely.
On the PANCE, you should be familiar with the mechanism of action of commonly prescribed medications. Following is an example question on mechanism.
Which of the following medications works by increasing the pancreatic secretion of insulin?
(A) Metformin (Glucophage)
(B) Acarbose (Precose)
(C) Glucagon (GlucaGen)
(D) Glimepiride (Amaryl)
(E) Cosyntropin (ACTH)
The answer is Choice (D). Glimepiride (Amaryl) belongs to the class of medications called sulfonylureas, which increase pancreatic secretion of insulin. Metformin (Glucophage) decreases liver production of glucose and increases peripheral utilization of glucose. Acarbose (Precose) inhibits carbohydrate absorption. Glucagon isn’t even applicable here; it’s used to treat life-threatening hypoglycemia. Cosyntropin (ACTH) is used to evaluate for adrenal insufficiency.
After the body processes the medication, the med needs to leave the body somehow. The main medication or its metabolites are eliminated either by the GI tract or more commonly via the kidney. Kidney disease can extend the half-life of many medications, such as insulin.