A Brief Overview of Pharmacology
Our body is composed of organs, tissues, and cells. Drugs work at the level of cells. There are four main ways that drugs enter the body, get to the target cells, and then exit the body.
Absorption: After the drug is swallowed, absorption occurs in the gastrointestinal tract, particularly in the small intestine, from which the drug enters the bloodstream. If the drug is given by injection or intravenously, the digestive absorption is bypassed and the drug enters directly into the bloodstream.
Distribution: The drug enters the bloodstream, initially goes to the liver, then leaves the liver in the bloodstream and courses throughout the body with particular affinity for its intended target cells in a specific organ or tissue system. However, the bloodstream takes the drug to almost all the cells in the body—both targeted and non-targeted. The unintended interaction of the drug with non-targeted cells is a major source of unwanted effects, often called side effects or adverse effects.
Metabolism: The liver has many capacities to change the absorbed circulating drug. The liver enzymes may activate or modify or deactivate a drug as it initially and then subsequently flows through the liver in the bloodstream.
Excretion: The metabolized drug is eliminated from the body via the urine and stool.
The initial impact of the drug at the cellular level occurs mainly at the cells’ outer surface membrane. This membrane has many different sites for interactions with the drug molecules. The sites include different receptors, ion channels, transporters, and enzymes. Once a sufficient number of drug molecules interact with the membrane sites, a cascade of events may occur where the membrane changes are transmitted into the internal cell cytoplasm. There they influence cell biochemistry in desired directions to benefit the condition for which the drug is being prescribed.
Examples of Drug Interactions
|Type of Interaction||Medication Examples||Interacts With||Increased Risk For|
|Drug-Drug||Aspirin||Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen||Stomach irritation and bleeding|
|SSRI antidepressants such as Paxil (paroxetine), Prozac (fluoxetine), and Zoloft (sertraline), or tricyclic antidepressants such as amitriptyline and imipramine||Tricyclic antidepressants (such as nortriptyline, desipramine, amitriptyline, and imipramine)||Lowered blood pressure, confusion, constipation, urinary retention, dry mouth because of increased levels of tricyclic antidepressant.|
|Antibiotic erythromycin||Anticonvulsant drugs such as Tegretol (carbamazepine)||Increased blood levels of anticonvulsant, causing drowsiness, gait disturbance|
|Antibiotic erythromycin||Statin drugs used to lower blood cholesterol||Increased risk of muscle soreness and damage|
|Pain medicines (opiates such as oxycodone and oxycontin)||Benzodiazepines [such as Valium (diazepam), Ativan (lorazepam)]||Sedation, difficulty breathing, psychological and physical dependency|
|Drug-Food||Cholesterol-lowering drugs (such as Mevacor (lovastatin), Zocor (simvastatin), Lipitor (atorvastatin)||Grapefruit||Can cause life-threatening muscle damage|
|Some antibiotics and heart drugs||Grapefruit||Can greatly increase the blood levels of the antibiotic and heart drugs, causing side effects|
|Monoamine oxidase inhibitor (MAOI) antidepressant such as Marplan (isocarboxazid), Nardil (phenelzine), and Parnate (tranylcypromine)||High tyramine content food (e.g., cheese, beer; Chianti wine, avocados, anchovies, herring, overripe fruit, chocolate, soy sauce, yeasts, yogurt, meat tenderizers, sauerkraut, broad beans)||Hypertension|
|Pain medicines (opiates such as oxycodone and oxycontin)||Alcohol||Sedation, difficulty breathing, psychological and physical dependency|
|Benzodiazepines (anti-anxiety drugs such as lorazepam, diazepam, and chlordiazepoxide)||Alcohol||Falls, sedation, forgetfulness|
|Drug-Plant||SSRI antidepressants||St.John’swort (an over-the-counter medication believed by some to improve mild depression but has properties that inhibit the enzyme monoamine oxidase)||Hypertension, nervousness, confusion|
|Anticoagulants such as Coumadin (warfarin ) or aspirin||Ginko biloba||Increased anticoagulation and possible bleeding|
|Types of Pain Medications|
|Class||Subclass||Examples (brand & generic)|
|Nonsteroidal anti-inflammatory (NSAID)||Aleve (naproxen) Advil & Motrin (ibuprofen) Toradol (ketorolac)|
|COX-2 inhibitors||Celebrex (celecoxib)|
|Narcotic||Opioids||Codeine (no brands) Demerol (meperidine) Dilaudid (hydromorphone) Duragesic (fentanyl) Oxycontin (oxycodone) MS Contin (morphine) Ultram (tramadol)|
|Opioid combinations||Opioid/ acetaminophen or NSAID||Percodan (oxycodone/aspirin) Vicodin (hydrocodone/acetaminophen) Tylenol with codeine (codeine/acetaminophen) Combunox (oxycodone/ibuprofen)|
|Corticosteroids to reduce inflammation||Cortisone (no brands) Decadron (dexamethasone) Deltasone (prednisone) Medrol (methylprednisolone)|
A number of cough medicines contain opioids such as codeine or hydrocodone. The additive effects of these medicines when combined with opioids for pain can cause serious and sometimes fatal interactions. As noted in the FDA communication (see footnote 9) , patients taking opioids with benzodiazepines, other CNS depressant medicines such as sleep medicines, antipsychotics, muscle relaxants, or alcohol, and caregivers of these patients, should seek medical attention immediately if they or someone they are caring for experience symptoms of unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.
Although the published guidelines are intended for your healthcare professionals, it is worth reviewing the CDC website that directly addresses patients. We encourage you to review this information. We supplement this with some important perspectives from the published guidelines that are helpful to know about.1
- Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred
- From the outset, treatment goals should be established that include realistic goals for pain and function. Function can include emotional and social as well as physical dimensions.
- When opioids are used for acute pain, the quantity of prescribed pills can be as little as three days or less; more than seven days will rarely be needed.
- There should be an evaluation of benefits and harms with patients within one to four weeks of starting opioid therapy for chronic pain or of a dose escalation. Thereafter there should be similar evaluations at least every three months.
- Ideally, Prescription Drug Monitoring Program (PDMP) data should be reviewed before every opioid prescription or at least every three months. The purpose is to see if the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose.
- Urine drug testing should be used prior to starting opioids and periodically to assess for prescribed opioids as well as other controlled substances and illicit drugs that increase risk for overdose when combined with opioids, including nonprescribed opioids, benzodiazepines, and heroin. The guidelines recommend that “before ordering urine drug testing, clinicians should explain to patients that testing is intended to improve their safety, should explain expected results (e.g., presence of prescribed medication and absence of drugs, including illicit drugs, not reported by the patient) and should ask patients whether there might be unexpected results.”
Effective Treatments for Opioid-Dependent Patients
Thanks to one of the benefits of the Affordable Care Act (ACA), health insurance policies are required to provide coverage for the treatment of addictions and psychiatric disorders. This has enabled thousands of previously uninsured Americans suffering from these treatable diseases to obtain and benefit from treatment.
Because over 50 percent of people dependent on opioids have a concomitant psychiatric diagnosis, such as a depressive or anxiety disorder, most treatment programs use a combination of medications for the addiction and co-occurring psychiatric disorder and educationally oriented individual, group, and family counseling. Special psychiatric and medical medications help patients who are experiencing uncomfortable withdrawal symptoms.
Three of the most commonly used medications for treatment of opioid dependency are methadone, buprenorphine-naloxone combination, and naloxone. Methadone is used in special methadone outpatient clinics and sometimes in rehabilitation hospital-like settings. Both the outpatient and hospital programs are highly structured with explicit rules forbidding illicit drug abuse, regular urine drug screens to detect drug abuse, and attendance at educationally oriented group, individual, and family counseling sessions. In-hospital treatment is sometimes needed for patients who are heavily addicted, at risk for life-threatening withdrawal symptoms requiring intensive medical and psychiatric treatment, and those with complicated medical and psychiatric problems.
The goal for in-hospital treatment is gradual tapering and eventual (when possible) discontinuation of methadone or buprenorphine-naloxone medication and a smooth transition to outpatient treatment. Good discharge planning is especially critical if a patient has had only a short (five- to seven-day) hospitalization mainly for drug detoxification, is without good family/peer support, and returns to a community where drug abuse is rampant.
A second very effective medication is Suboxone (trade name), which is a combination of buprenorphine and naloxone. The former is a partial opioid agonist that substitutes for the patient’s dependency on an opioid, such as oxycontin, hydrocodone, codeine, and heroin. Naloxone, the other component, serves as a deterrent. If someone dependent on an opioid were to use Suboxone intravenously, naloxone would block the opioid receptor and precipitate withdrawal symptoms. It is easier to slowly taper a patient off Suboxone than heroin and other opioids. Treatment with Suboxone can be carried out in the privacy of a physician’s office by a specially trained doctor who has a special prescribing license. Patients treated with Suboxone are required to participate in regular individual and/or group counseling sessions either with the doctor or his/her staff, have urine drug screens, and attend narcotics anonymous meetings. The treating physician has to obtain reports from the state’s prescription monitoring program to substantiate that the patient is not surreptitiously obtaining opioids or tranquilizers such as benzodiazepine from other physicians. Patients need to adhere to all these and other requirements in order to continue treatment. There are several generic versions of Suboxone that are much less expensive.
A third commonly used drug is naloxone, which can be used in an emergency for someone who is suspected of having overdosed on an opioid such as heroin. Because deaths from opioid overdose have become so prevalent and recognized by the United States Surgeon General as an epidemic, police in some cities have been trained to recognize comatose drug users
suspected of overdose and injecting naloxone. Many lives have been saved. Some patients, after successfully being weaned off Suboxone or methadone, agree to continue monthly naloxone injections or daily oral doses to deter them from abusing opioids, because naloxone will block the high if an opioid is used.
Since the majority of opioid-dependent patients have a concomitant psychiatric disorder, counseling and judicious use of psychiatric medication is often an essential component of long-term treatment.
Patients who are highly motivated and cooperative in their treatment with a good family/peer support system are most likely to benefit from treatment. Because addiction to opioids, like addiction to alcohol and other substances, is a chronic medical disease in many ways similar to other chronic medical illnesses, relapses often occur. So treatment teams have learned not to get discouraged and remain committed and available to their patients.