SIX PROBLEMS INVOLVING MEDICATION
Six primary problems regarding medications arise in austere medical situations. In some cases, more than one of these exist simultaneously. You can have (a) no medications; (b) medication, but have no clue what it is for or how to use it; (c) some medication, but not the primary choice for the condition you need to treat; (d) medication, but in the wrong form; (e) only outdated medication; or (f) medication that might have been contaminated or that has degraded. Each of these is discussed separately.
If you have no medication, you will have to use local herbal remedies, physical treatments (osteopathic manipulation, thermal treatment, surgery), street drugs, or donated medications.
When clinicians face medication and intravenous (IV) fluid shortages, pharmacy supervisors should not only communicate understandable information about the shortages to clinicians, but also build safeguards into their system. Use standard triage terms such as red, yellow, and green to categorize the severity of the shortage and its probable effect on clinical practice. Pharmacists should also help clinicians safely use unfamiliar substitute medications, including compounding medications and drips in the pharmacy.1
After disasters and in developing countries, the management of drug donations becomes extremely important. The key issue is to specify what you want and need, how much, and when it should arrive. Managing large quantities of unwanted and unneeded pharmaceuticals consumes valuable personnel time and space. After Hurricane Katrina, for example, the area was awash not only in water but also (figuratively) in cartons of ridiculously inappropriate donated medications. Safely disposing of this mountain of useless pharmaceuticals became an unwanted headache.
Similar problems occur across the globe. A Harvard School of Public Health study found that about 30% of donated medications had an expiration date <1 year from the time they were shipped; 6% had <100 days left before they (officially) expired. Up to 42% of the drugs were not on either the country’s list or the World Health Organization’s (WHO) list of essential drugs, nor were they therapeutic alternatives for the essential drugs.2
To help lessen problems with international drug donations, WHO has developed the following Guidelines for Drug Donations3:
All drug donations should be based on an expressed need and be relevant to the disease pattern in the recipient country. Drugs should not be sent without prior consent of the recipient.
All donated drugs or their generic equivalents should be approved for use in the recipient country and appear on the national list of essential drugs, or, if a national list is not available, on the WHO Model List of Essential Drugs (www.who.int/medicines/publications/essentialmedicines/en/), unless specifically requested otherwise by the recipient.
The presentation, strength, and formulation of donated drugs, as much as possible, should be similar to those of drugs commonly used in the recipient country.
All donated drugs should be obtained from a reliable source and comply with quality standards in both donor and recipient country. The WHO Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce (www.who.int/medicines/areas/quality_safety/regulation_legislation/certification/en/index.html) should be used.
No drugs should be donated that have been issued to patients and then returned to a pharmacy or elsewhere or that were given to health professionals as free samples.
After arrival in the recipient country, all donated drugs should have a remaining shelf life of at least 1 year. An exception may be made for direct donations to specific health facilities, provided that: The responsible professional at the receiving end acknowledges that (s)he is aware of the shelf life and that the quantity and remaining shelf life allow for proper administration prior to expiration. In all cases, it is important that the date of arrival and the expiration dates of the drugs be communicated to the recipient well in advance.
All drugs should be labeled in a language that is easily understood by health professionals in the recipient country; the label on each individual container should at least contain the International Nonproprietary Name (INN) or generic name, batch number, dosage form, strength, name of manufacturer, quantity in the container, storage conditions, and expiration date.
As much as possible, donated drugs should be presented in larger quantity units and hospital packs.
All drug donations should be packed in accordance with international shipping regulations and be accompanied by a detailed packing list, which specifies the contents of each numbered carton by INN, dosage form, quantity, batch number, expiration date, volume, weight, and any special storage conditions. The weight per carton should not exceed 50 kg. Avoid mixing drugs with other supplies in the same carton.
Recipients should be informed of all drug donations that are being considered, being prepared, or are actually underway.
The declared value of a drug donation should be based on the wholesale price of its generic equivalent in the recipient country or, if such information is not available, on the wholesale world-market price for its generic equivalent.
Costs of international and local transport, warehousing, port clearance, and appropriate storage and handling should be paid by the donor agency, unless specifically agreed otherwise with the recipient in advance.
Medications are worthless if clinicians do not know what they are or how to use them. Describing this situation at a World War II prisoner of war (POW) camp where Allied prisoners were in desperate condition, Dr. Ian Duncan wrote: “It was ironic that immediately after cessation of hostilities, a large carton of penicillin was dropped almost on top of the hospital in Camp 17, Omuta, Japan. Unfortunately, we had never heard of it and, as no instructions were enclosed, it was never used though we had many men suffering from pneumonia, osteomyelitis, infected wounds and boils.”4
Even when clinicians are familiar with a medication, if they can’t decipher the label due to an unfamiliar language or an unknown brand name, they will not be able to use it. Many common medications have different names in different countries. For example, US physicians would not recognize pethidine unless you told them that it was meperidine or know how to use paracetamol/panadol unless they knew that it was acetaminophen. Common drugs with alternative names exist throughout the world. If you face this problem, local practitioners, pharmacists, or Internet sources may provide a solution.
Some medications may no longer be used for their original indication in the most-developed countries, but are still in common use around the world. Four, as examples, are aspirin, scopolamine, chloramphenicol, and chlorpromazine.
Now relegated to the role of antiplatelet drug in developed countries, aspirin can still be used as a potent analgesic and anti-inflammatory agent when other nonsteroidal anti-inflammatory drugs (NSAIDs) are unavailable. The standard dose is 325 to 650 mg (po or rectally) q4-6hr prn; or 650 to 1300 mg (enteric coated) po q8hr (adult); 40 to 60 mg/kg/day divided q6hr po or rectally (pediatric). For juvenile rheumatoid arthritis, the dose can be up to 60 to 110 mg/kg/day divided q6-8h.
Scopolamine (Buscopan), common in “seasickness patches,” is a potent anticholinergic often used for stomach cramps, renal calculi, and bladder spasms. As hyoscine butylbromide, the dose is 10 to 20 mg intramuscularly (IM). Chlorpromazine (Thorazine, Largactil), a potent antipsychotic, antiemetic, and antihiccup medication, may be the only antipsychotic available. The adult dose is 50 to 100 mg parenterally. While it is generally administered intramuscularly (IM), it can also be given slowly intravenously (IV). Chloramphenicol (parenteral only) is an excellent antibiotic. It is recommended by WHO for severe infections and commonly used in the world’s least-developed regions.
Other medications are not used in some countries (such as the United States) or may be older versions of those currently used. These include flucloxacillin (antibiotic), quinine, a wide variety of artemisinin-based medications to treat malaria, and equine snake antivenin.
If you don’t have what you need, use what you have. A number of standard medications can be used for a variety of purposes. Use your normal pharmacology references, poison/drug information center, and pharmacist to determine all the possible uses for available medications.
Some commonly available medications with a wide variety of uses (not all listed) include the following:
Diphenhydramine: Sedative, antiemetic, antihistamine, local anesthetic
Chlorpromazine: Antipsychotic, hiccup therapy, local anesthetic, migraine treatment
Epinephrine/adrenaline: Asthma treatment, cardiac stimulant, vasoconstrictor, allergy/anaphylaxis treatment
Dexamethasone: Reduces tumor edema, bronchiolitis/croup treatment, allergy/anaphylaxis treatment, antiemetic, inflammatory/vasculitis treatment, chronic obstructive pulmonary disease (COPD) treatment
Lidocaine: Antiarrhythmic, local/regional anesthetic
Dextrose solution: Medication admixture, hypoglycemia treatment, osmotic diuretic, sedative (D25W) on a child’s pacifier (i.e., binky)
Oxygen: Hypoxia treatment, carbon monoxide poisoning treatment, cluster headache treatment, antiemetic5
With the caveat that the purity and even the identity of medications purchased from nontraditional sources may be in doubt, they may be beneficial when nothing else is available. Some uses for commonly available street drugs (most of which may be available as commercial medications or commodities) include:
Marijuana: Antiemetic, sedative
Heroin, fentanyl (and other narcotics): Analgesic, local anesthetic, cough suppressant
Ketamine: Analgesic, anesthetic, antidepressant
Cocaine: Local anesthetic, vasoconstrictor
Benzodiazepines (various): Antiepileptic, sedatives, antianxiety, muscle relaxant
Barbiturates (various): Sedative/hypnotic, antiepileptic
Ethanol: Sedative, disinfectant, antidote for methanol poisoning, anesthetic
Lysergic acid diethylamide (LSD) or psilocybin: Cluster headaches6
Healthy people who begin taking oral zinc within 24 hours of onset of common cold symptoms have a shorter duration of illness. However, zinc lozenges commonly produce adverse side effects, while not diminishing symptom severity. Used prophylactically, oral zinc is associated with a reduced cold incidence in children, but it has not been studied in adults.7
While many medications have therapeutic substitutes, medications in the following drug classes may be more amenable to substitution than others8:
|Calcium channel blockers||Angiotensin-converting enzyme (ACE) inhibitors||Tricyclic antidepressants|
|Nonsteroidal anti-inflammatory drugs (NSAIDS)||Diuretics||H2 antagonists|
|Sympathomimetic bronchodilators||Benzodiazepines||Topical agents|
|Cough and cold medications||Phenothiazines||Antibiotics (most)|
When substituting another medication, put a note on the medication label or give it to the patient, saying: “As a result of the recent emergency, your medication is very similar, but not the identical medication to the one you normally take. When possible, please go to your usual pharmacy to continue with your previously prescribed medication.”
Veterinary medications that are the same generics as those prescribed for people and that are labeled “USP” (pharmaceutical grade) are equivalent to those that human pharmacies distribute, although the dose may vary. In general, veterinary medications (excluding dietary supplements) are subject to the same good manufacturing practice regulations imposed by the Food and Drug Administration (FDA) as human medications. Examples that are commonly found include penicillin, amoxicillin, ciprofloxacin, doxycycline, and cephalexin.
A large percentage of the US rural population has used veterinary medication for their own medical needs, usually due to a self-sufficient attitude, availability, lower cost, and a belief that veterinary medications are stronger than comparable human medications. Most often, these are people involved with rodeo, horse racing, and health care; rural area residents; and those lacking health insurance. They most commonly use analgesics, anti-inflammatory medications, anti-arthritis medication, systemic and topical antibiotics, and topical corticosteroids.
Some deaths and serious reactions have been reported from humans using veterinary drugs. The most common complications have been from taking phenylbutazone (Butazolidin, “Bute”), a veterinary analgesic used for racing animals, which at one time was available to treat humans in the United States. Severe adverse effects have included aplastic anemia, gastrointestinal hemorrhage or ulcers, renal insufficiency, seizures, hepatitis, and respiratory failure.9 Those veterinary medications that have caused minor side effects when taken by humans include (o = oral, t = topical, p = parenteral): albendazole (o,t), amoxicillin (o,t), butorphanol (o,p), clindamycin (o,t,p), cyclosporine (o,t), dexamethasone (o), diclofenac (t), ketamine (t), mebendazole (o), and progesterone (t). Other common antibiotics and anti-inflammatory agents have not been reported as causing problems in humans. However, fenbendazole (o), isoflurane (inhalation), pentobarbital (p), roxarsone, tiletamine (unknown), monensin (o), and tilmicosin (o, unknown) have all caused deaths, although some were suicides.10
Often, medications will be available, but in the wrong form or dose for the patient and circumstances. Encourage the pharmacy staff to improvise (and search their literature) for ways to solve these problems. Powders may be used to produce injectables under emergency circumstances. Parenteral drugs can usually be administered rectally at the IV/IM dose. Consider using oral, rectal, and transmucosal medications when patients need analgesics, antimicrobials, and sedative-hypnotics. If IV etomidate, propofol, or succinylcholine is unavailable, consider using IV ketamine, methohexital, rocuronium, or vecuronium.11 Alternatives for local anesthetics are discussed in Chapter 15.
When a university pharmacy announced that they would be unable to procure IV nitroglycerine (NTG) for several months, some older physicians asked why they couldn’t simply compound it, as they had done when it was first being used. They came up with the following method (Megan Brandon, PharmD, University Medical Center, Tucson, Ariz. Personal communication, March 22, 2008.):
Prepare an NTG drip from tablets as follows:
Dissolve 125 tablets of 0.4 mg NTG sublingual (SL) in 50 to 60 mL of 5% dextrose. The pharmacy typically does this in a 60-mL syringe. The solution will be cloudy due to excipients (undissolved materials in the tablets).
Using a 0.22-micron filter needle, add the solution to a glass container of D5W and dilute to a final total volume of 250 mL.
This solution will be at its final concentration of 50 mg/250 mL.
If administering a continuous IV NTG drip, protect it from light by winding black tape around the IV tubing. (Sri Devi Jagjit, MD, Emergency Medicine, Georgetown, Guyana. Personal Communication, September 2014.)
Continuous SL administration: When a patient presented to the emergency department (Casualty; ED; A&E) in resource-poor rural Ghana with severe congestive heart failure and chest pain, it appeared as if he would soon die. Almost no options were available to us and we lacked sufficient NTG tablets—and a filter and a glass D5W container—to make a drip. Instead, we had his wife administer a tablet of 0.4 mg NTG SL about every 5 minutes for the next 6 hours. By morning, he was over the acute episode and was moved to the ward.
Nitroglycerine slurry: The following is the method used at Georgetown, Guyana’s Public Hospital (GPHC) to provide continuous NTG administration when IV NTG is unavailable.
Crush five tablets of 0.4 mg NTG.
Mix the powder in 5 cc normal saline.
Place the slurry in a 5-mL syringe and administer 1 mL sublingually every 3 minutes.
Monitor the blood pressure to maintain the Systolic BP ≥110 mm Hg.
A penicillin solution is used particularly to treat gonococcal conjunctivitis in newborns. To make a penicillin solution of 10,000 units/mL, use one of these two methods:
Boil a clean cup and let it cool. Then add 100 mL sterile water and one level teaspoon of salt or add 100 mL sterile saline. Dissolve 600 mg benzylpenicillin in the saline.
Dissolve 600 mg benzylpenicillin in 10 mL water for injection. Then mix 1 mL of this solution with another 10 mL of water for injection.12
Some patients (especially children, the elderly, and the less-than-conscious patient) cannot swallow tablets. Some medications don’t come as a liquid; in austere situations, you may not have the liquid form even if a medication is manufactured as a liquid.
There are several ways to convert tablets to a more palatable form. For non-extended-release drugs, break or crush tablets into sections—or open up the capsule and pour out the contents. Crush tablets using a hammer, after first putting the tablet in a plastic bag or wrapping it in a paper towel so the pieces do not escape. You can also use a mortar and pestle, a similar implement used to grind grains, or a coffee grinder.
If necessary, administer the medications through a nasogastric tube. Patients can dissolve the powder in liquid to drink, or sprinkle the powder onto food and eat it. Another alternative is simply to mix larger pieces into mashed potatoes, applesauce, or foods of similar consistency.
Splitting drug tablets not only is common among the general population, but also may be necessary when there is a limited supply of medications. It may also be needed to increase dosing flexibility, facilitate swallowing medication for patients, and reduce health care costs. The danger in doing this is that the doses in the two parts may not be equivalent, because the active drug may not be evenly distributed through many tablets, and tablets may break unevenly. How well a tablet splits depends on whether it has score marks and its size, shape, and fragility, as well as the splitter’s visual acuity, strength, dexterity, and cognitive ability.13 The accuracy of cutting a tablet in half varies. Many people cannot break scored tablets manually, so they use tablet splitters, razor blades, or kitchen knives. However, tablets could not consistently be accurately and precisely split into equal parts, even in studies with a tablet optimally designed for splitting (large, elongated tablets with deep score marks on both sides), an experienced splitter, and optimal equipment.14
When patients with human immunodeficiency virus (HIV) infection want to celebrate a cultural or religious fast over several days or weeks (e.g., Lent, Ramadan), clinicians can suggest that treatment-experienced stable patients take once-daily rather than twice-daily dosed ritonavir-boosted lopinavir, along with a once-daily fixed-dose tenofovir–emtricitabine. With this regimen, no changes have been found in adherence, diarrhea, CD4 cell counts, viral load, hematocrit, kidney, liver, and lipid tests. However, clinicians must carefully select patients for whom this regimen is appropriate.15
Don’t believe the expiration date you see on the pharmaceutical packaging. It has little relationship to the quality, potency, or safety of most medications. “Medical authorities uniformly say it is safe to take drugs past their expiration date—no matter how ‘expired’ the drugs purportedly are. Except for possibly the rarest of exceptions, you won’t get hurt and you certainly won’t get killed.”16
Two types of expiration dates may be on medications. The first is a manufacturer’s or pharmacist’s date, which generally has no major significance. The second type is placed on a partially used, often liquid, medication; pay close attention to this date.