Chapter 3

Drug dosing

I. Basic principles of drug dosing

Q. What is the difference between dose and dosage form?

A. The dose of a drug is a specified quantity of a drug; the size or frequency at which the drug doses are administered. The dosage form of a drug is the drug formulation such as a tablet, a capsule, syrup, a liquid suspension/solution or an ointment/cream that generally contains a mixture of the active drug substance, in association with one or more nonactive ingredients. The FDA has stated that a dosage form is the way of identifying the drug by its physical form, which is linked both to physical appearance of the drug product and to the way it is administered (http://www.fdalawblog.net/fda_law_blog_hyman_phelps/2009/05/fda-petition-response-reaffirms-fda-orange-book-dosage-form-nomenclature-policy.html).

    If the patient is instructed to take one 500 mg capsule po (orally) qid (four times a day) the total dose is calculated from the dose administered multiplied by the number of times a day the dose is administered; one tablet (500 mg) qid is 2000 mg or 2 g.

Q. Why are some tablets “candy coated”?

A. These “candy coated” tablets are referred to as enteric-coated. Some drugs are either irritating to the stomach lining or are inactivated, by different degrees, by acid in the stomach. To prevent the drug from dissolving in the stomach and allow it to get absorbed in the intestine the drug is available in enteric-coated tablets or are buffered to protect the drugs from gastric juices. Examples include erythromycin base, ibuprofen, and aspirin.

Q. Is it important to know the patient’s baseline hepatic and renal function when deciding on the proper dosage for a patient?

A. Yes. Most drugs require adequate hepatic function for metabolism and adequate renal function for elimination. It is important to review the medical history and specifically ask the patient if he/she has any liver or kidney problems.

Q. What is the principle of selection of a therapeutic regimen?

A. Since the outcome of drug therapy is the product of a multifaceted interaction between drug and patient, the selection of an appropriate drug and regimen is depend on a thorough evaluation of the patient’s medical and dental status and the actions and effects of the drugs to be used in treatment.

Q. What are the variabilities in drug dosage requirements?

A. There are many variabilities relating to alterations in drug dosing. The age of the patient, renal and liver function of the patient and pregnancy can change the way the body reacts to medications.

Q. What are the loading and maintenance doses of drugs?

A. Most drugs are not administered as a single dose. Rather, repeated doses resulting in an accumulation of the drug in the blood are needed to reach a plateau whereby the level of drug in the plasma is maintained constantly within the therapeutic range and avoid fluctuations in the concentration-time profile. A steady-state is achieved when the same amount of drug that is absorbed into the body equals the same amount of the drug leaving the body. To keep a proper steady-state, the drug dosing must be consistent and the drug must be taken at the same time every day. Not achieving and maintaining steady-state may make the drug ineffective. It must be emphasized to the patient that the drug must be taken as prescribed. The drug should be taken at the same time every day and no doses missed. In order to reach this steady-state, a loading dose is first administered on day 1, which is a higher amount of drug needed to quickly reach a therapeutic response. Without a loading dose it takes longer to reach steady-state. After the loading dose is administered and before the plasma levels drop, a maintenance dose is given to maintain plasma drug levels within the therapeutic range. This maintenance dose is given in sporadic doses after the loading dose. For example, penicillin VK is usually given as “1000 mg initially, followed by 500 mg every 6 hours”. Doxycycline is given as “100 mg every 12 hours on day 1, then 100 mg every day afterward”.

Q. How much loading dose is administered?

A. The loading dose is usually twice the regular dose.

Q. What drugs are given as an initial loading dose followed by a maintenance dose?

A. Antibiotics that are administered every 6 to 8 hours (also including azithromycin, which is dosed once every 24 h) usually require a loading dose in order to rapidly achieve a high tissue concentration for acute dental infections.

Q. How is a loading dose, followed by a maintenance administered?

A. The loading dose is given on day 1, followed by the maintenance dose on day 1, day 2 etc.…

Q. What is the proper duration of antibiotic treatment for dental infections?

A. Generally, the duration of antibiotic therapy has been variable and not evidence based. The current theory focuses on shortening the course of antibiotics, which might limit antibiotic resistance. Generally, most private practice and ­hospital-based dentists empirically prescribe antibiotics for 7 to 10 days. However, high-dose, short-term therapy has also been advocated. Prescribing antibiotics for 3 days has supported the fact of reducing the incidence of antibiotic resistance with prolonged antibiotic exposure. It is also important to take the antibiotic for the full course prescribed even if the patient is clinically responding in order to minimize the chance of the resistant bacteria not being targeted preventing a relapse. There are no dental guidelines or recommendations regarding the duration of antibiotic therapy. There are a few published medical guidelines that were found concerning the duration of antibiotic therapy. The Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) regarding hospital patients with pneumonia recommends that antibiotic therapy should be for a minimum of 5 days (Mandel et al., 2007). Important information for dental infections can be extrapolated from these guidelines.

Q. What is the importance of knowing the peak concentration of a drug?

A. Peak concentration is the maximum plasma concentration of a drug which is seen during dosing intervals. At the time (usually hours) of peak concentration, the drug has the highest concentration in the plasma. Knowing the peak concentration of a drug (e.g., antibiotic) is important because this is the time that is desired if antibiotic prophylaxis is warranted. Antibiotic prophylaxis is defined as prevention of the development of an infection at the surgical site (Munckoff, 2005). For example, recommending antibiotic prophylaxis according to the American Heart Association (AHA) for the prevention of bacteria or before a sinus graft is performed in anticipation of possible perforation of the Schneiderian membrane (creating signs and symptoms of a sinusitis). At these times having the antibiotic already in the systemic circulation before the surgical procedure is performed is idea for optimum therapeutic effects. Thus, before performing these surgical procedures the antibiotic needs to only be administered during the peak hours before the ­surgery and not days before.

Table 3.1 Peak blood levels of antibiotics.

Table 3.2 Peak levels of common analgesics.

Q. What are the peak blood levels of antibiotics used in dentistry?

A. See Table 3.1.

Q. What are the peak levels of common analgesics used in dentistry?

A. See Table 3.2

Q. What is the difference in prescribing capsules or tablets (e.g., doxycycline 100 mg comes in tablets and capsules)?

A. If a patient has difficulty swallowing capsules, prescribe tablets. To be absorbed capsules need to undergo dissolution or to be opened (usually takes about 4 minutes) and tablets need to undergo disintegration or to break up (takes slightly longer than a capsule) to release the active ingredient that will be absorbed. Both processes take time and absorption will occur in the duodenum (small intestine). A liquid gel capsule (Aleve, Advil) is formulated to dissolve quickly which allows the liquid inside the capsule to be absorbed fast. A gel capsule is a capsule-shaped tablet coated with gelatin for easy swallowing. Basically, it is a tablet and not a capsule. That means it will be absorbed like a tablet but it may take longer to disintegrate because the gelatin has to disintegrate first and then the tablet. Liquid drug form (e.g., solution) is absorbed the quickest, followed by liquid gel capsule, capsule, tablet and then gel capsule.

Q. What happens if a patient misses a dose of an antibiotic?

A. It is important not to miss a dose because drugs that require daily administration are only effective when they achieve steady-state in the blood, which is required for a medication to reach therapeutic and effective levels in the blood. This means that steady-state occurs when the same amount of drug entering the blood equals the same amount of drug being eliminated from the body.

    Ideally, doses should be equally spaced throughout the day and taken at the same times each day. This will help to ­maintain a constant level of antibiotic in the bloodstream. If the patient misses a dose of an antibiotic it is best not to double the next dose because this could increase the incidence of adverse effects. If you miss a dose, take it as soon as remembered; do not take if it is almost time for the next dose. Instead, skip the missed dose and resume your usual ­dosing schedule. Do not “double-up” the doses.

Q. What does first-pass effect have to do with drug dosing?

A. First-pass effect is defined as the biotransformation of a drug in the liver that occurs before the drug enters the systemic circulation. For example, sublingual nitroglycerin has a high first pass metabolism because 90% of it is inactivated by the liver before it enters the blood. Morphine and lidocaine are other drugs with high first-pass effect when administered orally. Because of a high first-pass metabolism these drugs cannot be given orally because it would be totally inactive before it reached the site of action.

Q. How does age affect drug metabolism?

A. Age often affects drug metabolism and drug dosages may need to be adjusted in children and the elderly. Years ago pediatric dosing was determined using pediatric formulas such as Clark’s Rule, Young’s Rule and Fried’s Rule, which were based on the weight of the child in pounds or on the age of the child in months. Today, these formulations are not used but rather the dose is based on body surface area or weight of the infant/child. In order to calculate the proper dosage the manufacturer’s appropriate dose (in mg/kg) of the prescribed drug which is safe must be known. This dose is a given and predetermined value from the manufacturer.

    Children and the elderly require lower drug doses than other individuals due to difference in their response to drugs.

II. Pediatric patient

* Note: The prescriber should use his/her own judgement in prescribing for a particular pediatric patient. The prescriptions in this section are not absolute numbers, only suggestions. These are just a few examples how you can calculate doses.

Q. Are there standardized dosage recommendations for children?

A. Yes. The dosage is dependent on the age and weight of the child. It should be noted that there is a wide range of correct dosages for a drug. Usually, drug information for pediatric dosage (mg/kg) is supplied by the drug manufacturers. For example, the dose recommendations for children on amoxicillin range from 20 to 45 mg/kg body weight per day depending on weight and height of the patient and the severity (mild or severe infection) of the medical condition. (http://www.emiphysicians.com/calculator1.html).

Q. Should a solid dose form such as tablets or capsules or liquid suspension or solution be given to a pediatric patient?

A. It depends on the age and the weight of the child but always ask the parent if the child can swallow a pill. Sometimes when doing dosage calculations it may be more accurate to give a liquid dosage form.

Q. What is the difference between mL and cc?

A. mL (milliliters) is sometimes referred to as cc or cubic centimeters. Sometimes, a medical dropper will have markers in cc; cc is the same as mL.

Q. How does the parent accurately measure out teaspoonfuls or mL?

A. A medicine dropper and spoon are available in the pharmacy. The dropper and spoon have measurements in medically or marked teaspoonful (tsp) and mL. The patient should be cautioned about a household teaspoon because it can vary in size.

Q. What should be prescribed if the calculation for a pediatric dose is, for example, 275 mg for penillicin VK?

A. Since there is no dosage strength available for 275 mg, it is recommended to always use the lower dose and then increase the number of days of therapy (prescribe the antibiotic for 10 days rather than 7 days)or to use the suspension instead.

Q. What directions should be given to the parent about oral suspensions?

A. Oral suspensions should be shaken very well and stored in the refrigerator. Any unused medicine should be discarded after 14 days.

Q. Given the following case, what dosage of penicillin VK should be prescribed to this child?

A. 10-year-old male patient that weighs 32 kg (70 lbs) has an endodontic abscess that is not draining. An antibiotic should be prescribed. Penicillin VK is the drug of choice. The antibiotic can be prescribed as an oral suspension or as a tablet.

Table 3.3 Calculation for correct dose to give to a pediatric patient.

* Each teaspoonful is 5 mL.

^¶ Calculation for 159 mg/dose÷125 mg/5 mL is the following: 159 x 5÷125=6.36.

Table 3.4 How the prescription is written.

*Advise the parent to get a medicine dropper/spoon rather than using an ordinary teaspoon because of variations in measurements of a teaspoonful. After penicillin V solution is mixed, it is best to store it in a refrigerator between 2 and 7°C (36–46°F); do not freeze. Throw away any unused medicine after 14 days.

a. Penicillin VK oral suspension

Steps to follow when prescribing for a pediatric patient: ht/>

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