The Dentist's Drug and Prescription Guide. Mea A. Weinberg
Drug distribution is the movement of an agent through the blood or lymph to various sites of action in the body. An important factor affecting drug distribution is protein binding. Many drugs in the blood are bound to circulating proteins such as albumin for acidic drugs (e.g., penicillin, barbiturates, aspirin, vitamin C) and acid glycoproteins and lipoproteins for basic drugs (e.g., narcotic analgesics, erythromycin). When drugs are bound to plasma proteins, they are inactive while circulating in the blood. This binding to proteins is temporary, reversible, and can convert to free drug. Only drugs that are not bound to plasma proteins are “freely active” and bind to specific receptors on the target tissue/organ. Another factor that affects drug distribution is blood flow to the target organs.
23 Q. What is the minimum effective concentration (MEC) of a drug?
24 A. The minimum effective concentration (MEC) is the amount of drug required to produce a therapeutic effect. This is important to know because a drug should not be given above the MEC as this will produce toxic concentrations. The ideal concentration of a drug should be between the MEC and the toxic concentration. This is referred to as the therapeutic range. For example, after periodontal surgery, it is recommended that the patient take ibuprofen (Motrin®, Nuprin®). If the patient decides to take only one 200 mg tablet during the day, they will still experience pain because the therapeutic range was not reached. The patient should take two or three tablets which will increase the plasma level of ibuprofen into the therapeutic range. If the patient takes five or more tablets at one time, then adverse effects may occur because the plasma level of ibuprofen is outside the therapeutic range and the maximum dose has been exceeded. Beyond the maximum dose, the analgesic effect does not increase.
25 Q. What does the term “dose” mean?
26 A. The dose of a drug is the amount of drug taken at any one time. Dose is expressed as the weight of drug (e.g., 500 mg), the number of dosage forms (e.g., one capsule), or the volume of liquid (e.g. two drops).
27 Q. What is the elimination half‐life of a drug?
28 A. The elimination half‐life (t½) of a drug is essentially the duration of action of a drug. Also, it is used to determine the dosing of a drug. The elimination half‐life of a drug is the amount of time required for a drug to decrease its original concentration by 50%. The second half‐life is when it removes another 50%, leaving 25% in the blood. The third half‐life is when it removes another 50%, leaving 12.5% in the blood. Drugs have different predetermined half‐lives. As repeated doses of a drug are administered, the plasma concentration builds up and reaches “steady state.” Steady state occurs when the amount of drug in the plasma builds up to a level considered therapeutically effective. In order to achieve steady state, the amount of drug administered must balance the amount being cleared from the body. It usually takes about between four and five half‐lives to reach clinical steady state and about six half‐lives before 98% of the drug is eliminated from the body (Ito 2011). For example, if a drug has a t½ of 2 hours, it will take about 8–10 hours to reach clinical steady state (Ito 2011).Drugs with a short t½ are eliminated faster than drugs with a long t½. For example, tetracycline HCl has a t½ of 6–12 hours and doxycycline hyclate has a t½ of 14–24 hours. Thus, tetracycline dosing is one capsule every four hours while doxycycline is dosed 100 mg every 12 hours on day 1, then 100 mg every day. On average, doxycycline's half‐life is around 19 hours. By multiplying 19 hours by six hours (average t½ to be 98% eliminated from the body) (19 × 6 = 114 hours), it takes 114 hours, or about five days, before 98% of the doxycycline has been removed from the body. Penicillin VK has a t½ of 30 minutes and amoxicillin's t½ is 1–1.3 hours. Thus, penicillin is given every six hours and amoxicillin is dosed every eight hours (Thomson 2004a,b).Ibuprofen has a short t½ and is cleared from the body more rapidly than a drug with a longer t½. Ibuprofen requires a more frequent, regular dosing regimen of 200–400 mg (OTC strength) q4–6h or prescription ibuprofen 600–800 q6–8h in order to build up and maintain a high enough concentration in the plasma to be therapeutically effective.
29 Q. What is the volume of distribution (VD)?
30 A. Apparent volume of distribution (VD) refers to the amount of drug in the various tissues of the body. Volume of distribution is a calculated value referring to the volume of fluid (e.g., plasma, interstitial fluid [fluid between the cells], and lymph) in which a drug is able to distribute to the organs. The volume of distribution can be used to calculate the LD, MD, and clearance of a drug (Aki et al. 2010; Thomson 2004a, b; Wesolowski et al. 2016).
31 Q. What is drug biotransformation?
32 A. Drug biotransformation (or metabolism, as it is sometimes called) terminates the action of a drug. It is a process by which a substance changes from one chemical form to another via a reaction in the body. Usually, biotransformation occurs in the liver but can also occur in the plasma and kidney.
33 Q. What is the importance of drug clearance?
34 A. Clearance refers to the volume of fluid (e.g., plasma) that would be completely cleared of drug if the entire drug being excreted were removed from that volume of fluid. Essentially, clearance is the removal of a drug from the plasma. It is a calculated value and measured in liters/hour. Clearance indicates the ability of the liver and kidney to eliminate a drug from the body (Doogue and Polasek 2013). Clearance may be reduced in the elderly. Both clearance and VD are important values in determining the half‐life of a drug (Gossel 1998a,b).
35 Q. What must happen to a drug in the body in order for a drug effect to occur?
36 A. The rate of absorption must be greater than the rate of elimination for the drug to have an effect on the body. Usually, the rate of elimination is slower than the rate of absorption so that the rate of elimination is the controlling factor in the presence of the drug in the body (Fujimoto 1979).
1.3 Pharmacodynamics
1 Q. What is the definition of pharmacodynamics and what is its significance in dentistry?
2 A. Pharmacodynamics deals with the mechanism of action of drugs or how the drug works in the body to produce a pharmacological response and the relationship between drug concentration and response. It is important to know the mechanism of action of drugs because it will help with understanding the reason for prescribing the drug.
3 Q. What is the definition of drug affinity?
4 A. Affinity is the ability of a drug to bind to the receptor to elicit a therapeutic response. If one drug has a greater affinity than another drug, it means that drug binds more readily to the receptor. If a drug has a high affinity, this means that a smaller dose can produce a therapeutic effect compared to a drug with a lower affinity for the same receptor.
5 Q. Do drugs bind strongly to a receptor?
6 A. Most drugs bind weakly to their receptors via hydrogen, hydrophobic and ionic bonds. Because these are relatively weak bonds, the drug can bind and unbind the receptor. Some drugs do bind strongly to the receptor via covalent bonds.
7 Q. Can drugs bind to other receptors besides their specific receptors?
8 A. Yes. For example, atypical antipsychotic drugs bind to dopamine receptors for their antipsychotic response but also bind to alpha receptors which cause adverse effects such as weight loss while binding to muscarinic receptors causes xerostomia.
9 Q. How do most drugs cause a therapeutic response?
10 A. Most drugs have an affinity for a specific receptor. Most receptors are proteins. Once the drug binds to the receptor, a therapeutic response occurs. Receptors have a steric or three‐dimensional structure so when the substrate or drug binds to that receptor, the receptor undergoes steric realignment which allows the drug to bind more precisely to the receptor with better efficacy.
11 Q. Do all drugs interact with receptors to cause a therapeutic response?
12 A. No. Epinephrine binds to alpha and beta receptors on the organs but also produces some of its effects by activating an enzyme called adenyl cyclase. Also, anesthetic gases do not bind to receptors in the central nervous system. Antacids do not work by interacting with receptors.
13 Q. What are drug agonists and