The rate and degree of blood and absorption into the blood is dependent on the route of administration. Effective absorption from the oral route depends on both the chemical properties of the drug and the functional efficacy of the GI tract. Parenteral absorption is dependant on the extent of blood supply. The bioavailability of a drug is the most critical part of pharmacokinetics.
Bioavailability is the amount of drugs that are available to the body to produce the therapeutic effect. There are two aspects of drug metabolism that determine this absorption and hepatic first pass. Bioavailability can be described as the percentage of the drug administered that is available therapeutically. This varies from 0% to 100%, and the route of administration affects the therapeutic dose.
The primary site of metabolism in the body is the liver. So any condition that affects affect the hepatic function will alter the rate and degree of metabolism. Drug metabolism is determined by the microsomal oxidative enzymes such as cytochrome P450 enzymes, and the liver’s capacity for conjugation.
After the drug has been absorbed in the GI, it is taken up in the bloodstream through the hepatic portal system. This is true of most substances that are absorbed from the Gi tract, the exception is lipids which enter the lymphatic system and are eventually deposited in the bloodstream via the thoracic duct system into the superior vena cover.
The Hepatic portal system is designed to take digested food staff to the liver, where they can be processed. In some cases, they can be stored, before they are distributed to the rest of the body. As the liver the main site for metabolism, some drugs may be extensively metabolised before reaching the rest of the body.
That means that there are some cases where an individual takes analgesia, might in theory never reach the site where the pain is. Some drugs that have a high hepatic first pass, sometimes never get passed the liver. This is true for the most Narcotics that are taken orally.
Hence the dose needed for drugs that need to be injected is usually lower than drugs given orally, for, example pethidine. Some drugs are completely metabolised in the liver that they can not be given orally. Otherwise, they will not have a therapeutic effect. Another example is, GTN, a medication used for angina if given sublingually it will evade the hepatic pass and will reach the site needed fast.
Diseases of the liver can lead to either the accumulation of pharmacologically active agents to toxic levels or prolonged effect of the drugs or both. The impact is most significant for medications that need to metabolised before they are excreted, for example of specific categorise are narcotics and non-specific beta blockers.
Effects of Diseases on Drug Action
GI diseases can affect the rate and degree of oral absorption. Conditions affecting GI peristalsis, such as severe vomiting diarrhoea or constipation. Or the rate of gastric emptying can alter the rate at which the drug is absorbed. An inflammatory condition that makes changes to the structure and function of the gut may also impede drug transit into the blood. But is this dependant on the region and the track affected and the usual site of drug absorption. Nutritional imbalances brought about by GI diseases can also affect drug metabolism.
Diseases like circulatory shock, congestive cardiac failure and peripheral vascular disorders often reduce tissue perfusion of blood. As a result of the blood levels may be lower than expected while the injection site at the site remains high. In effect, the injection becomes a drug reservoir. If under these conditions, perfusion was to suddenly increase, the levels of circulating blood may rise as well, leading to increased drug activity and possible toxicity.
The presence of food in the gut around the time of drug administration can affect. Nutritional elements compete with the drug for the sites of absorption. As a result of this peak plasma concentration of the drug is lower than expected and the drug action is prolonged.
However, drug solubility has a significant influence on the degree of absorption, lipid-soluble drugs are less affected by competition than water-soluble drugs. Some medications such as tetracycline antibiotics are chelated by calcium salts predominantly found in milk products but also present in some antacid preparations. Drug bioavailability is then lowered because the conjugated antibiotic is excreted in faeces.
The function of the drug Drug can also be altered by hormonal changes that happen during pregnancy. Peristalsis and gastric emptying may slow down to the extent that it affects the amount of blood being absorbed by the gut. During pregnancy gastric emptying is also erratic, which can affect the degree of absorption for acidic drugs. So when treating anyone in between the childbearing age, always inquire if the patient is pregnant.
The notes above were used to study for a pharmacology exam, if there are factual inaccuracies, kindly point them out and we will change them.
Shargel, L., Andrew, B. C., & Wu-Pong, S. (2015). Applied biopharmaceutics & pharmacokinetics (pp. 119-120). McGraw-Hill Medical Publishing Division.
Kanodia, J., Baldwin, M., Lo, A., Wang, D., Zhou, K., Lee, J., … & Bourdet, D. (2017). Safety, Pharmacokinetics and Pharmacodynamics of TD-0714, a Novel Non-Renally Cleared Neprilysin Inhibitor, in Healthy Humanvolunteers: Potential for Once-Daily Dosing and Predictable Exposure in Patients Regardless of Baseline Renal Function. Journal of Cardiac Failure, 23(8), S68.