GI system- Anatomy

INTERACTION BETWEEN HUMAN BODY AND DRUGS
Introduction

Drugs are the substance that are used to treat a disease. These are chemical substances derived from different sources (living or non- living things) which are sued to alter the functions of living/ bacterial tisseus by reacting with them.

Uses of drugs

Drigs are used for:

1. Diagnosis of diseases

2. Prevention of diesases

3. Treatment of diseases.

This chapter deals with the relationship between drug and the human body; the mechanism of drung' action, uses of drugs and the body's response to drugs.

Drugs are prepared in laboratories and experimented so that they are free of unacceable toxic substances which can harm the clients. Then only they are approved for use of human. The study of action of drug in man is called clinical pharmacology.

Clinical Pharmacology can be divided into two brances.

1. Pharmacokinetics.

Means what the human body dees to drungs it is the study of the movement of drugs in the body.

2. Pharmacodynamics

Means what a drug does to the human body. The knowledge about pharmacokinetics and pharmacodynamics is essential to know how the drugs are used for the best advantade of the patient.

Protein Binding

Most drugs bind to proteins, either albumin or alpha-1 acid glycoprotein (AAG), to a greater or lesser extent. Drugs prefer to be free, it is in this state that they can travel throughout the body, in and out of tissues and have their biological effect. The downside of this is that they are easy prey for metabolising enzymes.

As you would expect, more highly bound drugs have a longer duration of action and a lower volume of distribution. Generally high extraction ratio drugs' clearance is high because of low protein binding and, conversely, low extraction ratio drugs' clearance is strongly dependent on the amount of protein binding.

Why is this important? If a drug is highly protein bound, you need to give loads of it to get a theraputic effect; as so much is stuck to protein. But what happens if another agent comes along and starts to compete with the drug for the binding site on the protein? Yes, you guessed it, the amount of free drug is increased. This is really important for drugs that are highly protein bound: if a drug is 97% bound to albumin and there is a 3% reduction in binding (displaced by another drug), then the free drug concentration doubles; if a drug is 70% bound and there is a 3% reduction in binding, this will make little difference.

The drugs that you really need to keep an eye on are: warfarin, diazepam, propranolol and phenytoin. For example, a patient on warfarin is admitted with seizures, you treat the patient with phenytoin, next thing you know - his INR is 10.

The amount of albumin does not appear to be hugely relavent. In disease states such as sepsis, the serum albumin drops drastically, but the free drug concentration does not appear to increase

Degree of ionisation

This is really important with regard to local anaesthetics. The essential fact to know is that highly ionized drugs cannnot cross lipid membranes (basically they can't go anywhere) and unionised drugs can cross freely. Morphine is highly ionised, fentanyl is the opposite. Consequently the latter has a faster onset of action. The degree of ionisation depends on the pKa of the drug and the pH of the local environment. The pKa is the the pH at which the drug is 50% ionised. Most drugs are either weak acids or weak bases. Acids are most highly ionised at a high pH (i.e. in an alkaline environment). Bases are most highly ionised in an acidic environment (low pH). For a weak acid, the more acidic the environment, the less ionised the drug, and the more easily it crosses lipid membranes. If you take this acid, at pKa it is 50% ionised, if you add 2 pH points to this (more alkaline), it becomes 90% ionised, if you reduce the pH (more acidic) by two units, it becomes 10% ionised. Weak bases have the opposite effect.

Local anaesthetics are weak bases: the closer the pKa of the local anaesthetic to the local tissue pH, the more unionised the drug is. That is why lignocaine(pKa 7.7) has a faster onset of action than bupivicaine (pKa 8.3). If the local tissues are alkalinised (e.g. by adding bicarbonate to the local anaesthetic), then the tisssue pH is brought closer to the pKa, and the onset of action is hastened.

ADVERSE REACTIONS TO DRUGS

An adverse reaction to a drug has been defined as any noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment. Some drug reactions may occur in everyone, whereas others occur only in susceptible patients. A drug allergy is an immunologically mediated reaction that exhibits specificity and recurrence on re-exposure to the offending drug.

Classification of adverse reactions to drugs

Reactions that may occur in anyone

Drug overdose -Toxic reactions linked to excess dose or impaired excretion, or to both
Drug side effect - Undesirable pharmacological effect at recommended doses
Drug interaction - Action of a drug on the effectiveness or toxicity of another drug

Reactions that occur only in susceptible subjects

Drug intolerance - A low threshold to the normal pharmacological action of a drug
Drug idiosyncrasy - A genetically determined, qualitatively abnormal reaction to a drug related to a metabolic or enzyme deficiency.
Drug allergy - An immunologically mediated reaction, characterised by specificity, transferability by antibodies or lymphocytes, and recurrence on re-exposure
Pseudoallergic reaction - A reaction with the same clinical manifestations as an allergic reaction (eg, as a result of histamine release) but lacking immunological specificity

Incidence

Adverse reactions to drugs are very common in everyday medical practice. A French study of 2067 adults aged 20-67 years attending a health centre for a check up reported that 14.7% gave reliable histories of systemic adverse reactions to one or more drugs. In a Swiss study of 5568 hospital inpatients, 17% had adverse reactions to drugs. Fatal drug reactions occur in 0.1% medical inpatients and 0.01% of surgical inpatients. The main drugs implicated are antibiotics and non-steroidal anti-inflammatory drugs. Adverse reactions to drugs occurring during anaesthesia (muscle relaxants, general anaesthetics, and opiates), although less common (1 in 6000 patients receiving anaesthesia), are life threatening, with a mortality of about 6%.

Numerous mechanisms have been implicated in adverse reactions to drugs. However, these mechanisms are not fully understood, which may explain the difficulty in differentiating drug allergy from other forms of drug reactions and in assessing the incidence of drug allergy, evaluating risk factors, and defining management strategies.