All On Drugs. How Do They Work? Are They Safe?

 

One of the subjects we studied in biology and medicine is pharmacology, the study of drugs and their actions on living organisms and on the body, their applications and therapeutic uses. It encompasses the sources, chemical properties, biological effects, and therapeutic uses of drugs. Understanding pharmacology is crucial for developing new medications and for optimizing the use of existing ones.

The action of drugs on the body is divided mainly into two areas of study, namely, pharmacodynamics and pharmacokinetics that describe how drugs interact with the body and how the body affects drugs.

 Understanding both is essential for optimizing drug therapy and ensuring its safety and efficacy. Let's have a brief look. Pharmacodynamics (PD) refers to the effects of a drug on the body. It involves the study of how a drug interacts with its target, the mechanisms of its action, and the relationship between drug concentration and effect. Key concepts in pharmacodynamics include receptor binding, meaning drugs often exert their effects by binding to specific receptors on cells. This binding can activate or inhibit the receptor's function. They can act as agonists where they activate receptors to produce a response. They can also act as antagonists where they block receptors and inhibit their activity. Drugs act also as a dose-response relationship: The relationship between the dose of a drug and the magnitude of its effect. This relationship helps determine the effective dose and the dose at which the drug becomes toxic. The efficacy: of a drug is the maximum effect a drug can produce, whereas their potency is the amount of drug needed to produce a given effect.

The therapeutic window is the range of drug doses that produces a therapeutic response without causing significant adverse effects. This is the gap between the minimum effective concentration and the minimum toxic concentration. PD also studies the mechanisms of action. This study explains how a drug produces its effects at the molecular, cellular, or organ levels. This can involve various biological processes such as enzyme inhibition, receptor activation, ion channel modulation, or changes in cell signalling pathways.

Drug action also involves pharmacokinetics (PK). This describes how the body affects a drug over time. It involves the study of the absorption, distribution, metabolism, and excretion (ADME) of drugs. Key concepts in pharmacokinetics include its absorption, the process by which a drug enters the bloodstream from its site of administration (e.g., oral, intravenous, intramuscular), bioavailability, the fraction of an administered dose that reaches the systemic circulation and is available for action, the distribution which is the dispersion or dissemination of substances throughout the fluids and tissues of the body. Factors affecting distribution include blood flow, tissue permeability, and binding to plasma proteins depending on the volume of distribution (Vd), a theoretical volume that describes how extensively a drug is distributed throughout the body relative to the concentration of the drug in the blood. Next is how the drug is metabolized or used up by biochemical modification in the body, primarily by the liver. Metabolism can transform drugs into active or inactive metabolites.

First-pass effect is the metabolism of a drug within the liver immediately after it enters the bloodstream from the gastrointestinal tract, reducing its bioavailability. Next is the excretion or the removal of drugs and their metabolites from the body, primarily through the kidneys (urine) or the liver (bile / faces). This depends on clearance (Cl): The volume of plasma from which a drug is completely removed per unit time, the half-life (t1/2), meaning the time it takes for the concentration of the drug in the blood to reduce by half.

Understanding the integration of both pharmacodynamics and pharmacokinetics is crucial for optimizing dosing regimens to ensure that the drug concentration remains within the therapeutic window for the desired duration. Predicting drug interactions and anticipating how different drugs may interact based on their metabolic pathways and receptor targets is part of the study. Not just generalizing drug action on all populations but also in personalizing medicine where we tailor drug therapy based on individual patient characteristics, such as age, weight, genetic factors, and the presence of other diseases.

 Just to summarize, pharmacodynamics focuses on what the drug does to the body, including the mechanisms of action and the relationship between drug concentration and effect, while pharmacokinetics focuses on what the body does to the drug, including how the drug is absorbed, distributed, metabolized, and excreted.

Both are essential for understanding the overall therapeutic and adverse effects of drugs, helping healthcare professionals to use medications safely and effectively. Let us now briefly look at the different classes of drugs we use in medicine. 

Drugs can be broadly categorized based on their therapeutic effects, chemical characteristics, or mechanisms of action. 

Here are the major classes of drugs along with their primary mechanisms of action and applications. First, we have analgesics. We have opioids such as morphine, and fentanyl. Their mode of action is to bind to opioid receptors in the brain and spinal cord, inhibiting pain signals. Their applications are for severe pain, postoperative pain, chronic pain in terminal illnesses. The opioids are highly effective but with risks of tolerance, dependence, and addiction. Then we have another drug of choice, the non-opioid analgesics, such as acetaminophen, NSAIDs (Ibuprofen, Aspirin). Their mode of action is to reduce inflammation and pain through inhibition of cyclooxygenase (COX) enzymes. Their applications are for mild to moderate pain, inflammation, fever and they are effective for acute pain and inflammatory conditions, fewer risks than opioids.

Next, we can consider the antibiotics. These include (examples) the beta-lactams such as the penicillins and cephalosporins. Their mechanism is to Inhibit bacterial cell wall synthesis in applications where there are bacterial infections (e.g., pneumonia, strep throat). They are highly effective against susceptible bacteria, but resistance is a concern. There are also the macrolides such as, erythromycin and azithromycin Their mode of action is to inhibit bacterial protein synthesis which would be useful for respiratory infections, skin infections, and for certain infections in penicillin-allergic patients.

We can now consider the antivirals. These classes include the nucleoside analogues such as Acyclovir, and Zidovudine. Their action is to inhibit viral DNA/RNA replication in herpes simplex virus and in HIV. They are effective in reducing viral load to reduce prolonged disease progression. Other antivirals are the protease Inhibitors such as, Ritonavir and Lopinavir. Their mode of action is to inhibit viral protease enzymes, preventing viral replication. Their clinical application is on the management of HIV/AIDS, and they can be effective in combination therapy for managing HIV.

We will move on to the antifungals. Here we have the azoles such as Fluconazole and Itraconazole. These agents inhibit ergosterol synthesis, disrupting fungal cell membrane. Their clinical applications are indicated for candidiasis, systemic fungal infections. They are effective for a wide range of fungal infections, but resistance can develop.

Of course, I have not forgotten all those common non-communicable lifestyle diseases like high blood pressures and diabetes.  Here we offer you the antihypertensives to include. those ACE Inhibitors like Enalapril and Lisinopril. These drugs act by inhibiting angiotensin-converting enzymes to reduce blood pressure. Their applications are indicated for hypertension, heart failure by in lowering blood pressure and improving cardiovascular outcomes. 

Then we also have the beta-blockers, Atenolol and Metoprolol among others. These agents block beta-adrenergic receptors, reducing heart rate and cardiac output. We use them for hypertension, arrhythmias, and heart failure and for managing cardiovascular diseases, especially in combination with other agents. But first, the first line management is to use the diuretics, the thiazide diuretics such as the hydrochlorothiazide. The diuretics increase excretion of sodium and water by the kidneys, and they are indicated for the management of hypertension and oedema by effectively lowering blood pressure and reducing fluid overload.

 Ah, we now come to this rogue disease - diabetes that actually has no cure using pharmaceuticals unless we are willing to change our lifestyles, especially nutritional modification and restrictions. Anyway, since I am now writing about pharmacology we shall look at least two types of antidiabetic drugs, namely, insulin: e.g., regular insulin, and insulin glargine. These replaces or supplements our natural insulin, facilitating glucose uptake by cells. Insulin is essential for Type 1 diabetes, effective for Type 2 diabetes when oral agents are insufficient. Then we also have the oral biguanides such as the popular Metformin for Type 2 diabetes mellitus. The oral biguanides act by decreasing hepatic glucose production and increasing insulin sensitivity. As mentioned, the biguanides such as Metformin is used as the first-line treatment for Type 2 diabetes.

Next, comes all those statins for hypercholesterolemia. We will quote two examples of these drugs, the HMG-CoA reductase inhibitors, such as Atorvastatin and Simvastatin. They inhibit cholesterol synthesis in the liver, and they are indicated for hypercholesterolemia, and in the prevention of cardiovascular diseases by lowering LDL cholesterol and reducing cardiovascular risk, or do they? Doubtful? See my argument on this here:

Does Cholesterol cause coronary heart disease?

https://scientificlogic.blogspot.com/search?q=cholesterol+drugs

Unfortunately, chronic lifestyle diseases, such as hypertension, diabetes, and cardiovascular diseases, are major health concerns. The pharmacological management of these diseases often involves a combination of the above-mentioned drug classes. Just to summarize: 

Hypertension, managed with antihypertensives (e.g., ACE inhibitors, beta-blockers, diuretics) to control blood pressure and reduce the risk of complications.

Diabetes, managed with antidiabetics (e.g., insulin, metformin) to control blood glucose levels and prevent complications.

Cardiovascular diseases, managed with statins, antihypertensives, and antiplatelet agents to control risk factors and prevent events like heart attacks and strokes.

The effectiveness of pharmacological treatments for chronic diseases depends on various factors, including patient adherence, the presence of comorbid conditions, and the specific drug regimens used. Overall, these drugs have significantly improved the management and outcomes of chronic lifestyle diseases, leading to longer and healthier lives for many patients. However, more importantly, not just a clinician, but a nutritionist too, I am compelled to emphasize the importances of treating all these ailments by addressing the root causes such as bad nutrition, sedentary lifestyles, smoking, unnecessary anger, stress, obesity, lack of physical and even mental exercise, unnecessary medication with drugs, environmental and occupational exposures among others. All these need to be seriously addressed first using non-pharmacological methods. 

Please remember all drugs are chemicals alien to the body. All drugs have a chemical molecular formula and a chemical mass and are not safe for the body especially if given long-term. For instance, even if we think that acetaminophen (paracetamol), a very common antipyretic non-opioid analgesic is safe, it is still a chemical, technically called 4-acetamidophenol, N-(4-hydroxyphenyl) acetamide with a molecular formula C8H9NO2 and mass 151.18 g / mol 1. The molecule consists of a benzene nucleus substituted by a hydroxyl group and the nitrogen atom of the amide group in the para (1,4) position 2 

The body tries to break down all chemical drugs and excrete them as best as possible.  If these drugs are given long term even in very low dosages the body tries to tolerate them for some time till it can no longer. The body dies either of liver, kidneys and finally from multiple organ failures due to accumulative poisoning when chronic diseases are best treated by addressing their underlying root causes such as lifestyle modifications 

Emergency Drugs:

Then what about in a medical emergency when drugs are needed to stabilize a critically injured patient or in any critical medical emergency events. That is of course an exception. Emergency drugs are vital for stabilizing critically injured patients or managing acute medical emergencies. Let us have a look at some of the common emergency drugs along with their mechanisms of action and applications. 

First, we have the epinephrine (adrenaline).  Adrenaline stimulates alpha and beta-adrenergic receptors, leading to vasoconstriction, increased heart rate, and bronchodilation. We use adrenaline to treat anaphylactic shock, cardiac arrest, and severe asthma attacks. Adrenaline rapidly reverses anaphylaxis, restores cardiac activity in arrest, and relieves severe bronchospasm. Then we have the atropine which is an anticholinergic agent that blocks the parasympathetic nervous system, increasing heart rate. In a medical emergency, we use it for bradycardia (slow heart beats), organophosphate poisoning. Its mode of action is to quickly increase heart rate in bradycardia and counter the effects of poisoning.

Then we also have the amiodarone, an antiarrhythmic that prolongs the action potential and refractory period in cardiac tissues. We use this drug for ventricular fibrillation, ventricular tachycardia in stabilizing life-threatening arrhythmias. We also have in our disposal adenosine to slow conduction through the atrioventricular (AV) node, interrupting re-entrant pathways. In an emergency event, we use it for supraventricular tachycardia (SVT) This drug rapidly converts SVT to normal sinus rhythm. Lidocaine is also another emergency drug. Its mechanism as a sodium channel blocker is to stabilize neuronal membranes and cardiac cells in ventricular arrhythmias and can also be used as a local anaesthesia. Its pharmacodynamics is to suppress abnormal heart rhythms.

Let us look at naloxone (Narcan). Its mode of action as an opioid receptor antagonist is to reverse the effects of opioid overdose. Opioid overdose by quickly reversing respiratory depression caused by opioids.  I love dopamine, which is a dose-dependent stimulation of dopaminergic, beta-adrenergic, and alpha-adrenergic receptors. In emergency medicine, we use this to treat shock, heart failure, bradycardia to improve cardiac output and blood pressure. Then in the list of emergency medicines are the nitro-glycerine that is the vasodilator that relaxes smooth muscle in blood vessels, reducing preload and afterload. Its clinical application is for acute coronary syndrome, chest pain (angina) where it works by relieving chest pain and reduces cardiac workload 

Further down the list of emergency drugs is this furosemide (Lasix). This acts as a loop diuretic by inhibiting sodium and chloride reabsorption in the kidneys. Emergency clinicians use this for pulmonary oedema, heart failure, and in hypertensive emergencies. It works by rapidly reducing fluid overload and blood pressure. Next, we also have the calcium gluconate that provides calcium ions to stabilize cardiac cell membranes. We use this to treat hyperkalaemia, hypocalcaemia, and calcium channel blocker overdose. It is effective in correcting electrolyte imbalances and to stabilize heart function. On the list is also the magnesium sulphate.  Its mechanism acts as a calcium antagonist to stabilize cellular membranes, antiarrhythmic. Other applications are for Torsade’s de pointes, severe asthma, eclampsia. This drug stabilizes abnormal heart rhythms, relaxes bronchial muscles.

The most often used whether in an emergency or in non-critical cases is of course those glucose (dextrose) drips. It is used to increase blood glucose levels to manage hypoglycaemia to quickly restore normal blood glucose levels. We also have the hydrocortisones that are anti-inflammatory and immunosuppressive agents where we use it for severe allergic reactions, asthma, and adrenal insufficiency. Its effectiveness is to reduce inflammation and immune response.

The sodium bicarbonate is also frequently used in a medical emergency. The mechanism of bicarbonates is to neutralize acidosis by increasing blood bicarbonate levels as in metabolic acidosis, certain drug overdoses as well as to stabilize cardiac function.

Let me summarize how emergency drugs work. These drugs act rapidly to stabilize critical conditions by:

Restoring Cardiac Function: Drugs like epinephrine, atropine, amiodarone, and lidocaine are essential in managing cardiac arrest and arrhythmias, ensuring the heart resumes effective pumping.

Correcting Metabolic Imbalances: Glucose, calcium gluconate, and sodium bicarbonate address metabolic derangements that can occur in critical conditions.

Reversing Toxic Effects: Naloxone and atropine reverse the life-threatening effects of opioid overdose and organophosphate poisoning, respectively.

Relieving Respiratory Distress: Epinephrine, albuterol (bronchodilator), and magnesium sulphate help in severe asthma or anaphylaxis by opening the airways.

Reducing Inflammation and Immune Response: Hydrocortisone and other corticosteroids manage severe allergic reactions and adrenal insufficiency by reducing inflammation and modulating the immune response.

Emergency drugs are critical in acute settings, providing rapid intervention to stabilize patients, address life-threatening conditions, and prevent further deterioration. Their effectiveness lies in their ability to target specific physiological processes quickly and efficiently.

I shall write an article on natural medicines, those plant-based botanical medicines that have been used for thousands of years. How do these work, and how do they compare with all these dangerous chemical drugs conventional allopathic medicine we used today. Which is preferable? 

It shall be my next article. Wait for this. 

lim ju boo