How Do Drugs Work? Ultimate Guide

What Is a Drug?

A drug is a type of substance that’s often used to cure or prevent an ailment or disease.

It can also be used to alleviate symptoms. Drugs can typically be purchased over the counter or with a doctor’s prescription. In the majority of scenarios, more potent or specialized drugs require a subscription. The most common methods of taking drugs include:

By injection
Via an inhaler
Through a skin patch
Orally

Drugs can also be illegal substances that are used by people to get and maintain a high.

Overview of How Drugs Work

Drugs work by directly interacting with receptors that are located on cells or the enzymes within cells. Enzymes regulate the rate at which chemical reactions occur. Enzyme and Receptor molecules consist of a three-dimensional structure that allows substances with a precise fit to attach to them.

When you take any type of drug or medication, it will travel through your body in a four-step process that involves absorption, distribution, metabolism, and excretion (ADME). While this process might seem simple, it includes many smaller yet more complex processes that must occur naturally for the drug to be effective.

Getting a Drug Into the Body: Absorption

The first stage of this process involves getting a drug into the body through absorption. The absorption process largely depends on the drug’s primary delivery system. When an individual injects a drug into their body, it will bypass the entire absorption phase since it’s directly delivered to the bloodstream.

However, the majority of drugs and medications are taken in capsule or pill form, which involves absorption through the gastrointestinal tract. The drug must become soluble before it’s able to reach the circulatory system. Despite how simple this process has been up to this point, the rate of absorption differs from person to person.

The overall acidity of the gut and stomach will impact absorption. The makeup of the medication will also determine how well the body absorbs the drug. It’s important to understand that the stomach is a highly acidic environment. Medications like aspirin can be quickly absorbed in the stomach since they are weak to acid.

Morphine and similar medications have slower absorption rates since they must travel from the stomach’s high-acid environment to a neutral environment in the gut to be properly absorbed. The many factors that dictate how well the body absorbs a drug can be separated into factors relating to the drug and factors relating to the body.

Factors Relating To The Drug

The many factors that determine a drug’s absorption rate include:

Lipid water solubility
Dosage forms
Chemical nature
Particle size
Molecular size
Route of administration
Pharmaceutical formulation

Factors Relating To The Body

The absorption factors that relate to the body include:

pH levels in the stomach
Presence of additional substances
Gastrointestinal mobility
Area of absorptive surface

Methods of Absorption

There are three distinct methods of absorption that occur when taking a drug, which include:

Passive transport
Active transport
Specialized transport

Passive Transport

The three types of passive transport include simple diffusion, filtration/aqueous diffusion, and bulk flow.

The majority of drugs are absorbed via simple diffusion, which involves molecules moving from a higher concentration to a lower concentration. This kind of transport mainly occurs with lipid-soluble drugs. Carrier proteins aren’t required for this form of transport.

There are many factors that affect the simple diffusion process. For instance, the size of the particle or molecule determines how effective diffusion is. If a drug comes in different forms, it will have a different molecular size. Larger particles have slower diffusion and absorption in the body. If pharmaceutical companies want to maintain a slower absorption time, they can make the size of the particle larger.

The membrane surface area will also affect absorption. A larger surface area equates to better absorption. The intestinal lining and stomach are the main areas where absorption occurs for oral drugs, which means that absorption is better in the small intestine as a result of the sizable surface area.

The lipid water particle coefficient must be taken into account as well. Membranes consist of a thin layer of water that drugs need to dissolve in. The remainder of the drug is lipid soluble. If this particle coefficient is relatively large, additional diffusion will take place. The inverse is true if the lipid water particle coefficient is small.

Another factor is the ionization of drugs. The majority of drugs are considered to be either weak bases or weak acids, which means that they can be part unionized or part ionized. The ionized aspect is charged, which allows more water molecules to be attracted to the drug to form large complexes.

It’s impossible for large complexes to cross the membranes since they aren’t as lipid soluble. It’s easier for drugs to be absorbed when they are in unionized form. If you lower pH levels by a single unit, around 91% of the acid becomes unionized. The same amount of the base becomes ionized. When pH levels are lowered by two units, around 99% of the acid becomes unionized.

The ionization coefficient is another factor in the diffusion of a drug. This is the pH level that allows a drug to be 50% unionized and 50% ionized.

Filtration is a less common method of passive transport that involves the aqueous pores or channels that drugs can pass through. This process takes place in the proximal and jejunum tubules that are part of the kidneys. You can’t find these tubules in the urinary bladder lining or stomach. Only a small number of drugs are absorbed via filtration, the primary of which include glycerol and ethanol. The drug must have a low molecular weight for the process to work as intended.

The third and final method of passive transport involves bulk flow. In this process, the drug will pass directly through certain pores that are located between the capillary endothelial cells. This process doesn’t need lipid solubility or water to take place. Bulk flow primarily occurs when the drug is injected into the muscle in bulk form.

Once the drug molecules pass through your pores, they will diffuse directly into the blood, which usually leads to a strong reaction. Bulk flow doesn’t take place in the brain because of the absence of pores. Keep in mind, however, that bulk flow is completely dependent on a person’s blood flow. When the blood flow is high, the absorption should be rapid. Once an injection has been made, the area is typically rubbed to improve blood flow in the immediate vicinity.

Active Transport

The four types of active transport include:

Primary active transport
Secondary active transport
Pinocytosis
Phagocytosis

Active transport can be used by drugs that are unable to get across the lipid membrane and need to use transport proteins. The structure of these drugs is similar to other substances that use active transport, the primary of which include neurotransmitters, amino acids, and sugars. All of these substances have transport proteins.

The drug will move against the concentration gradient, which is a process that requires energy. The types of proteins that are bound depend on the drug, which means that the distribution and absorption methods can differ. This active transport technique is saturable, which means that it can be directly inhibited by other drugs.

Primary active transport occurs when the drug expends energy to move against the concentration gradient. Secondary active transport will also move against the concentration gradient. However, this process results from the energy that’s stored by the drug moving down the same gradient.

Pinocytosis can only take place by expending energy. Folic acid, fat-soluble vitamins, and protein molecules are only able to enter cells with this process. The phagocytosis form of active transport is referred to as cell eating. This transport is most often sought by drugs with a heavy molecular weight.

Specialized Transport Involving Facilitated Diffusion

Specialized transport can also occur with facilitated diffusion. This form of transport occurs when the drug moves down the concentration gradient with the assistance of transport proteins. This process can take place without using any energy. The primary goal with facilitated transport is that any lipid-insoluble drug transitions to a liquid-soluble one by combining directly with the carrier.

Getting a Drug to Its Site of Action: Distribution

Once the drug has been absorbed into the body, it will then need to be distributed. The distribution process is the transfer of a drug between different locations in the body, which can involve the organs and tissues.

The distribution process is the transfer of a drug between different locations in the body, which can involve the organs and tissues.

Determining Factors

The many factors that determine how a drug is distributed throughout the body include:

Tissue mass
Blood flow
Vascular permeability
The drug’s chemical characteristics
The pH partition in an area of the body
Tissue’s perfusion rate
How the drug binds to plasma proteins

Distribution Process

Once a drug enters the bloodstream, the blood will distribute it to the tissues in the body. The drug’s properties dictate what happens during this process. When someone takes a fat-soluble drug, the drug will be drawn to fat cells, which is where it will quickly dissolve before passing through the cell membranes.

An example of a fat-soluble drug is prednisone, which is a steroid commonly used as a treatment for inflammation. Other drugs may be water-soluble, which means that they will remain in the blood as well as the fluids that surround the affected cells.

Distribution can also be affected by the size of the molecules in the drug. The majority of drugs have smaller molecules, which allows them to easily pass through cell membranes. It’s more difficult for large-molecule drugs to permeate membranes, which is why they are usually administered through an injection. Insulin is an example of a large-molecule drug.

Inactivating Drugs Phase 1: Drug Metabolism

Once the drug has been distributed to the necessary cells, it will start to become inactivated during the drug metabolism phase. This stage of the process usually occurs in the liver. When a drug is being distributed, it will get to the liver with the assistance of “transporters” that are located on organ cells. The special enzymes found in the liver are able to chemically change the drug to transform it into a substance that can eventually be excreted.

If an individual is suffering from a health problem that affects the liver, the drug may not break down at the same rate. For instance, the presence of cirrhosis in the liver can make it more difficult for a drug to metabolize, which means that it will remain in the individual’s body for a lengthier period of time. While most drugs are metabolized in the liver, some can be metabolized in the kidneys.

There are also a small selection of drugs that are capable of inactivating the metabolizing transporters or enzymes, which may lead to the drug staying in the body for even longer. In this scenario, the possibility of toxicity becomes much more likely.

Inactivating Drugs Phase 2: Methods of Excretion

The last stage of this process is excretion, which is when the drug leaves your body for good. If a drug isn’t fully eliminated from the body with metabolism, it will be removed via excretion. While drugs are able to be excreted through the lungs, liver, skin, and gastrointestinal tract, this process almost always takes place in the kidneys.

If the kidney function is impaired, this can substantially alter how the drug progresses through the body. For instance, less of the drug may be excreted. It’s also possible that less of the metabolites will be excreted. When a drug isn’t correctly excreted, it will accumulate in the body and may eventually cause toxicity. Signs of toxicity include poor muscle control and hand tremors.

People who are experiencing renal impairment, usually need to take smaller doses of drugs to prevent accumulation and limit any adverse effects. Drug excretion can also be affected by:

A person’s age
Genetic variation
Any health conditions that alter renal blood flow
The intrinsic properties of the drug, which include size and pH levels

Once the excretion process is over, the substance is removed from the body forever. While the metabolism phase can be reversed, this isn’t true during the excretion phase. In the majority of situations, all materials related to the drug will leave the body, which include metabolites and the parent drug. As mentioned previously, the kidneys are the most important routes of excretion. However, the liver is also essential. It’s possible for the drug to be excreted through breath, sweat, and tears.

Drug’s Half-Life: An Estimate of the Rate of Elimination of Different Drugs

A drug’s half-life is the amount of time it takes for the drug to be reduced by one-half of what it was when it was initially taken. Different drugs have difficult half-lives. In the event that a 100mg drug with a half-life of around one hour is consumed, the amount that would remain in the body is:

50mg of the drug remains 60 minutes after it was administered
25mg of the drug remains 120 minutes after it was administered
12.5mg of the drug remains 180 minutes after it was administered
6.25mg of the drug remains 240 minutes after it was administered
3.125mg of the drug remains 300 minutes after it was administered

After 300 minutes has passed, nearly 97% of the drug will have been removed from the body. The majority of drugs are known to have only a small and negligible effect after around four or five half-lives. Keep in mind, however, that the drug can still be detected in the body when taking a drug test. Even though the drug will still be detectable, it won’t have an effect.

Half-life Factors and Variables

While the half-life of a drug varies depending on the drug, it can also vary from person to person because of the drug-specific and patient-specific factors that must be taken into account. These factors determine how well a drug is sent through a person’s body or how quickly the drug is excreted.

An IV drug known as gentamicin is excreted from the kidneys and has a half-life of around two-to-three hours in a younger individual who doesn’t have kidney disease. However, the half-life can be more than 24 hours for an individual who suffers from severe kidney disease. Many drugs work this way.

It’s challenging to identify how long it will take for a drug to be excreted from the body, which is an issue that athletes and people working in certain occupations must contend with. Some of the patient-specific variables that could affect half-life include:

Blood circulation
What the person’s diet looks like
If the individual has low fluid or excess fluid levels
Gender
Age
Any history of drug use
Liver function for any drugs that are metabolized directly through the liver
Kidney function for any drugs that are excreted from the kidneys
The presence of preexisting conditions like gastrointestinal disorders, pregnancy, or heart failure
Obesity
Genetics or race, can alter the drug’s metabolism
Smoking
Presence of any drugs that directly compete for the binding sites
Additional variables, which include the individual being on hemodialysis

There are also numerous drug-specific variables that are known to affect half-life, which include:

The method that’s used to administer the drug, which means that the half-life differs with IV administration when compared to oral or intranasal administration
How the drug reacts in the body
The drug formulation, which can result in the half-life being extended
How the drug leaves the body
If the drug is designed to bind to proteins in the body
If the drug builds up in fat or other kinds of tissue
Drug properties, which include charge, pKa, and molecule size
Presence of other interacting drugs or metabolites
How much of the drug is distributed throughout the body
Additional variables, which can include the drug being self-induced or actively transported

How Short Half-lives Differ from Long Ones

When a drug has a short half-life, it oftentimes acts quickly, which means that the effect can be more potent. However, the effects usually wear off just as rapidly, which means that the drug would need to be taken multiple times each day to generate the same effect. If a drug has a lengthier half-life, it would take a longer amount of time to begin working. However, the effects last for an extended period of time. A dose can also be taken less frequently.

If someone uses a drug with a high potential for addiction or dependence, it will be more difficult to stop using the drug if it has a short half-life instead of a long one. During treatment for drug addiction, it’s common for affected individuals to receive a long-acting equivalent of the drug they were addicted to, which helps ease the withdrawal process and the symptoms that come with it. Below is a comprehensive list of drugs, their half-lives, and their brand names.

Alprazolam – Xanax: Around 6-12 hours
Amiodarone – Pacerone: Around 15-140 days
Amphetamine – Adderall: Around 10-12 hours
Atenolol – Tenormin: Around six-to-seven hours
Clonazepam – Klonopin: Around 18-50 hours
Cocaine: Around 50-60 minutes
Diazepam – Valium: Around 20-100 hours
Donepezil – Aricept: Around 70 hours
Dutasteride – Avodart: Around five weeks
Erenumab – Aimovig: Around 28 days
Fluoxetine – Prozac: Around two-to-four days
Heroin: Around two-to-six minutes
Lead: Around 28-36 days
Mercury: Around 65 days
Methamphetamine – Desoxyn: Around 6.5-15 hours
Methylphenidate – Ritalin: Around two-to-three hours
Plutonium: Around 40 years in the liver and 100 years in the bones
Phenytoin – Dilantin: Around 7-42 hours
Marijuana: Around 1.3 days for infrequent users and 13 days for regular users
Warfarin – Coumadin: Around one week

Drugs and the Central Nervous System

While drugs that enter the bloodstream can impact the tissues in a person’s body, they also affect the central nervous system. When someone takes a mind-altering drug, it can speed up or slow down the central nervous system as well as the autonomic functions that are required to live.

These functions include everything from heart rate and blood pressure to body temperature and respiration. The levels of certain neurotransmitters in the brain can also be impacted when taking drugs of any kind. The effects of a drug on the central nervous system depend on the drug and the neurotransmitter that’s being impacted. Below are some examples of neurotransmitters in the brain and which drugs alter them.

Dopamine is a neurotransmitter that boosts feelings of pleasure, regulates moods, rewards behaviors, and increases motivation. It’s also directly involved with a person’s movement. The drugs that are known to affect dopamine levels include stimulants, opioids, and marijuana.

Serotonin is a neurotransmitter that’s responsible for regulating a person’s emotions and stabilizing their moods. Hallucinogens and ecstasy are able to alter serotonin levels.

Gamma-aminobutyric acid is a natural tranquilizer that’s capable of reducing anxiety levels and stress responses. The functions in the central nervous system can also be slowed down with this tranquilizer. Benzodiazepines are the primary drugs that impact this portion of the brain.

Norepinephrine is a hormone that’s similar to adrenaline and is known to speed up central nervous system actions because of a “fight-or-flight” response. Along with improving attention and focus, this substance also increases energy levels. Ecstasy and opioids are known to impact norepinephrine levels.

Different regions of a person’s brain can be disrupted through drug abuse. The cerebral cortex, limbic system, and brain stem are three areas that are most commonly affected. The brain stem is meant to control such life-sustaining functions as heart rate, sleeping, and breathing. As for the limbic system, it contains the reward circuitry in the brain that controls emotions.

The cerebral cortex is an area of the brain that’s designed to help with decision-making, planning, and problem-solving abilities. People can also better process information that their senses provide because of the cerebral cortex. Consuming higher amounts of drugs can lead to substantial impacts on brain circuitry and chemicals, which can result in the body becoming dependent on the drug.

Over time, drug cravings and withdrawal symptoms may develop. It’s because of these risks that many of the more potent drugs are only available with a prescription. Every prescription comes with a recommended dosage to make sure that the body doesn’t become dependent on it.

At the moment, marijuana is the most widely used drug that can significantly affect the central nervous system. The psychoactive chemical in this drug is known as TCH. It interacts and eventually binds with a person’s cannabinoid receptors to produce a more relaxing and mellow sensation. Areas of the brain that consist of high levels of cannabinoid receptors are impacted substantially.

One area of the brain that’s regularly affected is the hippocampus, which is responsible for managing short-term memory. As such, taking marijuana can create issues with recollecting any recent events. A couple of other areas of the brain that are commonly affected include the basal ganglia and cerebellum, which control involuntary muscle movements and coordination respectively. The most common short-term side effects that can result from taking too much of this drug include decreased memory, issues with thinking clearly, and distorted sensory perception.

Marijuana can also interfere with dopamine levels in the brain, which causes the high that many individuals experience. Over time, more long-term side effects could develop in the central nervous system. For instance, younger individuals may lose IQ points that can’t be recovered later on.

When a person gets older, the neurons within their hippocampus are lost. Marijuana has the potential to expedite this process, which can result in memory issues. Learning problems, sleep issues, and impaired coordination can also occur because of long-term marijuana use. There’s a possible link between using marijuana and the development of psychosis disorders as well.

Synthetic cannabinoids can also alter the central nervous system considerably. Synthetic marijuana is known to impact the brain just like natural marijuana. However, the effects are more pronounced. These drugs are specially designed to be much more potent than traditional marijuana, which means that they can be even more active in a person’s brain.

Synthetic cannabinoids are typically complete agonists. In comparison, natural marijuana is a partial agonist. It’s possible for the synthetic form of marijuana to be over 100 times stronger than the THC that’s present in natural marijuana. There are also hundreds of forms of synthetic cannabinoids on the market, which means that each variety comes with a different molecular and chemical structure. They can have effects on the central nervous system that can’t be accurately predicted.

Heroin and prescription opioids are among the strongest medications that can be prescribed by a doctor. The most common opioid drugs include oxycodone, acetaminophen, methadone, and fentanyl. These drugs are able to bind to a person’s opioid receptors in their brain, which triggers a release of dopamine. They take control of the brain’s limbic system before providing a potent high that can make people dependent on the drug.

Prescription opioids are known to be highly addictive, which is why doctors usually provide recommend extremely small doses. In 2015 alone, more than 2.5 million people in the U.S. suffered from opioid addiction. While fentanyl is a highly addictive drug that can quickly change the central nervous system, heroin is the fastest-acting opioid. In fact, it can take effect almost immediately, which is why it’s so addictive.

Once the body becomes used to the drug and the central nervous comes to expect it, the affected individual will need to take a higher amount of the drug to feel the same effects. Over time, the body will become used to the interaction the drug has with the brain. Once the body is dependent, withdrawal symptoms will likely be felt when attempting to stop using the drug.

Opioid dependence develops quickly. The withdrawal symptoms are similar to the flu. However, emotional symptoms like anxiety and depression might also develop. Keep in mind that opioid drugs are also capable of disrupting the production of norepinephrine, which means that these drugs exist as depressants to the central nervous system.

When taken, an opioid will block the sensation of pain and reduce body temperature while also slowing down respiratory functions, heart rate, and blood pressure. Drowsiness can also be induced. Because of how addictive opioids are, overdoses are exceedingly common and can lead to serious respiratory depression. Nearly 60% of overdose deaths are derived from opioid drugs.

The long-term effects in the brain can include a deterioration of white matter, which can worsen a person’s ability to maintain consistent emotions, make important decisions, and respond to stressful situations. Additional long-term concerns surrounding opioid abuse and addiction include infections in the heart lining and lung complications.

Receptors, Agonists, and Antagonists

Whether a medication is purchased over the counter, prescribed by a doctor, or obtained in an illegal manner, they all have similar functions and depend on the relationship between receptors, agonists, and antagonists. You may be wondering how antacids ease indigestion or how ibuprofen gets rid of your headache. The answer is much simpler than you might have realized. Drug mechanics are very straightforward and primarily revolve around receptors and the molecules that are able to activate them.

Receptors are relatively large protein molecules that have been embedded in the membrane, which is the cell wall. These receptors obtain chemical information from different molecules that are situated outside of the cell. These molecules can involve everything from drugs to neurotransmitters and hormones.

The outside molecules are capable of binding to the receptors on the cell, which ensures that the receptor is activated and that an electric or biochemical signal within the cell is generated. The signal will then push the cell to take specific actions, which could involve making you feel pain.

Agonist drugs are molecules that are made to bind to certain receptors in order to provide a boost to a process that takes place in the cell. The physiological response that an agonist causes in the cell can be either artificial or natural. As an example, endorphins are considered natural agonists for opioid receptors. In comparison, morphine is an artificial agonist for the primary opioid receptor.

While there are some slight differences between artificial and natural agonists, they usually have the exact same effect because of how structurally similar an artificial agonist is to a natural one. Many medications are designed to mimic a natural agonist to bind to the receptors and produce a strong reaction. While morphine isn’t produced by the body, it’s naturally found in opium poppies.

The primary ingredient in cannabis is THC, which is the agonist for the cannabinoid receptor. LSD is a type of synthetic molecule that performs the same actions as the serotonin neurotransmitters via the 5HT2A receptor.

Antagonist drugs are made to oppose actions that an agonist takes. Let’s say that the antagonist is a key that’s placed into a lock but doesn’t come with the correct shape to turn this lock. In comparison, the agonist is the correct key that would be able to turn the lock. If the antagonist key is placed in the lock, the agonist key won’t be able to be fitted in the same lock, which means that the antagonist blocks the agonist from taking any actions within the receptor molecule.

As mentioned previously, morphine is one of the agonists for the opioid receptor. In the event that a lethal overdose of morphine is given to an individual, the opioid receptor antagonist may be able to mitigate the effects. The antagonist for morphine is naloxone. Once naloxone is administered to the affected individual, it will quickly enter every opioid receptor in the body to make sure the morphine doesn’t activate the receptors.

Morphine can enter and exit receptors in seconds. If it’s not directly bound to a receptor, it’s possible for the antagonist to get there and block the connection. Since the receptors are unable to be occupied, there won’t be a reaction. Naloxone has proven to be a highly effective drug that is able to bring someone to full consciousness in seconds when they are suffering from an overdose and are either unconscious or close to death.

New drugs are being developed on a daily basis, which opens up more questions about how the drug will be implemented and what the effects will be. Regardless of the drug you take, always read the label to determine the correct dosage and the warning signs to look out for.