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Pharmacology
In pharmacokinetics, the elimination of drugs is closely related to the dosing interval. Even if the dosing interval is not a half-life, the blood drug concentration will still reach the square value after 46 half-life. After multiple medications, the time-dose relationship shows that when the total amount of medication is not changed per unit time, the time to reach the floor is not related to the medication interval and dosage. The loaded dose can quickly increase the blood drug concentration, while the partial dose can reduce fluctuations and keep the average steady-state concentration unchanged. Understanding these parameters and kinetic characteristics will help optimize medication regimens and ensure efficacy and safety.
Edited at 2025-03-10 15:22:48- Rumi 10 spiritual high-dimensional awakenings
Rumi: 10 dimensions of spiritual awakening. When you stop looking for yourself, you will find the entire universe because what you are looking for is also looking for you. Anything you do persevere every day can open a door to the depths of your spirit. In silence, I slipped into the secret realm, and I enjoyed everything to observe the magic around me, and didn't make any noise. Why do you like to crawl when you are born with wings? The soul has its own ears and can hear things that the mind cannot understand. Seek inward for the answer to everything, everything in the universe is in you. Lovers do not end up meeting somewhere, and there is no parting in this world. A wound is where light enters your heart.
- Pathophysiology - Heart failure
Chronic heart failure is not just a problem of the speed of heart rate! It is caused by the decrease in myocardial contraction and diastolic function, which leads to insufficient cardiac output, which in turn causes congestion in the pulmonary circulation and congestion in the systemic circulation. From causes, inducement to compensation mechanisms, the pathophysiological processes of heart failure are complex and diverse. By controlling edema, reducing the heart's front and afterload, improving cardiac comfort function, and preventing and treating basic causes, we can effectively respond to this challenge. Only by understanding the mechanisms and clinical manifestations of heart failure and mastering prevention and treatment strategies can we better protect heart health.
- Pathophysiology - ischemia - reperfusion injury
Ischemia-reperfusion injury is a phenomenon that cellular function and metabolic disorders and structural damage will worsen after organs or tissues restore blood supply. Its main mechanisms include increased free radical generation, calcium overload, and the role of microvascular and leukocytes. The heart and brain are common damaged organs, manifested as changes in myocardial metabolism and ultrastructural changes, decreased cardiac function, etc. Prevention and control measures include removing free radicals, reducing calcium overload, improving metabolism and controlling reperfusion conditions, such as low sodium, low temperature, low pressure, etc. Understanding these mechanisms can help develop effective treatment options and alleviate ischemic injury.
Pharmacology
- Rumi 10 spiritual high-dimensional awakenings
Rumi: 10 dimensions of spiritual awakening. When you stop looking for yourself, you will find the entire universe because what you are looking for is also looking for you. Anything you do persevere every day can open a door to the depths of your spirit. In silence, I slipped into the secret realm, and I enjoyed everything to observe the magic around me, and didn't make any noise. Why do you like to crawl when you are born with wings? The soul has its own ears and can hear things that the mind cannot understand. Seek inward for the answer to everything, everything in the universe is in you. Lovers do not end up meeting somewhere, and there is no parting in this world. A wound is where light enters your heart.
- Pathophysiology - Heart failure
Chronic heart failure is not just a problem of the speed of heart rate! It is caused by the decrease in myocardial contraction and diastolic function, which leads to insufficient cardiac output, which in turn causes congestion in the pulmonary circulation and congestion in the systemic circulation. From causes, inducement to compensation mechanisms, the pathophysiological processes of heart failure are complex and diverse. By controlling edema, reducing the heart's front and afterload, improving cardiac comfort function, and preventing and treating basic causes, we can effectively respond to this challenge. Only by understanding the mechanisms and clinical manifestations of heart failure and mastering prevention and treatment strategies can we better protect heart health.
- Pathophysiology - ischemia - reperfusion injury
Ischemia-reperfusion injury is a phenomenon that cellular function and metabolic disorders and structural damage will worsen after organs or tissues restore blood supply. Its main mechanisms include increased free radical generation, calcium overload, and the role of microvascular and leukocytes. The heart and brain are common damaged organs, manifested as changes in myocardial metabolism and ultrastructural changes, decreased cardiac function, etc. Prevention and control measures include removing free radicals, reducing calcium overload, improving metabolism and controlling reperfusion conditions, such as low sodium, low temperature, low pressure, etc. Understanding these mechanisms can help develop effective treatment options and alleviate ischemic injury.
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Chapter 2. Pharmacology
The process of drugs in the body
Transport of drugs
Passive fortune
Concept: diffuse from high C → low C, powered by concentration gradient
Most drugs are transported in a simple way
Features
High C→Low C
No energy consumption
No vector required
No saturation speed limit
No competition suppression
Factors
Fat soluble
Very fat-soluble
Molecular weight
Easy to have small molecular weight
fixed
Dissociation degree
The drug has a large polarity, that is, the dissociation degree is high and the fat is less soluble → the ionization form is not easy
Slight changes in environmental pH will significantly affect the degree of dissociation
Sub-theme
pKa
When the drug is half dissociated (dissociation type = non-dissociation type), the pH of the solution is the pKa of the drug
Actively transfer
Concept: From low C → high C
Features
Reverse concentration difference
Consumption of energy
Need a vector
Saturated speed limit
Constrain competition
Can concentrate drugs in a certain organ or tissue
ADME system
Transport-Absorb A
concept
The process of entering blood circulation from the medication site
Most are absorbed in passive form
Fast absorption → fast effect
e.g. Take under the tongue
More absorption→strong effect
e.g. Intravenous injection
IV injection. No absorption phase exists
Factors
Physical and chemical properties
Fat soluble
Molecular weight
Route of administration
oral
Convenient but obvious first pass elimination/first level effect
Oral drugs are absorbed into the cap in the gastrointestinal tract and then entered the portal vein of the liver (the concentration is very high at this time), but after reaching the liver, some of them are metabolized and inactivated, and the drug concentration decreases when entering the blood circulation.
Weak acidic drugs are absorbed more in the small intestine (weak alkali) than in the stomach (acid).
Large absorption area
High blood flow
Sublingual, rectal
Fast absorption
Sublingual mucosal blood vessels directly enter the superior vena cava after absorption
Suppository-direct absorption of rectal mucosa → direct entry into the inferior vena cava
First pass eliminates weakness
Inhalation
Quickly take effect
Large area of alveolar suction to blood
injection
Intramuscular injection im.
Larger doses can be used
Intravenous iv.
Quickly take effect
Intraperitoneal injection of IP.
Fast onset but often used in experimental animals
Topical medication: skin and eye spots
Bioavailability F
Concept: refers to the ratio of the dosage of the body to the dosage of the drug absorbed into the blood circulation
F=Doing dose/dose dosage × 100% of the blood circulation
Factors
Related to the manufacturer and pharmaceutical batch
e.g. Retesting of penicillin in different batches and manufacturers requires re-testing when using penicillin in different batches and manufacturers
Other factors
Drugs
Dosage form
Body aspect
When taken orally, it is related to the speed of gastric emptying and peristalsis.
The injection is related to the number of blood vessels at the injection site
Drugs bind to plasma proteins
Mainly binds to albumin in plasma
Features
The combination and free type are in dynamic equilibrium
The binding drug temporarily loses its pharmacological activity and is not metabolized, becoming a storage library for drugs in the body → the duration of its action
There is saturation (the amount of albumin is certain)
There is competition suppression
Transport-Distribution
Concept: The process of transporting from blood to tissue, intercellular fluid and intracellular fluid after the drug is absorbed into blood
Features
It is one of the ways to eliminate drugs, mostly passive transportation
Uneven distribution of drugs and insync
If it is an active transport method, the drug can be concentrated in a specific organ
Determinants
Physical and chemical characteristics
Fat solubility, molecular size, affinity with tissue, etc.
Local organ blood flow
The richer the easier it is to enter
Cell membrane barrier
Blood-brain barrier
High fat solubility, low polarity, low protein binding rate
Placenta barrier
Lower shielding effect than blood-brain barrier
Body fluid pH
Intracellular fluid = 7, extracellular fluid pH = 7.4
Transformation-Metabolic M
Concept: The chemical structure changes that a drug occurs in an organism, also known as drug conversion
Metabolism results
Most - Inactivated
Decreased or lost pharmacological activity
Increased polarity → low fat solubility → not easy to absorb → easy to discharge
It is one of the ways that drugs are eliminated from the body
A few - activation
Precursor activation
Metabolic activation
Both the parent and the transformants are active
From this perspective, it is not accurate to transform biological transformation into "detoxification".
Metabolism
Oxidation, reduction, hydrolysis, binding
Metabolic enzymes
Specialized enzymes
MAO monoamine oxidase
Hydrolyzed catecholamines
AchE Cholinesterase
Hydrolyzed acetylcholine
Non-specific enzymes
Liver drug enzymes
concept
Exist in the endoplasmic reticulum of hepatocytes
for liver microsome mixed functional enzyme system
The main enzyme of this system is cytochrome p-450
That is, the main peak of the absorption spectrum is at 450nm
Features
Poor specificity
Low activity, less metabolic substrate per unit time
Large individual differences
Hepatic drug enzyme activity is very different among individuals
Can be regulated by certain drugs
Enzyme inducers
Can be induced by certain drugs to increase activity
Enzyme inhibitors
Can be inhibited by certain drugs to reduce enzyme activity
Transport-excretion E
concept
The process of drug prototype (chemical structure not changing) or excretion of metabolites from the body
It is the process of thoroughly eliminating the effects of drugs
Most excrete through passive transport
Excretion pathway
Kidney - the main excretion organ
process
Glomerular filtration
Conjugated drugs are large and difficult to pass
Renal tubular secretion
High fat soluble can be reabsorbed
Actively transfer luck, competitive relationship
Certain drugs are excreted in prototype or active metabolites, and have a high concentration in the urinary system, which can treat urinary system infections.
Low renal function slows down excretion, which can easily cause accumulation poisoning → change the dosage time or dose
Bile excretion
Chronic acid secretion of certain drugs can treat bile infections
Intestinal liver circulation
Some drugs are discharged into bile through the liver and then enter the intestines with bile. The drugs entering the intestines can be partially reabsorbed and then enter the blood circulation.
Significance: The excretion of drugs entering the intestinal liver circulation slows down and the action time is prolonged
Other excretion pathways
Breast glands
Milk is acidic → alkaline drugs have high concentration in milk
Salivary glands, sweat glands
Anti-tuberculosis drug rifampin (tears, saliva, and sweat turn red)
lung
Volatile drugs, such as diethyl ether
Pharmacokinetics
Time volume curve
concept
After taking the drug, the concentration (quantity) of the drug in the plasma can change with time (time)
Draw the concentration/logarithmic concentration as the vertical coordinate and time as the horizontal coordinate
Curve graph
Three times
Incubation period
From the start of medication to the time it takes to produce efficacy
Continue
The time for drugs to maintain basic efficacy
Residual period
The drug concentration has dropped below the effective concentration, but has not been completely eliminated. Repeated use of drugs during this period is prone to accumulation and poisoning
Two levels
Poisoning concentration, effective concentration
Two points
Effective, peak value
Drug elimination dynamics
Most - First-order dynamics/linear dynamics elimination
-KC=dc/dt
K: Eliminate the rate constant
Constant, does not change with time
C: Original concentration
Features
The amount of drugs eliminated within a unit of time is not constant and is proportional to the concentration of drugs in the blood
When the vertical coordinate takes the logarithm, the time-elimination curve is straight
half life
Concept: The time it takes to drop drug concentration in half in plasma
T½=0.693/K
There is a constant T½, which is equivalent
That is, the elimination rate K remains unchanged
Generally speaking, drugs that are eliminated according to first-order kinetics can be considered to be basically eliminated after 5 half-life after one dose of the drug.
Great transport capacity, greater than drug concentration
Drugs that are eliminated by first-order kinetics will not exceed their elimination ability even if they are increased to the dose of poisoning.
Few - Zero order dynamic elimination
-K=dc/dt
Here K is Vmax
Features
The amount of drug eliminated within a unit of time is constant and has nothing to do with blood drug concentration
Eliminate at maximum elimination every time
Eliminate the curve as a straight line, and when the vertical coordinate takes the logarithmic concentration, it becomes a curve
half life
T½=0.5C₀/K
T½ is not constant and can vary according to dosage
Limited elimination capacity, drug concentration exceeds elimination capacity
Active transport, requires energy and carrier
Important parameters of pharmacokinetics
Transport constant K
Half life T½
Intraventricular model
concept
According to the pharmacokinetic model, the atrioventricular model is divided into one-room model, two-room model and multi-room model
Classification
One room model
The K value is consistent
Once the drug enters the blood, it is evenly distributed throughout the body and no longer distributed in a secondary manner. Therefore, the entire body is regarded as a model of the atrial chamber.
Two-room room model
Divide the body into two rooms
Central Room
The areas where the drug enters first, the K value is the same
Most blood vessels are rich and blood flow smoothly
Surrounding room
Enter the surrounding room when redistributed, the K value is small
Generally, tissue with fewer blood vessels and slow blood flow
e.g. fat, muscle tissue, etc.
Three-room room model
.........
Multi-room model
......
How to judge
Experiment, after measuring the drug concentration, draw the time volume (logarithmic) curve → whether there is a turning point in the connection line
Apparent distribution volume
concept
The theoretical amount of fluids that should be occupied by the total amount of drugs in the body according to the blood drug concentration
?
Vd=A/C
A: Dosage of medicine in the body, mg
C: Blood drug concentration, mg/L
Vd meaning
Convert blood drug concentration and dosage
Speculation on the distribution of drugs in the body
Take a person weighing 70Kg as an example, the total fluid is about 42L.
5L → in plasma
10-20L→Extracellular fluid
40L→Full body fluid
100L→Concentrated in a certain organ or tissue
Loading dosage
That is, the steady-state blood drug concentration of the drug Css
Css=【1.44×D×F×(T½/τ)】/Vd
To quickly reach Css, a loaded dose of the drug can be applied before routine administration.
When the medication time is close to T½, the loading dose is twice the conventional dose. That is, what is commonly called "first dose doubled"
Time-dose relationship after multiple medications
For multiple consecutive doses, as long as the dose and the interval between medication remain unchanged, after 4-6 T½ of the drug, the in vivo dose is close to the square value, that is, the steady-state blood drug concentration Css. At this time, the dosing speed and elimination speed are balanced.
When the dosage interval is not half-life, is it also the interval between 4-6 half-life reaches the ping level?
During the drug administration, the blood drug concentration fluctuated, with peak Cssmax and valley Cssmin. The dosage of the unit time remains unchanged, the interval becomes smaller, the more times the dose is, the smaller the fluctuation is, but the average steady-state concentration remains unchanged
e.g. sustained release tablet-small fluctuations-the patient feels that the fluctuations are not strong, and there is no fluctuation intravenous drip.
The total amount of medicine used per unit time remains unchanged, and the time to reach the square meter is not related to the interval and dosage of medicine (4-6 T½). When the interval remains unchanged, the dose increases, the Css increases, but the time to reach the ping meter remains unchanged, both of which are 4-6 T½.
In order to quickly reach the stagnant value of blood drug concentration, a loading dose (i.e., Cssmax) can be given at the first dose.
e.g. If the medication interval is close to the drug T½, the first dosage can immediately reach the square value. Sulfonamide-Two tablets for the first time, and one tablet afterward