what is the Pharmacokinetics
Pharmacokinetics
- Pharmacokinetics is a quantitative study of the drug movement, and it includes the response of the body to drugs.
- The pharmacokinetics involve
- Absorption
- Distribution
- Metabolism
- Excretion
- All of these processes involve the transport of drugs across the biological membrane.
Biological membrane-
It is a cell membrane or bilayer of a phospholipid, about 100 Å thick.
- The biological membrane is made up of cholesterol, phospholipid, and a small amount of carbohydrates.
- Lipid soluble substances easily cross the biological membrane and restrict the transportation of water-soluble substances.
- The drug transport the biological membrane by
- Passive diffusion
- Filtration
- Specialized transport.
- Passive diffusions – Mostly drugs are absorbed by the passive diffusion in which drugs cross the biological membrane from high concentration to low concentration.
- Use of energy is not required in this process.
- Lipid soluble drugs diffused through the membrane are called passive diffusions.
- Filtration – Water soluble drugs are filtered through aqueous pores in the membrane from high concentration to low concentration, is called filtration.
- Specialized transport
- Carrier transport – The drug is combined with a carrier that is present in the membrane, and transported from one side to another side of the membrane.
Carrier transport include (types of Carrier transport)
- Active transport
- Facilitated diffusion
- Active transport
- The movement of drugs against the concentration gradient.
- It is divided into primary and secondary active transport.
- In primary active transport, substances move low to high concentration, so require energy.
- In the second active transport, one substance moves low to high concentration and another substance moves high to low concentration.
- If both substances move in the same direction, it is called symport.
- If both substances move in the opposite direction it is called antiport.
- Facilitated diffusion – The drugs move from high to low, so no need of energy.
- Pinocytosis – The protein nature substances are uptake by the cells in the form of vacuoles.
Drug Absorption
- The meaning of absorption, the movement of drug from its site of administration in the bloodstream.
- Factors that affect the drug absorption
- Aqueous solubility – When a drug is taken through the oral route, it is available for absorption only after dissolution.
- More aqueous solubility has fast dissolution.
- Concentration – High concentrations of drugs have fast absorption.
- Solubility – The lipid-soluble drugs are absorbed faster.
- Area of absorbing surface – Large surface areas have faster absorption.
eg:- intestine is large surface area, so allows fast and more absorption, the stomach is less surface area, so allows slow and less absorption.
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Route of drug administration –
- Drug absorption is also affected by the route of drug administration.
- Lipid soluble or nonpolar drugs are absorbed orally and enter the cell.
- Water soluble or polar drugs are not absorbed orally and do not enter the cell.
- Vascularity – High vascular area allows fast absorption. Eg:- muscles.
- Less vascular area allowed the slow absorption.
eg:- subcutaneous tissue.
- Drug ionization – Unionized are the lipid soluble drugs, so well absorbed, and ionised drugs are less absorbed.
Drug Distribution
- After absorption, the drug enters the bloodstream and gets distributed to the various fluid compartments.
- Eg:- intestinal fluid and plasma compartment, CSF, cellular fluid, transcellular fluid, etc.
- Each drug is distributed throughout the body tissue.
Factors that affect the drug distribution process are
- Lipid solubility of drugs.
- Ionization of physiological PH
- Plasma protein binding
- Some diseases like cirrhosis, uremia, and CHF.
- Regional blood flow difference.
The volume of drug distribution (Vd)
Vd = Dose administer through Iv route / plasma concentration.
- If the volume of distribution is increased, when less concentration of plasma.
- If high concentrations of plasma conduct less volume of distribution.
Re-Distribution of Drugs
When highly lipid-soluble drug administration through the IV route
↓
Firstly drugs is distributed in the high vascular body organs like – the heart, brain, kidney, etc.
↓
High concentration of drug
↓
Laterly drug is redistributed to the less vascular body organs like muscles and fat.
↓
Decrease the concentration of drugs in the blood.
↓
The drug takes from the high vascular tissue
↓
Decrease concentration
The barrier to Drug Distribution
- The blood-brain barrier (BBBr)
- Placental barrier
- Blood, CSF.
- Only lipid-soluble drugs can cross the blood-brain barrier and restrict the water-soluble drug.
- The placental barrier allowed the lipid-soluble drug only.
- P-gaps are present in the placenta, so the placental barrier is incomplete, if there is a high amount of water-soluble drug for a long time, and then they also cross the placental barrier.
Plasma protein binding
- The drugs are bound with the plasma protein (Albumin or Alpha1 – acid glycoprotein).
- Plasma protein binding of drugs is dependent upon the nature of drugs. Eg:- diclofenac = 99% plasma binding
Lithium = 0% plasma binding.
- Acidic drugs bind with albumin protein and alkaline drugs bind with Alpha1 – acid glycoprotein.
eg:- Beta-blockers drug is – alkaline drug.
NSAID drug is – Acidic drug.
- Plasma protein binding acts as a temporary storage of the drug.
- Plasma protein bind drugs are not available for distribution, metabolism and excretion.
Drug displacement
- Drug displacement causes the drug toxicity.
- When 2 drugs are bound with the same plasma protein on the same side.
- A drug displaced to another drug and causes the free concentration of the drug in the blood and causes toxicity.
Tissue storage
- The storage of drugs in the specific tissue, which is based on active transport on continuous use.
- It is the cause of the toxicity.
- Eg:- Iodine drug storage in thyroid gland and tetracycline drug store in bone and teeths.
Drug Metabolism (Biotransformation)
- It is a chemical alteration of the drug in the body.
- The metabolism process of the drug converts the non-polar (Lipid soluble drug) into polar (Water soluble drug), to make the drug suitable for excretion.
- Many sites of the body, which take the metabolism process, like – liver, kidney, plasma, lungs etc.
- Mainly the metabolism process done in the liver.
- Biotransformation is a chemical alteration of a drug inside the body.
- The metabolism chemical reaction is done in the presence of enzymes (Microsomal and non-microsomal).
- Microsomal enzymes are stimulated by drugs, smoke, barbeque etc.
- Both enzymes are absent in the new-born.
- Biotransformation chemical reaction done into 2 phases
Phases 1 – Non Synthetic reaction
Phases 2 – synthetic reaction.
- Phase 1 (Non-Synthetic reaction) functionalization reaction that converts the drug to a more polar metabolite through oxidation, reduction, and hydrolysis.
- Phase 2 (synthetic reaction) is a conjugation reaction that is combined with sulphuric acid, glucuronic acid, glycine, acetylation, or methylation.
Factors affecting the drug metabolism
- Age and sex
- Nutrition and diet
- Disease condition
- Genetic variation
- Species.
Drug Excretion
what is drug excretion
- Excretion is a process, which passes out of the systemically absorbed through various channels are – urine, feces, saliva, sweat, milk, exhaled air, etc.
- Excretion is an essential process to determine the duration of drug action and toxicity.
- Urine – The kidney is the most important organ for the excretion of drugs through urine, also known as renal excretion.
- Renal excretion =
= {Glomerular filtration + tubular secretion} – tubular reabsorption.
- In the case of renal disorders, the kidney is unable to excrete drugs.
- After the glomerular filtration, the ionising drugs are not reabsorbed – Excrete.
- If unionizing drugs are 99% reabsorb and sent to the systemic circulation.
- Faces – Drugs are not absorbed in the GI tract that is excreted with faces.
eg:- sulphaguanidine drug.
- High molecular weight substance above 300, that is not easily excreted through urine, excrete via faces through the biliary excretion.
- Bile – Uncharged drug and their metabolic products are excreted with bile.
- Exhaled air – Some volatile gases are liquids that are excreted through the exhaled air.
eg:- nitrous oxides.
- Milk – Generally lipid-soluble drugs are entered in breast milk.
- Excretion of drugs through breast milk in small amounts.
Eg:- tetracycline, anti-cancer, lithium, sulphonamide, etc.
- Saliva and sweat – It is a minor route of drug excretion.
- Rifampicin drugs are excreted through sweat and tears.
- Lithium, phenytoin, and metronidazole drugs are excreted through saliva.
Key Points
- The study of drag movement is – Pharmacokinetics
- Which soluble substance crosses the biological membrane – Lipid soluble
- Lipid soluble drug diffused through the membrane is called – Passive diffusion
- Water soluble drug filters through pores in membranes are called – Filtration
- the movement of drugs against the concentration gradient – Active transport
- If drug distribution volume is increased when – Plasma concentration is low
- which type of drug crosses the blood-brain barrier – Lipid soluble drug
- which type of drug commonly crosses the placental barrier – Lipid soluble drug
- Diclofenac consists of plasma protein binding properties of about – 99%
- Lithium consists of plasma protein binding property – 0%
- Acidic drugs bind with the – Albumin protein
- Alkaline drugs bind with the – Alpha 1 acid glycoprotein
- The drug displacement process in the body causes the – Drug toxicity
- Metabolism of drugs in the body is called – Biotransformation
- Metabolism of drugs is a – Chemical alteration of drugs in the body
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