Pharmacokinetics

• The interactions between a drug and an organism are divided into pharmacokinetics and pharmacodynamics

Pharmacokinetics

• The actions of the human body on the drug
• Regulate absorption, distribution, and elimination of drugs
• Important for choosing and administering drugs, especially in patients with renal failure
• Studies the movement of drugs within a living organism
• The 4 fundamental stages are absorption, distribution, metabolism, and excretion
• Metabolism and excretion are involved in drug elimination
• Absorption is the passage of the drug from the application site into circulation across biological membranes
• Distribution describes the distribution of the drug from the circulation to various body compartments
• Metabolism, also called biotransformation, involves chemical changes the drug undergoes within the body, mainly in the liver
• Elimination is the removal of the drug from the body, primarily through the kidneys

Absorption

• Describes the passage of the drug from the application site into the circulation across biological membranes
• The extent and rate of absorption of a drug are essential
• They depend on the route of administration, pharmaceutical form, and lipid solubility of the drug
• pH and dissociation constant (pKa) are relevant for orally administered drugs
• Generally, about 75% of orally administered drugs are absorbed within 1-3 hours
• Absorption time can be influenced by additive factors related to the drug
• Examples include gastrointestinal motility, splenic blood flow, psycho-chemical factors, dimensions, and formulations
• Routes of drug administration include enteral, topical, and parenteral routes
• Absorption from the gastrointestinal tract is regulated by factors such as the absorption surface and blood flow to the site of action
• The physical state of the drug, its solubility in water, and its concentration at the absorption site are influential
• For orally administered drugs in solid form, the dissolution rate can limit absorption with low water solubility
• The rate of drug absorption in the intestine is generally greater than in the stomach
• This is the case even if the drug is predominantly ionized in the intestine and largely non-ionized in the stomach
• Factors that accelerate gastric emptying increase absorbtion
• Factors that delay gastric emptying should have the opposite effect regardless of the drug's characteristics
• Absorption from subcutaneous and intramuscular sites occurs through simple diffusion along a gradient and is limited by capillary membranes

Parenteral Administration Routes

• Endovenous
• Subcutaneous
• Intramuscular
• The speed is limited by the extent of the capillary membranes and the solubility of the substance in interstitial liquid
• Diffusion of molecules is independent of their lipid solubility
• Larger molecules access circulation slowly through lymphatic channels

Intravenous Injections

• Administration directly into the bloodstream guarantees complete bioavailability and bypasses first-pass metabolism
• A bolus injection produces a high drug concentration, first in the heart and lungs
• Infusion ensures certainty of the dose, whilst removing high plasmatic spikes

Subcutaneous Or Intramuscular Injections

• Leads to a more rapid absorbtion that oral administration, but depends on the injection site and local blood flow
• The factors that limit the rate are diffusion through tissue and removal from local blood flow
• The amount of the drug that finally reaches the systemic circulation depends not only on the dose administered
• It also depends on the fraction of these that is absorbed, i.e., the bioavailability
• The liver or intestinal epithelium metabolizes the drug, in this instance a part of the active drug absorbed from the gastrointestinal tract will be removed
• It can then be distributed to the action sites

Distribution

• Describes the movement from the blood stream to the tissues
• Post absorbtion, the drug circulates through the blood in free form (pharmacologically active) or attached to plasmatic proteins
• The protein binding leads to
  • A temporary depot, extending the action
  • Metabolical degradation
  • Excreation
  • Reduced neural system impact
• Distribution depends on hydro/liposolubility, mollecular weight and vascularity of the organ
• Hydrosoluble drugs can bypass the membrane passing through interstitial spaces
• Liposoluble drugs acummulate in both
• Speed is determined by weight and protein links
• Extent relies on lipid solubility at a phisological pH, transportor extent, diseases and any present restrictions

Barriers

• The distribution occurs through intersticial and intracelluar fluids
• Its speed is determined by cardiac output, blood and capillary flow, permeability and tissue volume.
• Initially, the liver and other well flowed organs receive most of the drug
• muscles, skin and fat all receive it more slowly
• the concentration normally equillibreates within minutes or hours of treatment

Protein Binding

• Many drugs exist primarly in a linked form
• The unassociated drugs can reach up to only 1%
• it is only unassociated drugs that have a pharmacological effect
• the most relative plasmatic protein being albumen

Albumen

• Links acidic medicine like warfarin and anti inflammatories
• and also antidepressives such as clopromazine
• other plasmatic proteins like beta-globulin, a glucoprotein, increase inflammation
• The ammount of linked drugs depends on the concentration, it's strength and the concentration of the proteins

Hypoalbuminemia

• In hypoalbuminemia, the efficacy is increased
• Some pharmaceuticals displace others so that the freed quantity is high
• The concept of a blood brain barrier was introduced by Paul Ehrlich based on observation
• A dye for intravenous injection only stained the body and not the brain

The Barrier

• Has a continous layer of endothelial cells linked by pericytes
• It is as such inaccessable for anti tumorals and aminoglycosides, which have low lipid solubilty
• inflamation can intrefere with its integritat
• which can then be administerd intravenously instead of intratecaly

Other Parameters That Set Drug Distribution

• Bioavailability;
• Disribution volume; volume of space that contains the substance
• Clearage; efficiency of the organisms to release the drug in systemic circulation
• Elimination half-life ; time its released from the system

Body Fluid Volume

• Divided primairly into 3 parts
• The ammounts vary based on gender
• Extra cellular fluis is blood (4,5%) interstatial and lymph
• It is typically greater in men than women
• Intracellur fluid is 30-40%, transcellur is2,5%

The Distribution Volume

• Shows the quantity of the drug in the body with the concentration in the plasma
• this is not a psysiological volume
• Required to contain all of an organisms drugs at the same concentration present in the plasma
• if the drug binds easily to plasmatic proteins it will be 1
• And will be quantifiable with plasma testing
• and distributed well into the tissue with low C, elevated Volume.

Drug Metabolism

• Describes how the body processes and breaks down drugs
• Involves pathways and transport systems also used for the metabolism of dietary components
• Humans contact many strange xenobiotics like contaminants in diets and the environment
• These are rapidly released so that they are not damaged
• Plants are also a source of xenobiotics since they contain phitoalexins, which protect the plants from predators
• A common example are fungy which carry many toxins like gyrometrin ochrellatin, all of which can be metabolized to origin vegetarian products
• Animals must be able to metabolise substances with origin in plants or other sources

Biotrasformation

• Transformation of pharmaceuticals to polar composits makes them easier to excrete from the body with urine or excreation
• Drugs then have three possible destiny's ; transformation by enzymes, change spontaniously into other subtances and become escreated
• This can activate or disactivate a drug
• This can generate an already active metabolisim of a pharmaceutical
• The reactions can be broken down into phases 1 and 2

Phase 1 Reatiions

• Enzymes, introduce groups of -OH, -COOH, -SH, -0, And NH2, to modify the drug
• this can alter the biological propieties
• Are classified as funcitionalisations and normally inactivate the active medicine
• In some cases, they are also in the intergrity
• Are classified as funcitionalisations and normally inactivate the active medicine
  • A particular example being, is an anti tumoral in a cell, that after metamorphism is turned into derivative electrofills kills
• Induce expressions of P450, which increases speed of synthesis or degrade reducing, which speeds up

The Toxicity

• Induction exacerbates the badness if transformed into a reactive metabolite
• medicine subtraits also prohibate activity of cythrom P450, through covalent interactions
• where the body is not in a state for new lunges or modifying the protien
• Phase 2 facillitates elimination and electrofilis inactivation which are made to look almost toxic
• they have improved H2o solubilty and are larger than predecessor s metabolites

Handle

• Medicine has "handles", made to be suceptible to comjugation
• Conjugation is where a subgroup in phase 2 is susceptible to attachment
• The resulting is normally inactive and less liposoluble
• Subsections also, are ; glycoronyl, sulphate, methile, aceti, Glycil and Glutatione
• Enzymes responisible for xenobiotic metabolism is all through the bodys tissue

Per Ora

• Must be asorbed in the portal and in the liver, where it becomes metabolised to the point of becoming prominent
• When the potion is active and is metabolized, several passes through the liver happens that remove the pharmaceuticals unit is completes and is metabolised from the system