Lesson 2 - Pharmacokinetics (CEU, 2024/25) PDF

Lesson 2 Pharmacokinetics 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  Summary 1. INTRODUCTION. 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES 3. LIBERATION 4. ADME: Ø Absorption Ø Distribution Ø Metabolism Ø Excretion 2...

Lesson 2 Pharmacokinetics 3° Medicine Professor: Vittoria Carrabs PhD Academic year: 2024/25  Summary 1. INTRODUCTION. 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES 3. LIBERATION 4. ADME: Ø Absorption Ø Distribution Ø Metabolism Ø Excretion 2  Summary 1. INTRODUCTION. 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES 3. LIBERATION 4. ADME: Ø Absorption Ø Distribution Ø Metabolism Ø Excretion 3 1. INTRODUCTION PHARMACOKINETICS Biological system Drug PHARMACODYNAMICS Pharmacokinetics: is a branch of pharmacology that studies the fate of the drug in the organism as a function of time and dose (LADME). *what body does to the administered drug (how the body absorbs, distributes, metabolises and eliminates the drug) 4 1. INTRODUCTION PHARMACOKINETICS Biological system Drug PHARMACODYNAMICS Pharmacodynamics: Is a branch of pharmacology that studies the mechanism of action of a drug and the drug-receptor interaction to give a pharmacological effect in organism. *what the drug does to the body and how it interacts with it 5 1. INTRODUCTION Patient's response to a drug, in terms of when it appears and the intensity and the duration of the same, depends on: Absorption of the drug from the site of administration, Distribution of the drug through the different tissues and site of action Elimination of the drug from the body. (Metabolism and Excretion) The set of these processes is called : LADME ü Mathematical models and curves of drug levels in the blood, which allow establishing the appropriate dosage regimens for therapeutic treatment. 6  Summary 1. INTRODUCTION. 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES 3. LIBERATION 4. ADME: Ø Absorption Ø Distribution Ø Metabolism Ø Excretion 7 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES Principles: biological membranes The biological membranes act as a selective barrier, within or around a cell. LL ULAR XTRACE E D FLUI Phospholipid CYT bilayer OPL ASM UNIT 2: Pharmacokinetics 8 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES Principles: biological membranes Biomembranes are selectively permeable structures. Molecules crossing will depend on size, charge, and other chemical properties. ü Drug's ability to cross biological membranes is important throughout the (L)ADME process. UNIT 2: Pharmacokinetics 9 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES Channel protein Carrier protein Phospholipid electrochemical gradient bilayer Passive diffusion Active transport Facilitated diffusion UNIT 2: Pharmacokinetics 10 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES. 1. Passive transport: » Passive diffusion » Filtration 2. Facilitated diffusion 3. Active transport 4. Pinocytosis UNIT 2: Pharmacokinetics 11 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES. 1. Passive transport: – Passive diffusion: » following the concentration gradient. » Membrane: no active role » Is the most important mechanism » No energy required It depends on the liposolubility of the drug. Only low molecular weight, neutral (uncharged or ionisable), non-polar molecules (they have to pass through the lipid bilayer) cross the lipid bilayer. UNIT 2: Pharmacokinetics 12  2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES. 1. Passive transport: – Passive diffusion: Influence of pH: Most of drugs are » weak acids (low ionised at acid pH) are absorbed in Non-Ionised Ionised form gastric environment form » weak bases (low ionised at alcaline pH. Are absorbed in the Intestine). Weak acids will pass through Weak bases will pass through membranes in acidic medium membranes in basic medium UNIT 2: Pharmacokinetics 13  2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES.. 1. Passive transport: – Filtration: Drug diffuses across the aqueous pores proteins imbibed into the membrane. – It is very important in capillary transport and for ionised drugs. UNIT 2: Pharmacokinetics 14  2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES.. 2. Facilitated diffusion Ø Transport takes place in favour of a concentration gradient mediated by a channel or transporter. Ø Higher speed. Ø No energy required. Ø Saturable. Ø Competitive or non-competitive inhibition. Ø Regulation by phosphorylation of the transporter protein or channel. UNIT 2: Pharmacokinetics 15  2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES. 3. Active transport: Transport protein carriers: » against the concentration gradient » energy is required.. UNIT 2: Pharmacokinetics 16  2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES.. 4. Pinocytosis: The drug is involved into a vesicle and transported into the compartment. It is used for big size molecules. UNIT 2: Pharmacokinetics 17  Summary 1. INTRODUCTION. 2. TRANSPORT ACROSS BIOLOGICAL MEMBRANES 3. LIBERATION 4. ADME: Ø Absorption Ø Distribution Ø Metabolism Ø Excretion 18  iberation is the process of release of drug 1 from the formulation. Absorption bsorption: is the process of a substance Liberation entering the blood circulation. istribution: is the dispersion or 2 dissemination of substances throughout the fluids and tissues of the body 3 Metabolism Distribution etabolism: is the irreversible transformation of compounds into metabolites. xcretion: is the elimination of the substances from the body. 4 Excretion 20 Questions????? 21