Pharmacokinetics.pdf

 PROF. MARIVIC E. ILARDE FACUTLY- COLLEGE OF NURSING OLFU-VALENZUELA CAMPUS At the end of the topic, learners will be able to: q Understand the concept of pharmacokinetics q Discuss the phases and processes of drugs once inside the body 3 Phases of PHARMACEUTIC Drug action PH...

 PROF. MARIVIC E. ILARDE FACUTLY- COLLEGE OF NURSING OLFU-VALENZUELA CAMPUS At the end of the topic, learners will be able to: q Understand the concept of pharmacokinetics q Discuss the phases and processes of drugs once inside the body 3 Phases of PHARMACEUTIC Drug action PHASE PHARMACOKINETIC PHASE PHARMACODYNAMIC PHASE 3 Phases of PHARMACEUTIC Drug action PHASE the 1st phase of drug action In the GI tract, drugs need to be in solution so they can be absorbed PHARMACOKINETIC The drug disintegrates into PHASE small particles to dissolve into a liquid The rate of dissolution is the time it takes the drug to disintegrate and dissolve to PHARMACODYNAMIC become available for the body to absorb it PHASE 3 Phases of PHARMACEUTIC Drug action PHASE 2 Phases of Pharmaceutic Phase 1. Disintegration – breakdown into smaller parts PHARMACOKINETIC PHASEinto even 2. Dissolution – further breakdown smaller parts in GIT for faster absorption; dissolve into liquid PHARMACODYNAMIC PHASE 3 Phases of PHARMACEUTIC Drug action PHASE Tablets are not 100% drug Fillers and inert substances – excipients PHARMACOKINETIC Allow drug to take on particular size and shape and to enhance drug dissolution PHASE PHARMACODYNAMIC PHASE 3 Phases of PHARMACEUTIC Drug action PHASE PHARMACOKINETIC PHASE Aid in the Protect, support or Assist in product Assist in the Assist in processing of the enhance stability, identification, and effectiveness and maintaining the drug delivery bioavailability, or enhance any /or delivery of the integrity of the system during its manufacture patient acceptability PHARMACODYNAMIC attribute of the overall safety drug in use drug product during storage PHASE Important Uses of Drug Excipients 3 Phases of PHARMACEUTIC Drug action PHASE Factors Affecting Rate of Dissolution Form of drug ( LIQUIDVS. SOLID) – liquids more PHARMACOKINETIC absorbed than solid, already a solution: rapidly available for PHASE GI absorption Gastric pH( acidic vs. alkaline) – acidic media: faster disintegration & absorption PHARMACODYNAMIC normal gastric pH – 1.5-3.5 Age – young & elderly – increase pH: PHASE decrease absorption 3 Phases of PHARMACEUTIC Drug action PHASE Factors Affecting Rate of Dissolution Enteric coated drugs – resist disintegration in PHARMACOKINETIC gastric acid: Disintegration occurs only in PHASE alkaline environment (intestine): Should not be crushed Presence of food – may interfere with dissolution & absorption, may enhance PHARMACODYNAMIC absorption of other drugs, may be protectants of gastric mucosaPHASE 3 Phases of PHARMACOKINETIC Drug action PHASE PHARMACOKINETIC PHASE PHARMACODYNAMIC PHASE - movement of the drug into the bloodstream after administration. - 80% of drugs are taken by mouth – enteral - Movement of drug molecules from site of Bioavailability administration to is availability of drug to circulatory system the general circulation or site of pharmacological actions.  Physico-chemical (Drug) Blood flow to solubility absorbing site Chemical stability Total surface area for absorption Lipid to water partition coefficient Time of arrival and contact time at absorption site Degree of ionization  Physico-chemical (Drug) Solubility Water soluble drugs: stay in the blood longer; absorbed slower Blood flow to absorbing site Fat soluble: stay in fatty tissues stays longer in the membrane, absorbed faster Chemical Large particles:stability absorbed slowly than small particles Total surface area for absorption Lipid to water partition coefficient Time of arrival and contact time at absorption site Degree of ionization  Physico-chemical (Drug) Chemical stability Solubility Blood flow to water or fat stability absorbing site Hydrophobic: non polarized Hydrophilic: polarized Total surface area for absorption Lipid to water partition coefficient Time of arrival and contact time at absorption site Degree of ionization  Physico-chemical (Drug) Solubility Blood flow to absorbing site Lipid to water partition Chemical stability coefficient Total surface area The greater the lipid water for absorption solubility coefficient, the more is the lipid solubility of the drug and the greater is the absorption Time of arrival and contact time at absorption site Degree of ionization  Physico-chemical (Drug) Solubility Blood flow to absorbing site Degree of Ionization Ionized areChemical stability slowly absorbed Total surface area because it can’t penetrate a for absorption semipermeable membrane, it needs ATP Lipid to water Weak acid+ acidic env’t= non partition ionized Time of arrival and Weak base+basiccoefficient env’t= non contact time at ionized absorption site Weak acid+ basic env’t= ionized Weak base+ acid env’t= ionized  Passive Pinocytosis Active transport Transport Passive transport 1.Diffusion Drugs move across the cell membrane from an area of Diffusion takes place in the aqueous and lipid environment higher concentration Aqueous: interstitial compartments that surrounds tissues to one of lower concentration  Passive transport 2. Facilitated diffusion requires a carrier such as enzyme or protein to move the drug against a concentration gradient does not require energy. Low lipid solubility like glucose penetrate membrane more rapidly Pinocytosis is the process by which cells carry a drug across their membrane by engulfing the drug particles in a vesicle  Active Transport requires energy to facilitate the transport of drug molecules against a concentration gradient, which usually occurs at specific sites Iron salts, levodopa for Parkinson’s in the small intestine disease, antithyroid drugs  process by which drug becomes available to body fluids and tissues. is the movement of the drug from the circulation to body tissues. Transporters help drugs get across biological barriers (such as the gut lining) or work to exclude them from a part of the body (such as the brain) are direct targets for many drugs, and most drugs are thought to interact with at least one transporter.  Factors Affecting the Distribution of Drugs Size of the organ  refers to the reversible association of a drug with the proteins of the plasma compartment of blood, and this binding is due to electrostatic and hydrophobic forces between drug and protein. Agents that are minimally protein bound penetrate tissue better than those that are highly bound, but they are excreted much faster. unbound drug are pharmacologically active AKA: biotransformation is the process by which the body chemically changes drugs into a form that can be excreted Active to inactive form  a drug gets metabolized at a specific location in the body that results in a reduced concentration of the active drug upon reaching its site of action or the systemic circulation some drugs are metabolized to an inactive form and excreted--- reduced amount of active drug Cytochrome P450 system (CYP) Heme-containing liver enzymes that convert drugs to metabolites, making the drug inactive Some metabolites are still pharmacologically active (PRODRUG) Decreased drug metabolism rate will result to excess drug accumulation that can lead to toxicity Drug half-life is the time it takes for the amount of drug in the body to be reduced by half Different drugs have different half-lives; however, they all follow this rule: after one half-life has passed, 50% of the initial drug amount is removed from the body. Therapeutic Effect of the Drug can be achieved when the amount of drug being administered is the same as the amount of drug being eliminated. a steady state of drug concentration is necessary to achieve optimal therapeutic benefit. Example: Ibuprofen has a half life of about 2 hours. if the patient takes 200 mg, in 2 hours, 50% of the drug will be gone, leaving 100 mg. after 2 hours - 50 mg. after 2 hours – 25 mg after 2 hours – 12.5 mg after 2 hours – 6.25 mg  Half-life/ Elimination half- life (t ½)- time it takes for one half of drug concentration to be eliminated Short t1/2= 4-8hrs: given several times a day (ex. Penicillin G) Long t ½ = >12 hours: given 2x or 1x/day (Ex. Digoxin)  FACTORS Drug Stress Metabolism Physiologic Genetics Environment  Genetics FACTORS Physiologic Drug Metabolism Environment Stress  some people metabolize Genetics drugs rapidly, others more slowly FACTORS Physiologic Drug Metabolism Environment Stress Liver disease Infants Genetics Elderlies FACTORS Physiologic Drug Metabolism Environment Stress  Genetics FACTORS Physiologic Drug Metabolism Environment Stress Smoking Drugs  Genetics FACTORS Physiologic Drug Metabolism Environment prolonged illness, surgery Stress  removal of the drug from the body Drug is changed into inactive form and excreted by the body Routes: Kidney- main organ for drug elimination: leave the body through urine Free or/unbound/water soluble drugs- filtered in the kidney: excreted easily (+) kidney disease- dose must be decreased Routes: Urine Bile Sweat Saliva Tears Milk Stool Routes: Urine Bile: digoxin, warfarin Sweat: opiates, amphetamines, and buprenorphine Saliva: caffeine, phenytoin, and theophylline. Tears: phenobarbital, carbamazepine, Milk: paracetamol, antibiotics Stool: streptomycin, neomycin  Factors Affecting Kidney Renal Molecular Concentration the Urine Rate diseasepH theof blood of drug weight inflow Drug plasma Elimination  Urine pH Factors Kidney Molecular Affecting disease weight the Rate of Drug Elimination Concentration Renal of drug in the blood flow plasma  DRUG Clearance urine pH influences drug excretion normal urine pH 4.6-8 acidic urine promotes elimination of weak base drugs like Amphetamine, diazepam alkaline urine promotes elimination of weak acid drugs like amoxicillin, aspirin  Bioavailability biotransformation Drug elimination of drug clearance