Pharmacology Lab PDF

31  1. drug moves freely 2 bounded drugs. Albumin – Acidic drugs...

31  1. drug moves freely 2 bounded drugs. Albumin – Acidic drugs Alpha 1-acid glycoprotein – Basic drugs memorize numbers don't Plasma protein are huge molecules so doesn't transport easily In the bloodstream, drugs are transported partly as free (unbound) drug and partly reversibly bound to blood components ( eg , plasma proteins, blood cells). Of the many plasma proteins that can interact with drugs, the most important are albumin, glycoprotein, and lipoproteins. Acidic drugs are usually bound more extensively to Albumin; basic drugs are usually bound more to glycoprotein, lipoproteins, or both. Only unbound free drug is available for diffusion to tissues to achieve pharmacologic effects of the drug bound to then gets distributed Major Plasma protein that drugs bound to it Albumin : basic plasma protein , acidic drugs Alpha 1 adid glycoprotein : 32  and bound drug non difference between bound Free/Unbound drug – Available for therapeutic (and adverse) effects; Also metabolized by liver. Bound drug – Do not move out of the systemic circulation; Not metabolized. Higher the protein binding, longer is the drug action. Protein-binding is a reversible process. not permenant Drug A: 20% protein bound Drug B: 60% protein bound smost likely to exibit longer duration When the drug is distributed in the systemic circulation, it is the free form of the drug that can move out of the blood vessels and produce therapeutic effect as well also be metabolized by the liver. The bound form of the drug will stay in the circulation and acts as a reservoir. Once the free form of the drug reduces, the drug which is bound to the plasma proteins become free and will be available for action and so the protein-binding is a reversible process. 33 not reala Drug-Drug interaction due to plasma protein displacement Example 1: Drug A is 20% protein bound Example 2: Drug A is 99% protein bound 8 molecules free 2 molecule bound Drug A 1 Drug A 2 3 I Y Albumin Albumin S 2 9 g 6 7 Drug B Drug B When two or more drugs that bind to the same plasma protein are administered, they interact and result in drug displacement. The effect would be much pronounced for a drug that has extensive plasma protein binding. 34  Disease states affecting the protein binding of drugs Unbound fraction of acidic drugs increase – May require dose reduction Unbound fraction of basic drugs decrease – May require dose increase In patients with hepatic insufficiency, there is a reduction in the synthesis of plasma proteins particularly albumin. Hence, there is reduced binding of acidic drugs. Similarly, in renal failure, more albumin is excreted and so there is reduction in the plasma albumin concentration. Hence, there is reduced binding of acidic drugs. On the other hand, in inflammatory states, there is more production of alpha-1 antiglobulin due to which there is an increased binding of the basic drugs. Patients who develop Kidney or liver problems , their plasma albumin can be if acidic low , so they're given drugs, doses should be reduced to reduce risk of adverse effect 35  Tissue distribution of drugs The unbound drug freely moves across the blood vessels and depending on their lipophilicity and molecular sizes, they enter the tissues either passively or through active transport. more fatty = easier transport big size and no lipophilicity bigger Size = easier transport use active transport blood when drug is circulating in either bound or free form free form has ability to cross blood vessels and reach tissue. 36 Organ blood flow varies and so influences the tissue distribution of the drug. - & -- Also, the amount of blood flow to each of the organs in the body varies. As the drug is present in the blood, due to this variation, there is a difference in the quantity of drug reaching each of these tissues. 37  More the tissue affinity of the drug, more will be the tissue distribution. attraction More the tissue affinity of the drug, more will be the tissue distribution. tissu distribution depend on - blood flow affinity of to peripheral +issue - drug 38  Central compartment Peripheral compartment Central compartment is the one in which drug enters from the site of administration and is metabolized and excreted. Peripheral compartment refers to the tissues in which the drug freely moves, stays there sometime, and returns to the central compartment. lood X Central compartment enters site of administration drug - and is metabolized 3, excreted all tissues Peripheral compartment - tissue in which drug moves freely stays , , then return to central compartment ↑ all tissues that recieves body in drug from centeral compartment 39  True or False v centeral Drugs get eliminated from peripheral compartment. F Drugs enter peripheral compartment directly without entering central compartment. F > first has to reach central More number of drug molecules can stay in the peripheral compartment compared to central compartment. T More number of drug molecules can stay in the central compartment relative to peripheral compartment. T 40 What is the parameter used for representing the rate and extent of drug absorption? bloavailability - 41  Volume of distribution (Vd) Volume of Distribution (L) = Amount of drug in the body (mg) Initial plasma concentration of drug (mg/L) (mg/L) Volume = 10 mg/10 mg/L =1L The volume of distribution (Vd) is a pharmacokinetic parameter representing an individual drug’s propensity to either remain in the plasma or redistribute to other tissue compartments. By definition, Vd relates the total amount of drug in the body to the plasma concentration of the drug at a given time. 42  not understood Determination of initial plasma concentration For IV administration, the initial dose can be found out. But for oral? There is a way. If you plot the concentrations in logarithmic format, it follows a straight line and extrapolation of that line will help you to find out the initial drug concentration. 43  Vd < 5 L = Confined to intravascular fluid, with less penetrating the extracellular space. blood vessel 5. staying in - mostly S L) are mainly confined to the intravascular Drugs with a very small Vd (