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    Drug Excretion

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    faisalnadeem
    Drugs are excreted from the body through renal and non-renal routes. Renal excretion involves glomerular filtration, tubular secretion, and tubular reabsorption in the nephron, with most drugs excreted in urine either unchanged or as metabolites. Non-renal routes include biliary, pulmonary, salivary, mammary, skin, gastrointestinal, and genital excretion. The physicochemical properties of drugs, along with biological factors like age, sex, disease state, and urine pH, influence the rate and pathway of drug excretion from the body.

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    Drug Excretion

    Uploaded by

    faisalnadeem
    3K views27 pages
    Drugs are excreted from the body through renal and non-renal routes. Renal excretion involves glomerular filtration, tubular secretion, and tubular reabsorption in the nephron, with most drugs excreted in urine either unchanged or as metabolites. Non-renal routes include biliary, pulmonary, salivary, mammary, skin, gastrointestinal, and genital excretion. The physicochemical properties of drugs, along with biological factors like age, sex, disease state, and urine pH, influence the rate and pathway of drug excretion from the body.

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    Drug excretion. pharmacology, pharmacokinetics, Drug elimination

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    Drug-Excretion.ppt

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    Drugs are excreted from the body through renal and non-renal routes. Renal excretion involves glomerular filtration, tubular secretion, and tubular reabsorption in the nephron, with most drugs excreted in urine either unchanged or as metabolites. Non-renal routes include biliary, pulmonary, salivary, mammary, skin, gastrointestinal, and genital excretion. The physicochemical properties of drugs, along with biological factors like age, sex, disease state, and urine pH, influence the rate and pathway of drug excretion from the body.

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    3K views27 pages

    Drug Excretion

    Uploaded by

    faisalnadeem
    Drugs are excreted from the body through renal and non-renal routes. Renal excretion involves glomerular filtration, tubular secretion, and tubular reabsorption in the nephron, with most drugs excreted in urine either unchanged or as metabolites. Non-renal routes include biliary, pulmonary, salivary, mammary, skin, gastrointestinal, and genital excretion. The physicochemical properties of drugs, along with biological factors like age, sex, disease state, and urine pH, influence the rate and pathway of drug excretion from the body.

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    The key takeaways are that drugs can be excreted through both renal and non-renal routes. The major renal excretion processes are glomerular filtration, tubular secretion, and tubular reabsorption. Factors like physicochemical properties of drugs, biological factors, drug interactions, and disease states can affect renal excretion.

    The different routes of drug excretion are renal excretion and non-renal excretions like biliary, pulmonary, salivary, mammary, skin/dermal, gastrointestinal, and genital excretions.

    The major processes involved in renal excretion of drugs are glomerular filtration, tubular secretion, and tubular reabsorption.

    DRUG EXCRETION

    DRUG EXCRETION
    The process by which drugs or metabolites are irreversibly transferred from internal to external environment through

    renal or non renal route.


    Most drugs are excreted in urine either as

    unchanged drugs or drug metabolites.

    TYPES OF EXCRETION
    1. RENAL EXCRETION 2. NON RENAL EXCRETION Biliary excretion. Pulmonary excretion. Salivary excretion. Mammary excretion. Skin / Dermal excretion.

    Gastrointestinal excretion.
    Genital excretion.
    3

    RENAL EXCRETION

    ANATOMY OF NEPHRON

    Major Excretory Processes in the Nephron

    1. 2. 3.

    Glomerular filtration Tubular secretion Tubular re-absorption

    GLOMERULAR FILTRATION

    It Is non selective , unidirectional process Ionized or unionized drugs are filtered, except those that are bound to plasma proteins.

    ACTIVE TUBULAR SECRETION

    This mainly occurs in proximal tubule. Active secretion is Unaffected by change in pH and protein binding.

    PASSIVE TUBULAR REABSORPTION


    most substances are reabsorbed across renal tubular cells if unionized and lipid soluble It occurs after the glomerular filtration of drugs. It takes place all along the renal tubules. Reabsorption results in increase in the half life of the drug.

    pH OF THE URINE

    It varies between 4.5 to 7.5 It depends upon diet, drug intake and pathophysiology .

    10

    Acidic drugs usually contain weakly acidic functionalities, such as COOH. Basic drugs usually contain weakly basic functionalities, such as amines. Drugs which are acidic are ionized in basic media (pH > 7). Drugs which are basic are ionized in acidic media (pH < 7) The ionized form of the drug provides it with improved water solubility But the unionized form generally passes nonpolar membranes more readily. Acidification of urine increases reabsorption and decreases excretion of weak acids and decreases reabsorption of weak bases. Alkalinization of urine has the opposite effect. In some cases of overdose, these principles are used to enhance the excretion of weak bases or acids. e.g. salicylate (Aspirin ) (a weak acid) overdose may be treated by making the urine more alkaline with sodium bicarbonate injection.

    Effect of lipid solubility and pH


    Glomerular blood flow; filtrate

    ionised drug is less lipid soluble


    99% of GF is re-absorbed; concentration of drug rises in tubule

    If lipid soluble drug moves down concentration gradient back into blood

    Re-absorption

    FACTORS AFFECTING RENAL EXCRETION


    1.

    Physicochemical properties of drug


    Molecular size: Drugs with Mol.wt <300, water soluble are excreted in kidney. Mol.wt 300 to 500 Dalton are excreted both through urine and bile.

    Binding characteristics of the drug: Drugs that are bound to plasma


    proteins behave as macromolecules and cannot be filtered through glomerulus. Only unbound or free drug appear in glomerular filtrate. Protein bound drug has long half lives. Biological factor: Age, sex Drug interaction: increase or decrease Disease state Urine pH: RF Blood flow to the kidney
    14

    2.

    3. 4. 5.

    Handling of Drugs by the Nephron


    1000

    Glomerulus

    Proximal tubule

    Distal tubule

    Collecting tubule
    pH control

    Flow ml/min

    100

    Water Drugs

    Filter Filter

    80% reabsorb. secretion

    10 - 20 % reabsorbed Reabsorption

    Blood Flow in the Kidney Is Important


    Renal blood flow is ~25% of cardiac output

    1.3 L/min
    650 ml/min 130 ml/min In 24 hr, 185-190 Liters are filtered by the glomerulus 24 hr urine output is 1.5-1.7 Liters More than 99% of glomerular filtrate volume must be reabsorbed

    Renal plasma flow is 50% of renal blood flow

    Glomerular filtration rate (GFR) is 20% of plasma flow


    BUT water reabsorption does NOT equal solute reabsorption

    PULMONARY EXCRETION Gaseous and volatile substances such as general anesthetics (Halothane) are absorbed through lungs by simple diffusion. Pulmonary blood flow, rate of respiration and solubility of

    substance effect PE. Intact gaseous drugs are excreted but not
    metabolites. Alcohol which has high solubility in blood and tissues are excreted slowly by lungs.

    SALIVARY EXCRETION

    The pH of saliva varies from 5.8 to 8.4. Unionized lipid soluble drugs are excreted passively. The bitter after taste in the mouth of a patient is indication of drug excreted. Some basic drugs inhibit saliva secretion and are responsible for mouth dryness. Compounds excreted in saliva are Caffeine, Phenytoin, Theophylline.

    MAMMARY EXCRETION Milk consists of lactic secretions which is rich in fats

    and proteins.
    Excretion of drug in milk is important as it gains entry in breast feeding infants. pH of milk varies from 6.4 to 7.6. Free un-ionized and lipid soluble drugs diffuse passively..

    SKIN EXCRETION

    Drugs excreted through skin via sweat may lead to urticaria and dermatitis.

    Compounds like benzoic acid, salicylic acid,

    alcohol and heavy metals like lead, mercury and arsenic are excreted in sweat.
    20

    GASTROINTESTINAL EXCRETION
    Excretion of drugs through GIT usually

    occurs after parenteral administration. Water


    soluble and ionized from of weakly acidic and

    basic drugs are excreted in GIT. Example are


    nicotine and quinine are excreted in stomach.

    Drugs excreted in GIT are reabsorbed into


    systemic circulation & undergo recycling.

    CLEARANCE

    A very important concept for drug use Clearance (Cl) is the VOLUME of fluid (plasma) cleared (freed) of drug per unit time

    Clearance of most drugs is a first order process


    A constant

    fraction of drug is cleared per unit time

    A fraction is NOT a concentration Therefore, first order clearance is independent of drug concentration

    CLEARANCE

    Clearance is independent of the method and route of clearance


    Hepatic

    clearance Renal clearance Lung (inhalational) clearance Saliva Mothers milk

    Therapeutic Implications of Clearance

    Highly ionized drugs tend to be rapidly cleared


    Minimal

    tubular reabsorption since only non-ionized drug is reabsorbed

    Alkalinizing urinary pH with Na bicarbonate can accelerate clearance of WOAs


    Salicylate

    and barbiturates

    Acidifying urinary pH with arginine hydrochloride can accelerate clearance of WOBs


    Amphetamines

    Therapeutic Implications of Clearance

    Drug forms that are quite lipid soluble at the pH of the urine (5.5) are readily reabsorbed
    Maximal

    tubular reabsorption since non-ionized drug is reabsorbed

    Increasing osmolarity of urine (mannitol) may increase elimination of a lipophilic drug

    Therapeutic Implications of Clearance

    Tubular secretion of a drug may be inhibited by another drug by competition for the transporter
    Probenecid

    competes with penicillins

    Thus prolongs action of antibiotic

    Probenecid

    competes with some diuretics (furosemide) and thus may prevent diuretic access to the tubule which is where they act

    Decreases effect of diuretic

    Therapeutic Implications of Clearance

    Drug clearance is decreased by renal disease


    Measured

    by creatinine clearance Caused by


    Decreased renal blood flow Glomerular tubular damage Tubular nephropathy

    Drug clearance is greater in an adult than in


    Children

    (immaturity of kidney function) Elderly (decreased renal function Alcoholics

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