Routes of Administration PDF

Routes of Administration  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ Drugs usually enter the body remote from the target tissue or organ and require transport by the circulation to the intended site of action ▪ BIOAVAILABILITY ▪ amount absorbed into the systemic circulat...

Routes of Administration  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ Drugs usually enter the body remote from the target tissue or organ and require transport by the circulation to the intended site of action ▪ BIOAVAILABILITY ▪ amount absorbed into the systemic circulation amount of drug administered  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ ORAL (swallowed) ▪ Maximum convenience ▪ Absorption maybe slower, and less complete ▪ Some drugs have low bioavailability when given orally ▪ Subject to first-pass effect (significant amount of the agent is metabolized in the gut wall, portal circulation, and liver before it reaches the systemic circulation)  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ INTRAVENOUS (IV)/PARENTERAL ▪ Instantaneous and complete absorption ▪ Bioavailability is 100% ▪ Potentially more dangerous, high blood levels reached if administration is too rapid  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ INTRAMUSCULAR (IM) ▪ Absorption is often faster and more complete (higher bioavailability) than oral ▪ Large volumes (>5 ml into each buttock) if the drug is not irritating ▪ First-pass effect is avoided ▪ Heparin cannot be given by this route, causes bleeding in the muscle  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ SUBCUTANEOUS ▪ Slower absorption than IM route ▪ First-pass effect is avoided ▪ Heparin can be given by this route, does not cause hematoma  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ BUCCAL AND SUBLINGUAL ▪ Buccal route (in the pouch between gums and cheeks) ▪ Permits absorption direct into the systemic circulation, bypassing hepatic portal circuit and first-pass metabolism ▪ Slow or fast depending on formulation of the product ▪ Sublingual route (under the tongue) offers the same features  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ RECTAL (suppository) ▪ Partial avoidance of first-pass effect (not completely as the sublingual route) ▪ Suppositories tend to migrate upward in the rectum where absorption is partially into the portal circulation ▪ Larger amounts of unpleasant drugs are better administered rectally ▪ May cause significant irritation  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ INHALATION ▪ For respiratory diseases ▪ Delivery closest to the target tissue ▪ Results into rapid absorption because of the rapid and thin alveolar surface area ▪ Drugs that are gases at room temperature (eg, nitrous oxide), or easily volatilized (anesthetics)  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ TOPICAL ▪ Application to the skin or mucous membrane of the eye, nose, throat, airway, or vagina for local effect ▪ Rate of absorption varies with the area of application and drug’s formulation ▪ Absorption is slower compared to other routes  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ TRANSDERMAL ▪ Application to the skin for systemic effect ▪ Rate of absorption occurs very slowly ▪ First-pass effect is avoided  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ BLOOD FLOW ▪ Influences absorption from IM, subcutaneous, and in shock ▪ High blood flow maintains a high drug depot-to-blood concentration gradient ▪ Maximizes absorption  ROUTES OF ADMINISTRATION ▪ ABSORPTION OF DRUGS ▪ CONCENTRATION ▪ Concentration gradient ▪ Major determinant of the rate of absorption (Fick’s law)  DRUG DISTRIBUTION ▪ DETERMINANTS OF DISTRIBUTION ▪ Size of the organ ▪ Size of the organ determines the concentration gradient between blood and the organ ▪ Eg, skeletal muscle and brain  DRUG DISTRIBUTION ▪ DETERMINANTS OF DISTRIBUTION ▪ Blood flow ▪ Important determinant of the rate of uptake ▪ Well-perfused organs ▪ Brain ▪ Heart, kidneys ▪ Splanchnic organs  DRUG DISTRIBUTION ▪ DETERMINANTS OF DISTRIBUTION ▪ Solubility ▪ If the drug is very soluble in cells, the concentration in the perivascular space will be lower and diffusion from the vessel into the extravascular tissue will be facilitated  DRUG DISTRIBUTION ▪ DETERMINANTS OF DISTRIBUTION ▪ Binding ▪ Binding of drugs to macromolecules in the blood or tissue compartment will tend to increase the drug’s concentration in that compartment  DRUG DISTRIBUTION ▪ APPARENT VOLUME OF DISTRIBUTION ▪ Vd ▪ Amount of drug in the body to the concentration in the plasma  DRUG METABOLISM ▪ AS MECHANISM OF TERMINATION OF DRUG ACTION ▪ Action of many drugs is terminated before they are excreted ▪ Metabolized to biologically inactive derivatives ▪ Conversion to a metabolite is a form of elimination  DRUG METABOLISM ▪ AS MECHANISM OF DRUG ACTIVATION ▪ PRODRUGS ▪ Inactive as administered and must be metabolized in the body to become active ▪ Eg, levodopa, minoxidil ▪ Many drugs are active as administered and have active metabolites as well ▪ Some benzodiazepines  DRUG ELIMINATION ▪ DRUG ELIMINATION WITHOUT METABOLISM ▪ Drugs not modified by the body ▪ Continue to act until they are excreted ▪ Eg, lithium  DRUG ELIMINATION ▪ ELIMINATION OF DRUGS ▪ Determinants of the duration of action for most drugs ▪ Dosage ▪ Rate of elimination following the last dose ▪ Disappearance of the active molecules from the bloodstream ▪ Drug elimination is not the same as drug excretion ▪ A drug maybe eliminated by metabolism long before the modified molecules are excreted from the body  DRUG ELIMINATION ▪ ELIMINATION OF DRUGS ▪ For most drugs, excretion is by way of the kidneys (except anesthetic gases-lungs) ▪ For drugs with active metabolites (eg, diazepam), elimination of the parent molecule by metabolism is not synonymous with termination of action ▪ For drugs that are not metabolized, excretion is the mode of elimination  DRUG ELIMINATION ▪ ELIMINATION OF DRUGS ▪ A small number of drugs combine irreversibly with their receptors, disappearance from the bloodstream is not equivalent to cessation of drug action ▪ Very prolonged action ▪ Eg, phenoxybenzamine, irreversible inhibitor of alpha receptors is eliminated from the bloodstream in 1 h or less after administration, drug’s action lasts for 48 h  DRUG ELIMINATION ▪ ELIMINATION OF DRUGS ▪ FIRST ORDER ELIMINATION ▪ Rate of elimination is proportionate to the concentration (ie, the higher the concentration, the greater the amount eliminated per unit time) ▪ Drug’s concentration in plasma decreases exponentially with time ▪ Half-life of elimination is constant regardless of amount of drug in the body ▪ Concentration of such drug in the blood will decrease by 50% for every half-life ▪ Most common process ▪ Followed by most drugs  DRUG ELIMINATION FIRST ORDER KINETICS 5 units/h Plasma conc. 2.5 units/h (Cp) 1.25 units/h Time (h)  DRUG ELIMINATION ▪ ELIMINATION OF DRUGS ▪ ZERO ORDER ELIMINATION ▪ Rate of elimination is constant regardless of concentration ▪ Occurs with drugs that saturate their elimination of mechanism at concentrations of clinical interest ▪ Concentration of such drugs in plasma decrease in linear fashion over time ▪ With higher doses, there will be bigger chances of toxic effect because the patient may not be able to eliminate it ▪ Eg, alcohol, phenytoin, aspirin  DRUG ELIMINATION ZERO-ORDER KINETICS 2.5 units/h 2.5 Plasma units/h conc. (Cp) 2.5 units/h Time (h)