Pharmacology I

Pharmacology: Study of drugs that alter functions of living organisms. Pharmacokinetics: K-NEX=MOVES "Art" HOW DRUG MOVES THROUGH YOUR BODY How the body interferes with drugs. (Involves drug movement through the body to reach site of action, metabolism, and excretion. Specific processes are absorption, distribution, metabolism, and excretion) Pharmacodynamics: DOES "Science" EFFECT OF THE DRUG ON THE BODY How drugs interact with cells, tissues, and organs. (Involves drug actions on target cells and the resulting alterations in cellular biochemical reaction and function). Pharmacoeconomics: Involves the cost of drug therapy, including cost of purchasing, dispensing, storage, administration, lab, and other tests used to monitor patient responses, and losses due to expiration.

1. Plants: Digitalis purpurea- foxglove- plant 2. Animals: Thyroid of animals 3. Minerals: Gold (not used) 4.Synthetic- versions of drugs originally derived from plants and animals, chemical structures made in lab, more standardized 5. Biotechnology: use of recombinant RNA and DNA technology which uses strains of E. Coli to form biosynthetic substances such as human insulin. The recombinant insulin is identical to insulin produced by the pancreas. Another example is Epogen used in anemia of chronic renal failure.

CRITICAL CONCENTRATION: the amount of drug needed to cause a therapeutic effectLOADING DOSE: for some drugs that take a prolonged period to reach a critical concentration, if their effects are needed quickly, a loading dose is recommended ( a HIGHER dose than that usually used in treatment)

This is the FIRST phase in drug action. In the GI tract, drugs need to be in a solution so that they can be absorbed. A drug in SOLID form (tab/cap) must DISINTEGRATE into small particles to DISSOLVE into a liquid, a process known as DISSOLUTION. Drugs in liquid form are already in a solution. after the drug is in liquid-->absorption can begin.
TABLETS first DISINTEGRATE then DISSOLVE into a liquid

Absorption Process:* *the process that occurs from the time a drug enters the body to the time it enters the blood stream to be circulated. - determined by rate of absorption and intensity by extent of absorption-IV>IM>SUB Q>ORAL* IV doentt need to be absorbed bc its placed right into the bloodstream* Onset of drug action is determined by rate of absorption Drugs are absorbed(into circulation) through the mucosa of the stomach (aspirin) and/or small intestine or large intestine ( rectally administrated drugs for nausea) Normally ORALLY-->absorbed from the small intestine lumen (villi) into the mesenteric blood stream--> portal vein of the liver Small intestine= LARGE surface area (for absorption of drugs and nutrition) Enteric coated meds are intended for intestinal dissolution and absorption Parenteral Absorption: (Parenteral= any other route of administering drugs other than the GI tract) Fastest route by which a drug can be absorbed Route by-passes the first-pass effect of the liver Ex: IM drugs are absorbed over several hours, or special formulated IM's are called Depot Drugs and are designed for slow absorption over several days, months or longer
Factors: (that affect rate and extent of drug absorption) = Dosage form, Route of administration, Administration site blood flow, GI function Factors: (that influence enternal drug absorption)= Age Type of meds such as anti-cholinergic meds which slow down the GI tract Food Beverage (type and amount of fluid taken with med) Portions of small bowel removed Blood flow decreased to an area such as in exercise Drug is lipid or water soluble (needs a carrier) Route such as sublingual route absorbed rapidly under the tongue which has large blood supply

(Most oral drugs must be swallowed, dissolved in gastric fluid, and delivered to the small intestine. Rapid movement through the stomach and small intestine may increase drug absorption by promoting contact with absorptive mucous membrane, it may also decrease absorption because some drugs may move through the small intestine too rapidly to be absorbed. For many drugs, the presence of food in the stomach slows the rate of absorption and may decrease the amount of drug absorbed)

The portion of a dose that reaches the systemic circulation and is available to act on body cells IV: always 100% bioavailable Oral: virtually always > 100% (GI, liver and partialy metabolized)

Distribution: *TRANSPORT OF DRUG MOELCULES W/IN THE BODY*Depends on adequacy of blood circulation (bigger=better)* Protein binding is important factor: allows part os a drug dose t be stored and released as needed. Drugs that are highly bound to plasma proteins or stored extensively in other tissues have long duration of action.*Only the FREE or UNBOUND portion of drug acts on body cells.bound to plasma proteins inactive(r/t large size: unable to leave blood stream and pass through capillaries). Drugs are carried by blood and tissue fluids to--> action, metabolism and excretion sites Distribution process affected by--> Protein binding, Blood-brain barrier, Pregnancy and lactation Drug distribution to the CNS is limited because the blood-brain barrier limits movement of drug molecules into brain tissues Blood-brain barrier: (Composed of capillaries with tight walls, highly selective permeable membrane to protect the CNS) This capillary network prevent certain drugs from crossing the cell membrane. Only certain LIPID soluble drugs such as anesthesia or drugs with a LIPID transport system go into the brain and cerebral spinal fluid. (CHILDREN not fully formed- meds are more effective) Placenta and Lactation: Drugs cross the placenta: placenta= less selective Ex of drugs that are easily transported across the placenta: Steroids, Narcotics, Anesthesia, and some antibiotics Most systemic drugs are excreted to some extent in breast milk and reach the infant.

Metabolism: Process by which chemical structure of a drug is modifies or altered for kidney excretion. GI tract and liver metabolize drugs, THE LIVER PRIMARY SOURCELIVER can convert active drug to an active metabolite with similar effectsDrugs can increase the metabolism of another drug by stimulating LIVER ENZYME--> these are called ENZYME INDUCERSDrugs called ENZYME INHIBITORS DECREASE specific liver enzymes needed by some drugs to be metabolizedHEPATIC ENZYMES ACTIVATE a PRO-DRUGPRO-DRUG: an inactive substance that must be converted to an active substance through liver metabolism. Once converted then it can exert its effects
method-->drugs are INACTIVATED OR BIOTRANSFORMED Converts fat-sol drugs--> h2o sol metabolites Prodrugs: initially inactive until metabolized As drug pass liver to be metabolized--> become metabolites(different forms of the drug) GOAL FOR METABOLITES: to become inactive and excreted MANY TRIPS PAST LIVER Drug Metabolizing ENZYMES located in: LIVER #1 TQ: LIVER AND KIDNEYS kidneys RBC& plasma lungs GI mucosa
FIRST PASS:

Excretion: Elimination of a drug from the body. Need functioning circulatory system& organs Most drugs are excreted by the kidneys and eliminated in the urine. (MUST BE WATER SOLUBLE) Primarily in URINE Lungs- Anesthesia FECES Exocrine (mammory glands) Intestinal Tract: (Bile and feces) Skin and sweat: Minimal excretion Saliva

IS REVERSIBLE The degree and duration of receptor binding are functions of how well the drug fits the receptor, the nature of the bond or attraction, and the concentration of the drug at its site of the receptor.
(most receptors are proteins located on surface or within cells) 1. When drug binds with receptor-->complex is formed= physiochemical reaction that STIMULATES or INHIBIT normal cellular function 2. Drugs cause reaction that CHANGES permeability of cell membrane to one or more ions (K, Na, or CA channels) 3. Drugs cause a SYNTHESIS, RELEASE, or INACTOVATION of neurohormones Non-receptor: do not act on receptor (act on problem): antacids osmotic diuretics several anticancer drugs metal chelating agents

DOSAGE: frequency, size, number of doses ROUTE OF ADMINISTRATION: influences absorption and distribution DRUG-DIET INTERACTIONS: GRAPEFRUIT increases the adverse effects. Conains substance that strongly inhibits the meatbolism of drugs normally metabolzed by the CYP344 enzyme DRUG-DRUG INTERACTIONS: basic cause is altered drug metabolism ADDITIVE EFFECT, SYNERGISM, INTERFERNCE, DISPLACEMENT and ANTIDOTE DRUG AGE: 1mo-1yr= Adult levels of protein binding and kidney finction -->UNDEVELOPED blood-brain barrier nd IMMATURE liver function. (wont metabolize as quickly, and will go right to CNS) Children= period of increased activity of drug-metabolsing enzymes-->DRUGS ARE RAPIDLY METABOLIZED AND ELIMINATED 65+= LITTLE change in drug ABSORPTION, but decrease in cardiac output= SLOWER DISTRIBUTION TO ACTION METABOLISM AND EXCRETION. (metab slower= longer action, more likely to accumulate with chronis administration) GENETICS, ETHNICITY, GENDER PHARMACOGENETICS: each person is genetically unique and must be treated as an idividual rather than a part of en ethnic group PATHOLOGIC CONDITIONS PSYCHOLOGICAL CONSIDERATIONS ENVIRONMENTAL

SYNERGISM: unlike 2 drugs administered together interact in a way that together combined effect are greater than the sum of the effects for each drug given alone 1+1= MORE THAN 2 ADDITIVE: like 2 drug similar actions are given together, they have an additive effect 1+1=2 can give a SMALLER dose INTERFERENCE: one drug with the metabolism of a second drug may result in intensified effects of the second drug. DISPLACEMENT: (i.e a drug with a strong attraction to protein binding sites may displace a less tightly bound drug) of one drug from plasma protein-binding sites by a second drug increase the effects of the displaced drugs. ANTIDOTE DRUG: can be given to antagonize the toxic effects of another drug

MEC: (determined by dose, and absorption into blood stream)THE LEAST AMOUNT OF DRUG PRESENT TO GET DESIRED ACTION. must be present BEFORE a drug exerts its pharmacological action on body cellsONSET OF ACTION: THE TIME IT TAKES TO REACH THE MEC AFTER A DRUG IS ADMINISTERED.
*continues as long as the SERUM LEVEL is above the MEC, wanes as drug molecules are metabolized and excreted( if no more doses are given) and STOPS when the serum level drops below the MEC*
DURATION OF ACTION: THE LENGTH OF TIME THE DRUG HAS PHARMACOLOGICAL EFFECT
goal of drug therapy:enough drug to be beneficial and not toxic. between the low and high concentration is THERAPEUTIC RANGE.
SERUM DRUG LEVEL: Lab measurement of the amount of drug in the bloodstream at particular time

THERAPEUTIC RANGE.: Concentration of the drug in plasma. The concentration should be between the MEC and the MTCMTC: excessive level (higher than MEC)at which toxicity occurs. A drug level that is too high ABOVE THE MEC
CAUSED BY:single large doserepeated small dosesslow metabolism of med