Drug Action Klas 1

8/2/2019 Drug Action Klas 1

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Ilmu tentang obat(pharmacon danlogos)

Ilmu yang mempelajari interaksi obatdengan organisme hidup

Studi terintegrasi tentang sifat-sifat zatkimia dan organisme hidup serta segalaaspek interaksinya


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I. PHARMACEUTICAL PHASE

II. PHARMACOKINETIC PHASE

III. PHARMACODYNAMIC PHASE


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Is the first phase of drug action

A solid drug (tablet) has to disintegrate before it can be absorbed

The process where a solid (tablet) goesinto solution is known as dissolution

ALL drugs must be in solution to crossbiologic membranes


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Is the process of drug movement to achievedrug actionWhat the body does to the drug- refers to

the study of how the body processes drugsIt includes the 4 basic components of :1# Absorption2# Distribution

3# Metabolism (Biotransformation)4# Excretion


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Movement of drug particles from Gastrointestinal tract to the body fluids

Movement of a drug from the site ofadministration into the bloodstream .

Absorption determines how long it takes for adrug to take effect.

Usually the more rapid the absorption, fasterthe drug works


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1.Passive absorptionOccurs mostly by diffusion (movement from higherconcentration to lower concentration)

2. Active absorption

Requires protein or enzyme to move the drug against aconcentration gradient.

3.PynocytosisIs a process by which cells carry a drug across theirmembrane by engulfing the drug particles

drugs that are lipid soluble and non ionized are absorbedfaster then water soluble and ionized drugs.


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Surface areaContact time with surfaceCirculationSolubility (water soluble vs lipid soluble)Ionization (weak versus strong acid/base)Drug form & drug concentrationBioavailability ( after first pass thru liver)Route of administration (enteral &parenteral)


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Greater the surface area faster the drug will work

Longer the drug is in contact with surface area the greater theBioavailabilityCirculation- blood flow to the area enhances drug absorption. Drugsplaced directly into the blood stream (IV) are totally available forabsorption.Solubility - Remember in order to work, a drug must be soluble inbody fluids. The more lipid soluble a drug is, the faster it will crossbiologic membranes. Water-soluble drugs cross biologic membranesslowly or not at all and may stay in the intestine or in the bloodstream.Ionization - An ion is a molecule with an electrical charge. Mostdrugs are either weak acids or weak bases and can exist in either anionized or nonionized form depending on the pH. Nonionized drugs

are more lipid soluble and readily cross biologic membranes.Drug dosage form-Liquids (suspensions, elixirs) are readily availablefor absorption because they are already in solution. Solids must firstdisintegrate and dissolve before absorption can occur.


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Drug concentration- higher concentrations of drugs are absorbedmore rapidly than drugs given at lower concentrations. Bioavailability readiness to produce a drug effect. It is apercentage of active drug absorbed and available to the targettissue.

Intravenous drugs are 100% available. Many antibiotics are givenby this route to obtain maximum effect. Drugs given by other routesvary in Bioavailability.

Bioavailability affects the :a. time of onset of drug effect.- how long before drug begins to workb. the time and magnitude of peak effect when it reachesmaximum levelc. the duration of effect how long drug response will last

Bioavailability readiness to produce a drug effect. It is apercentage of active drug absorbed and available to the targettissue.


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Additives : alter the location of disintegration of drugsas well as increase or decrease the rate of absorption

Enteric coating allows a drug to dissolve only in analkaline (pH greater than 7.0) environment such as thesmall intestine.

Sustained release drugs : allow drugs to be releasedslowly over time, rather than quickly, like conventionaltablets.

Size of drug particles: smaller the particle, faster theonset. Ex: The generic drug Glyburide has tradenames Micronase and Glynase. Glynase (micronized)onset is faster than Micronase (non-micronized)

Factors AffectingAbsorption


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Liquids, elixirs, syrups FastestSuspension solutions

Powders Capsules Tablets Coated tablets

Enteric-coated tablets Slowest


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Mucous membranes of the mouth: Buccal or Sublingual forms of drugsHighly vascular absorbing surfaceAvoids first pass phenomenon that occursin the liver

Absorptive area is small therefore Only small amounts of drugs can be given


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Oral Route: StomachHas low pH (about 1.4) the rate of gastric

emptying & pH changes will affect how fastor how slow meds are absorbed.Has rich blood supplySusceptible to first pass phenomenonLipid soluble substances and those that

are relatively nonionized are well absorbedhere.


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Oral Route: Small IntestinesMost important site for absorption of oraldrugs as it has extensive absorptivesurface due to many villi.Peristalsis and mixing encouragedissolution of drugs.Highly vascular and has a pH of 7.0 to 8.0


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Mucus Membranes of the LowerIntestine: Rectal Route Avoids most first pass effects in the liverHas extensive vascularity.Limited surface areaDrugs need to be in solution or absorptionis erratic and unpredictable.


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PULMONARY: LungsGases or aerosols can be delivered by thisroute.

Rapid absorption occurs due to largesurface area, rich blood supply and highpermeability of the alveolar membrane.Provides a local effect

( ex:bronchodilation ), but may alsoproduce unwanted systemic effects ( ex:sympathetic nervous system stimulation)


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TOPICAL ROUTE: Epidermis is low inlipid and water content, so it is a barrier toabsorption.Dermis allows rapid absorption therefore:Abraded skin could allow an overdose ofthe drug so only use intact skin.Effects are usually localLipid soluble drugs can penetrate lipid by-layers of the epidermal cells.


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Transdermal: A disk or patch containing adays or weeks medication-Absorbed at asteady rateEyes - produces a local effect. Instructpatient to put pressure on the side of the noseafter placing drops to decrease possibility ofsystemic effect.Ears - used for local treatment of infection or

waxNasal mucosa - instilled in droplet form or byswab for local or systemic effect.


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intravenoussubcutaneousintramuscularintradermal

REMEMBER

Parenteralmeds retain 100%bioavailabilityTHEREFORE smallerdoses are appropriate

intraarticular -synovial cavityintrathecal - spinalsubarachnoidspace

or epidural spaceintraperitoneal


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Subcutaneous and intramuscular injectionsare affected by tissue compositionIntramuscular route is more effective thanthe subcutaneous route because there is agreater blood supply in muscle tissue.Application of heat or massage canincrease vasodilation and improveabsorption


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Distribution : is the process by which thedrug becomes available to the body fluidsand body tissues.the transport of drugs from the blood to

the site of action .A drug must be distributed to its site ofaction to have an effectDrugs are also distributed to tissues whereit has no effect. Competition for drugbinding sites affects the amount of drugavailable for action in the body


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Volume of Distribution (Vd) - The degreeof distribution of a drug into various bodycompartments and tissue

Cardiac output and capillarypermeability affect the regional blood flow,

perfusion of tissues and therefore thevolume of distribution


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Plasma Protein Binding - drugs bind toproteins in the blood (albumin, globulins) invarying degrees, from highly bound to poorlybound

Protein binding decreases the concentration offree drug in circulation therefore there is alimited amount of drug available to travel tothe site of action. Only free drug is able todiffuse into tissues.

Only free drug is able to diffuse into tissues,interact with receptors, and produce biologicaleffects. Bound drugs are pharmacologicallyinactive.


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When free drug is eliminated by the body somebound drug is released from protein binding.Some drugs persist in the body for three days bythis mechanism.(2) drugs given concurrently & highly bound tothe same site on a plasma protein will competefor the binding site resulting in a greaterproportion of free drug .This effect may increase the free drug to toxic levels .


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Tissue Binding/Affinity: force by whichatoms are held together in chemicalcompounds Lipid soluble drugs have a high affinity for

fat tissue and this is where these drugs arestored. Drugs can be held in reservoirs

such as adipose tissue or bone.


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Blood Brain Barrier - The structure of braincapillaries are less permeable than other body capillaries. Most drugs cant pass this bloodbrain barrier. This protects the brain from theharmful effects of many drugs. Drugs thatDO cross are highly lipid soluble. ( Ex:phenytoin, antidepressants, caffeine, nicotine)Placenta : the placental membrane is lipid innature and readily allows non-ionized, lipidsoluble drugs to cross the membrane. Theuse of many drugs has resulted in teratogeniceffects on the developing fetus


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The elderly have less effective blood-brainbarriers.Symptoms of dizziness andlightheadedness are more common asside effects to many drugs taken by theelderly.


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Biotransformation: process by which thebody changes the chemical structure of adrug to another form called a metabolite.Metabolite: a more water solublecompound that can be easily excreted. Themajor organ for this process is the liver


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First Pass Phenomenon - Drugs are firstabsorbed through the small intestine thanarrive at the liver via the portal circulation There they undergo considerablebiotransformation before entering thesystemic circulation. There will be less active drug available for

action in the body cells after thisfirst Pass through the Liver !


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Excretion: process where drugs are removedfrom the body. Kidneys are the major organsof excretion.

Lungs excrete gaseous drugs.Biliary excretion (bile & feces) is important for

a few drugs. These drugs may be reabsorbedwhen passing through the intestines from theliver

( enterohepatic re-circulation ).Intestines, sweat, saliva and breast milk constitute minor routes of drug excretion.


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Clearance of drugs - elimination of drugsfrom circulation by all routes. It affects thetime a drug remains in the body and thedosage required.Renal ClearanceHepatic clearance


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The amount of time a drug stays in the body ismeasured by the elimination half-life.This is the time required for the concentration ofdrug in the blood to decrease by 50%.Half-life affects the frequency of administrationDrugs with short half-lives are quickly eliminatedfrom the body. ( Ex: PCN given several X per day )Drugs with longer half-lives stay in the body longer

(Ex: Digoxin given once a day )


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What a drug does to the body- refers to thestudy of the mechanism of drug action on livingtissue.

Is the study of drug concentration and its effect on

the body.Drugs may increase, decrease or replace

enzymes, hormones or body metabolic functions.

Chemotherapeutic drugs alter an abnormalparasite or growth on the body such as bacteria,viruses or neoplastic tissue. examples: antibiotics and antineoplastic drugs .


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The majority of drugs are believed to exert their effects bycombining with a specialized area on the cell or within the cellcalled receptors . Drug + Receptor Drug receptor(binding) = Response A drug receptor may be on the cell surface or within the cellReceptors come in many shapes that are specific for particulardrugs.The greater the degree of specificity and selectivity forreceptors, the fewer undesirable side effects and the greaterdrug efficacy.


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Agonists : Drug that has the ability toproduce a desired therapeutic effect whenbound to the receptor.Antagonists : Drugs that bind well to thereceptor but produce no receptorresponse. This can prevent other drugs

from having an effect, thus they are calledblockers.


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Competitive antagonist : agonist drug andantagonist drug are each competing for thesame site.The drug present in the greatest number

will get bound.Therefore a higher dose of agonist is

required to overcome this response


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The frequency and duration of drug dosing caninfluence the safety and efficacy of drug therapy.

Onset of drug action is the time it takes after the drugis administered to reach a concentration that producesa response.Duration of action is the time during which the drug ispresent in a concentration large enough to produce aresponse.Peak effect is the time it takes for the drug to reach itshighest effective action.


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Toxicity studies of drugs determine twodosage levels for drugs.The effective dose is the dose of a drugnecessary to produce the desired intensityof effect in one-half of all patients.The lethal dose is the dose of a drug that

elicits an undesirable toxic or lethalreaction in one-half of all patients.


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A drug with a wide therapeutic index hasa high safety margin and is relatively safe;the lethal dose is greatly in excess of the

therapeutic dose.A drug with a narrow therapeutic index ismore dangerous for the patient becausesmall increases over normal doses mayinduce toxic reactions . Peak and troughlevels may need to be monitored


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Therapeutic range : plasma drugconcentration between minimum and toxicconcentrations.

Loading doses : higher amount of druggiven once or twice to achieve maximumeffective dose quicklyMaintenance dose : intermittent dosesgiven to maintain plasma levels.


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General broad term that describes anyadverse outcome to medicationadministration.Can be due to: staff error (preventable) ORCan be an adverse drug reaction (non-preventable)


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Unintended, undesirable or unpredictabledrug effects. More than 50% of adversereactions occur from drug-drug, drug-food,or drug-laboratory test interactions.


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Adverse Effects : are unwanted and/orunintended action that may occur duringdrug therapy. Every drug has the potentialto produce adverse effects.Side Effects : Undesirable but mildunavoidable/predictable pharmacological

effects of a drug.


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Toxic Effects : More serious effect. Lifethreatening. Each drug has characteristictoxic effects. May be due to theaccumulation of the drug in the body r/tdecreased renal functionTeratogenic Effects : Drug induced birth

defects which follow drug therapy inpregnant women.


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Occur when 1 drug and a 2 nd drug orelement such as food may have an effecton each other.These interactions may or thetherapeutic effect of 1 or both drugs, createa new effect or incidence of adverse

effects


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Additive effects : 2 or more similar effect drugs arecombined. The result equals the sum of the individualagents Each drug is given in a lower dose for an equaleffect of either drug given separately. 1+1=2 .Ex: Percodan ( oxycodone + acetominophen) improvespain relief

Synergism : The harmonious action of two unlike drugs

producing an effect which is greater than the total effectsof each drug acting by itself. 1+1=3 .Ex: Advicor ( niacin + statin drugs) improves lipidlowering action.


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Potentiation : One drug improves the performance of the

other drug. This is a particular type of synergistic effect. + 1 = 2 Ex: amoxicillen + probenecid (anti-gout)prolongs serum levels of the antibiotic

Idiosyncratic Reactions : Unusual, unexpectedreactions to a drug, which may be genetically caused.Sometimes the person will react with the opposite effectto the desired one. (Also called paradoxical reaction)Ex: Genetic G6PD enzyme deficiency (prevents RBChemolysis) idiosyncratic reactions to ASA, sulfonamides


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Drug Action Klas 1

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