2 December 1951Bukit TinggiPhD in Clinical PharmacologyFUSA-Flinders Medical Centre Australia, 1988ProfessorHead of DepartmentPharmacology & TherapeuticSchool of Medicine, USUJln. Tridharma 22Kampus USU, Medan SpFK, Clinical PharmacologistPB-IDI & FK UI, 1995MD, FK USU, 1978Email: aznanlelo@yahoo.com

Aznan Lelo

Dep. Farmakologi & Terapeutik, Fakultas KedokteranUniversitas Sumatera Utara2 Februari 2010, D-3 Ners, USU

Setiap kali ke rumah sakitdi INFUSSetiap kali ke dokter di resepi ANTIBIOTIKAdi SUNTIK

Apakah setiap penderita rawat inap harus diberi terapi cairan

nangisanti-infeksidemamcemasbatukdiareetc,etc,etcetcsusahtidursesakanti-infeksianti-infeksianti-infeksianti-infeksianti-infeksianti-infeksianti-infeksi

ANTIBIOTIKA bukan ANTIPIRETIKA ANTI-TUSIVA ANTI-DIARE ANTI-ANXIETYANTIBIOTIKA hanya diberikan bila terbukti atau disangka kuat ada proses INFEKSI (kuman, jamur, virus, protozoa)ANTIBIOTIKA TUNGGAL lebih baik daripada ANTIBIOTIKA KOMBINASIWaspada terhadap interaksi ANTIBIOTIKA dengan OBAT LAIN

HUBUNGAN PENDERITA dan DOKTER KELUARGApenderitaDokterkeluhankeluhangejalapenyakitgejalaOBATOBATOBAT

Sakit kepalaNyeri pinggangNyeri lututNyeri tumityang penting hilang NYERI-nyaurusan kardiovaskular, belakanganmudah sesak,darah tinggi

urutan tindakan yang mungkin dilakukanCukup dengan memberi informasi atau nasehatPengobatan tanpa obat-obatanPengobatan dengan obatMelakukan rujukan(kombinasi)Pengobatan - P

mengurangi penderitaan, mencegah atau mengobati penyakit memaksimalkan khasiat, menghindari efek samping dan menghemat biaya obat dan pengobatanTujuan pemberian obat

Treatment of hypertension

Anamnesis Pemeriksaan Diagnosis tentukan problema utama penderita yang merupakan sasaran pengobatan Pemilihan obat Pengobatan Evaluasi

PEDOMAN PENGOBATANPEDOMAN DIAGNOSISStandard operating procedure (SOP)

remember that 90% of the time the patient will get bettereven if you do nothing so first do no harm!

PRIMUM NO NOCERESo, every doctor should do understand with the pharmacology of medicines prescribed

definisiObat : zat kimia yang :mempengaruhi proses kehidupandigunakan untuk pencegahan, diagnosis & terapi

FARMAKOLOGIilmu yang mempelajari tentang obat :sejarah, sumber, sifat kimia & fisik, efek fisiologi & biokimia, mekanisme kerja, absorpsi, distribusi, biotransformasi, ekskresi & penggunaannya (proses penggunaan obat sampai dihasilkan efek obat)

FARMASI :ilmu yang mempelajari tentang obat :cara membuat, memformulasi, menyimpan, menyediakan obat (proses sampai dihasilkan obat)

Cabang ilmu farmakologiFarmakognosi : mempelajari sifat tumbuhan & bahan obat lainFarmakoterapi : penggunaan obat untuk pengobatan & pencegahan penyakitFarmakologi eksperimental: pada hewan cobaFamakologi klinik : pada manusiaToksikologi : keracunan zat kimia (obat/zat yang digunakan dalam rumah tangga mis: insektisida, pestisida, zat pengawet, dll)Farmakoekonomi : mempelajari hubungan obat & nilai ekonomis dari obat tsb.Farmakoepidemiologi dsb

Cabang ilmu farmakologiFarmakodinamik :mempelajari efek obat thd fisiologi & biokimia organ tubuh & mekanisme kerjanya (pengaruh obat terhadap tubuh)

Farmakokinetik :mempelajari absorpsi, distribusi, metabolisme & ekskresi obat dalam tubuh (pengaruh tubuh terhadap obat)

SUMBEROBAT

FORMULASIOBAT

PENGGOLONGANOBATDaftar OOpiat/BiusObat BebasDaftar WBebas TerbatasDaftar GDIRESEPKANObatMODERENObatTRADISIONAL

INDIKASIOBATKEBUGARANPENGOBATANPENCEGAHANDIAGNOSISKURATIFSIMTOMATIS

INDIKASI KONTRAOBAT

NyeridengkullaksansiaOAINSdstantasidaterapi ikutanterapiKeadaan awalKaskade peresepan di klinik pribadidiareNyeriulu hatiSimtom barukonstipasi

Hipertensiremato-logisOAINSgastro-entero-logismisoprostolseranganGOUTPSMBAdiare . . . . .hidrokloro-tiazidaIATROGENIK(iatro = dokter)

AgitasiDepresiARTRITISAINSAntipsikotikAntikolinergikAntidepresanAnti-parkinsonPencaharAnti-hipertensiKekakuanKonstipasiPeninggiantensiTerapiikutanSimtombaruTerapikeadaanawalKASKADE PERESEPAN OBAT

EFEK SAMPINGOBATIATROGENIK(iatro = dokter)

INTERAKSIOBAT

Si nenek mengalami syncope akibat hyperkalemia, bradycardiaAINS loxoprofen diresepkan olehortopedik untuk mengobati keluhan lumbagoKurata etal., (1999)Apa yang terjadi?

Faktor risikoKeadaan penderitaUsiaLANSIA (80 tahun)Gender Perempuan Penyakit penyerta (CVS, kidney & liver)hipertensiObat penyertayang digunakanACE-Inhibitor imidapril

CARA PEMBERIANOBAT

lupabutapekakanorexialemahkonstipasisesakpenyakit jantunggangguanfungsi ginjalgangguanfungsi hatirematikkankerProblem farmakologi pada lansia

Sudah diminum atau belum?Ini dia,tapi aku lupa bagaimana cara menggunakannya

Dimana obatku ?3 x 1 1 x 3 Efek terapeutik Efek samping obatHindari pemakaian obat yang berbahaya . . . . . . . . . . . . . . . . pilihlah obat yang aman. . dengan regimen obat yang sederhana

Persentase masyarakat yang peduli membaca aturan pakai obatmenurut jenjang pendidikan (n = 663)

Harus menulis RESEP dengan JELAS dan RASIONAL, teristimewa kombinasinyaR/ FeldenR/ IntidrolR/ VoltarenR/ LasixR/ TanapressR/ DextrometorphanR/ AlludonaR/ SuprafluR/ PiroxicamINTERAKASI OBATcitalopram (Celexa). a selective serotonin (5-HT) reuptake inhibitorCELEXA for CELEBREX? A Case of Medication Sample Error

Bradley Moyer,MD; Walter Shrading,MD; Keith K. Burkhart, MD, FACMTThe Pennsylvania State University, Hershey, PA Int J Med Toxicol 2000; 3(2): 7SILABAT for SILAMOXDIAMICRON for DRAMAMINPREXUM for VALIUM

R/tulisbacakeluhan dan gejala penyakitperiksa dandiagnosisDrAptPasienAPOkeberhasilan pengobatanberi label padaKemasan obat

IATROGENIK(iatro = dokter)GAGALBERHASILEVALUASIpengOBATan

sekitar 90% penderita akan merasa lebih sehatmeskipun dokter tidakmelakukan sesuatu

oleh karena itu PRIMUM NO NOCEREpertama sekali jangan bikin celaka!first do no harm!

Pendekatan keperawatan dlm pemilihan & pemberian obatPengkajianDari penderita:Indikasi (petunjuk, alasan penggunaan), Kontra-indikasiDari obatBentuk sediaan, kadaluwarsaDiagnosisKelas terapiKompetitor (obat lain yang sama khasiatnya)PerencanaanMekanisme kerja obatEfek terapiEfek yang takdiinginkan (efek samping, efek toksik)PelaksanaanCara pemberian obat (formulasi, dosis)FarmakokinetikInteraksi PenilaianKapan dinyatakan ber-HASIL atau GAGALPeningkatan atau pengurangan dosis, penghentian obat dan penggantian obat

Drug Names and FormA drug is a chemical substance that alters the function of an organism and may or may not have a therapeutic effect.A medication is a drug that is being used for an intended therapeutic effect.A generic name is the name assigned to a drug when it is first manufactured.The trade name (brand name) is a copyrighted name given by a manufacturer to a medication it produces.Prescription and Non-prescription Medications

Drug FormsMedications are manufactured in a variety of forms to make it more useful or easily administered (ex. tablets, suspensions, suppositories, and ointments).The form of a drug guides it route of administration.One form should not be exchanged for another without a specific physician order because the rate of absorption or bioavailability may differ among forms or even among brand names.

Measuring the DoseTo correctly administer medications, you must be able to accurately calculate and measure the drug dose.Computation errors could be harmful, or even lethal, to the patient.To ensure accuracy in drug calculation and measurement, become comfortable working with the three systems of weight and volume measurement currently in use:metric, apothecary, household.

General PharmacologyPharmacokineticsWhat happens to a drug following administration:AbsorptionDistributionBiotransformationEliminationProtein bindingHalf-life

Routes of Administration

RouteIVSolutionTablet Suppositoryetc.Dosage RegimenDistributionEliminationMetabolitesEffectBeneficial or Adverse ?FactorsGenderAgeWeightDiseaseOther DrugsConc. Response

Concentration in Blood

How Much?How Often??

NASIBOBAT

Drug Transport Mechanisms

Routes of drug administration and absorptionSkinMucous membranesInhalationInjectionIntravenous injectionOral ingestion

Drug AbsorptionMechanisms:DiffusionActive TransportPinocytosis

Passive diffusion

Facilitated diffusion

Normal NaK-pump

Abnormal NaK-pump

Other Factors influencing drug distributionBlood-brain barrierPlacental membranes

Drug biotransformationThe process of drug metabolism involving the breakdown, detoxification and removal of chemicals from the body

Drug biotransformationLiver is primary site of drug metabolismOxidation: drug conversion to more water soluble compoundIsoenzymesMetabolite formation

Enzyme Inhibition and InactivationEnzyme Inhibitorcompound that slows or blocks enzyme catalysisWhy inhibit an enzyme?Enzyme substrate beneficial (essential), but depletedlow levels of GABA lead to seizurestherefore inhibit GABA aminotransferase to prevent degradation of GABAEnzyme product harmfulexcess uric acid leads to goutinhibition of xanthine oxidase prevents conversion of xanthine to uric acid

Drug SynergismCases where therapeutic effect of two or more drugs used in combination is greater than the sum of the effects of the drugs administered individually

Mechanisms of Synergisminhibition of drug-destroying enzymesequential blockinginhibition of enzymes in different metabolic pathwaysmultiple drugs for same target

Factors influencing drug biotransformationAgePregnancyDiseaseGenetics

Drug eliminationSites of elimination:Renal: Kidneys, primary siteCreatinine clearanceGI tract: biliary-fecalLungsExocrine glands

C maks

Half Life (T 1/2)The length of time required by the body to biotransform and decrease the concentration of a drug by half Implications for:Dosing intervalsPatient monitoring for drug effects

Half-lifeShort half-life vs. long half-life

Drugs that are cleared through the kidneys have a prolonged half life in patients with renal failureDecreased dosageLonger dosing intervalsDrugs cleared by dialysis are given after the cycle

Steady state

Steady StateDrug absorption equals drug elimination during the dosing interval: therapeutic level

PIROXICAM : long t1/2 (> 45 hr) enterohepatic cycleSystemic effect

Time (hour)The pattern of NSAID plasma concentration based on the dose and half-life of drug given

Sudah diminum atau belum?Ini dia,tapi aku lupa bagaimana cara menggunakannya

Dimana obatku ?3 x 1 1 x 3 Efek terapeutik Efek samping obatHindari pemakaian obat yang berbahaya . . . . . . . . . . . . . . . . pilihlah obat yang aman. . dengan regimen obat yang sederhana

General pharmacologypharmacodynamic: How a drug works in the bodyTherapeutic effectsAdverse effectsAznan Lelo

Therapeutic EffectThe therapeutic effect is the intended effect or action of the medication. The therapeutic action or effect of a drug is accomplished when a drug interacts with cell mechanisms, producing a change in cellular function.Every drug has at least one therapeutic effect, and some drugs have several.

Drug and Receptor

Amplification:Hormone/drug Receptor

Effectors

Second Messengers

Activation by second messengers

Competitive inhibition

Therapeutic Index:Dose at which a drug is effective but not toxic

Side EffectsSide effects are effects of a medication that are not intended or planned but may occur as a result of use.Although all side effects cannot be avoided, teaching methods to reduce common side effects may help the client tolerate his medication.

Side effectsDesirable vs. undesirableWill differ from patient to patientMust guide prescribing decisionsMildMay be tolerable, may not be noticedMay lessen with duration of treatmentSevereLife-threateningWhen giving drugs you must know the common and severe side effects

Side Effects: clinical implicationsThink about side effects before giving drugsNew symptoms: evaluate drug profiles Patient Education

Adverse Drug ReactionsUndesired responses to drugsIatrogenic effectsAdverse side effectsCarcinogenicityTeratogenicityDependence

Adverse EffectsAn adverse effect is a medication side effect that is potentially harmful to a client. can occur even when taking normal drug doses.Toxic effects are serious adverse effects of medications that may even threaten life.A client exhibiting toxic effects of a medication should not be given the next scheduled dose. Immediately report signs to the physician.Allergic responses in an antigen-antibody response to a medication. usually it requires previous exposure. could be triggered by the drug itself, a preservative, or a metabolite.

Adverse EffectsAnaphylaxis is a life-threatening allergic reaction.this is a medical emergency.that requires immediate intervention to prevent possible death.Idiosyncratic response is an unexplained and unpredictable response to a medication. It may be a sub-optimal response, an exaggerated response, or an abnormal type of response. for example, some medications that usually cause drowsiness may cause excitability in children

Iatrogenic effectsIllness caused by a medical treatmentExamples:Procainamide: drug-induced lupusAmiodarone: pulmonary fibrosis

Adverse side effectsMildMay be tolerable, may not be noticedMay lessen with duration of treatmentSevereLife-threateningWhen giving drugs you must know the common and severe side effects

Allergic ReactionsRash & itching (urticaria)Anaphylaxis: life threateningLaryngeal edema, dyspnea, wheezingShock, blood pressure drop, cardiovascular collapseTreatment: epinephrine, benadryl, steroidsNursing implications:Document drug name and type of responseAssess patients carefully with first doseEmergency equipment must be available

Toxic Drug ReactionsHarmful effects of a drug due to high levels of the drug in the bodyContributing Factors:High drug doseDosing too frequentlyPatient sensitivityReduced excretionNarrow margin of safety (therapeutic index)

Most significant drugs used in long term careCardiacPsychotropic drugsAnti-convulsantsDiureticsAnti-inflammatoryAnti-neoplasticOral hypoglycemicLaxativesAntacidsPhenothiazines

Seminar "Puyer, Kawan atau Lawan"Hotel Grand Antares, 30 Mei 2009Organized by "Medical 27"*****Routes of drug administration and absorptionSkin: most drugs applied to the skin have local effects such as a hydrocortisone cream applied to a rash., or though more systemic treatments are being developed such as the nicotine patch, estrogen patch and fentanyl patch.Mucous membranesSublingual, buccal, nasal, conjunctival, vaginal, and rectal mucosaRapid systemic absorptionVariety of methods of administration: spray, tablet, drop, suppository, applicator & creamOral ingestionLocal effects: laxatives, antacidsMost oral drugs have systemic effects Forms: tablets, capsules, suspensions, powdersInhalationInjection: drugs may be injected into almost any tissue of the body including bone. Injections nurses give are primarily intramuscular, subcutaneous and intradermal.Intravenous injection*Mechanisms of absorption:How molecules of drugs enter the tissues and bloodstream.fig 4-2 page 47: Illustration of mechanisms of absorptionDiffusion is a passive method of transport in which molecules move across a membrane from an area of high concentration to an area of low concentration

Active transport involves the movement of a molecule across a membrane regardless of the concentration gradient, and requires energy in the form of ATP.

Pinocytosis is the transport of a molecule across a membrane enclosed in a pouchlike fold of the membrane. The molecule is enveloped in this pouch, moves across the membrane and is freed on the other side*Drug biotransformationThe process of drug metabolism involving the breakdown, detoxification and removal of chemicals from the body*

The Liver is the primary site of drug metabolismAfter oral ingestion, the drug is absorbed from the intestine into the portal circulation, passing it through the liver for detoxification and metabolism before it enters the general circulation.Protects the body from the ingestion of harmful substancesReduces the amount of drug reaching the bloodstreamThis is why oral doses are frequently larger than intravenous dosesMetabolites are formed by enzyme interaction which alters the drugs chemical composition, forming compounds which differ from the original drug. Metabolites have unique properties which may have different effects than the original drug. Metabolites may be helpful, harmful, or neutral.I.e. procainamide forms a metabolite called NAPA which may be harmful above a certain level, blood drug levels measure both substances.Acetaminophen forms a metabolite that produces the liver toxicity associated with high doses.

Because the liver is very important in drug metabolism, people with liver failure can predictably have problems with drug metabolism, making drug administration in that population a challenge.

*Factors influencing drug biotransformationGenetic : Enzymes: increased, decreased or absenteach person metabolizes drugs in a unique way.Physiologic: Age: reduced metabolism, nutrition, diseaseEnvironmental*Drug excretion:

Sites of excretion:Kidneys: primary siteimplications for renal failureLungs: ethanol-alcohol smell on breathinhaled anesthesia- deep breathing-med clears fasterGI tract: liver and intestinesExocrine glands: sweat glands, mammary glands, salivary glands*Half Life (T 1/2)The length of time necessary for the concentration of a drug to decrease by half through metabolism or excretionImplications for:Dosing intervalsPatient monitoring for drug effects

*Short half-life Vs............ long half-lifeGreat variation of half-life from drug to drugAdenosine: T 1/2=