PHARMACOLOGY

DR.CH.PAVAN KUMARMBBS

• They are not magical spells.• Egyptian payrus - 1600bc

• Charaka - susrutha - vagabhatta• Evidence based medicine

• Definitions

Sources

• Plants• Animals• Minerals• Microbes-cephalo,pencil,tetra

• Human-hormones,ab

• Synthetic–Cellular-urokinase

–rDNA-tpa

–Hybridoma-mab

Drug compendia

• DRUG FORMULARY• PHARMACOPEIA

ROUTES• Parenteral

– Injection• im, iv, ip, ia, it, i.medullary.

– Inhalation• Best absorption

– Transdermal• BCG, SMALL POX• DERMOJET, PELLET, SIALISTIC IMPLANT..• TRANSMUCOSAL.

– transmucosal• TOPICAL

– OCUSERT,PROGESTASERT, OSMOTIC PUMP, COMPUTERISED PUMPS.

• Enteral– Advantages– disadvantages

• TRANSMUCOSAL– S.L, NASAL, RECTAL.– ENEMA

• RETENTION• EVACUATION

• TRANSDERMAL– OUTER LAYER– DRUG– POROUS MENMBRANE– ADHESIVE.

PHARMACOKINETICS

• Body does to drug• Travel of drug in the body

–ABSORPTION–DISTRIBUTION–METABOLISM–EXCRETION–INTERACTION

ABSORPTION

• Site of administration to site of action• Factors

– Disintegration or dissolution time– Formulation– Particle size-antihelminthics,steriods– Lipid solubilty– pH and ionosation– Area and vascularity– GI motility– Presence of food– Metabolism– Disease

ABSORPTION• Site of administration to site of action.• First pass metabolism• Bioavailabilty• Bioequivalence potency of two drug formulations

• TRANSPORT• Ionised – water soluble -charged• DIFFUSION• PASSIVE • ACTIVE

– For natural metabolites only

DISTRIBUTION• Plasma protien binding warfarin –

ethosuximde,lithium• Blood brain barrier

– Tight junctions,glial paint on capillaries.• Placental barrier• Tissue binding

– Adipose tissue-thiopentone– Muscle – emetine– Bone – tetracycline ,lead– Retina – chloroquine– Thyroid - iodine

METABOLISM• Biochemical alteration of the drug• Site liver,kidney,gut mucosa,lungs,blood,skin.• Result

– Inactivation or activation• Enzymes

– Phase 1 oxidation– Phase 2 more polar compound

• Enzyme induction ,inhibition

EXCRETION• Renal – Passive tubular reabsorption

• Diuretic + sod.bicarb + IV Fluids to alkalinise urine.

• SWEAT,SALIVA,MILK.• PULMONARY EXCRETION

– GA,ALCOHOL.• Fecal and biliary excretion

– Water soluble conjugates excreted in bile– Enterohepatic circulation– Action increased in chloramphenicol, tetracycline,

OCP, ERYHROMYCIN.

PHARMACODYNAMICS

• STIMULATION• DEPRESSION• IRRITATION• REPLACEMENT• ANTI INFECITVE• CYTOTOXIC• MODULATION OF IMMUNE STATUS

ACTION

• RECEPTORS– AGONIST,ANTAGONIST,PARTIAL AGONIST

• ENZYMES• ION CHANNELS• PHYSICAL ACTION• CHEMICAL INTERACTION• ALTERATION OF METABOLIC PROCESS

SYNERGISM ANTAGONISM

• ADDITIVE–NO + ETHER

• ANTAGONISM–CHEMICAL,PHYSIOLOGICAL,RECPTOR

• SYNERGISM–LEVODOPA + CARBIDOPA

ADDICTION

• PHYSICAL : TOLERANCE WITH WITHDRAWL SYMPTOMS• PSYCHOLOGICAL : COMPULSIVE DRUG SEEKING

BEHAVIOUR

DRUG DEPENDANCE

• WONT STOP EVEN WITH HARM .

• Adverse drug reactions

• Drug development• Rationale• Chemotherpy

–Quinolones–Aminoglycosides–Cotrimoxazole–Sulfonamides

ADVERSE DRUG REACTIONS• SIDE EFFECTS• TOXIC EFFECTS• INTOLERANCE = QUANTITATIVE • IDIOSYNCRASY = QUALITATIVE• ALLERGIC REACTIONS = IMMUNOLOGICAL• IATROGENIC• TERATOGENICITY• ORGANIC TOXICITY• SYSTEM DISTURBANCES

THERAPEUTIC DRUG MONITORING• TO MONITOR AND INDIVIDUALISE THE DRUG

DOSAGE

– DIGOXIN,ANTIDEPRESANTS.

THERAPEUTIC WINDOW

• INDIVIDUALISED– RANGE OF PLASMA LEVELS OF A DRUG BETWEEN

EFFICACY AND TOXICITY .

DRUG DEVELOPMENTPHASE VOLUNTEERS REMARKS

PRECLINICAL 50 SAFETY, BIOACTIVITY

PHASE I 50 SAFETY, DOSAGE

PHASE II 200 EVALUATION OF EFECTIVENESS

PHASE III 2000 CONFIRMATION ,COMMON SE.

PHASE IV POST PRESCRIPTION,POST

FDA

RARE SE.

ESSENTIAL DRUGS CONCEPT

• MINIMUM DRUGSTHAT TO BE AVAILABLE IN PHC– CORE LIST– COMPLEMENTARY LIST – SQUARE BOX - SAME EFFICAY

RATIONALE OF DRUGS

• DOSE AND DURATION• COMBINATION• ESCALATING TH EDRUGS

CHEMOTHERAPY

• Classification• Spectrum

–Narrow • penicillins gm + ve• Aminoglycosides gm- ve

–Broad• Chloramphenicol,tetracyclines

FACTORS

• Site• Concentration• Host defense• sensitivity

RESISTANCE

• Acquired • Mutation• Transfer of genetic

material• Transduction• Transformation• conjugation

FLOUROQUINOLONES• Quinolones : naoxalinic acid, lidixic acid, cinoxin.• Bactericidal,gm – ve. not very good PPB.• Flouroquinolones :• Newer trova,gatiflox,moxiflo.• MOA: DNA gyrase inhibition no positive coiling.• SPECTRUM: gm –ve.newer anaerobes

strep.pnuemoniae• PK :

– without food, PEFLOX cross BB .– microsomal enzyme inhibiton.

• ADV REACTIONS : N,V ADB, Arthropathy, Tendon Rupture.

• CONTRAINDICATIONS : pregnancy ,pediatric, not with theophylline, antiarrhythmics,

• Uses : – UTI– TYPHOID– DIARHHEA– GONORRHEA– RTI ,NUETROENIA– ORTHOPEDICS , ANTHRAX.– CHANCROID, TB.

SULFONAMIDES

• Limited role now ,bacteriostatic. • Short

– Sulfisoxazole, sulfadiazine• Intermediate

– sulfamethoxazole• Long

– Sulfamethoxypyridazine, sulfadoxine• Poorly absorbed

– sulfasalazine• Topical

– Sulfacetamide, mefenide,silver sulfadiazine

• MOA : – stop PABA to DHFA – Competitive inhibition of folica acid synthetase– Not efective in pus,blood tissue breakdown

products (rich in PABA)• Resistance :

– Mutation,alteranative pathway, low permeability• SPECTRUM:

– GRAM POSITIVE AND SOME GM –VE• PK : well absorbed, PPB,liver by acetylation

• Adverse effects : – Renal : – HSN : SJ

SYNDROME .– ANEMIA– KERNICTERUS

USES :•UNCOMPLICATED UTI•WITH PRIMETHAMINE NOCARDIA , TOXOPLASMA, CHL RES MALARIA•SECOND CHOICE FOR TRACHOMA, LGV, STREP PHARYNGITIS•TOPICAL•ULCERATIVE COLITIS

CO - TRIMOXAZOLE• Trimethoprim with

sulfamethoxazole ,bactericidal.• MOA : sulfa goes for folic acid syntetaseTrimethoprim goes for dihydro folete reductase• Resistance : mutation, plasmid.• SPECTRUM: gm + ve, gm - ve

PABA

DIHYDROFOLATETETRAHYDROFOLT

E

folic acid syntetase

dihydro folete reductase

• ADV EFF : ANEMIA, UREMIA• T 80+ S 400 ;T160 + S 800

–UTI ,PROSTATIS–RTI–BAC G ENTERITIS–TYPHOID–PNEUMOCYSTIC JIROVECII–CHANCROID

AMINOGLYCOSIDES

• Amino sugars with glycosidic linkage• Streptomyces,micromonospora

(GENTAMICIN).• Amikacin ,netilmycin semisynthetic .

• Not oral preparations• Poor CSFpenetration, ionisable, extracellular,

bactericidal, gm –ve, otonephro toxic.• Aerobic gram –ve e

coli,proteus,ps,brucella,salmonella.

• MOA : binds to 30s part of ribosomes inhibits synthesis. Postantibiotic Efect.

• RESISTANCE : enzymes,dec binding,permeabilty.• PK : im route,no PPB,BBB.• ADV EFECTS :NEPHRO OTO TOXIC,NM blockade.• CONTRAINDICATIONS :no mixing,not with loop

diureics,not for pregnant.• USES :TB,SBE,PLAGUE,TULAREMIA,UTI,TOPICAL.• NEOMYCIN : ORAL DRUG for bowel preparation,

hepatic coma.

TODAY

• PENCILLINS AND CEPHALOSPORINS• MACROLIDES AND UTI• COMPARITIVE CLASSIFICATION

BETA LACTAMS

• 1928 Sir.Alexander Fleming dicovered• Penicillium notatum,Penicillin chryosogenes.• Classification

– Natural• Penicillin G

– Semisynthetic• Acid resistant penicillin V• Penicillinase resistant methi,cloxa,oxa,naf• Aminopenicillins amoxi,ampi cillin• Antipseudomonal carboxy ureido

• MOA: inhibition transpeptidases in the peptidoglycan synthesis

• Resistance : penicillinase that opens the b lactamase ring, modification .

• PK : HCl inactivates. Probenicid retains from kidney.BBB in inflammation.

• Route : oral benzyl peniciilin, i.m repository procaine,benzathine

• ADV : hypersensitivity ,local,• Jarisch Herxheimer Reaction (Syphilis).• Pnuemococci,streptococci,menigicocci,staphylococci,syphi

ls,diphthteria,anthrax.• Prophylactic : Rheumatic Fever, Gonnarea, Syphilis,

Bacterial Endocarditis

SEMISYNTHETIC PENICILLINS• Acid resistant penicillins : peniciilin V • Mild strep pharyngits,sinusitis, 550mg qid.• Penicillinase resistant penicillins : • Methicillin not for p.o• Cloxacillin for p.o• Nafcillin most potent• Cloxaciilin, Methicillin, Vancomycin,

Linezolid.

Extended Spectrum Penicillins• AMINOPENICILLINS • Ampicillin : • For gm –ve also,non penicillase resistant.• P.o qid.,renal clearance.adv : d,rash• Uses : RTI,UTI,MENIGITS,TYPHOID.SEPTICEMIA.• BACAPMICILLIN,longer acting.• Amoxicillin :• preferred.peptic ulcer with h.pylori. P.o tid.

Anti Pseudomonal Penicillins• Carboxy penicillins :

– Gm-ve,gm +ve,ps,proteus. 2-5gm qid im ,iv ,p.o .– Ticarcillin,with aminoglycosides.Severe UTI .– ADV : slat and water retention.

• Ureidopenicillins : more gm-ve.Less ADV.– Azlocillin,mezlocillin,piperacillin. i.v .– Piperacillin with b.lactamse inhibitor, 3-4gm

hid,qid iv severe ps.• Beta lactamase inhibitors :

– Amoxyclav,ampicillin sulbactum,piptaz

CEPHALOSPORINS• Mother compound :acremonium fungus CEPHALOSPORIN

A• MOA ,RESISTANCE : same• I generation : gm + ve ,cephalothin penicillase reistant, • II generation : gm –ve ,anaerobes. cefuroxime

resistant,BBB.• III generation : gm –ve, weakly for gm +ve.highly

resistant.ceftriaxone,BBB,ceftazidime against ps.• IV generation : cefime,cefipirome,no oral preparations.• V generation: Ceftobiprole, ceftaroline, ceftolozane• ADV:HSN,NEPHROTOXIC ,d, bleeding,leucopenia,

pain.DISULFIRAM LIKE REACTION.

CARBAPENEMS • Spectrum : gm +,gm -,anaerobes.• M O A : same• Imipenem : i.v with dihydropeptidase inhibitor

Cilastatin.• Uses. Penicillin res pnuemococci,with

aminolycoside in ps.• Meropenem : ,Ertapenem not for

ps. ,faropenem p.o .• Monobactams : Aztreonam gm-ve,ps. i.v .

MACROLIDES

• Erythromycin and other semisynthetics as roxithro,clarithro,azithromycin.

• Spectrum : aerobic gm+ve.• MOA : bacteriostatic and bactricidal.• Binds to 50s ribosomes (amino to 30 s).• Resistance : plasmid (enzymatic,inhibition to entry)• PK :enteric coated, not BBB,microsomal inhibitor. • ADV : Hepatitis,cholestatic Jaundice, Allergy,

cardiac ,SNHL.• Uses :atypical pn,legionnaires,croup, topical.• Roxithromycin, clarithromycin for H,pylori.• Azithral no drug interactions.• Ketolides : Modified macrolides for macrolide

res.pneumococci .ex.telithromycin for CAP.

U.T.I

• URINARY ANTISEPTICS : – NITROFURANTOIN

• bactriostatic,bactricidal.gm+ve, gm-ve, 50-100mg qid ,100mg od p.o.

– Methanime mandelate• Release formaldehyde in acidic urine,bactericidal.• Resistant chronic UTI.

• URINARY ANALGESICS– PHENOPYRIDINE

• Relieves urgency, dysuria.• Others

– Sulfa, nalidixic acid, penicillins, tetracyclines, cotrimoxazole.

Miscellaneous

• SPECTINOMYCIN– Aminoglycoside,gm-ve.for pen allergic gonnarea.

• CLINDAMYCIN– 50s ribososmal inhibition as macrolide not as aminogly– Pn.jirovecii,tooplasma,VHD.

• GLYCOPEPTIDES– VANCOMYCIN I.V

• Streptococcus orientalis for MRSA.• OTO,NEPHROTOXIC.RASH. REDMAN SYNDROME.• Pen.res.pneumo ,ps.colitis,enterococcal

endocarditis.• TEICOPLANIN i.m safer ,MRSA, ENTEROCOCCI.

• POLYPEPTIDE ABX : – Polymixin (Bacillus polymyxa), colistin (Bacillus

colistinus).– MOA : leakage of cellular contents– Uses : topical, diarr due to gm –ve in pediatrics.

• Bacitracin : Bacillus subtilis ,gm +ve, inhibits cell wall synthesis, bactericidal ,topical (bacitracin + neomycin)

• Sodium fusidate : Fusidium coccineum ,gm +ve ,bactericidal,p.o,topical.

• Mupirocin : Ps.flourescens ,bactericidal gm+ve,-ve, MRSA. Topical, intranasal.

• Fosfomycin : gm +ve,-ve, inhibits cell wall synthesis ,p.o, i.v uncoplicated UTI.

• Cycloserine : Streptomyces orchidaceus +ve ,-ve ,m.tb

CLASS M O A PK SPECTR

ADV REMARKS

F Q BACTERICIDALDNA GYRASE INHIBITION

WITH FOOD,PEFLOX CROSS BBB, ENZYME INHIBITION

-VE, ANAEROBE

ARTHROPATHY

TROVA, GATI, MOXI

UTI, TYPHOID, DIARRHEA, ANTHRX, CHANCROID, TB , Post antibiotic efect

SULFA BACTRIOSTATICFOLATE MET.

BBB,PPB +VE RENAL,SJ SYNDROME, KERNICTERUS

WITH PYRIMETHAMINE= NOCARDIA, TOXOPLASMA, CHL RES MALARIA

B LACTAMS

INHIBITS TRANSPEPTIDASE

BBB, +VE

+, -, - VE

HSN, JH REACTION, PENICILLINASES, DISULFIRAM REACTION

GONOCOCCI, SYPHILIS, MENINGOCOCCI

NH 2 GLYCO

BACTERICIDAL30 S AS TETRACYCLINES

NO BBB, PPPB +VE OTO,NEPHRO TB, SBE, UTI, PLAGUEPost antibiotic efect

MACROLIDES

BACTERICIDAL, 50SCHLORAMPHENICOL

NO BBB, ORAL ,ENZYME INHIBITION

+VE HEPATITIS, JAUNDICE, ALLERGYAnti inlam, immnomod

ATYPICAL PN, LEGIONNAIRES, CROUP, TOPICALTACROLIMUS

?• ENTERAL ROUTE CRIETERIA• FIRST PASS METABOLISM• BBB• COTRIMOXAZOLE• PREVIOUS QUESTION PAPERS

TODAY

• Broad Spectrum Antibiotics• Anti Tubercular Therapy• Anti Leprotic Therapy

Broad Spectrum Antibiotics TETRACYCLINES

• SOURCE : soil Actinomycetes• Natural : Chlor,etra,oxytetra. • Semisynthetic : demeclocycline, methacycline,

doxycycline, minocycline.• SPECTRUM : gm-ve,+ve ,anaerobes, rickettsiae,

chlamydiae, mycoplasma, protozoa• MOA :30s ribososmes, bacteriostatic• PK : oral,calcium chelation.not with iron, milk,

antacids.excreted by kidneys.doy,mino by gut.• ADV : Hepatotoxic, Nephrotoxic,

Phototxic ,Osteoodonto ,Suprainfections ,HSN, • Minocycline causes vestibular toxicity .

• Uses : doc rickettsial ,chlamydia, aty pn ,cholera ,brucellosis ,plague .

• Also for diarrhoae, STD, acne, protozoal infections .

• Contraindications : not in pregnancy,<8yrs .• Tigecycline :

– Derivative of minocycline ,for mrsa,vmrsa, – I v 100 50 mg bd– Excreted by gut.

CHLORAMPHENICOL• Source : Streptomyces venezulae• M O A : Bacteriostatic, Bactericidal . 50 s

ribosome.• Spectrum : +Ve, -Ve, Anaerobe, Rickettsiae,

Chlamydiae, Shigella, Bordetella, Cocci .• PK : PO ,BBB ,Liver .• ADV : Bone Marrow Depression, Gray Baby

Syndrome, HSN, Superinfection .• Uses : Typhoid, Bac Menigitis, Anaerobic, Rick,

Topical E/D.

Anti Tubercular Therapy

• I line :H R Z E S• II line :Ethionamide ,Thiacetazone, PAS,

Amikacin, Rifabutin, Kanamycin, Ciprofloxacin.Etc

Isoniazid : • Intra and extracelluar organisms, • Moa : inhibits mycolic acid synthesis by active

form.• PK : PO, BBB, LIVER, slow and fast acetylators • Adv : Peripheral Nueritis, Hepatitis ,Hemolysis

in G6PD def.

RIFAMPICIN• Semisynthetic der of Streptomyces mediterranei.• Bactericidal ,only drug fro persisters dormants.• Sterilizing agent .• Binds to DNA dep RNA polymerase.• Pk : oral ,bbb ,enzyme inducer .• Adv : Hepatits, Git ,Flu Like ,HSN ,Staining Of

Secretions .• Uses : TB ATYPICAL TB ,LEPROSY ,H I,RES STAPH with

VANCOMYCIN,BRUCELLOSIS with DOXYCYCLINE ,NIESSERIAE.

• Rifabutin for TB in HIV,Other Rifapentine.

• Pyrazinamide : –against intracellular, active in acid

ph ,unknown moa, bbb, hyperuricemia. , • Streptomycin :

– i.m ,OTO NEPHRO toxicity.optic nueritis, • Ethambutol :

–static ,inhibit mycolic acid incorporation by inhibiting arabinosyl transferases.adv:

Second line drugs :• Thioacetazone : decreases resistance.• Ethionamide :static drug ,intra and

extracellular ,peripheral nueritis.• PAS : sulfa drug, poor tolerance .• Amikacin, kanamycin, capreomycin : • Cycloserine : CNS TOXICITY• FQ, Linezolid.

• Decreases Resistance, Reduce Toxicity ,Shorten Course• Two phases intensive ,continuation.

– CAT I. • 2 H3R3Z3E3 4H3R3

– CAT II• 2H3R3Z3E3S3 OR 1H3R3Z3E3 5H3R3E3

• Resistant TB : Positive Sputum after 6months • DOTS PLUS CAT IV MDR TB :• XDR TB :• Steroid in TB :TB serositis ,miliary TB,renal TB not ileal TB.• CHEMOPROPHYLAXIS : contacts, old TB ,HIV with contact.

INH +-R• MAC : Clarithromycin + ethambutol +-rifabutin

LEPROSY• Sulfones, Rifampicin, Clofazimne, Ethionamide,

Protionamide.• Dapsone : diamonodiphenylsulfone ,MOA :as

sulfa .leprostatic.oral.adv:G6PD hem anemia, hepatits, lepra reactions.

• Uses : leprosy, p.jirovecii, dermatitis herpetiformis.• Rifampicin• Clofazimine :dye,suppress lepra reactions.reddish black

discolration .• Ethionamide ,protinamide :peripheral

nueritis,hepatotoxicity.• F Q : lepricidal ,others as Minocycline, Clarithromycin.

• Paucibacillary 6 months– D 100 / R600

• Multibacillary 24 months – D100 C50 / R600 C 300

• ROM 600 + 400 +100• CHEMOPROPHYLAXIS D100 o.d +R600 o.m ;ACEDAPSONE

i.m 10 weekly.– LEPRA I

• TUBERCULOID LEPROSY .TYPE IV HSN • STEROIDS +CLOFAZIMINE

– LEPRA II • LEPROMATOUS LEPROSY.ENL.TYPE II ,ARTHUS TYPE,• CLOFAZIMINE,CHLORQUINE, STEROIDS,

THALIDOMIDE.ASPIRIN.

• SUPERINFECTION ,CROSS RESISTANCE

Today• Antiviral Agents

• Antifungal Agents• Anti malarial agents

Antiviral agents : Antiherpes agents• Acyclovir :

– acyclovir triphosphate ,inhibits viral DNA synthesis.

– HSV 1,2,VZV,EBV.– ADV : PO rash,TOPICAL irritation, IV

nephro,nuerotoxicity.• Valacyclovir : prodrug of acyclovir• famiciclovir prodrug of peniciclovir.• Idoxuridine,trifluridine topical for HSV keratitis.• Ganiciclovir , foscarnet : CMV, acyclovir res.HSV.

Anti influenza agents• Amantidine ,rimantidine (long acting)

–Inhibit the repication influenza viruses.–Uses : influenz A 200mg od po 5 days–Prophylaxis –Parkinsonism

• Amantidine enhances dopamine release .

Anti Retroviral Agents• NRTI Zidovudine, Stavudine, Zalcita, Lamuvudine.• NNRTI Nevirapine, Efavirenz .PPB.• NtRTI Tenofovir• PI Saquinavir ,enzyme inhibitors.• FI enfuvuritide, maraviroc• Maturation inhibitor beviramat• Integrase strand Transfer I Raltegravir(RAL)

• Myelosuppression ,peripheral nueropathy, hyperuricemia, pancreatitis.

• Resistance : Acquired ,Transmitted

• HAART–2 NRTI + 1 NNRTI–2NRTI + boosted PI

• PMTCT NVP, Zidovudine• POST EXPOSURE PROPHYLAXIS

–ZIDOVUDINE 600mg 4WEEKS–LAMIVUDINE 15 mg bd 4 weeks–+/- INDINAVIR /SAQUINAVIR 800mg tid /

Miscellaneous agents• Ribavirin :

–broad spectrum antiviral agent.–Flu A,B ,RSV ,measles. Aerosol spray

/po / iv .• Interferon :

–immunomodulating, antiproliferative effects

–Myelosuppression, alopecia, cardiac, nuerotxicity.

Anti Fungal Agents• Antifungal antibiotics

– AMB,NYSTATIN, HAMYCIN, GRISEOFULVIN

• Antimetabolites– FLUCYTOSINE 5FC

• Azoles– IMIDAZOLES : CLOTRI,MICANO,

KETOCONA– TRIAZOLES : FLUCON, ITRACON,

TERACON• Misc

– TERBINAFINE, PNUEMOCANDINS• Other topical

– TOLNAFTATE, BENZOIC ACID, SEL.SULFIDE, SALICYLIC ACID.

• AMB : –Streptomyces nodosus –Candida, Histoplasma, Cryptococcus,

Coccidoides, Aspergillus, Leishmania. –Static and cidal –MOA : porosity by binding ergosterol in

mebrane. No PO.–Adv : pain,thrombophlebitis,

nephro,nuero,myelo toxicity .

• Griseofulvin : – penicillium griseofulvum , – p.o.antimitotic by binding to microtubules. – for dermatophytoses,

• Nystatin : topical oral,vaginal candidiasis.• Hamycin : topical otomycosis, cut candidiasis.• Flucytosine : cryptococcus neoformans, candida.DNA

synthesis inhibition.with AMB useful.myelosuppression. • Azole :

– dermaophytes, candida, cryptococcus, histoplasma, deep mycoses.

– MOA : inhibition of formation of ergosterol

• Ketoconazole :– po, empty stomach, adrenal gonadal suppression.

P.o,shampoo, oint.– Uses :mucocutaneous candidiasis, dermatophytosis,

cushings syndrome.• Fluconazole : bbb, cryptococcal meningitis.• Itraconazole : po,i.v ,with food.• Econazole,terconazole,…topical• Terbinafine :

– dermatophytes, candida.– Po,fungicidal, inhibits formation of ergosterol, deposits

in keratin.– Doc for systemic mycoses, onychomycosis, candidiasis,

pityriasis.

• Topical for dermatophytes, pityriasis versicolor

• Pnuemocandins : –inhibits the formation of cell wall–capsofungin ,micafungin.–For candidiasis, aspergillosis.

Anti Malarial Agents• Protozoa plasmodium• Prophylactic primaquine, pyrimethamine• Blood Shizonticides CQ, Q, MQ, HF,

pyrimethamine, artemesinin• Tissue schizonticides PQ• Gametocidal PQ, CQ, Q

• CQ : – Inhibition of heme polymerase ,po, liver, gut.– Adv : cardiac, per nueropathy, retinopathy.– Malaria, Amoebiasis, Lepra reaction, rheumatoid

arthritis• Q :

– cinchona officinalis ,Analgesisc, cardiac depressant, L.A, skeletal muscle relaxant, abortificient.

– For CQ resistant malria. Next is halofantrine.– Adv : hypoglycemia, disulfiram like reaction, cinchonism.

• MQ : CNS ADV. • Pyrmethamine : DHFR ase inhibition , malaria,

toxoplasmosis.

• Artemesinin– Artemesisa annua,qinghaosu,– Develops free radicals from heme that binds

membrane protiens of the protozoa.– Cerebral malaria,i.m, i.v, rectal, p.o .– Use :acute attacks of CQ res malaria.

• PQ : hemolysis in G6PD .• CQ SEN MALARIA

– CQ 600 0+ 300 6+ 300 24+ 300 24• CQ RES MALARIA

– Q600 TID 3DAYS + DOXYCYCLINE 100 BD 7DAYS– ARTMESININ 100BD + 50 BD 5DAYS

TODAY

ANTIPROTOZOAL AGENTS

ANTIHELMINTHIC AGENTS

ECTOPARASITIDES

ANTI CANCER AGENTS

IMMUNOSUPPRESSANTS, IMMUNO

STIMULANTS

ANTI PROTOZOAL AGENTS

• ANTIAMOEBIC DRUGS : INTRA AND

EXTRAINTESTINAL : METRO,EMETINE .

• LUMINAL : DILOXANIDE ,TETRACYCLINES,

PAROMOMYCIN <amino glyco>.

• EXTRAINTESTINAL : CQ

• METRO :– Active drug binds to DNA for inhibitionn. – PO, BBB, – Adv: hepato, nuerotoxic, metallic taste,

disulfiram like drug reaction, cimetidine enhances conc.

– Amoebiasis, Trypanosomiasis, Giardiasis, Anaerobics, H.pylori, Ps colitis, Dracunlosis, topical preparation.

• Tinid : 2g P.O OD 3days.• Emetine : ipecac,s.c, i.m, cardiotoxicity.• Diloxanide furoate : with metro 500mg tid.

• Pnuemocystosis : cotrimoxazole ,pentamidine ,atovaquone.

• Trypanosomiasis.– Suramin sodium, ighly toxic pentamidine is

best alternative.Melarsoprol, Eflornithine.• Leishmaniasis :

– Sod.Stibogluconate : i.m, i.v, carditoxic.– Others Meglumine Antimonate, Ethyl

Stibamine, Pentamidine ,Miltefosine.– Amb,ketoconazole, Allopurinol,

Paromomycin.

• Antihelminthics : – Benzimidazoles :– Thiabend, Albend, Mebend.– Binds to βtubulin inhibits the uptake of glucose.– With fatty food, PPB, 100mg po bd 3 days.– Round, pin, hook, tape.– ALBEND : better tolerable, single dose,effective against

Trichomonas, Giardia, Wuchereria. Adv . Granulocytopenia. – Pyrantel pamoate : dep.NM Blockade.– 10-15/kg od.– Oxantel pamoate.– Piperazine citrate : flaccid paralysis ,safe in pregnancy.

– Levamisole : immunomodulator.– Niclosamide : Tapeworm ,– Prizaquantel :Schistosomes, increase calcium

permeabilty to cell causing paralysis.• Nuerocysticercosis, Tapeworms,, Schistosomiasis.

– DEC : OPSONISATION, IMMOBILISING THE ORGANISM.• FILARIASIS, TROPICAL EOSINOPHILIA.

– IVERMECTIN : Streptomyces avermitilis• paralysing the worm,. W.Bancrofti, B,malyi, Ascris,

Strogyloides.Oncocerciasis, Lymp Filariasis, Strogyloidosis, Cut.Larva Migrans,scabies, Pediculosis, Ascariasis.

• Benzyl benzoate : 25 % emulsion fro scabies.• Permethrin : 5% cream • Lindane ,Gamma Benzene Hexa Chloride : • BHC 1% ,aplastic anemia,cardiac toxicity.• Crotamiton : lice and scabies ,10% cream tid

two days.• Ivermectin : 200mcg/kg .sulfur : 10 % oint.• DDT : 2%• TETMOSOSL SOAP : Monosulpiram. 5% cream • Pediculosis : Permethrin topical, Ivermectin

systemic.

ANTICANCER AGENTS• ALKYLATING AGENTS • ANTIMETABOLITES• NATURAL PPRODUCTS• MISC• HORMONES AND ANTAGONISTS• Adv :bonemarrow,alopecia,gonads,

teratogenicity, carcinogenicity.

ALKYLATING AGENTS

• CYTOTOXIC, IMMUNOSUPPRESSANT, RADIOMIMETIC.

• Alkylation of DNA to break it.• Mechlorethanamine : i.v irritant.• CPS : p.o ,causes cystitis relieved with

MESNA and acetyl cysteine.• Chlorambucil ,busulfan CML.

ANTIMETABOLITES• FOLATE ANTAGONIST : METHOTREXATE

– DHFRase inhibitor. ,cytotoxic, immunosuppressant, antiinflammatory.

– Prophylactic folinic acid .– Choriocarcinoma, acute leukemiaa, breast ca, soft

tissue sarcoma,rhe arthritis, psoriasis.• Purine analogue : 6MP ,thioguanidine, fludarabine,

cladiribine .– Inhibition of DNA .– AC.LUEKEMIA, CHORIOCARCINOMA, SOLID TUMORS,

CHRONIC LEUKEMIA, NHL.– DOSE TO REDUCEDIN ALLOPURINOL.

NATURAL PRODUCTS • ANTIBIOTICS

– Actinomycin D, Daunorubicin, doxorubicin, epirubucin, mitomycin, bleomycin

• Epipodophyllotoxins : etoposide, teniposide,• Taxanes :paclitaxel;Captothecins ;Vinca alkaloids :• Misc :procarbazine, cisplati, l asparginase, imatinib,• Hormones: gc, estrogen, progestins, androgens,• Hormone antogonists : aromatase I ,• Radiophosporous, hematopoietic growth factors, Mab• PYRIMIDINE ANALOGUES :

– 5FU : CA STOMACH,COLON, RECTUM, BREAST,OVARIES.

– CYOSINE ARABINOSIDE : AML,ALL.– GEMCITABINE :

TodaySYS : GIT• ANTISEPTICS AND DISINFECTANTS

• DRUGS IN PEPTIC ULCER• EMETICS AND ANTIEMETICS• DRUGS IN CONSTIPATION• DRUGS FOR DIARRHEA

• ANTITUSSIVES

ANTISEPTICS AND DISINFECTANTS• Disinfection : Destruction of all pathogens on

nonliving things, except spores.• If spores also lost it is sterilisation.• Antiseptic : disinfectant on living tissues.• MOA :

– OXIDATION– DENATURATION– DETERGENT LIKE ACTION– SUBSTRATE COMPETITON

CLASSIFICATION • ACIDS : BORIC,BENZOIC ACID• ALCOHOLS : ETHANOL, ISOPROPYL ALCOHOL• ALDEHYDES : FORMALDEHYDE, GLUTALDEHYDE.

– ALKYLATION OF PROTIENS.• SURFACTANTS : SOAP, CETRIMDE, • PHENOL DERIVATIVES : CRESOL, PHENOL,

CHLORHEXIDNE, CHLORXYLENOL.– DENATURES BAC PROTIEN.

• HALOGENS : IODINE, CHLORINE.– TICTURE IODINE,MANDLS PAINT, IODINE OINT.

• OXIDISING AGENTS : H2O2, KMNO4,C2H5OH.• DYES :GENTIAN VVIOLET, METH BLUE, ACRIFLAVINE.• METALLIC SALTS : Hg, AgNO3, Zn.

• VAGUS +GASTRIN +HISTAMINE• ANTACIDS : Mg(OH)2, Al(OH)2, CaCO3, NaHCO3.• H2 RECEPTOR BLOCKERS : CIMETI, RANIT,

FAMOTID, ROXATI, NIZATID.• PPI : OMEP, LANSOP, ESOMEP, PANTOP, RABEP.• ANTI MUSCARINICS : PIRENZEPINE,

TELENZEPINE.• ULCER PROTECTIVES : SUCRALFATE, BISMUTH.• OTHER ;CARBENOXOLONE, CISAPRIDE,

PROSTAGLANDINS.

PEPTIC ULCER

• ANTACIDS : DECREASES ACTTIVITY OF PEPSIN.– SYSTEMIC : SOD.BICARB.

• SHORT ACTING, REBOUND HYPERACIDITY, ALKALINISATION OF URINE.

– NON SYSTEMIC : AlOH, MgOH, Mg TRISILICATE, CAL CARBONATE.• NOT ABSORBED, DELAYED

EMPTYING,HYPOPHOSPHATEMIA AL.• OSMOTIC PURGATION MG.• LIBERATES CO2,CONSTIPATION AND

HYPERCALCEMIA.HYPERACIDITY, PEPTIC ULCER, REFLUX ESOPHAGITIS.

• H2 BLOCKERS : – COMPET INHIBITION OF H2 RECEPTORS, 70% REDUCTION

IN ACIDITY. – PK : CIMETAC NO PPB, NO BBB, ANTIANDROGENICS.

• ANTICHOLINERGICS : PIRENZEPINE.– ADJUVANT, INHIBITS SECRETION OF GASTRIN.

• PPI :– SULFENIC ACID,SULFENAMIC ACID IRREVRSIBLE BINDING– MOST EFFICACIOUS, INHIBITION OF H+ K+ ATPase PUMP. – MICROSOMAL INHIBITORS RAISES TOXICITY OF

WARFARIN, PHENYTOIN. ENTERIC COATED, LOCATES AT PARIETAL CELL CANILICULI.

– ADV REACTIONS : BAC OVERGROWTH, RED B12 ABSORPTION, INCRE GASTRIN, ATROPHIC GASTRITIS.

• ULCER PROTECTIVES : – SUCRALFATE : NO ANTACIDS, DECR ABS OF

TETRACYCLINES, DIG, PHENYTOIN, CIMETAC.– BISMUTH : CHELATES PROTIEN ,FORMS

LAYER.• CONSTIPATION, BLACK STOOLS.

• PROKINETICS :– D2 BLOCKERS METOCLOP,DOMEPERIDONE

• CARBENOXOLONE ,PROSTAGLANDINS.

THERAPY H.PYLORI PEPTIC ULCER

• PPI 20-40 BD + CLARITHROMYCIN 500 BD+

AMOXYCLAV 1gm BD/ METRO 500 TID

• PPI + METRONIDAZOLE 500 + TETRACYCLINE

500 + BISMUTH COMPUOND 525 TID

• DRUG INDUCED PEPTIC ULCER

– PPI

CLASSIFICATION• Prokinetics : Metoclopramide, Domeperidone• 5HT3 antagonists : Ondem, Grani, Dola, Tropi• Antimuscarinics : Hyoscine, Cyclizine,

promethazine (pregnancy), Diphenhydramine.

• Nueroleptics : Chlorpromazine, Prochlorperazine, Haloperidol

• Others : Cisapride, Corticosteroids.

• D2 antogonists :– METOCLOPRAMIDE : increases tone of LES,

promotes gastric emptying, BBB.– DOMEPERIDONE : CANT CROSS BBB.

• 5 HT3 ANTAGONISTS : ONDEM : In stomach, CTZ centre, vomiting caused by anticancers, radiotherapy. PONV , DRUG induced vomiting.

• Antimuscarinincs : Hyoscine ; motion sickness.• Nueroleptics : Chlorpromazine ,

Prochlorperazine. D2 blockers, CTZ receptors.

DRUGS FOR CONSTIPATION• Bulk laxatives : Bran, Plantago, Agar,

Methylcellulose, Isphagula Husk.• Fecal softeners : Docusate Sod, Liq Paraffin

Lipid Pneumonia, Anal Discomfort.• Osmotic purgatives : MgSO4, MgOH2,

NAPO4, NASO4, Mg citrate, Lactulose, Sorbitol.

• Stimulant purgatives : Phenolpthalein, Bisacodyl, Castor Oil, Senna.

ANTIDIARRHEAL MEDICATION• Fluid and electrolyte replacement :

– ORS, NaCl 3.5gm, KCl 1.5gm, sodium citrate 2.9gm, GLUCOSE 20gm in 1 ltrs of water.

– Isotonic, Hypotonic, Hypertonic Solutions.• Treatment of cause :• Antibiotics, adsorbents :Kaolin, Magnesium and

Aluminum Silicate.• Antimotilty drugs : Codeine ,Diphenoxylate,

Loperamide.• Proboitics : Lactobacillus

acidophilus ,antispasmodics(propantheline, dicyclomine) .

Antitussives• Central cough suppressants – Codeine : Constipation,drowsiness, Noscapine– Synthetic : Dextrometharphan,pholcodeine,

Antihistamines, • Pharyngeal demulscents :Vicks , Lozenges, Cough

Drops,linctuses.• Expectorants : Neb. KI , Guaiphensin,

NH4Cl ,Ipecacuanha.• Bronchodilators : • Mucolytic :Bromhexine, Acetylcysteine,

Carbocysteine.• Steam inhalation : Rehydration.

TODAY

DRUGS FOR BRONCHIAL AASTHMAPOISIONING

Bronchial aasthma• Bronchodilators :

– SYMPATHOMIMETICS :–Salbutamol,terbutaline, Salmeterol.

• Selective beta 2 agonists, tremor, palpitations, nervousness.

– METHYL XANTHINES : –Theophylline, Aminophylline.

• Bronchodilators, low therapeutic window, delirium, arrhythmia,convulsions.

– ANTICHOLINERGICS : – Ipratropium Bromide

• Muscarinic receptors

• Antiinflammatory agents – Systemic :GLucocorticoids.– Inhalational :Beclomethasone, Budesonide,

Flunisolide, Fluticasone.• Mast cell stabilisers

– Disodium Cromoglycate, Nedocromil Ketotifen.• Miscellaneous.

– Omalizumab– Anti IgE mab .

STATUS ASTHMATICUS • Nebulisation of Salbutamol and Ipratropium

Bromide R10min• Inj.Salbutamol 0.4mg i.m /s.c R/O Tachycardia• Inj.Hydrocortisone i.v 100mg stat. R8H p.o

prednisolone.• Inj.AMinophylline 250mg slow i.v in 20mins.• Mechanical ventillation• Oxygen inhalation• Antibiotics• IVF

POISIONING• Stop the source • Limit the absorption

– Vomiting, stomach wash, cathartics, washing• Supportive therapy

– C A B– COMA COCKTAIL

• NALOXONE 2mg + THIAMINE 100mg +DEXTROSE 50%• Specific therapy

– ANTOIDOTE, ANTIVENOM, ANTITOXIN– ethanol in methanol posioning. – nitrite in cyanide poisioning.

• Other measures• Diuresis, dilysis, hemoperfusion fat soluble drugs

• Gut decontamination : – emesis by ipecac, mustard powder solution luke

warm water.– Not in corrosives, petrol, unconsious

• Stomach wash :– in few hrs to few days– In all cases unless contraindicated.– Not in corrosives, petrol, FB, convulsant.

• Medicoal.– For PCM, babiturates, salicylates, antidepressants,

anticonvuksants– Not for alcohol, corrosives,heavy metals.

• Purgatives :– MgSO4, Na2SO4, fluid intake– polyethylene glycol and electrolytes in iron poisioning.

• Circulatory failure :– Foot end elevtion– Plasma expanders– Vasopressors

• Respiratory failure : – Clearance of airway– Aspiration– Intubation– Oxygen support

• Fluid and electrolyte balance :–Hyponatremia –Hypernatremia diuresis–Hypokalemia KCl –Hyperkalmia K+ sparing diuresis, Ca

gluconate–Hypocalcemia Ca gluconate

• Metabolic complications Acidosis, Convulsions

• ANTIDOTES : physical – activated charcoal chemical – KMnO4 for barirurates p , alkalies.chelators.

• UNIVERSAL ANTIDOTE–1 TANNIC ACID–2 MILK OF MANESIA–2 BURNT TOAST

ORGANOPHOSPOROUS POISIONING

• Accidental, suicidal, occuptional.• Treatment :

– Stop contamination– Reduce contamination– Supportive menagement – Inj.Atropine i.v 2mg R10min till pupillary dilation– Choineesterase reactivators

• Inj . Pralidoxime ,diacetyl monoxime • Not useul in carbamate poisioning.• Inj.PAM 1-2gm slow i.v

C V S Today

DiureticsDrugs for congestive heart failureDrugs for arrhythmia

diuretics• High efficacy diuretics

– Furosemide, torsemide .• Sulfa derivative, lop diuretic• Blocks Na+ K+2Cl- in thick ascending limb, Ca i• PK: short acting, PPB• Adv : • ↓K+, Na+, Ca2+, Mg2+• met alkalosis, dehydraton, hyperuricemia,

ototxicity , hyperglycemia, hyperlipidemia, allergy.

• Uses : edema, ARF, Ac.pul.edema., cer.edema, HTN with RENAL REPLACEMENT.

• Moderate efficacy drugs– Thiazide

• Chlorthiazide, hydrochlorthiazide• DCT, Blocks Na+ Cl- ,Ca i• PK: p.o • Adv : hypokalemia, hypercalcemia,

hyperlipidemia, hyperglycemia, impotence in men, photosensitivity.

• Uses : HTN, CHF, EDEMA, RENAL STONES, DI– Thiazide Like Drugs

• Chlorthalidone, metalazone,clopamide.

• Low efficacy drugs– K + sparing :

triamterene,amiloride,aldosterone• Aldosterone antagonist-

spironolactone.enhance Na+excretion nd reduce K+ loss .

• Adv: gynecomastia, hyperkalemia, met acidosis, rash,

• Uses : edema, HTN, ALDOSTERONISM.

– CA inhibitor :Acetazolamide• H2O + CO2 H2CO3

• H2CO3 H+ + HCO3-

– IN GLAUCOMA, EPILEPSY, MOUNTAIN SICKNESS, HYPERPHOSPHATEMIA, ALKALINISATION OF URINE, MET ALKALOSIS. REDUCTION OF CSF

– ADV :MET ACIDOSIS, RENAL STONES, HYPKALEMIA

– Osmotic diuretics : Mannitol, glycerol– Methylxanthine : theophylline

• Newer agents : tolvaptan, lixivaptan, conivaptan

CONGESTIVE HEART FAILLURE

• DIURETIC :Frusemide, Bumetanide• Vasodilators

– Hydralazine, organic nitrates, ACE inhibitors, ARB, nitroprusside, prazosin, CCB.

• Positive ionotropics : – Cardiac glycosides : digoxin, digitoxin. With a.fib.– Β adrenergic agonist : dobutamine, dopamine,

dopexamine.in renal impairment– Phosphodiesterase inhibitor :amrinone,

milironone.– Newer agents : isatrxime, levosimenden.

• Others : B blockers

Antiarrhythmics• Class I :Na+ channel blockers

– A :prolong repolariisation • Quinidine, procainamid,disopyramide.

– B Shorten repolarisation • Lignocaine, mexilitene

– C Minimal effect on repolarisation• Flecainide, propafenone.

• Class II : beta blockers: propranlol, acebutol, esmolol.• Class III : K + channel blockers :

Amiodarone,bretyllium, stalol, dofetilide, ibutilide.• Class IV Ca2+ channel blockers : Verapamil,

diltiazem.

TODAY

ANTI ANGINAL DRUGSANTIHYPERTENSIVE

HYPOLIPIDAEMICS DRUGSHEMATINICS

ANTIANGINAL • NITRATES

– NITROGLYCERIN ,ISOSRBIDE DINTRATE, MONONITRATE,

– Converted to NO ,release cGMP.– Reduction of preload, coronary dilation, inhibition

of platelet aggregation.– P.o extensive first pass. – Adv :headache, pos hypotnsion, tolerance,

dependance, acute angina.Not with sildenafil.– Uses : exrtional angina, vasospastic angina,

unstable angina, cardiac failure, MI, cyanide poisioning,esophageal spasm, biliary colic.

• CCB : • Verapamil, Diltiazem, Amlodipine, Nifedipine,

Trimetazidine.• Misc : Ranolazine

– Trimetazidine congener, – Prolong QT, headache, constipation.

• Dilate arterioles, coronaries, releases afterlod, decrease myocardial contractility,.

• Reduced workload, reduced myocardial oxygen demand.prophylactic.

• Use : vasospastic angina, exrtional angina.

• Dipyradamole ,Aspirin–Prophylactic, coronary dilator antiplatelet.

• Beta Blockers : –Propranolol, Atenolol.–Prophylactic,decreases sympathetic

stimulation.• Potassium Channel Openers : • ATPsensitive K+

–Also Acts By Releasing NO.–Nicorandil, Pinacidil.

ANTIHYPERTENSIVE• Diuretics

–Thiazides : hydrochlorthiazide, chlorthiazide, chlorthalidone, ndapamide.

–Loop diuretics : frusemide, torsemide.

–K+ sparing diuretics :spironolctone, amrinone, milirinone.

• Drugs on RAS system– ACE I

• Captopril ramipril, enalipril• P.O , renal clerance• ADV : dry cogh, hypotension, hyperkalemia,

dysguesi, angionuerotic edema, rash, teraogenicity,.

• Uses :HTN, CCF, MI, CAD, CR, scleroderma.– ARBs

• Losartan, irbesrtan, olmesartyan, valsartan.– Renin antagonists :aliskiren

• Sympatholytics : – Centrally acting drugs : clonidine, methyl

dopa • Seletive alpha 2 agonist• Adv :dryness of mucosa, parotid swelling,

constipation, impotence, rebound hypertnsion.

• Uses : opiod withrawl, DM NEPHROPATHY, PREANAESTHETIC MEDICATION.

– Ganglion blockers :trimethapan SEVRE ADV.

• Adrenergic nueron blockers : – Guanethidine, Reserpine.

• Adrenergic receptor blockers : – α block :

• Prazosin, Erazosin,doxazocin, Phenoxybanzamine, Phentolamine.

– β block : • Propranoolo, Atenolol, Emolol, Metoprolol.

– α block β block :• Labetolol, Carvedilol.

• Calcium channel blockers : –Verpamil, Nifedipine, Nicardipine,

Nimodipine, Amlodipine, Felodipine.• Vasodilators :

–Arteriodilators : Hydralazine , Minoxidil

–Venodilators : Sod.Nitroprusside

HYPOLIPIDAEMICS DRUGS

• HMG COA reductase inhibitors :• Hydroxymethyl co A inhibitors • Rte controlling enzyme in synthesis of

cholesterol.

HEMATINICS• Compounds for formation of blood.• Iron :

– RDA : 0.5 -5 mg– Source :– Absorption : 10% absorbed .

• Site : duodenum• Increased with acid, vit c,met.• Decreased with antacids , phopshate, phytate,

tetracyclines.– Transport : transferrin ,ferrritin.– Excretion :0.5 -1 mg

• Oral iron– Ferrous sulphate,fumerate,gluconate– adv : metallic taste, diarrhea constipation.

• Parenteral iron – Deep i.m z technique, slow i.v

• Indications :–Intolerance, malbsorption, non

compliance, ever deficiency.– : iron dextran, iron obitol citric acid.

• Acute iron poisioning : –pain ,hematemesis, malena, shock,

acidosis, CVS collapse–Lavage with sod.bicarb.–Deferrioxamine i.v / i.m ,correction of

acidosis and shock.

B12• DNA synthesis, RBC maturation .• RDA : 1-5µgm• SOURCE :gut flora, liver, meat, pulses.• ABSORPTION :terminal ileum .• Deficiency : Pernicious Anemia, Gasrtectomy,

Chronic Gastritis, Malabsorption, Fish Tapeworm.

• Cyanocobalamin 100µgm/ml i.m /deep s.c• Hydroxycobalamin 100, 500, 1000µgm/ml• Deficiency, nueropathy.

• DNA synthesis, RBC maturation .• RDA : 50-400µgm• SOURCE :liver ,yeast, egg .• ABSORPTION :duodenum, jejunum.• Deficiency : dietary, malabsorption, folate

inhibitors(phenytoin, MTX, OCP)• Folic cid 2-5mg/day p.o /i.m• In pregnancy 500mg p.o od• Folinic acid:

Hematopoietic growth factors• ERYTHROPOIETN

– Binds to progenitors in marrow.– Adv :HTN, thrombosis, allergy.– Uses :marrow failure, renal failure,malignancy,

HIV.• MYELOID GROWTH FACTORS

– GM –CSF, G-CSF, M-CSF– Adv :bone apin, fever, arthralgia.

• MEGAKARYOCYTE GROWTH FACTORS– Thrombopoietin ,Increases platelet productionin

cancer chemotherapy.

Oral anticoagulants p 119

• Warfarin :– Interferes synthesis of K dependant factors Ii,

VII, IX, X – Blocks ɣ dependant carboylation of glutamate– PK :PO, 99% PPB, slow onset of action, affect

loses 5 days after stopping the drug.– PT is for monitoring.– Adv : hemorrhage ,teratogenicity.

• Uses :venous thrombosis, pulm embolism, post op, post stroke ,bed ridden ,ARF, Unstable angina, heart valves.

• Contraindications :–Bleeding disorders, sever HTN,

mlignancy, bac endocarditis, liver and kidney disease, recent surgery, CVA.

Thrombolytics (fibrinolytics)• STK :

– βhemolytic streptococci– Ab s can inactivate adv : allergy, hypotension.– anistrptlase i.v bolus (long acting STK)

• UK:culture of human kidney cells.• tPA :activatesplasminogen

– Alteplase, duteplase ,reteplase rDNA tPA.– Tenectaplase binds to fibrin.

• Adv :bleeding, allergy,.• Uses : AMI, DVT, PUL EMBOLISM.• CONTRAINDICATIONS :

Plasma expanders• High molecular weight substances oncotic pressure.• Colloids :

– Dextran ,interferes with coagulation, blod grouping, cross amtching.

– Long shelf life short acting causes allergy.– Gelatin :allergy ,not interferes with hemotolgy– HES , Human albumin .– Polyvinyl pyrrolidone : histamine release, interferes

with coagulation• Uses : Severe hypovolemic shock, hypoprotienemia,

burns.

SHOCK • C / O acute sympathetic overactivity• Pallor, sweating, cold clammy skin, tchycrdia.• Hypovolemic Shock : H2O,electrolyte balance• Septic Shock : abx• Cardiogenic Shock : MI• Anaphylactic Shock : Type I HSN .adrenaline.• Nuerogenic Shock : SA, testicular trauma.

Management• Foot end elevation• Maintain BP and plasma volume.• Correcion of acid base balance.• Maintain adequate urine output.• Drotecogin alpha

– Activated protien C– Inhibition of coagulation,– Improves fibrinolysis– Inhibition of TNF aplha

TODAYCENTRAL SYMPATHOLYTICS

GENERAL ANESTHETICSLOCAL ANESTHETICS

ANTIEPILEPTICSSKELETAL MUSCLE RELAXANTSANTI PARKINSONISM DRUGS

CENTRAL SYMPATHOLYTICS109• Clonidine :

– selective α2 agonist (vasomotor centre in IV ventricle)

– Blocks release of NA, – Adv : drowsiness, dryness of eyes, prarotid

swelling, constipation, impotence– Rebound hypertension.– Use : mild hypertension ,opioid withdrawl,

diabetic nueropathy, with anaesthetics.

• αmethyl dopa:–Prodrug that forms alpha methyl

norepinephrine, alpha 2 gonist.–Renin levels fall, LVH is revetrsed

In 12 weeks of treatment.–Safe in pregnancy

GENERAL ANESTHETICS

Classification p131Stage of analgesiaStage of deliriumStage of surgical anaesthesiaStage of medullary paralysis

• Nitrous oxide :– Inhalational gas, sweetish odor, smooth induction and

recovery ,.– Diadv : light anesthesia, teratogenicity.

• Halothane :– Colorless volatile liquid, non irrtant, non inflammable– Adv :potent, smooth and rapid induction and recovery.– Disadv :

• not a good analgesic, not a good muscle relaxant.• Myocardial depressant.• Respiratory depression, hepatitis, • malignant hyperthermia.

Preanaesthetic medication• Anxiolytics, amnesia: diazepam• Preop pain relief :OPIODS

(MORPHINE , PETHIDINE)• Safer anasthesia :PROMETHAZINE,

ONDEM, METOCLOPRAMIDE• Anti acidity measures : PPI

LOCAL ANAESTHESIA

• INJECTABLE ,SURFACE ANAESTHETICS • LIGNOCAINE :

– MOA :blockad of Na+ channels.– Smaller fibers are more susceptible– Addition of vasoconstrictor as adrenaline,

phenylephrine.• Slowed absorption• Reduced sysemic toxicity

– Adv :tremors,restlessness, convulsions.cardiac depressant, allergy,.

– Use : surface ,infiltration, field block, nerve block, S.A,

ANTIEPILEPTICS P 148

• Phenytoin :–Blocks Na+ channels, poorly watersolubel,

99%PPB, enzyme inducer.–Adv :nystagus, diplopia, ataxia.–Gingival hyperplasia, perpheral

nueropathy, HSN, megaloblastic anemia, teratogenicity.

SKELETAL MUSCLE RELAXANTS P 55

• Drugs acting on peripheral NMJ– Competitive blockers

• D.tubocurarine, vecuronium, atracurium.– Depolarising blockers: SuCh .– Others :botulionum toxin

• Drugs acting centrally: diazepam, baclofen.• Drugs acting directly on muscle : dantrolene

• Competitive blockers: – blocks Nm receptors, reversible.– Adv :hypotension, histamine release, only i.m,

inv– Treatment of toxicity :neostigmine.

• Depolarising blockers : – low amount of depolarisation .– Abscense of pseudocholinesterase, rYR

recptors.• Centrally acting

– P.o, blocks spinal cord impulse transmission.• Dantrolene Ca 2+ influx at SER.

ANTI PARKINSONISM DRUGS P 154

• Drugs that increase dopamine–DA precursor :

• Levodopa–Drugs that release dopamine

• Amantadine–Dopaminergic agonists

• Bromcriptine, cabergoline, lisuride, ropinirole, pramipexole

– Inhibit dopa metabolism• MAO inhibitors

–Selegeline, rasagiline• COMT inhibitors:

–Tolcapone, entacapone.• Drugs that influence cholinergic system :

– Central anticholinergics• Benztropin, benzhexol, biperidine

– Antihistamines • Diphenhydramine, orphenadrin,

promethazine

Levodopamine• Prodrug crosses BBB, taken up by nigrostriatal

tract.• Converted to DA.• Other actions :

– Irritates CTZ– It causes postural hypotension, tachycardia

arrhythmias suppresses prolactin.• PK : PO, with food, liver, small intestine.• ADV : abnormal involuntary movements, on-off

phenomenon.

ANALGESICS , ANTIPYRETICS HYPNOTICS AND SEDATIVES

CHOLINERGICS AND ANTICHOLINERGICSCNS STIMULANTS

ANTIPSCHYCOTICS ANTI MANIACS 188

ANTI DEPRESSANTS AND ANTI ANXIETY DRUGS 191

NSAIDS• NONSELECTIVE

– SALICYLATES :ASPIRIN– PARAAMINO PHENOLS PCM– PYRAZOLINE :PHENYL BUTAZOE– INDOLE ACETIC ACID : INDOMETHACIN, ETODOLAC– ARYL ACID DER : DICLO,ACECLO, KETOROLAC– PRPIONIC ACID DER : IBU, FENO,NAPROXEN,– ANTHRANILIC ACID DER : MEFENAMIC ACID– OXICAM : PIROXICAM, MELOXICAM– ALKANONES ; NABUMETONE

• SELECTIVE : NIMUSELIDE, CELECOXIB, ETORICOXIB, ETODOLAC

• TOXICITY OF PCM : N ACETYL CYSTEINE.• TOXICITY OF ASPPIRIN : ALAKALINE

DIURESIS

• USES :ANALGESIC, FEVER, INFLAMMATORY, ARF, RA,OA,POST MI, POST STROKE, IBD,.

RHEUMATOID ARTHRITIS• NSAIDS • DMARDS

– IMMUNOSUPPRESSANTS :MTX, CPS, CS, AZT.• BIOLOGICAL AGENTS

– TNF ALPHA BLOCKERS: ETANERCEPT, INFLIXMAB.– INHIBITORS OF T CELL ACTIVATION : ABATACEPT– IL 1 ANATAGONIST : ANAKINRA– ANTI B LYMPHOCYTE ANTIBODY : RITUXIMAB– GOLD SALTS ;AURONIFIN, AUROTHIOMALTE– OTHERS :PENICILLAMINE, SULPHASALAZIN,

CHLORQUINE, HYDROXYCHLOROUINE.• ADJUVANTS :CORTICOSTEROIDS

GOUT

• ACUTE GOUT : COLCHICNE, NSAIDS• IN CHRONIC GOUT :

–URIC ACID SYNTHESIS INHIBITOR : ALLOPURINOL, FEBUXOSTAT

–URICOSURICS :PROBENICID, SULPHINPYRAZONE.

DIAZEPAM• prodrug.• benzodiazepine receptor is an integral part of the

GABAA receptor • enhance gaba-mediated synaptic inhibition.• PK : p.o , 99%ppb,short acting, major metabolite

of diazepam, n-desmethyl-diazepam• adv :withdrawl symptoms• uses :

– antiepileptic, sedative

HYPNOTICS AND SEDATIVES• Barbiturates : amobarbital, pentobarbital, phenobarbital,

secobarbital, and sodium thiopental.• Quinazolinones : cloroqualone, diproqualone, etaqualone• Benzodiazepines : alprazolam (Xanax), lorazepam (Ativan),

diazepam (Valium), and clonazepam (Klonopin) zopiclone (Imovane, Zimovane), eszopiclone (Lunesta), zaleplon (Sonata), and zolpidem (Ambien, Stilnox, Stilnoct)

• Nonbenzodiazepines :• Others

– Antihistamines : diphenhydramine (Benadryl) and doxylamine,

– Antidepressants : Trazodone[2

– Antipsychotics : Chlorpromazine

ANS - Sympathetic nervous system (Adrenergic)

• Sympathetic Nervous System (adrenergic) Norepinephrine = neurotransmitter

- Drugs that mimic = adrenergic drugs, sympathomimetics, or adrenomemetics

* Adrenergic agonists - Drugs initiate a response

- Drugs that block = adrenergic blockers, sympatholytics or adrenolytics

* Adrenergic antagonists - prevent a response

ANS

• 4 types of adrenergic receptor organ cells:1. Alpha-1 = vasoconstriction of blood vessels inc. blood return to heart, inc. circulation, inc. BP2. Alpha-2 = inhibits release of norepinephrine dec. in vasoconstriction, dec. BP3. Beta-1 = inc. in heart rate & force on contraction4. Beta-2 = relaxation of smooth muscle in bronchi, uterus,

peripheral blood vesselsDopaminergic = dilate vessels, inc. in blood flow - only dopamine

activates this receptor

ANS - Parasympathetic Nervous System (Cholinergic)

• Parasympathetic or Cholinergic Nervous System Acetylcholine = neurotransmitter - Drugs that mimic = cholinergic drugs,

parasympathomimetics Cholinergic agonists - initiates a response - Drugs that block = anticholinergic, parasympatholytics Cholinergic antagonists - prevents a response

CHOLINERGICS AND

ANTICHOLINERGICS

• CHOLINERGICS :– ESTERS

• Acetyl choline, methacholine, carbachol, bethachol.

– Cholinemimetic • Pilocarpine, muscarine

– Anticholinesterases• Reversible :

–Neostigmine, physostigmine, pyridostigmine

• Irreversible :–organophosphorous

ACETYL CHOLINE• Muscarinic actions :

– Vagal stimulation– Vasodilation, decreases PVR.– Increase tone of non vascular smooth

muscle cells (peristaltic, voiding of urine, bronchospasm)

– Enhances secretion of all glands, Miotic• Nictoitnic actions :

– Persistent depolarisation, paralysis, stimulatory of ANS.

Anticholineesterases uses

• AS A MIOTIC• MYASTHENIA GRAVIS• POISIONING OF ANTICHOLINERGICS• CURARE POISIONING• POST ILEUS• ALZHEIMERS DISEASE

GLAUCOMA• Decrease formation of aqueous

• Beta blockers: Timolol, betxolol, levobunolol• Adrenergics : Apraclonidine ,dipivifrine.• Carbonic anhydrase

inhibitors :acetazolamide• Increase drainage of aqueous

• PG analogues–Latanoprost

• Cholinergic drugs–Carbochol, pilocaropine, physostigmine

ANTICHOLINERGICS P 52

• Actions :–CVS : tachycardia, reduces all

secretions, mydriatic, reduce motility.

• Uses :–As antispasmodics, as mydriatic,

as preanaesthetic medication.

ADRENERGICS • Adrenaline

– CVS : cardiac stimulant via β1– Vascular : biphasic response– Renal, mesentric, pulmonary vasoconstrictin.– Bronchodilator, relaxation of gut, spleenic

contraction, hepatic glycogenolysis, inhibition of insulin.

– Uses :• Anaphylactic shock, cardiac arrest, control

of hemorrhage

α blockers• Prazosin :

– Potent, highly selective– Decreases PVR, no significant tachycardia.– Decreases central sympathetic flow.– Inhibition of phosphodiesterase, causing vasodilation– Decrese LDL cholesterol.– Relaxes urinary bladder neck causing voiding of

urine.– ADV : first dose phenomenon :hypotension.– Headache, dizziness.– Uses :

• HTN, peripheral vascular disease, CCF, BPH.

β blockers• Propranolol :

–Non selective blocker–CVS : decrease HR,force, CO,

bronchoconstriction, decreased secretion of aqueous, blocks lipolysis, glycogenolysis,

–ADV : bradycardia, CCF, cold extremities, insomnia, depression, fatigue, rebound hypertension,

CNS STIMULANTS196

• Respiratory stimulants (analeptics)–Doxapram, nikethaide

• Psychomotor symptoms–Amphetamine, cocaine,

methylxanthine• Convulsants

–Leptazol, strychnine

CORTICOSTEROIDS• CYTOPLASMIC RECEPTORS ,DRUG RECEPTOR COMPLEX

ENTERS THE NUCLEUS AND REGULATE PROTIEN SYNTHESIS.

• HIGH FIRST PASS ,99%PPB,• SHORTACTING : HYDROCORTISON P 318• INTERMEDIATE ACTING : PREDNSIOLONE• LONGACTING :DEXAMATHASONE,

BETAMARETHASONE.• ADV :cushings, hyperglycaemia, infection,

osteoporosis, avscular necrosis, peptic ulcerarion, mental, cataract, glaucoma, delayed wound healing,HPA axis suppressioon.

uses• Acute adrenal insufficiency, rheumatod

arthritis, allergy,bronchial aasthma, collagen vascular diseases, eye,renal, skin,git,liver, hematology.

• Mineralocorticoids :• Promote water retntion by mineral corticoid

receptor at DCT,promotes loss of potassium loss.

• Fludrocortisone• Aldosterone deficiency disease.

Diabetes mellitus• Insulin• Banting,best• Actions :

– metabolism of glucose and uptake. inhibits glucose storage.

– inhibition of lipid breakdown , forms triglycerides.promotes protien synthesis.

• DM, BURNS, HYPOKALEMIA, ANOREXIA NERVOSA.

• Adv :– Hypoglycaemia, allergy, lipodystrophy, edema.

• Table 40.1 338

SULFONYUREAS

I INSULIN RELEASE, I TISSUE SENSITIVITY

HYPOGLYCEMIACHOLESTATIC JAUNDICE

BIGUANIDES DEC HEPATIC GLUCONEOGWENESISINC SENSITIVITY

DIARHHEA, METALLIC TASTE,LACTIC ACIDOSIS

MEGLITINIDE INSULIN RELEASE HYPOGLYCAEMIA

THIAZOLIDONEDIONES

INC GLUCOSE TRANSPORT DEC HEPATIC GLUCONEOGENESIS

WEIGHT GAIN, EDEMA,

ALPHA GLUCOSIDASE INHIBITORS

DEC CARBOHYDRATE ABSORPTION

FLATULENCE, DIARHOEA, ABDOMINAL DISTENTION.

• AMYLIN ANALOGS :–INHIBITS GLUCAGON SECRETION,

DELAYS GASTRIC EMPTYING, SUPPRESS APETITE.

• GLUCAGON LIKE PEPTIDE ANALOGS :–EXENATIDE, LIRAGLUTIDE.

• DIPEPTIDYL PEPTIDASE INHIBITORS: –SITAGLIPTIN,INHIBITOR OF INCRETIN

INHIBITOR. PRAMLINITIDE,

• Calcium : – Tissue excitability.– Secretion of glands – Cardiac muscular contraction.– Essential for coagulation– Increased by paratharmone, decreaed by

calcitonin– Normal level 9-11mgdl

• Adv :constipation– Uses : calcium def, osteoporosis, rickets,

anatacid, placebo.

• Phosphorous :• RDA : 1000mg

–Formation of bones and teeth–phosphorylation reasctions–component of nuceli, cytoplasm, –phosphate buffering system–enzymatic reactions

• Vitamin D :• Fat soluble vitamin , • Actions :• RDA : 10mg• Uses :

–Prophylaxis ,nutrional rickets, osteoprosis, hypoparathyroidism.

• Calcitonin parafollicular cells of thyroid.• bisphosphonates

VACCINATION

• Active immunisation– Toxoids – component – Live attenuated– Inactivated– Polyaccharides– live

• Initial dose• booster

Passive immunisation• Anti sera• Immunoglobulins• Primary immunisation and

secondary immunisation

Lead posioning

• HEAVY METAL, SINDOR, SURMA.• Fatal dose :10-70gm• c/o metallic taste, abdominal pain, irratability,

lead pasy, lead lines, lead encephalopathy, pallor, basophilic stippling of wbc.

• plumbism• Also with thiamine, stomacvh wash

Arsenic poisioning

• m/c poisioning ,HOMICIDAL• Fatal dose : 200-300mg arsenic trioide,gas• Moa :binds to sulphhydryl groups of enzymes• Deposits in bone,hair.• C/o pigmentation, mees lines,

hyperkeratosis, • Chelstion by BAL,DMSA, PENICILLAMINE,

ESTROGEN

• Replacement therapy• Post menopusal symptoms• Senile vaginits• Osteoporosis• Oral contraceptives• Dysmenorrhea• Dysfunctional uterine bleeding• Carcinoma prostate

SERM ‘S

TamoxifenOrmeloxifene

Clomiphene citrate

Combined contraceptives• Coc

– Monophasic– Biphasic– Triphasic

• Minipill pop• Postcoital pill

– Diethylstilbestrol 25mg/day od 5 days– COC ee 50mg + levonorgesterol 0.75mg stat

and 12 hrs after

HYPOTHALAMUS

GnRH

FSH LH

OVARY

Anterior pituitary

Progesterone inhibits mid cycle

LH release,inhibit ovulation

OESTROGEN PROGESTERONE

Estrogen inhibits FSH release, decreases follicle dev

Inhibit passage of ovumNot favourable for implantationThicken cervical mucus

Anabolics 333

• Synthetic androgens with higher anabolic activity and low androgenic activity–Catabolic states–Osteoprosis–Growth stimulationabuse in athletes

• Methandienone, stanazolol.

Uterine stimulants

• Oxytocin ,ergometrine, pg (dinoprost, carboprost, misoprost)

• Hormone of posterior pituatary• Uterus : contracts pregnant uterus• Mammry gland : milk ejection, • Pk :oxytocinase• Uses :induction, pph, milk ejection, abortion.

TOCOLYTICS332

• Adrenergic agonists : Salbutamol Terbutaline, Isoxsuprine .

• Misc : Ethyl Alcohol,CCB, Magnesium Sulfate.• Uses :delays premature labour• Inhibits uterine contraction in threatened

abortion.• dymenorrhea

• Papaver somniferum • opioid analgesic drug. It is the main psychoactive

chemical in opium. • addiction; tolerance and psychological depende• PK:PO,PPB, BBB.• Adv :• Contraindications :

– acute respiratory depression– renal failure– chemical toxicity– raised intracranial pressure, including head injury– Biliary colic.[13]

IMIPRAMINE

• tricyclic antidepressant (TCA) of the dibenzazepine group.

• Reuptake inhibiton of nuerotransmitters• Metabolism

–Within the body, imipramine is converted to desipramine, another TCA.

PETHIDINE

• synthetic opioid analgesic of the phenylpiperidine class

• analgesic effects by acting as an agonist at the μ-opioid receptor

• analgesic in labour and delivery , pain control in diverticulitis

• Adv : dizziness, diaphoresis, urinary retention,

HEPARIN

• Can not be found in circulating blood• Heparan sulphate, heparin like molecule is found

on endothelial cells .• Heparan sulphate has anticoagulant activity.• MOA : Antithrombin inhibitor,• Unfractionated , low mol heparin.• Pk : i.v ,s.c,• Uses : dvt,pe, cad, • Adv :hemorrhage, throbocytopenia, osteoprosis,

196

Class Representative

Thioamides

propylthiouracil

methylthiouracil

methimazole

carbimazole

Iodides KI, NaI

Radioactive iodine β-adrenoceptor blockers

131I propranolol

Antithyroid drugs

● Drugs

calcitonin

• Neural crest derivatives • thyroid medullary C cells that produce calcitonin, a

calcium-lowering hormone. • antagonist to PTH• inhibition of osteoclast-mediated bone resorption

and secondarily by stimulation of renal calcium clearance

• analgesic effects directly on cells in the hypothalamus and related structures

• Paget's disease, hypercalcemia of malignancy

PARATHARMONE

• maintain the extracellular fluid (ECF) calcium

concentration within a narrow normal range

• directly on bone and kidney and indirectly on

the intestine

• regulated by the concentration of serum

ionized calcium.

Prostanoids Therapeutic UsesUterine Stimulation

• Dinoprostone (PGE2): Prostin E2 vaginal suppositories used to induce abortion between 12th -20th gestational weeks

Prostin E2 oral tablets for elective induction of labbour/obliged induction because of HTN, toxemia, intrauterine death

• Treatment of duration ≤ 18 hrsProstin E2 vaginal gel used for induction of

labour at term or near term (I-2 mg intravaginal, repeated Q 6hrs according to response)

Prostanoids Therapeutic UsesUterine Stimulation

• Carboprost (15-methyl PGF2α)• Used by IM route for induction of abortion

between 12th -20th gestational weeks• Used at a dose of 250 μg every 1-3 hrs• Dinoprost (PGF2α)• Injection form for intra-amniotic

administration• Used to induce labour or abortion

Prostanoids Therapeutic UsesGIT

• Misoprostol is a synthetic methyl ester analogue of PGE1

Used to prevent drug-induced gastric ulceration during NSAIDs, corticosteroid or anticoagulant therapy

It can be used alone or in combination with antacids for duodenal ulcer treatment

Not used for pregnant women or whom are planning pregnancy

Prostanoids Therapeutic UsesPlatelet Aggregation

• Epoprostenol (PGI2):• It is used as a heparin replacement in some

hemodialysis patients• Used to prevent platelet aggregation in

extracorporal circulation systemsImpotence

Alprostadil (PGE1) was used by in jection into corpora cavernosa to maintain erection

Replaced by PDE-V inhibitors

Leukotriens Therapeutic Importance

LTs have no therapeutic uses, but LTs antagonists have

Anti-asthma medications: 5-Lipoxygenase Inhibitors, e.g., zileutinLeukotriene-receptor antagonists;

montelukast, & zafirlukast

204

Vitamins

• Vitamins are organic (carbon) compounds needed for normal function, growth and maintenance.

• Vitamins are cofactors, they don’t do anything by themselves.

• They are not a source of calories.

205

The Nature of Vitamins

• Organic cofactors – what is a cofactor?– Water analogy, scissor analogy

• Physiological role – specific metabolic function• Prevents disease – unlike “supplements” which

may promote “some thing” or have general metabolic effect

(ex. Omega 3s, fibers)

• Natural = Synthetic (except Vitamin E)

206

The Nature of Vitamins

• Nutritional Value lost by:– Light– Heat– Oxidation– Bacteria– Enzymes– Insects– (Nutritional value of baby

food must be assured.)

Effect of packaging on nutrient loss in milk.

207

Fat Soluble Vitamins• A – orange, carotenoids, vision, antioxidant- used as color and

antioxidant

• D – we make it with sunlight, deficiency causes rickets, in milk, regulates Ca:P ratios

• E – tocopherols, antioxidants, role in preventing stroke, cancer, heart disease- used as antioxidant

• K – contributes to blood clotting factor

208

Vitamin A

• Carrotinoids Used in food industry as a colorant (orange) (label friendly)

• Antioxidant (label friendly)• Stored in liver• Important for sight

– Deficiency causes ~500,000 cases of “night blindness” worldwide

• Genetically engineered rice with high Vitamin A can prevent night blindness

• Carrotenosis

209

Vitamin D• Also known as calciferol due to its role in calcium

absorption

• Main role is to maintain calcium and potassium levels

• It is the only fat soluble vitamin that we can make- in the presence of sunlight

• Can be made from cholesterol

210

Vitamin D

• Can be stored in fat tissues (as can all fat soluble vitamins)• Elderly and shut ins are at risk- not enough sunlight• We get vitamin D form fortified milk and cereal• Toxicity is very dangerous

– Occurs only from excess supplementation– Can lead to calcium deposits in kidneys, heart and blood

vessels

211

Vitamin D

Rickets can be caused by lack of sunlight, but also from insufficient calcium. Vitamin D linked to calcium absorption.

(Rickets reported in NYC.)

212

Vitamin E

• A family of eight naturally occurring compounds• Used as an anti-oxidant in foods• Since aging is considered an “oxidation” reaction, many

“anti-oxidants” are used as dietary supplements• Deficiencies are not well understood• Role is stroke, cancer, heart, and immune response• Americans spend $300 million per year on vitamin E

supplements

213

Vitamin K • Contributes to synthesis of seven blood clotting factors

• Can be reactivated to continue biological action

• Works as a cofactor for an enzyme that makes two bone proteins

214

Water Soluble Vitamins

• Relatively cheap to add to food

• Only Vitamin C is used for its functionality

215

Water Soluble Vitamins• B1, thiamine• B2, riboflavin• B6, pyridoxamine• B12

• Biotin • Panothenic acid • Niacin• Folacin• Vitamin C

Water Soluble Vitamins• Vitamin B1

– Thiamine– Involved in carbohydrate metabolism– Helps body metabolize glucose, affects central nervous

system– Deficiency causes Beri beri (Singlese, “I can’t, I can’t”)

• B2- riboflavin– Energy metabolism

217

Water Soluble Vitamins

• B6 - Pyridoxamine– Neurotransmitter, co-enzyme in over 100

reactions

• B12 – – Development of red blood cells– Lack of it makes one anemic– Hard for vegans to get

218

Water Soluble Vitamins

• Biotin – – Involved in fatty acid synthesis– Deficiency causes skin disease and hair loss

• Panthothenic acid– Found in many foods– Essential for metabolism of carbohydrates,

protein, alcohol and fat

219

Vitamin C

• Ascorbic acid• Very inexpensive to add to food, marketing

tool. Antioxidant• Deficiency leads to bleeding gums,

hemorrhages • High in citrus fruits, limes, (Limeys)

220

Niacin (B3)

• Energy metabolism• Disease – pellagra – The Four D’s

– Dermatitis– Diarrhea– Dementia– Death

ZINC :

• Good sources: shellfish, beef and other red meats• Absorption :In small intestine• EXCRETION :Primarily in fecal material

– Unabsorbed Zn– Secreted Zn (endogenous sources)

• From pancreatic and intestinal sources• age-related macular degeneration• Acrodermatitis enteropathic• Gastroenteritis3• ANTI DANDRUFF• SUNLOTION

Dermatology• Keratolytics : issolve intercellular cement

substance.peeling.• Salicylic acid, lactic acid, propylne glycol, urea,

podophyllum resin,benzyl peroxide.• Sunscreens :

– UVA : PHOTOAGING ,PHOTOXICITY, – UVB: BURNS AND TANNING– UVC :SKIN CANCER

• REFLECTS : CALAMINE, TITANIUM DIOXIDE.• ABSORPTION : SALICYLATES, BENZOPHENONES .

ANTIMICROBIALS :TOPICAL ANTIFUNGALSTOPICAL ANTIVIRALS :ACYCLOVIRTOPICAL GLUCOCORTICOIDSACNE:CLINDAMYCIN, ERYTHROMYCIN, +-METRORETINOIDS :EISOTRETIONOIN, RETINOIN.PSORIASIS :TOPICAL ETRETINATE, CALCIPOTRIOL, MMUNOSUPPRESSANTS, ANTIPROLIFERATIVE AGENTS,

PATHOLOGY

• OLD QUESTION PAPERS BOOK .

• HOLIDAYS MENTION.