ACE INHIBITORS Drugs : captopril, enalapril Mainly used in CHF and hypertension Basis of use;

Angiotensinogen(α2 globulin) ↓Renin from JG cells of kidney Angiotensin I ACE inhibitor - ↓ACE Decreased Angiotensin II

↓ ↓

Decreased preload and afterload Decreased blood pressure i.e

↓ relieves HTN

Increasd cardiac output

↓

Relieves CHF

Indications HTN CHF MI Angina pectoris Left ventricular hypertrophy

decreased angiotensin II

increased vasodilatation of vascular smooth muscle

decreased Na+ and water retention

Decreased output of sympathetic nervous system

increased bradykinin level

Diabetic nephropathy Adverse effects

HTN Hyperkalemia Dry cough Loss of taste sensation Rashes, fever,urticaria Angioedema Foetopathic Headache,dizziness,nausea Acute renal failure

Contraindications Pregnancy Hyperkalemic patients,patients on potassium sparing diuretics Bilateral renal artery stenosis

Difference among ACE inhibitors

captopril enalapril Linsopril perindopril ramiprilChemical name sulfhydryl carboxyl Carboxy

lcarboxyl carboxyl

Activity status active prodrug Active prodrug prodrugbioavailability 70% 50% 25% 20% 60%Time to pick action 1 hr 4-6hr 6-8hr 6hr 3-6 hrElimination t-half 2 hr 11 hr 12 hr 25-30 hr 8-48 hrMode of excretion renal renal renal renal renalDuration of action 6-12 hr 24 hr ≥24 hr ≥24 hr ≥24 hrDaily dose (mg) 25-150 2.5-40 5-40 2-8 1.25-10

ANGIOTENSIN ANTAGONISTS

Drugs: losartan Uses: HTN and CHF Basis of use:

Acts as competitive antagonists of angiotensin II ↓ Blocks all actions of angiotensin II

1. ↓decreased outflow from sympathetic nervous system2. Increased vasodilatation of vascular smooth muscle3. Decreased sodium and water retention4. Decreasd ADH release and promotion of growth of blood vessels and heart

↓ ↓

Decreases B.P. that lasts

Decreased preload and afterload for 24 hrs ,relieves HTN.

↓Increased cardiac output

Differences between ACE inhibitors and angiotensin II antagonists.

ACE Inhibitors Angiotensin II antagonists1.interfere with degradation of bradykinin→increases bradykinin level

1.no such interference

2.alternative pathway of A-II production and AT-I receptor activation remain intact with them

2.causes complete inhibition of AT-I receptor

3.causes inactivation of AT-1 and AT-2 receptor 3.causes indirect AT-2 receptor activation

4.has more potential to cause cough and dysguesia 4.has very less potential to cause

“ β BLOCKER”

CLASSIFICATION1)non selective (β1 and β2) a)without intrinsic sympathomimetic action: propranolol , timolol b)with intrinsic sympathomimetic activity: pindolol c)with additional α blocking property:labetalol2)cardioselective (β1) Metoprolol, atenolol3)selective β2 Butonamide

Basis of use of β blocker in1)HTN

long time use of β blocker

decreased activation of β1 receptor on heart

decreased renin release from JG cell of kidney

decreased noradrenalin release and decreased

sympathetic tone

2)Arrythmia Β blockers causes diminision of phase 4 depolarisation

↓

1)Decreased automatic firing of SA node

2)prolongation of AV conduction

3) decreased heart rate and contractility

↓

Helps in the treatment of :

a)tachyarrythmia due to sympathetic overactivity

b)atrial flutter

c)digoxin induced dysrhythmia

d)WPW syndrome

3)Angina pectoris

Bloackade of β1 receptor on heart

↓

Decreased heart rate, force of contraction and cardiac output

↓

Decreased cardiac work and oxygen demand

↓

Relieves stable angina by reducing its frequency and severity

NOTE: Propranolol is used in the chronic management of stable angina and not in an acute attackQ)Why β blockers are contraindicated in variant angina ?Ans) Variant angina is due to spasm of coronary artery. Use of β blockers leads to unopposed α receptor mediated constriction of coronary artery.This leads to the aggravation of variant angina.

Indications of β blocker: Angina pectoris Hypertension Cardiac arrhythmias Acute MI Migraine prophylaxis Anxiety neurosis

Chronic open angle glaucoma

Chronic open angle glaucoma Pheochromocytoma Thyrotoxicosis Tetralogy of fallot Essential tremor

Adverse effects of β blockers: CCF Bradycardia Aggravates AV conduction defects Bronchoconstriction Hypoglycaemia Nausea vomiting and constipation Uterine hypomotility and prolonged labour Fatigue depression and hallucination Cold extremities Nightmares Impotency

Contraindications of β blockers Bronchial asthma CCF Heart block Cardiogenic shock Bradycardia Patients on oral hypoglycaemic agents

NITRATES

Classification:

Short acting: Glyceryl trinitrate (nitroglycerin) Long acting : Isosorbide dinitrate,Isosorbide mononitrate

Main action:→relaxation of vascular smooth muscleBasis of use in Angina and CHF. Nitrates administered ↓ Increased nitrates ↓ Increased nitric oxide(NO). ↓ GTP → cGMP. ↓

Inactive protein kinase G→Active protein kinase G ↓ Dephosphorylation of myosin light chain kinase ↓ No activation of myosin ↓ No actin –myosin interaction ↓ Vascular smooth muscle relaxes ↓ a)great dilation of large veins b)small dilation of arterioles c)increased coronary artery dilation ↓ ↓ ↓ Peripheral pooling of blood decreased T.P.R Increased blood and Oxygen supply

↓ ↓ To heart

Decreased venous return decreased afterload

↓

Decreased preload

Indications:

Angina pectoris CHF and acute LVF MI Pulmonary HTN Biliary colic Esophageal spasm Cyanide poisoning

Adverse effects: Fullness of head, throbbing headache Flushing Weakness Sweating Palpitation Dizziness Fainting Methenoglobenemia Rashes

Contraindication: Glaucoma Hypertrophic cardiomyopathyss Hypotension

CALCIUM CHANNEL BLOCKERSDrugs:

Phenylalkylamine: Verapamil Benzothiazepine:Diltiazem Dihydropyridine: Nifedipine, Amlodipine

Differences between nifedipine and amlodipine:

AMLODIPINE NIFEDIPINE1 Slow oral absorption Fast oral absorption2 Complete absorption Incomplete absorption3 No early adverse effects like flushing ,palpitation seen Early adverse effects seen4 Low first pass metabolism High first pass metabolism5 High volume of distribution and t-⅟2 Low volume of distribution and t-⅟26 Long duration of action Short duration of action

Basis of use of CCB:

Blockade of L-type Ca2+ channel in heart and vascular smooth muscle

↓

Blockade of inward movement of Ca2+

↓

No triggering of release of Ca2+ from sarcoplasmic reticulum and mitochondria

↓

No/low availability of Ca2+ in cytosol

no/low availability of calcium in the cytosol

VERAPAMIL,DILTIAZEM(acts on heart↓

no seperation of troponin-tropomyosin complex↓

no actin myosin interaction↓

decreased HR ,force of contraction,and conduction velocity

decreased cardiac work and oxygen

requirements↓

releives angina

decreases total peripheral resistance

↓releives HTN

DHPS acts mainly on vascular smooth muscle↓

no phosphorylation of MLCK↓

NO EXITATION-CONTRACTION COUPLING↓

vascular smooth muscle relaxation, mainly a

decreased total peripheral resistance↓

releives HTN

Indications

Angina pectoris HTN Hypertrophic cardiomyopathy Arrhythmias Others: premature labour

Adverse effects: Tachycardia Ankle edema Flushing Hyperplasia of gums Hyperkalemia Headache Constipation Lethargy Bradycardia

Contraindications: Hypotension Cardiogenic shock Acute MI 2nd and 3rd degree heart block

Differences among CCBs

Properties Diltiazem Verapamil Nifedipine1 Channel blocking power + ++ +++2 Frequency dependence of

channel blockade+ ++ _

3 Channel recovery rate delayed Much delayed _4 Cardiac effects

Heart rate ↓,_ ↓ ↑AV conduction velocity ↓ ↓↓ _Contractility ↓,↑ _,↓ ↑Output _,↑ _,↓ ↑

5 Vascular smooth muscle relaxation

+ ++ +++

6 Uses Angina,HTN,(Arrythmia) Angina,arrhythmias,(HTN) Angina,HTN

CARDIAC GLYCOSIDES(DIGOXIN)Drugs: Digoxin, DigitoxinUse: Mainly used in CHFBasis of use in CHF: Binds reversibly with Na+K+ATPase enzyme of cardiac cell membrane ↓ Inhibition of Na+K+ATPase pump ↓

Increased intracellular concentration of Na+ ↓ Increased intracellular Na+ leads to increased Ca++ influx via Na+Ca++ exchange pump ↓ Increased contraction of heart ↓ Increased cardiac output of filling pressure that doesnot produce congestive symptoms ↓ Improved circulation decreases sympathetic tone and hence total peripheral resistance ↓ Decreased heart rate and oxygen demand ↓ Provides relief in CHF

Indications:

Congestive cardiac failure Left ventricular failure Atrial fibrillation &flutter Premature beat Supraventricular tachycardia

Contraindication: Hypokalemia Renal&hepatic disease M.I Thyrotoxicosis Myxoedema Ventricular tachycardia Partial A-Vblock Acute myocarditis Wolf-parkinsons white syndrome

Adverse effects:I)Cardiac effects

Premature beats Atrial and ventricular tachycardia Heart block Sinus bradycardia

II)GI effects Anorexia Nausea Vomiting

III)Neurological Vertigo Headache Visual hallucination

IV)Others: Skin rashes Eosinophilia Gynaecomastia

DIURETICSHigh ceiling diuretics/loop diuretics: FurosemideMedium efficacy diuretics: ThiazidesBasis of use of diuretics:

THIAZIDES FUROSEMIDEDrug of choice in uncomplicated HTN Drug of choice in complicated HTN with

chronic renal failure,CHFInhibition of Na+Cl- symport in early DCT ↓ ↓plasma and ECF volume ↓ ↓cardiac output ↓Compensatory mechanism almost restores C.O.,but slight Na+ and volume deficit persists ↓↓Na+ level in vascular smooth muscle ↓↓stiffness,↑compliance,and ↓response to constrictive effects of NA ↓ ↓TPR ↓ ↓BP

Inhibition of Na+K+2Cl- cotransport in thick ascending loop of henle ↓ ↓plasma and ECF volume ↓ Decreased C.O. ↓ Decreased BP

VASODILATORSDrugs:I)Arteriolar dilators(↓afterload)

Hydralazine,minoxidil CCBs:Nifedipine K+ channel opener:Nicorandil

II)Venodilators(↓preload)

Nitrates:Glyceryl trinitrate, glyceryl dinitrateIII)Mixed dilators(↓preload and afterload)

ACE inhibitors: enalapril AT-1 antagonist:losartan α-1 blocker:prazosin

Na nitroprusideBasis of use:

CENTRAL SYMPATHOLYTICS Drugs: clonidine and methyldopaUse: HTNBasis of use:

clonidine MethyldopaActs on α2a- receptor agonist in vasomotor centre in medulla ↓ ↓sympathetic activity ↓ Decrease BP

Acts on α2a-receptor agonist in vasomotor centre in medulla ↓ ↓sympathetic outflow ↓ Decreased TPR ↓ Decreased BP

Dopamine in therapy: cardiogenic shock

vasodilators

dilatation of venous blood vessels↓

↑peripheral pooling of blood↓

↓in preload

provide releif in CHF

decreased TPR and CO↓

Decreased BP

Dilation of arteriolar blood vessels↓

↓ed arteriolar resistance↓

↓in afterload

RESPIRATORY SYSTEMDRUGS FOR COUGHClassification:

Pharyngeal demulcents:logenges, cough drops Expectorants(mucokinetics)

a)Directly acting:citrate of Na+/K+,KIb)Reflexly acting:ammonium chloride/carbonate,KIc)Mucolytics:bromhexine

Antitussives (cough suppressants)a)opiods:codeine,morphineb)non opiods:Noscapine,dextromethorphanc)antihistaminics:promethzine,chlorpheniramine

Basis of use of mucolytics in therapy: Bromhexine ↓ a)by direct action b)by liberation of lysosomal enzymes ↓ Dissolves the mucopolysaccaride fibers ↓ Liquefaction of tenacious sputum occurs

↓Liquid sputum is easily removed out of tract

Short note :cough supressant/antitussives Mention classification from above

dopamine

stimulates β1 receptors on heart↓

↑ed heart rate and force of contraction↓

increased BP

stimulation of D1and D2 receptor↓

dilation of renal and visceral arterioles↓

↑ed blood flow to kidney and viscera

provides quick relief in shock

Mode of action: Cough suppressants

↓1) Acts on CNS to raise threshold of cough centre2) Acts on respiratory tract to reduce production of cough impulse

↓Controles cough of types1)dry ,unproductive2)tiring and sleep disturbing

DRUGS FOR BRONCHIAL ASTHMA

I)Bronchodilators a)sympathomimetics:salbutamol,terbutalin b)methylxanthines:aminophylline,theophylline c)anticholinergics:ipratropium bromideII)leukotriene antagonists:monteleukast,zafirleukastIII)Mast cell stabilisers:sodium cromoglycateIV)Corticosteroids: a)systemic:hydrocortisone,prednisolone b)inhalational:beclomethasone dipropionateV)Anti IgE-Antibody:omalizumab a)sympathomimeticsDrugs: salbutamol, terbutalin(selective β2 agonists)Basis for use in bronchial asthma:

Note:when inhaled produce bronchodilation within 5 min. And action lasts for 2-4 hrs only.so it is used for terminating an attack of asthma instead of round the clock prophylaxisAdverse effects of salbutamol MARcH PANT

Muscle tremor Ankle edema Restlessness Hypokalemia Palpitation Arrhythmia Nervousness Tachycardia

b)methylxanthinesdrugs:aminophylline,theophyllineBasis of use: Adverse effects of aminophylline ,theophylline:(µg/ml)

acts as selective β2 agonist↓

↑cAMP level in

bronchial muscle cell↓

bronchodilation occurs

mast cell and other inflammatory cell↓

↓ed response of inflammatory mediators

improves the airway obstruction, releives asthma

c)anticholinergics

drug:ipratropium bromidebasis of use in asthma: blockage of cholinergic receptor in large airways ↓ Bronchodilation occurs ↓ Provides relieve in asthmaNote:more suitable for regular prophylactic use,not for acute symptomatic relief Preferred because it has no effect on mucociliary clearance and respiratory secretions II)Mast cell stabilisersDrug: sodium cromoglycate,ketotifen

ABOVE

35:DEATH

AT35:CONVULSIONS,ARRYTHMIAS SHOCK

AT30:DELIRIUM,INCRE

ASED

MUSCLE

TONE, EXTRASYSTOLE

AT25:FLUSHING,AGITATION ,TACHYPNOE

AAT20:PALPITATION,VOMITING,RESTLESSNESS,TREMOUR,DIURESI

SAT15:HEADACHE,INSO

MNIA,NERVOUSNESS,DYSPEPSIA

AT10:MINI

MAL SIDE

EFFECTAT5:NO SIDE

EFFECT

Basis of use:

Mainly used for prophylactic purpose.

III)corticosteroids Systemic:hydrocortisone,prednisolone Inhalational:beclomethasone dipropionateBasis of use:

NASAL DECONGESTANTS:These are α agonists which when applied as a dilute solution produce local vasoconstrictionDrugs:naphazoline,xylometazoline,oxymetazoline,phenylephrine,pseudoephedrineMOA: Acts as α agonist ↓ Produce vasoconstriction and shrinkage of nasal mucosa ↓ Provides relief from nasal obstructionAdverse effectsSAARC

Stinging sensation Atrophic rhinitis Anosmia CNS depression Rise in BP

Uses:common cold ,allergic rhinitis

provides relief in asthma

inhibit degranulation of mass cells caused by triggering stimulus

↓inhibit release of inflammatory

mediators like LTs,PAF,from mast and other inflammatory cells.

decreased inflammatory response of bronchial muscle.

↓↓ed bronchospasm caused by allergens ,cold,irritants

Contraindication:HTN,patients on MAO inhibitors

DRUGS FOR TUBERCULOSIS:

First line drugs Second line drug Newer drugsIsoniazid(H) Thiacetazone CiprofloxacinRifampin(R) PAS OfloxacinPyrazinamide(Z)

Ethionamide Clarithromycin

Ethambutol(E) Cycloserine azithromycinStreptomycin(S) Kanamycin

Amikacin

Basis for use of Isoniazid: Sensitive bacteria concentrates isoniazid and convert it into active metabolite by catalase peroxidise enzyme. ↓Active metabolites binds with INH-A gene and inhibit synthesis of fatty acid synthase enzyme ↓ Inhibition of mycolic acid synthesis responsible for cell wall formation ↓ Produce bacteriocidal effect both extracellularly and intracellularlyBasis for use of rifampicin: Inhibits DNA dependent RNA polymerase ↓ Stoppage of expression of bacterial gene ↓ Tuberculocidal effect is exertedAdverse effects of anti-tubercular drug

ISONIAZID RIFAMPIN PYRAZINAMIDE ETHAMBUTOL STREPTOMYCINPeripheral neuritis Liver damage Hepatitis Optic nerve damage OtotoxicityPsychosis Influenza like rxn Hyperuricemia,gout Anaphylactic rxn NephrotoxicityHepatitis Orange –red

urineArthralgia Nausea,vomiting Anaphylaxis

Rashes,fever Fever,skin rash photosensitivity Confusion,headache eosinophilia DOTS regimen for TBDOTS strategy:emphasize on the use of all first line anti-tubercular drugs in single daily dosingBasis of combination of anti-tubercular drugs:

To prevent the emergence of resistant organisms and relapse of TB Use of H and R reduces duration from more than 12 months to less than 9 months whereas

addition of Z reduces it to 6 months

GASTRO INTESTINAL SYSTEM

DRUGS USED FOR PEPTIC ULCER

I)H2 antihistaminics:cimetidine, ranitidine

II)proton pump inhibitor:omeprazole ,pantoprazole, lansoprazole

Basis for use in peptic ulcer:

At acidic pH of canaliculi of parietal cell it get converted into active cationic forms

↓

Binds to cysteine residue of H+K+ATPase by stable covalent bond

↓

Inhibits H+K+ATPase pump irreversibly

↓

Inhibition of secretion of H+ ion into lumen

↓

No gastric acid secretion

Note: both basal and stimulated gastric acid secretion are inhibited

Also inhibit gastric mucosal case enzyme.

III)Basis for use of sucralfate in peptic ulcer

Acquire -ve charge at acidic pH due to seperstion of Al

↓

Binds to protein molecule tranducing from damage to ulcer base

↓

A viscous paste is formed that adheres to the ulcer base

↓

Protects ulcer base from actions of HCl ,pepsin and bile salts

Note: acts by inactivating bile acids and pepsin

Activate mucosal PG synthesis

IV) basis for use of bismuth chelate in peptic ulcer

↑es PG synthesis leads to ↑ed mucous and bicarbonate secretion Forms glycoprotein –bi complex with mucous which coats ulcer and prevent action of HCl Removes H.pylori from mucosal surface and kills it .so it prevents cause and relapse of ulcer Heals 60% ulcer in 4 wks and 90% ulcer in 8 wks.

Drugs Uses Adverse effectsH2 antihistaminics

Duodenal ulcer,gastric ulcer, stress ulcer,gastritis,ZEsyndrome,GERD,Prophylaxis of aspiration pneumonia

Dry mouth, headache, dizziness,bowel upset,rashes;CNS effects like confusional state ,convulsion coma

PPI Peptic ulcer,bleeding peptic ulcer,stress ulcer,GERD,ZE syndrome

Abdominal pain, muscle and joint pain,atrophic gastritis

sucralfate Peptic ulcer constipationANTIEMETICS

5HT-3 ANTAGONISTS( ondansetron)

Basis of use:

Prokinetic drug (metoclopramide,domperidone,cisapride)

-----------

Bisacodyl in laxative.

Note: bisacodyl is an stimulant purgative

Dose:5-15 mg :one to two semiformed motionafter 6-8 hrs

Given as suppository it irritates rectal and anal mucosa

↓

Reflex increase in GI motility

net accumulation of water and

elecrolyte in lumen

inhibition of Na+K+ATPase at basolateral membrane of

villous cells↓

↓reabsorption of water and eletrolytes

stimulation of adenyl cyclase

↓↓secretion of water and

elecrolytes

↑motility↓

↓reabsorption

↓

Evacuation in 20-40 hrs

LACTULOSE IN THERAPY:

Semisynthetic dissaccaride of fructose and lactose Neither digested nor absorbed in small intestine ,so retains water Changes to more osmotically active substance in colon and absorbs water due to bacterial action Dose:10mg BD with plenty of water produces soft stool ↓ ammonia level in hepatic encephalopathy patients

ALBENDAZOLE IN THERAPY

DIFFERERENCES AMONG/BETWEEN:

I)ACE inhibitors and Ang-II antagonists

ACE INHIBITORS ANG-II ANTAGONIST Interfere with the degradation of bradykinin

which leads to ↑ed bradykinin level Has no any such interference

Alternative path of A-II production and AT-1 receptor activation remains intact

Causes complete inhibition of AT-1 receptor

Causes inactivation of AT-1 and AT-2 receptor

Causes indirect AT-2 receptor activation

Has more potential to cause cough and dysguesia

Has very less potential to cause cough and dysguesia

II) Amlodipine and Nifedipine

AMLODIPINE NIFEDIPINE Slow oral absorption Fast oral absorption Complete absorption Incomplete absorption No early adverse effects flushing ,palpitation Early adverse effects seen Low 1st pass metabolism High 1st pass metabolism High volume of distribution and t⅟2 value low long duration of action short duration of action

immobilization and death

of worms

Binds with β tubulin protein in susceptible

worms↓

no microtubule synthesis in worms

III) TETRACYCLINES

Tetracycline Domecycline Doxycycline Potency Low Intermediate High Plasma protein binding Low High High t⅟2 6-10hr 16-18hr 18-24hrAlteration of normal flora

Marked Moderate Least

Diarrhoea High Intermediate Low Phototoxicity Low Highest High

IV)Proton punp inhibitors

Omeprazole Lansoprazole Pantoprazole Esmoprazole Inhibition of H+K+ATPase pump

irreversible Partly reversible Irreversible Irreversible

Effect on H.pylori infection

Less More Less Less

Oral bioavailability and t⅟2

↓ ↑ ↓ ↓

Onset and duration of action

Relatively slow Fast Slow Slow

Route Oral Oral i.v Oral

V)β BLOCKERS

Propranolol Timolol Metoprolol Atenolol

Labetalol

Drug type β 1+β2 β 1+β2 β 1 β 1 β +αPotency on β1 1 6 1 1 ⅓Partial agonists - - - - -Membrane stabilising action ++ +- +- - +Lipid solubility ++ + + - +1st pass metabolism Yes Partial Yes No Yes Route of excretion Hepatic Hepatic +renal hepatic renal HepaticOral bioavailability 30 50-75 40-50 50-60 20

VI)CEPHALOSPORINS

1st generation 2nd generation 3rd generation 4th generationparenteral: cefazoline,cephalothin.Oral:cephalexin

Parenteral :cefuroxime,cefoxitin.Oral:cefaclor

Parenteral :ceftriaxoneOral : cefixime

Parenteral:cefepime

Gram +ve /gm-ve cocci except E.coli, proteus,K.pneumoniae

Gm-ve coverage with some anaerobes

Gm+ve/gm-ve cocci with gm-ve rods

Broad spectrum

None enters CNS Only cefuroxime enters CNS

None None

VII)Macrolides

Erythromycin Clarithromycin Azithromycin 1 Metabolised by liver,excreted through

bileMetabolised by liver, excreted through bile

Excreted by kidney

2 Inhibits cytochrome P450 inhibits No inhibition3 Unsafe in pregnancy unsafe Safe4 Destroyed by gastric acid so tab. Is

coatedNot effected Not effected

5 Food interfere with absorption ↓es absorption interferesVIII)Aminoglycosides

Streptomycin Gentamycin Tobramycin Amikacin Neomycin narrow spectrum:gm-ve bacilli and few gm+ve cocci

broad spectrum like gentamycin but 2-4 times more potent against pseudomonas and proteus

wide spectrum due to resistance to bacterial aminoglycoside inactivating enzyme

Wide

ineffective against pseudomonas and proteus and effective against only only few strains of E.coli,klebsiella and enterobacter

effective against pseudomonas,and proteus and also against most strains of E.coli,klebsiella,enterobacter

lownephrotoxicity and ototoxicity than gentamycin

Use like gentamycin but less potent against pseudomonas and proteus

Not effective against pseudomonas and streptococcal pyogenes

effective against M.TB.,staphylococcus pneumonia,strept.pyogenes

not effective Mainly in hospital infection

Systemic toxicity is high ,used topically

less potent more potent

low nephrotoxicityhigh nephrotoxicity

IX)FLUROQUINOLONES/QUINOLONES

Oral bioavailability%

PPB% Route Indications

1st generationCiprofloxacin 60-80 20-

35Oral/i.v

UTI,gonorrhoea,chanchoroid,MDRTB

Norfloxacin 35-45 15 Oral UTI,GI InfectionOfloxacin 85-95 25 Oral/iv Alternate drug for NSV,cervicitisPefloxacin 90-100 20-30 Oral/

i.vMeningitis,UTI,GI INFECTION

2nd generation

Lomefloxacin 90 10 Oral Like ciprofloxacin but increases activity of gm –ve bacteria

sparfloxacin 90 40 oral Pneumonia,exacerbation of acute bronchitis,sinusitis

X)Cough suppressant drugs:

Pharyngeal demulcents Opoids Non opoids Antihistaminics Acts peripherally,soothes the throat and reduce afferent impulse from pharyngeal mucosa

1)acts on CNS to raise threshold of cough centre2)has abuse liability3)more constipating effect.4)action blocked by naloxone.

1)acts on CNS to raise threshold of cough centre2)no abuse 3)no constipating effect4)no such blockade occurs

Suppresses cough by sedative and anticholinergic action

SHORT NOTE

1)bioavailability measure of fraction of administered dose of drug that reaches systemic circulation in unchanged

form bioavailability of different routes:

i.v.=100%s.c/i.m =less than 100% due to local PPBoral=much less due to first pass metabolism

factors affecting bioavailability are:a)route of administrationb)physical properties of drugsc)chemical properties of drugsd)individual variation

e)first pass metabolism

2)first pass metabolism refers to the metabolism of drug during its passage from site of absorption into the systemic

circulation all orally administered drugs are expsosed to metabolising enzymes in liver and intestine. Occurs even in skin and lungs Different for different drugs and it determines oral bioavailability Degree of first pass metabolism ;

a)low:phenobarbitoneb)intermediate:aspirinc)high:propranolol

3)metabolism of drugs(biotransformation) Chemical alteration of drug in the body Lipid soluble drug is converted into lipid insoluble drug which is not reabsorbed and is excreted Sites:mainly liver,also in kidney ,intestine,lung It leads to

a)inactivation of drugs;morphineb)activation of inactive drug:levodopa is converted into dopaminec)active metabolite production from active drug:digitoxin is converted to digoxin

Classification of metabolism

Nonsynthetic/phase I/Functionalization rxn

Synthetic/conjugation/Phase II reactions

1.oxidation 1.glucuronide conjugation2.reduction 2.acetylation3.hydrolysis 3.methylation4.cyclization 4.sulfate conjugation5.decyclization 5.glycine conjugation

6.glutathione conjugation 4)phase II metabolism/synthetic rxn Involves conjugation of drug or phase I metabolite with endogeneous substance to form highly ionised

organic acid so that it is excreted in urine or bile It requires very high energy Involves following reactions

a)glucuronide conjugation:conjugated by glucoronic acid eg:aspirin ,morphineb)glutathione conjugation eg:paracetamolc)glycine conjugation:conjugated by glycine eg:salicylatesd)methylation:conjugated by methionine eg:adrenalinee)acetylation:conjugated by acetyl coAf)ribonucleoside synthesis:for purine and pyrimidine antimetabolite used in cancer therapyg)sulphate conjugation: conjugated by sulfokinase eg:sex steroids

5)criterias for essential drug selections Adequate data regarding efficacy and safety of drug should be available through clinical studies In case of two or more similar drug choice should be based on their relative efficacy,safety,

quality,price and availability Choice should be based on pharmacokinetic properties Should be single compound

6)disadvantages of antimicrobial combination therapy It prevents proper diagonis of infection and choice of AMA Increased incidence of side effects as toxicity of one agent can be enhanced by another Increased chances of superinfection Inadequate dose of drug may lead to emergence of resistance Increases cost of therapy

7)low dose aspirin

Balance between the above two helps in the maintainance of circulation When low dose aspirin is used ↓ Inhibition of cycloxygenase enzyme occurs in platelets by acetylation to great extent as compared to endothelial cells ↓ Failure of platelet to resynthesize cox enzyme results in decreased TXA2 and ↑ed PGI2 level ↓ No platelet sticking and thrombus formation occurs ↓ Helps in prevantion of attack of MI

8)drugs used to decrease platelet aggregation NSAIDs:aspirin Dipyridamole Clopidogrel Ticlopidine Abciximab

9)uses of vitamin K preparations Adult vitamin K deficiency(malabsorption,obstruction,jaundice) Vitamin K deficiency in infant following acute diarrhoea Neonatal vitamin K deficiency Bleeding state during oral coagulant therapy

10)oral rehydration solution Used for mild (5-7%BW) or moderate (7.5-10%BW) type of dehydration Composition of ORS(WHO)

OLD NEWNaCl 3.5g 2.6gKCl 1.5g 1.5gTrisodium citrate 2.9g 2.9gGlucose 20g 13.5gWater 1litre 1litre

arachidonic acid↓cycloxygenase

in platelets↓

TX-A2 formation↓

promote platelet aggregation and thrombi formation

in endothelial cells↓

PGI2 formation↓

inhibit platelet aggregation

310mosm/i 245mosm/l

The old ORS formulation was mainly effective for cholera diarrhoea,but when used in non cholera diarrhoea it causes periorbital edema due to excess Na+ reabsorption

So in new ORS formulation the concentration of sodium and glucose is reduced but it has the disadvantage of causing hyponatremia if used in cholera diarrhoea in adults

Rational of components useda)Na and water facilitates each others absorption in GITb)KCl :to compensate acute diarrhoeal K+ loss

c)bicarbonate,citrate, lactate:to correct acidosis Uses:

a)diarrhoeab)non diarrhoeal reasons: heat stroke,post burn/post surgical maintainance of hydration and nutrition.