ACE INHIBITORS

 Drugs : captopril, enalapril

 Mainly used in CHF and hypertension
 Basis of use;
Angiotensinogen(α 2 globulin)
↓Renin from JG cells of kidney
Angiotensin I
ACE inhibitor - ↓ACE
Decreased Angiotensin II

i
d
s
a
e
r
c
n
s
e
a
r
c
D
d
e
s
a
r
c
n
i
d
e
s
d
a
N
d
+
n
e
s
o
ti
a
t
w
p
u
v
l
i
d r
f
o
en
t
o
i
g
n
k
y
d
a
r
b
h
t
u
c
s
r
p
y
e
v
a
l
o
m i
s
c
ti
h
t
o
ti
t
r
n
e
l
c
s
u
m
o
I
v
e
l
s
u
o
v
r
e
n y
s
t
m
e

↓ ↓

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
  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 enalapri Linsopril perindopril ramipril

l
Chemical name sulfhydryl carboxyl Carboxyl carboxyl carboxyl
Activity status active prodrug Active prodrug prodrug
bioavailability 70% 50% 25% 20% 60%
Time to pick action 1 hr 4-6hr 6-8hr 6hr 3-6 hr
Elimination t-half 2 hr 11 hr 12 hr 25-30 hr 8-48 hr
Mode of excretion renal renal renal renal renal
Duration of action 6-12 hr 24 hr ≥24 hr ≥24 hr ≥24 hr
Daily 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 system
2. Increased vasodilatation of vascular smooth muscle
3. Decreased sodium and water retention
4. 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 antagonists

1.interfere with degradation of bradykinin→increases bradykinin 1.no such interference
level
2.alternative pathway of A-II production and AT-I receptor 2.causes complete inhibition of
activation remain intact with them 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”
 CLASSIFICATION
1)non selective (β1 and β2)
a)without intrinsic sympathomimetic action: propranolol , timolol
b)with intrinsic sympathomimetic activity: pindolol
c)with additional α blocking property:labetalol
2)cardioselective (β1)
Metoprolol, atenolol
3)selective β2
Butonamide
 Basis of use of β blocker in
1)HTN

l
m
ti
g
n
o
d
s
a
r
c
e e
d
s
a
r
c
e
d
1
β
βd
v
ti
c
i
l
e
d
a
r
o
n
f
o
e
s
u
o
t
p
c
e
r
G
J
m
o
f
s
r
c
e
d
n
a
a
l
e
s
r
f
o
n
e
f
o
l

r
e
k
c
o
l
b
c
ti
e
h
t
a
p
m
y
s
t
r
a
e
h
y
e
n
d
i
k
e
n
o
 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 attack
Q)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 muscle
Basis 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 cardiomyopathy
 Hypotension
 CALCIUM CHANNEL BLOCKERS
Drugs:
 Phenylalkylamine: Verapamil
 Benzothiazepine:Diltiazem
 Dihydropyridine: Nifedipine, Amlodipine
Differences between nifedipine and amlodipine:

AMLODIPINE NIFEDIPINE
1 Slow oral absorption Fast oral absorption
2 Complete absorption Incomplete absorption
3 No early adverse effects like flushing ,palpitation seen Early adverse effects seen
4 Low first pass metabolism High first pass metabolism
5 High volume of distribution and t-⅟2 Low volume of distribution and t-⅟2
6 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

↓
V
c
a
(
Z
T
D
,
L
I
M
P
A
R
E
r
e
h
n
o
s
t
↓
u
v
y
l
i
m
S
H
-
f
ti
p
x
C
K
X
O
N
G
U
d
n
w
l
/
o
a
c
t
s
d
o
e
r
b
l
i
a
v
n
o
t
d
g
y
x
e
s
l
e
r
t
n
m
u
q
a
h
i
p
u
i
c
l
a
m
n
↓
H
s
v
i
l
e
r
N
T
n
a
o
t
y
c
s
v
i
l
e
r
g

Indications






No/low availability of Ca2+ in cytosol

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
t
i
d
r
l
a
c
w
k
o
y
f
o
i
e
c
n
a
t
s
t
e
h

a
 Properties Diltiazem Verapamil Nifedipine
1 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, Digitoxin
Use: Mainly used in CHF
Basis 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

DIURETICS
High ceiling diuretics/loop diuretics: Furosemide
Medium efficacy diuretics: Thiazides
Basis of use of diuretics:

THIAZIDES FUROSEMIDE
Drug of choice in uncomplicated HTN Drug of choice in complicated HTN with
chronic renal failure,CHF
Inhibition of Na+Cl- symport in early DCT Inhibition of Na+K+2Cl- cotransport in
↓ thick ascending loop of henle
↓plasma and ECF volume ↓
↓ ↓plasma and ECF volume
↓cardiac output ↓
↓ Decreased C.O.
Compensatory mechanism almost restores C.O.,but slight ↓
Na+ and volume deficit persists Decreased BP
↓
↓Na+ level in vascular smooth muscle
↓
↓stiffness,↑compliance,and ↓response to constrictive
 effects of NA
↓
↓TPR
↓
↓BP

VASODILATORS
Drugs:
I)Arteriolar dilators(↓afterload)
 Hydralazine,minoxidil
 CCBs:Nifedipine
 K+ channel opener:Nicorandil

II)Venodilators(↓preload)

 Nitrates:Glyceryl trinitrate, glyceryl dinitrate

III)Mixed dilators(↓preload and afterload)
 ACE inhibitors: enalapril
 AT-1 antagonist:losartan
 α-1 blocker:prazosin
 Na nitropruside
Basis of use:

r
a
e
s
o
ti
t
v
c
d
l
i
D
n
f R
P
T
d
o
a
e
i
l
r
n
s
u
p
e
d
i
v
o
r
o
s
a
v
l
e
s
v
d
o
b
n
O
C
a
d
↓ d
l
i
a
l
o
i
r
e
t
p
h
↑
d
↓ g
n
i
o
l
f
n
f
i
l
e
r
n
d
o
l
b
↓
a
t
i
s
r
e
c

r
o
t
a
C
F
H
e
s
a
r
c
D
↓
ft
d
p
a
n
i
↓
o
l
r
e
s
B
d
P

CENTRAL SYMPATHOLYTICS
Drugs: clonidine and methyldopa
Use: HTN
Basis of use:
s
r
2
d
1
D
f
n
o
a
l
u
m
ti
t
p
c
e
↓
v
i
↑
y
k
w
fl
b
p
c
e
β
u
s
e
t
a
l
m
ti
p
es
d
i
v
o
r
n
t
r
a
e
o
h
↓
d
r
e
t
a
↑
h
q
r
k
c
i
u
n
i
m
f
i
c
a
r
t
n
o
i
c
o
h
s
n
↓
i
B
d
s
a
e
r
c
n
P
d
n
f
e
c
r
o
f
i
l
e
e
k
clonidine
Acts on α2a- receptor agonist in vasomotor centre in
medulla

DRUGS FOR COUGH

Classification:
↓
↓sympathetic activity
↓
Decrease BP

Dopamine in therapy: cardiogenic shock

o
p
d
1
r
o
t
a

RESPIRATORY SYSTEM

 Pharyngeal demulcents:logenges, cough drops

 Expectorants(mucokinetics)
a)Directly acting:citrate of Na+/K+,KI
b)Reflexly acting:ammonium chloride/carbonate,KI
c)Mucolytics:bromhexine
Methyldopa
Acts on α2a-receptor agonist in vasomotor centre in
medulla
↓
↓sympathetic outflow
↓
Decreased TPR
↓
Decreased BP
  Antitussives (cough suppressants)
a)opiods:codeine,morphine
b)non opiods:Noscapine,dextromethorphan
c)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
 Mode of action:
Cough suppressants
↓
1) Acts on CNS to raise threshold of cough centre
2) Acts on respiratory tract to reduce production of cough impulse
↓
Controles cough of types
1)dry ,unproductive
2)tiring and sleep disturbing

DRUGS FOR BRONCHIAL ASTHMA

I)Bronchodilators
a)sympathomimetics:salbutamol,terbutalin
b)methylxanthines:aminophylline,theophylline
c)anticholinergics:ipratropium bromide
II)leukotriene antagonists:monteleukast,zafirleukast
III)Mast cell stabilisers:sodium cromoglycate
IV)Corticosteroids:
a)systemic:hydrocortisone,prednisolone
b)inhalational:beclomethasone dipropionate
V)Anti IgE-Antibody:omalizumab

a)sympathomimetics
Drugs: salbutamol, terbutalin(selective β2 agonists)
Basis for use in bronchial asthma:
b
a
i
h
c
n
o
r l
s
e
v
o
r
p
m
i e
h
t
d
n
a
l
c
t
s
e
u
m e
h
t
o
r
v
ti
c
l
m
a
o
t
w
r
i
y
fl
n l
e
c
2
s
i
n
o
g
a
β
↓ t
↓
o
e
n
p
s
r
d
↓
ti
c
u
t
b f
,
n
o
d
h
c
n
o
r
b a
l
i
n
o
ti
l
P
M
A
c
↑
e
m
a
o
t
fl
n
y
s
v
i
l
e
r n
i
l
e
v
m
e
s
d
t
i
a
h
r
o
s
r
u
c
o

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 prophylaxis
Adverse effects of salbutamol  MARcH PANT
 Muscle tremor
 Ankle edema
 Restlessness
 Hypokalemia
 Palpitation
 Arrhythmia
 Nervousness
 Tachycardia
b)methylxanthines
drugs:aminophylline,theophylline
Basis of use:

Adverse effects of aminophylline ,theophylline:(µg/ml)

 E XT R AS Y S TO LE
EF FE CT
A SE DO UM USDCYSP
SN ESS, TI ONE
L EEPS A ,
AT15 AT5 :NO SIDE
:D EACH
A T 3:H0EAD E,I U
LI R MM,INN
IN SO I A,C ERV
N RE
N ESS, TRE M
TL ES S O UR , DIU RES IS
AT20 :PA L PIT AT ION , VO MI TI NG ,R ES
R Y T HMEIAFFEC
R SIDE TK
S S HOC
, TAC HYPN OEA
AT 3 5 :C ON V ULS I ONS , A
AT25 :F L USH ING , AG ITA TIO N
AT1 0:MINIMAL
A B OV E 3 5 :D E A T H

c)anticholinergics

drug:ipratropium bromide
basis of use in asthma:
blockage of cholinergic receptor in large airways
↓
Bronchodilation occurs
↓
Provides relieve in asthma
Note: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 stabilisers
Drug: sodium cromoglycate,ketotifen
 v
ti
g
F
A
P
T
L
.fl
Basis of use:
m
f
p
h
↓
y
b
e
u
s
n
a
t
ir
ld
o
,c
k
Mainly used for prophylactic purpose.

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

NASAL DECONGESTANTS:
These are α agonists which when applied as a dilute solution produce local vasoconstriction
Drugs:naphazoline,xylometazoline,oxymetazoline,phenylephrine,pseudoephedrine
MOA: Acts as α agonist
↓
Produce vasoconstriction and shrinkage of nasal mucosa
↓
Provides relief from nasal obstruction
Adverse effectsSAARC
 Stinging sensation
 Atrophic rhinitis
 Anosmia
 CNS depression
 Rise in BP

Uses:common cold ,allergic rhinitis

Contraindication:HTN,patients on MAO inhibitors

DRUGS FOR TUBERCULOSIS:

First line drugs Second line drug Newer drugs

Isoniazid(H) Thiacetazone Ciprofloxacin
Rifampin(R) PAS Ofloxacin
Pyrazinamide(Z Ethionamide Clarithromycin
)
Ethambutol(E) Cycloserine azithromycin
Streptomycin(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 intracellularly
Basis for use of rifampicin:
Inhibits DNA dependent RNA polymerase
↓
Stoppage of expression of bacterial gene
↓
Tuberculocidal effect is exerted
Adverse effects of anti-tubercular drug

ISONIAZID RIFAMPIN PYRAZINAMIDE ETHAMBUTOL STREPTOMYCIN

Peripheral neuritis Liver damage Hepatitis Optic nerve damage Ototoxicity
Psychosis Influenza like rxn Hyperuricemia,gout Anaphylactic rxn Nephrotoxicity
Hepatitis Orange –red Arthralgia Nausea,vomiting Anaphylaxis
urine
Rashes,fever Fever,skin rash photosensitivity Confusion,headach eosinophilia
e
DOTS regimen for TB
DOTS strategy:emphasize on the use of all first line anti-tubercular drugs in single daily dosing
Basis 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
 H2

u
n
w
ile
N
b
o
c
s
a
m
↑
r
↓
ti
h
P
T
A
K
+
v
p
f
d
y
t
 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

antihistaminics

PPI

sucralfate
ANTIEMETICS

Basis of use:
Uses
Duodenal ulcer,gastric ulcer, stress
ulcer,gastritis,ZEsyndrome,GERD,Prophylaxis of
aspiration pneumonia

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

syndrome
Peptic ulcer

5HT-3 ANTAGONISTS( ondansetron)

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

↓
Adverse effects
Dry mouth, headache,
dizziness,bowel
upset,rashes;CNS effects like
confusional state ,convulsion
coma
Abdominal pain, muscle and
joint pain,atrophic gastritis
constipation
lp
z
aβ
b
u
c
↓
rm
d
Bo
iw
e
th
n
y
s
fti



Reflex increase in GI motility

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
Interfere with the degradation of bradykinin
which leads to ↑ed bradykinin level
Alternative path of A-II production and AT-1
receptor activation remains intact
Causes inactivation of AT-1 and AT-2
receptor
Has more potential to cause cough and
dysguesia

II) Amlodipine and Nifedipine

AMLODIPINE
 Slow oral absorption
 Complete absorption
 No early adverse effects flushing ,palpitation
 Low 1st pass metabolism
 High volume of distribution and t⅟2 value
 long duration of action
ANG-II ANTAGONIST
 Has no any such interference

 Causes complete inhibition of AT-1 receptor

 Causes indirect AT-2 receptor activation

 Has very less potential to cause cough and

dysguesia

NIFEDIPINE
 Fast oral absorption
 Incomplete absorption
 Early adverse effects seen
 High 1st pass metabolism
 low
 short duration of action
III) TETRACYCLINES

Tetracycline Domecycline Doxycycline

Potency Low Intermediate High
Plasma protein binding Low High High
t⅟2 6-10hr 16-18hr 18-24hr
Alteration of normal Marked Moderate Least
flora
Diarrhoea High Intermediate Low
Phototoxicity Low Highest High

IV)Proton punp inhibitors

Omeprazole Lansoprazole Pantoprazole Esmoprazole

Inhibition of irreversible Partly reversible Irreversible Irreversible
H+K+ATPase pump
Effect on H.pylori Less More Less Less
infection
Oral bioavailability ↓ ↑ ↓ ↓
and t⅟2
Onset and duration Relatively slow Fast Slow Slow
of action
Route Oral Oral i.v Oral

V)β BLOCKERS

Propranolo Timolol Metoprolol Atenolo Labetalol

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

VI)CEPHALOSPORINS

1st generation 2nd generation 3rd generation 4th generation

parenteral: Parenteral Parenteral :ceftriaxone Parenteral:cefepime
cefazoline,cephalothin. :cefuroxime,cefoxitin. Oral : cefixime
Oral:cephalexin Oral:cefaclor
Gram +ve /gm-ve cocci Gm-ve coverage with Gm+ve/gm-ve cocci with Broad spectrum
 except E.coli, some anaerobes gm-ve rods
proteus,K.pneumoniae
None enters CNS Only cefuroxime enters None None
CNS

VII)Macrolides

Erythromycin Clarithromycin Azithromycin

1 Metabolised by liver,excreted through Metabolised by liver, excreted through Excreted by
bile bile kidney
2 Inhibits cytochrome P450 inhibits No inhibition
3 Unsafe in pregnancy unsafe Safe
4 Destroyed by gastric acid so tab. Is Not effected Not effected
coated
5 Food interfere with absorption ↓es absorption interferes
VIII)Aminoglycosides

Streptomycin Gentamycin Tobramycin Amikacin Neomycin

narrow spectrum:gm-ve broad spectrum like gentamycin wide Wide
bacilli and few gm+ve but 2-4 times spectrum due
cocci more potent to resistance
against to bacterial
pseudomonas aminoglycosi
and proteus de
inactivating
enzyme
ineffective against effective against lownephrotoxici Use like Not
pseudomonas and pseudomonas,and ty and gentamycin effective
proteus and effective proteus and also against ototoxicity than but less against
against only only few most strains of gentamycin potent pseudomon
strains of E.coli,klebsiella E.coli,klebsiella,enterobac against as and
and enterobacter ter pseudomonas streptococc
and proteus al pyogenes
effective against not effective Mainly in Systemic
M.TB.,staphylococcus hospital toxicity is
pneumonia,strept.pyoge infection high ,used
nes topically
less potent more potent
high
low nephrotoxicity nephrotoxicity
IX)FLUROQUINOLONES/QUINOLONES

Oral bioavailability PPB% Route Indications

%
1st generation
Ciprofloxacin 60-80 20- Oral/i. UTI,gonorrhoea,chanchoroid,MDRTB
35 v
Norfloxacin 35-45 15 Oral UTI,GI Infection
Ofloxacin 85-95 25 Oral/iv Alternate drug for NSV,cervicitis
Pefloxacin 90-100 20-30 Oral/i. Meningitis,UTI,GI INFECTION
v
 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 1)acts on CNS to 1)acts on CNS to Suppresses cough by
and reduce afferent impulse from raise threshold of raise threshold of sedative and
pharyngeal mucosa cough centre cough centre anticholinergic action
2)has abuse liability 2)no abuse
3)more constipating 3)no constipating
effect. effect
4)action blocked by 4)no such blockade
naloxone. occurs
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 PPB
oral=much less due to first pass metabolism
 factors affecting bioavailability are:
a)route of administration
b)physical properties of drugs
c)chemical properties of drugs
d)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:phenobarbitone
b)intermediate:aspirin
c)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;morphine
b)activation of inactive drug:levodopa is converted into dopamine
c)active metabolite production from active drug:digitoxin is converted to digoxin
 Classification of metabolism

Nonsynthetic/phase I/ Synthetic/conjugation/
Functionalization rxn Phase II reactions
1.oxidation 1.glucuronide conjugation
2.reduction 2.acetylation
3.hydrolysis 3.methylation
4.cyclization 4.sulfate conjugation
5.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 ,morphine
b)glutathione conjugation
eg:paracetamol
c)glycine conjugation:conjugated by glycine
eg:salicylates
d)methylation:conjugated by methionine
eg:adrenaline
e)acetylation:conjugated by acetyl coA
f)ribonucleoside synthesis:for purine and pyrimidine antimetabolite used in cancer therapy
g)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

 e
p
s
a
i
l
h
t
o
d
n s
l
e
c
r
h
c
a
d
i
↓
X
T
2
A
-
ti
f
a
m
r
o
c
i
n
o
n
o
f
2
I
G
a
m
r
o
↓
P
tin
d
i
c
a t
p
e
t
m
o
r
a
l
↓
p
t
b
i
h
n
a
e
l
e
t
l
↓
a
n
o
ti
e
g
c
l
y
s
r
x d
n
f
i
b
h
m
r
o
t n
o
ti
a

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 NEW
NaCl 3.5g 2.6g
KCl 1.5g 1.5g
Trisodium citrate 2.9g 2.9g
Glucose 20g 13.5g
Water 1litre 1litre
 310mosm/ 245mosm/l
i

 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 used
a)Na and water facilitates each others absorption in GIT
b)KCl :to compensate acute diarrhoeal K+ loss
c)bicarbonate,citrate, lactate:to correct acidosis
 Uses:
a)diarrhoea
b)non diarrhoeal reasons: heat stroke,post burn/post surgical maintainance of hydration and
nutrition.