ADRENALINE /EPINEPHRINE

WHICH GROUP DOES THIS DRUG BELONGS TO?

• It is a naturally occurring catecholamine

sympathetic transmitter secreted primarily by
the adrenal medulla.
• Responsible for “fight and flight” startle
reaction
OTHER MEMBERS BELONGING TO SAME GROUP?

• Others belonging to this group are

norepinephrine and dopamine
• Synthetic catecholamines are dobutamine and
isoproterenol
PREPARATION?
• It comes as a clear solution for injection
containing 1 mg/ml of adrenaline
hydrochloride.
• It also comes as aerosol spray delivering 160-
275 μg metered dose of adrenaline
• Racemic adrenaline 2.25%
 Receptors

• Nine different adrenoreceptors (α1A,B,D,

α2A,B,C, β1, β2, β3)
• Alpha 1 & 2: skin, mucosa and hepatorenal
system causing vasoconstriction, inhibits release
of insulin
• Beta 1 causes increased liver glycogenolysis,
adipose tissue lipolysis, B1 causes increase in
HR, BP, CO
• Beta 2 – bronchodilation and vasodilation of
skeletal muscle vasculature
DESCRIBE THE MECHANISM OF ACTION IN CPR

• In CPR, Epinephrine causes a substantial

redistribution of blood flow away from skin
and visceral organs, to the heart.
ROUTES OF ADMINISTRATION?

• IM or IV
• SC (slow absorption because of local
vasoconstriction)
• Inhalational
What are the various dosages?
Dose regimen for pressor support

• (a) 1–2 μg/min predominantly activates β2 receptors leading to vascular and

bronchial smooth muscle relaxation

• (b) 2 – 10 μg/min β1 and β2 action. Heart rate, contractility and conduction

through AV node increased.

• (c) > 10 μg/min marked α and β2 stimulation and generalized

vasoconstriction

• CPR= 1 mg (ie 0.02 mg/kg) IV adrenaline every 3-5min

• As an inotrope: 0.05 to 0.2 μg/kg/min infusion

• As an additive to local anaesthetics: Used in a concentration of

1:200,000(5μg/ml)
 Dose for bronchodilation
Racemic adrenaline(2.25%)
• mixture of laevo and dextro-isomers of adrenaline.
• This causes less tachycardia and is used to treat laryngeal
oedema. The doses are as follows :
• Adults:0.75ml, child: 0.5ml and in a
child<6months,0.25ml. This is diluted with 3ml of saline
and nebulised. It may be repeated in 30minutes. If
racemic epinephrine is not available, there is evidence in
the literature that 0.5 ml/kg of 1:1000 adrenaline (laevo-
isomer) upto a maximum of 5ml nebulisation undiluted
may be helpful in children with severe croup.
• Heart rate must be monitored closely after nebulisation
• To treat anaphylaxis:100μg boluses IV or 1mg
IM, if intravenous access is not available. It is a
histamine antagonist.
• To treat bone cement reaction, adrenaline is
used in intravenous boluses of 25μg-50μg
What does 1:200000 solution means?

• This means that there is 1g of adrenaline in

200,000ml of the solution.
• This works out to be 1000mg in 200,000ml or
1mg in 200ml of the solution. This means it
contains 1000μg in 200ml of the solution. In
other words, each ml of this solution contains
5μg of adrenaline.
What are its interaction with anaesthetic drugs?

• Adrenaline (0.1 mg adrenaline is added to 20 ml LA to give

a 5 μg/ml concentration) for increasing the duration of
action of local anaesthetic by reduced systemic absorption
and to reduce its dosage
• Improves depth of analgesia by direct stimulation of
receptors located on the dorsal horn of spinal cord.
• adrenaline used in presence of halogenated inhalational
anaesthetics during general anaesthesia may cause
dysarrythmias, conduction block and cardiac arrest
Pharmacokinetics
• Onset: Immediate if given IV.
• Duration: 3–5minutes when given IV
• Metabolism and elimination: It is metabolized by COMT(catechol-O-methyl transferase)
and MAO (monoamineoxidase) enzymes.

Adverse effects:
• Tachycardia, hypertension, myocardial ischaemia, arrhythmiasetc

Cautions:
• To be used with caution in patients with cardiovascular and cerebro vascular disease.
• All catecholamine infusions can contribute to hyperglycaemia.

Special precautions:
• Maximum recommended dose of adrenaline that can be used for local
infiltration:3.3μg/kg with Halothane (except in children upto10μg/kg can be
used),6μg/kg with Isoflurane,10μg/kg with Sevoflurane. [Easytoremember:HIS—
3x1,3x2,3x3
 Noradrenaline bitartarate

• Availability: It is available in 2ml ampoules

containing 2mg/ml of noradrenaline
bitartarate. This is equivalent to 1mg/ml of
noradrenaline.
• Receptors and effects: It is an agonist at α1,α2
and β1 receptors
Uses,dose and route:
• As a vasopressor: Noradrenaline is a naturally occurring,
directly acting catecholamine.
• It is a powerful vasopressor, acting on the alpha1 receptors.
It is also an inotrope as it has beta1 receptor stimulant
properties but the vasoconstrictive properties predominate.
• It is given as an intravenous infusion only. The dose is 0.05
to 0.2μg/kg/min(2–10μg/min).It is the vasopressor of
choice in septic shock. It may also be used to counter
profound peripheral vasodilatation(e.g.,drug-induced as
with milrinone in the treatment of left ventricular failure).
• Onset:Immediate.
• Duration:3–5minutes
• Metabolism and elimination: It is metabolized
by COMT (catechol-O-methyltransferase) and
MAO (monoamineoxidase)enzymes.
• Adverse effects: Hypertension, myocardial
ischaemia, arrhythmias
Cautions:
• cardiovascular and cerebrovascular disease.
• Infusions of catecholamines should preferably be given through central
venous catheters.

Special precautions:
• Since it is a powerful vasoconstrictor, it can increase the afterload to
the left ventricle, can affect splanchnic circulation and Other peripheral
tissues if used indiscriminately. Hence, whenever noradrenaline
infusion is required, invasive blood pressure monitoring is warranted. It
is desirable that the systemic vascular resistance is measured,
particularly when renal dysfunction is also present and higher dose of
Noradrenaline is be in used to maintain blood pressure.
 Dopamine hydrochloride

• Availability: It is available in 5ml ampoules

containing 40mg/ml of dopamine
• Receptors and effects: It is an agonist at α1,
β1, β2 and DA1 receptors
Uses,dose and route:
• As an inotrope and vasopressor: Dopamine is a directly-acting
inotrope and vasopressor. It is always used as an infusion in a
dose ranging from 2–20μg/kg/min. By its indirect action,
dopamine aids in release of norepinephrine.
• Its actions are dose-dependent.
• At 1-2 μg/kg/min, it acts on dopaminergic (DA1) receptors and
has a renal vasodilatory effect.
• At 5-10 μg/kg/min, it acts on beta receptors and improves
contractility of the heart, increases heart rate and cardiac output.
• At a rate of more than 10 μg/kg/min, it begins to act on the alpha
receptors also and increases blood pressure
• Onset: Immediate if given IV.
• Duration:3–5minutes when given IV
• Metabolism and elimination: It is metabolized
by COMT (catechol-O-methyl transferase) and
MAO (monoamineoxidase) enzymes.
• Adverse effects: Dose related tachycardia.
When administered in higher
doses(>10μg/kg/min), it behaves like
noradrenaline.
 Dobutamine hydrochloride

• It is a synthetic catecholamine.
• Availability: It is available in 5ml ampoules
containing 50mg/ml of dobutamine
• Receptors and effects: It is anagonist at α1,β1
and β2 receptors. However, its major effects
are on the β1receptor
Uses,dose and route:
• As an inotrope: Dobutamine is a directly-acting inotrope
and is always used as an infusion in doses of
2-20μg/kg/min. It is a beta1 and beta2 stimulant.
• It acts on beta1 receptors and improves contractility of
the heart but has a more predominant action on beta2
receptors causing peripheral vasodilatation and reduction
in afterload. Consequently the heartrate and cardiac
output increase. Thus it acts similar to an inodilator
(inotrope+ vasodilator). Hence, it is very useful to improve
cardiac output in patients with low ejection fraction
• Onset: Immediate if given IV.
• Duration: 3–5 minutes when given IV
• Metabolism and elimination: It is metabolized
by conjugation in the liver and eliminated by
kidney.
• Adverse effects: Dose related tachycardia, may
cause hypotension and Should not be used as
an inotrope if the systolic blood pressure is less
than 80mmHg.
 Phenylephrine hydrochloride

• Availability: It is a synthetic noncatecholamine. It

is available in 1ml ampoule containing 10mg/ml
of phenylephrine
• Uses,dose and route: As a vasopressor:
Phenylephrine is a directly-acting vasopressor,
acting on the alpha receptors. It has no inotropic
action. It may be given as a bolus (1 to 2μg/kg). It
may also be given as an infusion at a rate of 1-
2μg/kg/min and titrated to blood pressure
• It is most often used to treat hypotension due to vasodilatation in
patients with ischaemic heart disease where any tachycardia may be
undesirable.
• It is a useful drug for management of patients with hypertrophic
obstructive cardiomyopathy or stenotic heart disease (mitral stenosis
and aortic stenosis) as this drug can improve systemic vascular
resistance and blood pressure without increasing heart rate.
• It may also be used to treat hypotension consequent to
spinal/epidural anaesthesia in pregnant patients for Caesarean
section.
• As a mydriatic: It is used as a 10% eyedrops to produce mydriasis.
When used for this purpose, it is important to monitor the patient
for its haemodynamic effects.
• Onset: Immediate if given IV.
• Duration: <5minutes when given IV
• Elimination: It is readily metabolized by liver
and gastro-intestinal tract.
• Adverse effects: Dose related hypertension and
reflex bradycardia
• Special precautions: Since it is a powerful
vasoconstrictor, it can increase afterload to the
left ventricle
• 1.Name:Hydrocortisonehemisuccinate
• 2.Specialfeatures:Itisaglucocorticoidwithmildmineralocorticoid
• effects.
• 3.Availability:Itisavailableinvialscontaining100mginpowderfor
m
• forreconstitution.
• 4.Mechanism
ofaction:Hydrocortisoneproducesbronchodilatationby
• reducingmucosalinflammation(anti-inflammatoryeffectshelpin
• reducingtheoedemaoftheairwaythuscontributingtoreliefof
• bronchospasm)
• 5.Uses,doseandroute:
•  Asabronchodilator,itisusedinadoseof100mgbolus+100mg8th
• hourly.
•  Itmayalsobeusedforsteroidreplacementinpatientswhohave
• beenonsteroidsintheprecedingsixmonths.(20mgmorning+10
• mgafternoonorally).Thesepatientsmightbehavingadrenocortical
• suppressionandmaynotbeabletorespondtothestressofsurgery.
• Thiscouldresultinrefractoryhypotensionandcardiovascular
• collapse.Thisiscalledadrenalcrisis/hypothalamo-pituitary-adrenal
• axissuppression(HPAsuppression).Thiscanbeavoidedby
• exogenoussteroidsupplemen-tation.Hydrocortisoneisusuallyused
• forthispurposeandisgiveninabolusdoseof25mgfollowedby
• 100mgeitherascontinuousinfusionorindivideddosesover24h.
•  Itisalsousedinthetreatmentofallergicreactions,anaphylaxis,
• septicshockwithacuterespiratorydistresssyndromeandthyrotoxic
• crisis(preventsperipheralconversionofT4toT3).
•  Recommendationsforhydrocortisoneuseinsepticshock—Consider
• (<300mg/d)whenthesepticshockisnotresponsivetoadequate
• fluidsandinotropes/vasopressors.Steroidtherapymaybeweaned
• oncethepatientisoffinotropes/vasopressors.
• 6.Onset:Onehour
• 7.Duration:Fourtosixhours
• 8.Elimination:Itismetabolizedbyliver
• 9.Side-effects:Hyperglycaemia,fluidretention,infections,
• hypokalaemia,hypertension,muscleweakness(especiallyin
critically
• illpatients)onlongterm use.Itmayalsocausegastricero-
sionsand
• concurrentuseofH2blockersorprotonpumpinhibitorsis
• recommendedwithsteroidtherapy.
 HYDROCORTISONE
• 1.Name:Hydrocortisonehemisuccinate
• 2.Specialfeatures:Itisaglucocorticoidwithmildmineralocorticoid
• effects.
• 3.Availability:Itisavailableinvialscontaining100mginpowderfor
m
• forreconstitution.
• 4.Mechanism
ofaction:Hydrocortisoneproducesbronchodilatationby
• reducingmucosalinflammation(anti-inflammatoryeffectshelpin
• reducingtheoedemaoftheairwaythuscontributingtoreliefof
• bronchospasm).
Uses,doseandroute:
•  Asabronchodilator,itisusedinadoseof100mgbolus+100mg8th
• hourly.
•  Itmayalsobeusedforsteroidreplacementinpatientswhohave
• beenonsteroidsintheprecedingsixmonths.(20mgmorning+10
• mgafternoonorally).Thesepatientsmightbehavingadrenocortical
• suppressionandmaynotbeabletorespondtothestressofsurgery.
• Thiscouldresultinrefractoryhypotensionandcardiovascular
• collapse.Thisiscalledadrenalcrisis/hypothalamo-pituitary-adrenal
• axissuppression(HPAsuppression).Thiscanbeavoidedby
• exogenoussteroidsupplemen-tation.Hydrocortisoneisusuallyused
• forthispurposeandisgiveninabolusdoseof25mgfollowedby
• 100mgeitherascontinuousinfusionorindivideddosesover24h.
•  Itisalsousedinthetreatmentofallergicreactions,anaphylaxis,
• septicshockwithacuterespiratorydistresssyndromeandthyrotoxic
• crisis(preventsperipheralconversionofT4toT3).
•  Recommendationsforhydrocortisoneuseinsepticshock—Consider
• (<300mg/d)whenthesepticshockisnotresponsivetoadequate
• fluidsandinotropes/vasopressors.Steroidtherapymaybeweaned
• oncethepatientisoffinotropes/vasopressors
• 6.Onset:Onehour
• 7.Duration:Fourtosixhours
• 8.Elimination:Itismetabolizedbyliver
• 9.Side-effects:Hyperglycaemia,fluidretention,infections,
• hypokalaemia,hypertension,muscleweakness(especiallyin
critically
• illpatients)onlongterm use.Itmayalsocausegastricero-
sionsand
• concurrentuseofH2blockersorprotonpumpinhibitorsis
• recommendedwithsteroidtherapy
 DEXAMETHASONE
Special features:
• Very potent,long acting,highly selective glucocorticoid.
• Availability: It is available in 2ml vials containing
4mg/ml.

Mechanism ofaction:
- steroid receptor
- antiemetic effect by acting on receptors in the
chemoreceptor trigger zone of the medulla.
 Uses, dose and route

• It may be used as an antiemetic agent, commonly used for

the prevention of PONV.
• To reduce cerebral oedema (4-20mg/day iv/im),
• Laryngeal oedema and tissue oedema.
• Inflammatory and allergic conditions.
• Potent immunomodulatory effects, used in the treatment of
acute allograft rejection.
• May also be used for thyrotoxic crisis (prevents peripheral
conversion ofT4toT3), addisonian crisis, bronchospasm.
• Perineural administration of dexamethasone with LA
prolongs
 Pharmacokinetics
• Onset:Fiveminutes
• Duration:Eighthours
• Elimination:Itismetabolizedbyliver.

Effects on the body:

• It exerts the same effects as any other steroid on the body.It may
stimulate gluconeogenesis and produce hyperglycaemia,
particularly in diabetics. Prolonged use may cause myopathies,
especially in critically ill patients. Causes marked pituitary adrenal
suppression. It may cause hypokalaemia. It may predispose
patients to infection. It can also cause gastric/peptic ulcers and
upper gastro-intestinal tract bleeding.
What are the actions of mineralocorticoids and glucocorticoids ?

Mineralocorticoid actions
• Increased reabsorption of Na+ from urine, sweat, colon. Increased K+
and H+ excretion in urine. (via exchange of Na+)

Glucocorticoid actions
• Increase blood glucose levels (increased glucose release from liver, decreased
tissue utilization of glucose).
• Increased lipolysis (increased breakdown of triglycerides)
• Increased protein catabolism
• Suppression of inflammation
• Decreased absorption of Ca2+ from GIT, increased resorption of Ca2+ from bone
(osteoporotic action).
• Stimulate secretion of gastric acid
• Inhibit allergic/hypersensitivity reactions.
• Maintenance of normal GFR, secretory activity of renal tubules, vasomotor tone
requires corticosteroids. These functions makes Adrenal Cortex essential for life.
Indications of steroids in present day anaesthesia

• Perioperative replacement therapy

• Anti-inflammatory uses and hyper-reactive airway
• Post operative nausea and vomiting (PONV)
• Analgesia adjunct
• Day care surgery
• Anaphylaxis
• Septic shock
• Transplantation of solid organs.
• Spinal cord injuries (within 8hours of injury)
• Other indications like – cerebral oedema, various surgical causes
• In perioperative period if hypotension persists even after adequate
resuscitation with fluid and inotropes, one can consider adding steroids in
such patients.
• Monitor Na+, K+, glucose levels and taper dose over 5–7 days.
 Recommendations for perioperative steroids ?
Patients currently taking < 10 mg day¹1 Assume normal HPA response
steroids
10 mg day¹1
Minor surgery (e.g., inguinal Herniorrhaphy) 25 mg hydrocortisone @ induction
Moderate surgery (cholecystectomy, lower Usual pre-operative steroids + 25
extremity revascularization, total joint mg hydrocortisone @ induction
replacement, abdominal hysterectomy þ100 mg day¹1 for 24 h
segmental colon resection)
Major surgery (e.g., Whipple procedure, Usual pre-operative steroids þ 25
total colectomy, esophageal resection, mg hydrocortisone @ induction
cardiac surgery involving bypass) þ100 mg day¹1 for 48– 72 h

High-dose immunosuppression Give usual immunosuppressive

doses during peri-operative period

Patients stopped taking < 3 months Treat as if on steroids

steroids > 3 months No peri-operative steroids
necessary
 Relative activity of systemic steroids
class compound GC MC Equivqle
nt doses
Glucocortico Short acting Hydrocortisone 1 1 20mg
id (t ½ < 12hrs)
Intermediat Prednisolone 4 0.8 5
e acting 12-
36hrs
Methylprednisolone 5 0.5 4
Triamcinolone 5 0 4
Deflazacort 4 0 6
Long Dexamethasone 25 0 0.75
term(>36hrs
)
Betametasone 25 0 0.75
Mineralocor DOCA 0 100 2.5
ticoid
fludrocortisone 0 150 0.2
 Mention few Drug interactions of steroids?

• Anticonvulsants (e.g., carbamazepine, phenobarbital, phenytoin)= ↓ GC

exposure and efficacy; may persist for weeks following discontinuation of
anticonvulsant
• Anticoagulants (e.g., warfarin)= May ↑ anticoagulant effects of warfarin and
↑ risk of GI bleeding
• Antifungals (e.g., itraconazole, ketoconazole)= ↑ GC exposure and toxicity
• Antibiotics (macrolides) (e.g., clarithromycin Antivirals (e.g., atazanavir,
indinavir, ritonavir, saquinavir) = ↑ GC exposure and toxicity
• Antidiabetic agents= GC initiation can lead to glucose dysregulation, thereby
counteracting the effects of antidiabetic drug

• Diuretics, potassium wasting (e.g., furosemide, HCTZ)= GCs may ↑ kaliuretic

effects of these diuretics
• NSAIDs= May ↑ risk of GI ulcers when given concomitantly with
corticosteroids
Diuretics
 CLASSIFICATION

1.HIGHEFFICACY DIURETICS[INHIBITOR OF Na-K-2CL COTRASPORTER]

• Furosemide, Bumetanide, Torsemide

2.MEDIUM EFFICAY DIURETICS [INHIBITOR OF Na-K SYMPORT]

• BENZOTHIAZIDES- Hydrochlorthiazides, Bezthiazide, Hydroflumethiazide ,
Bendroflumethiazide
• THIAZIDE LIKE– Chlorthalidone, Matolazone, Xipamide, Indapamide, Clopamide

3.Weak adjuvants –
CA sinhibitors-acetazolamide
K sparing diuretics-
• Aldosterone antagonist-spironolactone, eplerenone
• Renal epithelial Na inhibitor-triamterene
Amiloride

Osmotic diuretics-mannitol,isosorbide,glycerol
 LOOP DIURETICS
• High celling diurectis

MECHANISM OF ACTION:
• •Luminal side of thick ascending limb of loop diuretics
• •Inhibit NA-K-CL co transport
• •Cortico-medullary gradient is abolished
• •Positive and negative Free water clearance is blocked
• Weak carbonic anhydrase inhibitory activity-increases HC03 excretion
• •Increased k excretion–increased Na load t oDT (less then thiazides)
• •Diuretic action increases with increasing the dose
• They do not alter the acid base balance of the body.

• •INTRARENAL EFFECTS-increased LOCALPGs, Transient increase in RBF-

redistribution of blood flow from Outer to midcortical zone
• GFR-unchanged
• increases Ca and Mg excretion
 Furosemide
• 10mg/ml, 2ml Ampoule
• Oral – 40 and 50mg tablets

Dosage –
• Bolus- 0.1-1mg/kg iv, 1-3mg/kg oral
• Infusion less than 4mg/min

• Side effects – hypotension, ototoxicity, interstial

nephritis, hyperlipidemia, hyperglycemia, potentiate
NDMR, allergy
• A glycoprotein with 12membrane
• Spanning domains functionasNA-K-CL co transport

PHARMACOKINETICS
• Rapidly absorbed orally,bioavailability-60%
• Onset of action-
IV-2-5min
IM-10-20min
ORAL-20-40min
• Duration o faction-3-6hrs
• Highly plasma protein bound
• •Low lipid solubility
• •Partly conjugated –glucuronide
• Excreted unchanged
• GF and tubular secretion.
• •T1/2-1-2hrs
• •Prolongs in hepatic and renal diseases
• Uses:
• Edema–renal,hepatic,cardiac
• Acutepulmonary edema,acuteLVF
• Cerebraledema
• Hypertension
• Hypercalcemia of malignancy
 COMPLICATIONS-LOOP
• Hypokalemia
• Dilutional hyponatraemia
• GIT and CNS-headache,dizziness,weakness
nausea,vomiting,diarrhea
• Hearing loss
• Allergic manifestation
• Hyperuricaemia
• Hyperglycaemia,hyperlipidemia
• hyperuricaemia
• Hypocalcaemia
• Hypomagnesemia
 HYDROCHLORTHIAZIDE
• Oral only, 25-50mg tablets
• Medium efficacy Diuretic
• Moa – Luminal sideof diluting segmentor early DT
• Inhibits Na-Cl symport
• CM gradient Intact
• Positive freewater clearance is reduced
• Negative freewater clearance is not affected.
• Weak carbonic anhydrase inhibitory activity-increases
HC03excretion
• •Increased k excretion –increased Na load to DT
• Flat dose response curve-little diuretic effect with increasing
thedose to 100mg of Hydrochlorthiazides or equivalents
• They do not alter the acid base balance of the body
• Decreased blood volume
• Decreased GFR
• Decreases urate excretion(> frusemide)
• Decreases Ca excretion, Increase Mg excretion
• A glycoproteinwith 12membrane spanning domains functionas
NA-K symport
• Well absorbed orally, noinjectable preparations.
• Onsetofactionwithin1hr
• Durationofaction-6 -48hr
• Plasmaprotein bindingisvariable
• •morelipidsolubility
• •Large volume of distribution
• •Lowerrateof clearanceand longeracting
• •Littlehepatic metabolism
• •Excreted unchanged
• •T1/2 hydrochlorthiazide- 3-6hrs
• • Chlorthalidone- 40-50hr longacting
• Uses – hypocalcemia, Edema–renal,
hepatic,cardiac, Hypertension
• DI-decreasing Positivefreewater Clearance
(nephrogenic DI)
• Complications- hypercalcemia
• COMPLICATIONS-THIAZIDES
• Hypokalemia
• Dilutionalhyponatraemia
• GIT and CNS-headache,dizziness,weakness,
nausea,vomiting,diarrohea
• Hearing loss
• Allergic manifestation
• Hyperuricaemia
• Hyperglycaemia,hyperlipidemia
• hyperuricaemia
• Hypercalcemia
• Hypomagnesemia
 MANNITOL
• Non electrolyte of low molecular weight
• Increases osmolarity of plasma and tubular fluid
• Minimally met.,freely filtered and limited reabsorption
• Excellent osmotic diuresis
MECHANISMOFACTION-
• 1.Retains water iso-osmotically in PT-dilutes luminal fluid which opposes
NACL reabsorption
• 2.Inhibits transport process in the thick Asc LH
• (UNKOWNMECH)
• 3.Expands extracellular fluid volume–increaseGFR
• -inhibits renin release
• 4.Increases renal blood flow
• cortico-medullary osmotic gradient is dissipated-passive salt
reabsorption is reduced.
 PHARMACOKINETICS:
• Not absorbed orally
• I.V route
• 10-20%solution, t1/2 – 0.5-1.5hrs
• Uses:Increased ICP and IOP
• Impending ARF
• Dialysis disequilibrium
• Contraindication-
• Acute tubular necrosis
• Anuria
• Pulmonary edema
• Acute LVF
• CHF,cerebral hemorrhage
• Side effect-headache,nausea,vomiting
 POTASIUM SPARING DIURETIC
• SPIRONOLACTONE- ALDOSTERONE INHIBITOR
• It is steroid,chemically related to the mineralocorticoid aldosterone
• Site of action-late DT and CD cells
• Mechanism of action-by combining with Intracellular MR Receptors
(mineralocorticoid receptors)-induce the formation of ALDOSTRONE
INDUCEDPROTEINS(AIPs)- Promotes Na reabsorption and k secretion.
• Spironolactone act by interstitial side of tubular cells-combing with MR
and inhibits AIPs ina competitive manner-increase Na excretion and
decreases k excretion.
• K retaining action develops over 3-4days
• Spironolactone–increases Ca excretion

• PHARMACOKINETICS- Oral bioavailability-75%

• Highly bound to plasma proteins
• Completely metabolised in liver
• Active metabolite- CANRENONE(T1/2-18hrs, T1/2 : 1-2hrs
• Uses–spironolactone
• 1.Tocounteractklossduetothiazideorloop
• diuretics
• 2.Edema-cirrhoticornephrotic
• 3.Hypertension-adjuvanttothiazides
• 4.CHF
• SIDEEFFECTS-drowsiness,ataxia,mentalconfusion,
• epigastricdistress,loosemotion,gynaecomastia,
• erectiledysfunction,lossoflibido,breasttenderness,
• irregularmenustrations
 Acetazolamide
Availability – 125, 250, 500mg tab/capsule
500mg powder for IV
MOA
• 1.Non-competitive but reversible inhibitor of CA in
PT ,decreased availability of H+ toexchange with luminal Na
through Na-H+ antiport.
• 2.Inhibition of brush border CAs causes HCO3 wastage

• Urine produced under Acetazolamide-alkaline,rich in

HCO3,matched with both Na and k
•
PHARMACOKINETICS:
• Well absorbed orally,Excreted unchanged inurine
• Duration of action-8-12hrs
Uses-
• To alkalinize urine
• high altitude sickness
• periodic paralysis
• pseudotumor cerebri
• Epilepsy
• glaucoma

• Adverse effects- Acidosis•Hypokalemia, •Fatigue, Hypersensitivity reaction,

Bonemarrow depression
What are the drug interactions?
• Furosemide + Aminoglycosides →Increased ototoxicity
• NSAIDs inhibit prostaglandin synthesis and cause
decrease in its efficacy.
• Probenecid inhibit tubular secretion of furosemide.
• Enhances neuromuscular blockade by reducing
transmitter release at nerve synapse
• terminal. Moreover hypokalemia produced by the drug
potentiates neuromuscular blockade even further.
ANTICHOLINERGICS
 Classification
• Natural- atropine, scopolamine
• Synthetic
- structural analogue to atropine
tertiary: homatropine
quaternery : ipratropium, tiotropium
• - structurally non related to atropine
 tertiary: dicyclomine, tropicamide
quaternery: propantheline,glycopyrrolate
Mechanism Of Action?
• Anticholinergic drugs are reversible,
competitive antagonist which inhibit action of
acetylcholine at muscarinic receptors. They
are basically antimuscarinic drugs. There are
five types of muscarinic receptors. M1-5
Atropine Glycopyrollate scopalamine
tertiary amine Semisynthetic, quaternary tertiary amine
natural, belladonna plant ammonium compound natural
0.6 mg/ml of atropine sulphate 0.2 mg/ml of glycopyrrolate. 0.4 & 1mg/ ml of hyoscine
hydrobromide.
Hyoscine butyl bromide comes as
10 mg tablet and 20 mg/ml
injection
Patch 1mg/3days
anticholinergic effects are mainly clearance frm plasma is rapid thn Scopolamine is 1 –
due to the levorotatory atropine n eliminated 80% hyoscine.
form. unchanged in urine 1% unchngd in urine
18% unchngd in urine Elimination in uremic pts is
prolonged

Iv onset within 1min, Duration of Iv onset of action 2-3min. onset of action 10-15min.
action 30 to 60 min duration 2 hours duration 2 hours

Antisialagogue

+ ++ +++

10 to 20 mic/kg 5 to 8mic/kg, longer n potent 5mic/kg and ocular effects

antisiala gogue are more
More effect in heart,
bronchial smooth muscle, GIT
Atropine Glycopyrolate Scopalamine
tachycardia +++ ++ +
Bronchodilation ++ ++ +
CNS EFFECTS + Does not cross blood +
brain
Can cause central Sedation +++,
anticholinergic syndrome. No effect on pupil size or antiemetic(motion induced
accommodation. No sedation. nausea- transdermal),
Sedation is less marked DISADVANTAGES= antanalgesic,
than hyoscine. causes Glaucoma
Central anticholinergic
syndrome.
Marked cycloplegia and
mydriasis.
0.01 to 0.02 mg/ Kg 0.005 to 0.01 mg/Kg for 0.01 to 0.02 mg/Kg for
for premedication Premedication premedication
- Vagolytic dose is 2 – 3
mg.
Sweating is Inhibited leading
to increase in body
temperature
 Atropine
Why Paradoxical bradycardia can occur at low
doses of atropine?.

Mechanism:-
• Paradoxical bradycardia at low doses suggest
a Partial agonist action of these drugs to the
levorotatory form
• Why glycopyrolate is given along with
neostigmine?
– onset and duration of action of both the drugs are
similar
– minimal impairment of parasympathetic nervous
system control of HR specially in IHD
– prevent excess peristalsis produced by
Neostigmine in high doses
 What are the uses of anticholinergics?

• Premedication
• Treatment of reflex mediated bradycardia
• Reversal
• Treatment of OP poisoning
• Less commonly in treatment of –
bronchodilation, biliary and urethral smooth
muscle relaxation , production of mydriasis and
cycloplegia
• Prevention of motion induced nausea
 Role as premedication?

• Previously atropine was used as premedication to prevent

vagal reflexes and secretion during induction, but now
because of improved pharmaodynamic profile of
inhalational and induction agents its use as
premedication may not be required. It causes
unnecessary tachycardia and thickening of secretions.
• Scopalamine and atropine can be used as premedication
if sedation and antisialogue effect is required.
• Careful in glaucoma and parturient patients but
glycopyrolate can be used as it has minimal effect on pupil
size
 Drug interactions
• Morphine and scopolamine have additive actions
• Anticholinergic with opioids and benzodiazepines
• Inhalational can potentiate anticholinergic drug effects on
CNS-> restless, somnoloscence (treatment: physostigmine)
• During anaesthesia which includes volatile agent, the dose
of atropine required to increase heart rate is less
compared to awake patients may be due to depression of
vagal centres under anaesthesia-
• If treatment for glaucoma are continued atropine /
glycolpyrolate will not cause increases in IOP when used as
premedication
• Atropine 0.5mg iv can treat hiccughs due to LMA after its
placement
 What is CAS?

• Central anticholinergic syndrome

• restlessness, haluccinations, somnoloscence,
unconciousness, can be DD for delayed
recovery
• Treat with physostigmine anticholinesterase
drug 15-60mic/kg iv, repeat the dose hourly as
it is metabolized fast
Thank you.......