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ATROPINE &
GLYCOPYROLATE
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z ATROPINE

 NATURALLY OCCURING ANTICOLINERGIC ANTI

MUSCARINIC DRUG

 EXTRACTED FROM BELLADONA PLANTS

 TERTIARY AMINE COMPOUND

This Photo by
Unknown Author is
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STRUCTURE

 (C12H23NO3)2H2SO4.H2O

 Ester of tropic acid and organic base of tropine

 Recemic mixture of d& l isomer

 L isomer is anticholinergic
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PRESENTATION

 CLEAR COLOURLESS SOLUTION

 0.6mg / ml of ATROPINE SULPHATE

 1% EYE DROPS / OINTMENTS

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MECHANISM OF ACTION

 COMBINES REVERSIBLY WITH MUSCARINIC CHOLINERGIC

RECEPTOR

 COMPITATIVE INHIBITOR
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MUSCARINIC RECEPTOR

 SITES

 Heart

 Blood vessels

 Eye

 Smooth muscle &glands of GIT, RT,UT

 Sweat glands

 Cns
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SUB TYPES

 M1-M5

 M1 CNS AND STOMACH

 M2 HEART AND LUNGS

 M3 CNS SMOOTH MUSCLES AND GLANDS

 M4 & M5 CNS
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PHARMACOKINETICS

 ROUTES

 IV

 IM

 ORAL

 ENDOTRACHEAL

 TOPICAL

 S/C
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ONSET DURATION
IV 1 MIN 30-60 MIN
IM 30-45MIN 2-3 HRS
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METABOLISM

 LIPID SOLUBLE AND 50% PROTEIN BOUND

 LIVER - HYDROLISIS

 18% EXCREATED UNCHANGED IN URINE

 ELIMINATION t half 2-3 hrs

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PHARMACODYNAMICS

 CVS

Inhibition of vagal influence on SA node --- TACHYCARDIA

Reduces refractory period of AV node & facilitates AV conduction

Weak muscarinic agonist action ------ bradycardia at low dose

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CNS

STIMULANT ACTION

STIMULATES MEDULLARY CENTERS VAGAL ,RESPIRATORY AND

VASOMOTOR

BASAL GANGLIA – BLOCKS COLINERGIC OVER ACTIVITY

DEPRESS VESTIBULAR EXCITATON – PREVENTS MOTION SICKNESS

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 CNS OVERDOSE

 CORTICAL EXCITATION

 RESTLESSNESS

 DISORIENTATION

 HALLUCINATION

 DELIRIUM

 RESPORATORY DEPRESSION

 COMA
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EYE

TOPICAL

Ciliary muscle relaxation

mydriasis

abolition of light reflexes

cycloplegia

lasts for 7-10 days

IOP raises ( open angle glaucoma)

Parenteral – no effect
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Body temptarure

 Rise body temperature at higher doses

 Inhibition of sweating & stimulation of temp regulatory centre

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Smooth muscles

GIT – TONE AND AMPLITUDE OF CONTRACTIONS REDUCED

CHYME PASSAGE SLOWED

REDUCES OPENING PRESSURE OF LES

RESP- BRONCHO DIALATION & REDUCES AIRWAY

RESISTANCE

RELAXANT ACTION ON URETER & URINARY BLADDER

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GLANDS

 REDUCES SWEAT SALIVARY TRACHEOBRONCHIAL AND

LACRIMAL SECRETIONS

 SECRETION OF ACID PEPSIN & MUCUS IN STOMACH

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USES

 PRE OP MEDICATION

 ANTI SIALOGOGUE EFFECT

 Rx of reflex mediated bradycardia

 Antidote for cholinergic drug over dose

 In AV block

 As mydriatic and cycloplegic

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ADVERSE EFFECTS

 DRYNESS OF MOUTH

 BLURED VISION , PHOTOPHOBIA

 ANHYDROSIS

 CONSTIPATION

 DIFFICULTY IN MICTURATION

 HEADACHE DIZZINESS RASH

 RISE IN TEMPRATURE

 ATROPINE CONVULTIONS
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CENTRAL ANTICHOLINERGIC
SYNDROME

 RESTLESSNESS,
HALLUCINATION,SOMNOLENCE,UNCONCIOUSNESS

 BLOCKADE OF MUSCARINIC CHOLINERGIC RECEPTORS

IN CNS

 TREATEMENT- PHYSOSTIGMINE 15-60mcg/kgIV

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ATROPINE TOXICITY
Hot as a hare , blind as a bat, dry as a bone , red as a beet and mad as a wet hen.

 Dry mouth, difficulty in swallowing & talking

 Blurred vision

 Tachycardia

 Excitement, psychotic behaviour, ataxia,delirium

 CV collapse

 Respiratory depression

 Convultions

 Coma

 RX –PHYSOSTIGMINE 15-20 mcg/kg

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PRECAUTIONS

 NARROW ANGLE GLAUCOMA

 PROSTATIC HYPERTROPHY

 FEBRILE CHILDREN
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DRUG INTERATION

 TCA, phenothizides, diisopyridine, anti histamines – additive

synergistic effect

 Delays absorbtion of drugs

 Antacids interfere absorbtion of atropine

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DOSE

 PREMEDICATION 0.01 mg/kg

 Reversal of NDMR BLOCK :0.02mg/kg

 Oral 0.04mg/kg
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GLYCOPYRROLATE

 SYNTHETIC

 QUATERNARY AMINE

 ANTI MUSCARINIC

 ALSO CALLED GLYCOPYRRONIUM

 COMBINE REVERSIBLY WITH MUSCARINIC RECEPTORS

 PREVENT ACCESS TO Ach to RECEPTOR

 COMPETATIVE ANTAGONISM
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 ORDER OF BLOCK

 -M3RECEPTOR(SALIVARY AND BRONCHIALSECRETIONS)

 – M2 RECEPTORS ( HEART EYES)

 M1 RECEPTOR (INHIBIT GASTRIC SECRETION OF H+

IONS)-
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 SMALL DOSES OF ATROPINE & GLYCOPYROLATE

PRODUCE BRADYCARDIA

 Blockage of presynaptic muscarinic receptors on vagal post

ganglionic fibers that normally limit Ach release in SAnode
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DISTRIBUTION

 REDISTRIBUTION RAPID

 90% DOSE DISSAPEAR IN 5 MIN

 CLEARENCE RAPID THAN ATROPINE

 ELIMINATION T1/2-1.25 HRS ( ATROPINE 2-3 HRS)

 VOLUME OF DISRIBUTION 0.2-0.64L/kg

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METABOLISM
 Hydroxylation & oxidation in liver

 EXCRETION
 80% EXCREATED UNCHANGED

 URINE 85%, BILE 15%

 RATE OF CLEARENCE 0.89L/MIN

 ELIMINATION T1/2 0.6-1.1 HRs

 Elimination t1/2- PROLONGED IN UREMIA

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cvs
 Tachycardia—

IV

DOSE >0.2 mg

Slow onset than atropine

Protect against drug induced & reflex bradycardia

Blood pressure –little effect in normal doses

Dysrhythmia less than atropine

Vagolytic effect- last for 2-3 hrs

most marked in those with high vagal tone

less marked in infants and elderly

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RESPIRATORY SYSTEM

 Bronchodilator- significant and long lasting

 Large medium sized airways

 Decrease airway resistance

 Increase physiological dead space

 Effect more in patients with airway disease

 Reduces resp tract secretions

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CNS

 NOT CROSS BBB IN USUAL DOSES

 DEVOID OF CENTRAL EFFECTS

 NO EFFECT ON PUPIL SIZE OR ACCOMODATION

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ALIMENTARY SYSTEM

 ANTI SIALAGOGE EFFECT –LAST FOR 8 HRS

 5 TIMES MORE POTENT THAN ATROPINE

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OTHER ACTIONS

 SWEAT GLAND-INHIBIT

 WEAK LOCAL ANESTETIC EFFECT

 MAY CROSS PLACENTA – FEATAL TACHY

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 CLEAR AQUEOUS SOLUTION FOR INJECTION CONTAINS

 GLYCOPYRRONIUM BROMIDE 0.2 MG/ML

 BENZYL ALCOHOL -0.9%(PRESERVATIVE)

 PH ADJUSTED WITH HCL OR NaOH

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 FIXED DOSE COMBINATION OF 0.5 MG GLYCO WITH 2.5 MG

OF NEOSTIGMINE FOR NM REVERSAL

 TOPICAL APPLICATION 0.5% POWDER CREAM OR

SOLUTION
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ROUTES

 IV

 IM

 TOPICAL
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USES

 PREMEDICATION

 TREATEMENT OF REFLEX BRADYCARDIA

 PROTECT AGAINST PERIPHERAL MUSCARINIC EFFECT OF

ANTICHOLINEESTERASES
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ADVERSE EFFECTS
 DRY MOUTH

 DIFFICULTY IN MICTURATION

 INHIBITION OF SWEATING

 RISE IN BODY TEMP

 DIFFICULTY IN SWALLOWING AND TALKING

 BLURRED VISION AND PHOTOPHOBIA

 PALPITATION

 LOSS OF TASTE

 DROWSINESS

 CONFUSION OR EXCITEMENT IN ELDERLY

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PARAMETER ATROPINE GLYCOPYROLATE

NATURAL/ NATURAL SYNTHETIC
SYNTHETIC
TYPE TERTIARY AMINE QUATERNARY AMINE
LIPID SOLUBLITY HIGH LOW
ORAL ABSORBTION MORE LESS
CLEARENCE LESS RAPID RAPID
T1/2 2-3 HRS 1.25 HRS
EXCREATED UN 18% 80%
CHANGED
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PARAMETER ATROPINE GLYCOPYROLATE

CNS STIMULATION PRESENT ABSENT

BBB CROSS NO
EYE MYDRIASIS NA
DOSE 10-20mcg/kg 4-10mcg/kg
Oral absortion more less
Duration of action less more
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