Atropine drug profile

Atropine drug profile

1. DRUG PROFILE
LAHORE PHARMACY COLLEGE

AMMARA BATOOL
ALLOTTED DRUG: Atropine Drug category: parasympatholytics
WHO essential medicine list: present National essential medicine list: present
Generic Atropine
Synonyms Jimsonweed deadly nightshade [4]
Atropiini; Atropin; Atropina; Atropinas; Atropinum; (±)-Hyoscyamine.
(1R,3r,5S,8r)-Tropan-3-yl (RS)-tropate.[2]

Structure,
Mol Formula&
Mol. Weight.



Molecular Formula: C17H23NO3

Molecular Weight: 289.4 g/mol
[2]






Chemical Name Atropine sulphate ( tertiary amine alkaloid ester)[4]
Class Chemical Tropane alkaloids [1]
Pharmacological Muscarinic receptor blocking drugs[1]
Therapeutic Parasympatholytics[1]
Main structural
activity

Atropine, a naturally occurring belladonna alkaloid, is a racemic mixture of equal
parts of d- and 1-hyocyamine, whose activity is due almost entirely to the levo

2. isomer of the drug.[6]
inhibitors of the actions of acetylcholine
at the muscarinic receptor[1]

Physicochemical
properties
Acidic/Basic/Neutral
Weekly acidic drug [3]
PKa=9.7
[4]
pH=
4.5-6.2[2]

USP 31 (Atropine). White crystals, usually needle-like, or white
Crystalline powder. Soluble 1 in 460 of water, 1 in 90 of water at
80°, 1 in 2 of alcohol, 1 in 1 of chloroform, and 1 in 25 of ether,
Soluble in glycerol. Its saturated solution in water is alkaline to
Phenolphthalein. Store in airtight containers. Protect from light. [2]

Mechanism of
action

Atropine cause reversible blockage of cholinomimetic actions at muscarinic
receptors.
When atropine binds to the muscarinicreceptor, it prevents actions such as the
release of inositol triphosphate and the inhibition of adenyl cyclas that are caused
by muscarinic agonists.
Atropine is highly selective for muscarinic receptors .its potency at nicotinic
receptors is much lower. [4]


PHARMACOKINETICS
Absorption Absorbed rapidly
from the GI tract and mucosal surfaces; absorption from intact skin is
limited, although efficient
absorption does occur in the postauricular region for some agents, allowing
delivery via transdermal
patch. [1]
Distribution Bioavailability
%
95% [3]
PPB % 50% [3]
T1/2 4 hr [2]
Clearance Rapidly cleared from blood [2]
Vd 1-6l/kg [3]
BBB Yes [2] No
Cross Placenta Yes [2] No
Prodrug No
Metabolism
and
elimination

Mechanism
/CYP

NA

Active
metabolites
Yes

Main route


Hepatic
metabolism [2

incompletely
metabolized
in the liver
[2]
Name (if yes):

Noratropine (24%),
atropine-N-oxide
(equatorial isomer) (15%),
tropine (2%) and tropic
acid (3%) appear to be the
major metabolites, while
50% of the administered
dose is excreted as
apparently unchanged
atropine. No conjugates
were detectable. Evidence



excreted in
the
urine as
unchanged
drug and
metabolites

3. [2]

that atropine is present as
(+)-hyoscyamine was
found, suggesting that
stereoselective
metabolism of atropine
probably occurs.[14]

4. PHARMACODYNAMICS
Onset of action 7-8 minutes[6]
Duration of action 7-10 days [4]
Spectrum
(In case of
antibiotics)


NA




Contra-indications
Glaucoma, especially angle closure glaucoma ,acid peptic disease[4]in
myasthenia gravis paralytic ileus, pyloric stenosis,
toxic mega colon, and prostatic enlargement[7]
Side effects /ADRs At
therapeutic
dose


At therapeutic doses, adverse effects include dryness of
the mouth with difficulty in swallowing and talking,
thirst, reduced bronchial secretions, dilatation of the
pupils (mydriasis) with loss of accommodation (cycloplegia)
and photophobia, flushing and dryness of
the skin, transient bradycardia followed by tachycardia,
with palpitations and arrhythmias, and difficulty in
micturition, as well as reduction in the tone and motility
of the gastrointestinal tract leading to constipation [2]

Effects of Atropine in Relation to Dose
Dose Effects
0.5 mg Slight cardiac slowing; some dryness of mouth;
inhibition of sweating
1 mg Definite dryness of mouth; thirst; acceleration of
heart, sometimes preceded
by slowing; mild dilation of pupils
2 mg Rapid heart rate; palpitation; marked dryness of
mouth; dilated pupils; some
blurring of near vision
5 mg All the above symptoms marked; difficulty in
speaking and swallowing;
restlessness and fatigue; headache; dry, hot skin;
difficulty in micturition;
reduced intestinal peristalsis
10 mg and more Above symptoms more marked; pulse
rapid and weak; iris practically
obliterated; vision very blurred; skin flushed, hot, dry, and
scarlet; ataxia,
restlessness, and excitement; hallucinations and delirium;
coma[1]

In overdose In over dosage, the peripheral effects become more

5. pronounced and other symptoms such as hyperthermia,
hypertension, increased respiratory rate, and nausea
And vomiting may occur. A rash may appear on the
Face or upper trunk. Toxic doses also cause CNS stimulation
marked by restlessness, confusion, excitement,
ataxia, in coordination, paranoid and psychotic reactions,
hallucinations and delirium, and occasionally
Seizures. [2]
In sever
intoxication

in severe intoxication, central stimulation
may give way to CNS depression, coma, circulatory
and respiratory failure, and death[2]



Precautions
Atropine should be used with caution in children and
the elderly, who may be more susceptible to its adverse
effects
[2]

Pregnancy
category (FDA)
A B C [5]

D X
Lactation Excreted in milk Yes[2] No

During lactation Continue [2] Discontinue

6. INDICATIONS & POSOLOGY
Indications Route of
Administratio
n
Posology
Doses Neonates Childs Adults
Eye disorders
(uveitis
or iritis
,(cycloplegia)
Topical Drops NA Cycloplegia
Child 3
months–18
years apply
drops or
ointment
twice daily for
3 days before
procedure

1 or 2 drops 4
times a day[7]
Anterior
uveitis
Child 2–18
years 1 drop
up to 4 times
daily [8]

Divided
doses
2 or 4 4
Max daily
dose
NA 4 drops[7] 8 drops[7]
Duration of
therapy
NA Until required Until required
Antidote to
organophosphorus
poisoning
(Control of
muscarinic side-
effects of
neostigmine
50
micrograms/kg
in reversal of
competitive
neuromuscular
block)




Control of
muscarinic side-
effects of
By
intravenous
injection
mg/kg/dose 20 Child 1
month–12
years 20
micrograms/kg
[8]
2mg
20mg [7]
Child 12–18
years 0.6–1.2
mg[8]


Child 1
month–18
years 7
micrograms/kg
[8]

Max daily
dose
1.2mg [8]
Duration of
therapy
Every 5-10
minutes [7]
Every 10-30
minutes [7]

7. edrophonium
in reversal of
competitive
neuromuscular



Anesthesia By
intravenous
injection
immediately
before
induction of
anaesthesia











By
subcutaneou
s or
intramuscular
injection
30–60
minutes
before
induction of
anaesthesia
microgram/
kg/dose
10


10 [8]
Child 1
month–12
years 20
micrograms/kg
(minimum 100
micrograms,
max. 600
micrograms)
Child 12–18
years 300–
600
micrograms




Child 1
month–12
years 10–30
micrograms/kg
(minimum 100
micrograms.
[8]



300-600
microgram [7]
Child 12–18
years 300–
600
micrograms[8]


mg/kg/day
Max daily
dose
600
microgram[8]
600 microgram
[8]

Duration of
therapy
Until required Until required Until required
Other indications Arrhythmias after myocardial infarction, As an antidote to
organophosphorous (insecticides) poisoning, Asthma,
Cardiopulmonary resuscitation, Choroiditis, Control of
muscarinic side-effects of neostigmine, Diarrhoea, Drying
secretions, Dysenteries, Intra-operative bradycardia,

8. Iridocyclitis, Irritable colon syndrome, Myocardial infarction,
Peptic ulcer, Poisoning, Pyloric disease, Tetanus.[2] [3] [4] [7]

Dosage
Adjustment
(In case of Renal
& Hepatic
impairment)
Renal dose adjustment:No adjustment recommended
Liver Dose Adjustments: Only for patients with mild liver disease.
Initial dose: 1 tablet (or 5 mL of liquid) orally 2 to 4 times a day.
Maintenance dose: 1 tablet (or 5 mL of liquid) once a day.[6]

9. ADMINISTRATION GUIDELINES
Route NTRAMUSCULAR, INTRAVENOUS, SUBCUTANEOUS, ENDOTRACHEAL.
Reconstitution
and Storage
condition



RECONSTITUTION:
For new born use:
Dilute 1ml (600mcg) of atropine with
5ml
of water for injection to make
100mcg/ml solution [12]
STORAGE:
Discard unused portion.[12]
Protect from light[2}
Store Below 40°C. Do not Freeze.
[3]

Rate &Method of
administration




Slow IV bolus injection using the proximal IV bung. May be given via ETT
if
IV access is not available.[12]

Compatible I/V
fluids
NA
Pharmaceutical
Incompatibilities
Incompatibility between atropine sulfate and
hydroxybenzoate preservatives has been seen,1 resulting in a
total loss of the atropine in 2 to 3 weeks.[2]
CLINICAL MONITORING

Injection
Monitor for acute glaucoma, conversion of partial organic pyloric stenosis into complete obstruction,
complete urinary retention, inspissation of bronchial secretions, formation of viscid plugs, and other
possible adverse effects.[11]

Atropine ophthalmic:
Monitor for BP elevation and other adverse reactions.[11]

10. INTERACTIONS & MANAGEMENT
Interactions Class Drugs Effects
Drug-Drug Alcohol



antimuscarinics

Analgesics






Nitrates







Antidepressants






Antihistamines






Antipsychotics






Ethanol

Benztropine

codeine
nefopam



glyceryl nitrate






MAOIs or tricyclics




Antazoline,diphenhydramine
azelastin
bromphenaramine
carbinoxamine

Haloperidol ,clozapine




Increase sedative
Effect
increase
antimuscarinic side
effects
increase antimuscarinic
side effects

reduce effects of
sublingual tablets of
nitrates (failure to
dissolve
under tongue owing
to dry mouth)



increase antimuscarinic
side effects




increase risk of
antimuscarinic side
effects


increase
antimusuranic side
effect

11. Cardiac glycosides





Benzodiazipine




Anti ulcer


Digoxin


Chlordiazepoxide



Cinitapride
Metclopramide


increase digoxin effect


increase effect of
chlordiazepoxide


reduce action of
metclopramide and
cinitapride [7][3]
Svere

 ambenonium
 eluxadoline
 pramlintide
Moderate

 amantadine
 amitriptyline
 amoxapine
 anticholinergic
 aripiprazole
 belladonna alkaloids
 belladonna and opium
 benztropine
 bethanechol
 chlorpromazine
 clomipramine
 clozapine
 cyclizin
 digoxin
 diphenhydramine
 droperidol
 fentanyl
 haloperidol
 homatropine
 imipramine
 ipratropium
 meclizine
 scopolamine
 neostigmine
 nortriptyline
 paliperidone
 perphenazine
 physostigmine [10]
Mild
 amitriptyline
 amoxapine
 atenolol
 chlorpromazine
 clomipramine
 desipramine
 dimenhydrinate
 donepezil
 dosulepin
 doxepin
 fluphenazine
 galantamine
 imipramine
 levodopa
 lofepramine
 maprotiline
 mianserin
 nortriptyline
 perphenazine
 prochlorperazine
 promazine
 promethazine
 protriptyline
 tacrine
 thioridazine
 trazodone
 trifluoperazine
 trimipramine [10]

12. Drug-Food


Avoid alcohol.
Take with food.[13 ]


















TOXICITY
Type Signs Management
Severe in severe intoxication,
central stimulation
may give way to CNS
depression, coma,
circulatory
and respiratory failure,
and death.[2]

If a patient presents within an hour of an overdose of
atropine by mouth the stomach may be emptied or
activated
Charcoal given to reduce absorption. Supportive
Therapy should be given as required.
Physostigmine has been tried for antimuscarinic poisoning
but such use can be hazardous and
Is not generally recommended. Diazepam may be given
to control marked excitement and convulsions;
phenothiazines
should not be given as they may exacerbate
Antimuscarinic effects. Antiarrhythmics are not
recommendedif arrhythmias develop; hypoxia and acidosis
should be corrected and sodium bicarbonate may be given
even if acidosis is not present.[2]

13. Moderate Toxic doses also cause
CNS stimulation
marked by restlessness,
confusion, excitement,
ataxia, incoordination,
paranoid and psychotic
reactions, hallucinations
and delirium, and
occasionally
seizures.[2]





























Mild

In overdosage, the
peripheral effects
become more
pronounced and other
symptoms such as
hyperthermia,
hypertension, increased
respiratory rate, and
nausea
and vomiting may
occur. A rash may
appear on the
face or upper trunk.[2]

14. PATIENT COUNSELING
Purpose For different conditions as mentioned in indications.
Instruction for use
 Oral
 Advise patient using atropine for GI problems to take prescribed dose
30 to 60 min before meals and at bedtime.
 Advice patient using atropine for other conditions to take as prescribed
without regard to meals, but to take with food if stomach upset occurs.
 Advise patient that dose and/or frequency of use may be changed
periodically to achieve max benefit.
 Caution patient not to change the dose or stop taking unless advised by
health care provider. Advise patient to notify health care provider if
symptoms do not improve, appear to worsen, or if bothersome side
effects occur.
 Instruct patient to stop taking the drug and notify health care provider
immediately if any of the following occur: rash, flushing, eye pain,
inability to urinate, confusion, disorientation, hallucinations, change in
behavior.
 Advise patient to avoid strenuous activity during periods of high
temperature or humidity.
 Advise patient to take sips of water, suck on ice chips or sugarless hard
candy, or chew sugarless gum if dry mouth occurs.
 Inform patient that medication may cause pupils to dilate, resulting in
intolerance to bright lights or sunlight. Advise patient to wear dark
glasses to make bright lights or sunlight tolerable.
 Advise patient that drug may cause drowsiness, dizziness, or blurred
vision, and to use caution while driving or performing other tasks
requiring mental alertness until tolerance is determined.
 Ophthalmic
 Remind patient or caregiver that solution and ointment are for use in
the eye only.
 Teach patient or caregiver proper technique for instilling ophthalmic
solution or ointment: wash hands; do not allow tip of dropper bottle or
tube to touch eye, eyelid, fingers or any other surface. Tilt head back,
look up; pull lower eyelid down to form pocket; place prescribed
number of drops or amount of ointment in the pocket; look downward
before closing eye; compress lacrimal sac for 2 to 3 min after
instillation complete. Caution patient not to rub eye(s).
 Advise patient or caregiver that if more than 1 topical ophthalmic drug
is being used, instill eye drops first, wait at least 5 min, and then instill
ointment last.
 Caution patient that blurred vision may occur and not to drive or
engage in hazardous activities while pupil(s) are dilated.
 Advise patient or caregiver to contact health care provider if eye drops
or ointment cause intolerable stinging, if eye or eyelid inflammation is

15. noted, or if eye symptoms do not improve or worsen.
 Injection
 Advise patient that medication, with exception of auto-injector, will be
prepared and administered by a health care provider in a medical
setting.
 Review the patient information leaflet and instruction guide with
potential user of auto-injector. Ensure that potential user of the auto-
injector understands the indications for and use of the auto-injector,
including symptoms of poisoning and preparation and use of the auto-
injector.
 Emphasize to potential user of auto-injector that medical attention must
be sought immediately after use of the auto-injector.
 Caution potential user of auto-injector that the primary protection
against exposure to chemical nerve agents and insecticide poisonings is
the wearing of protective garments, including masks designed
specifically for protection.[6]


Cautions Use caution when driving, operating machinery, or performing other hazardous
activities. Atropine may cause dizziness, drowsiness, or blurred vision. If you
experience dizziness, drowsiness, or blurred vision, avoid these activities.
Use alcohol cautiously. Alcohol may increase drowsiness and dizziness while
you are taking atropine.
Avoid becoming overheated in hot weather. Atropine increases the risk of
heat stroke because it causes decreased sweating.[6]
Antimuscarinics should be used with caution
in Down’s syndrome, in children and in the elderly;
they should also be used with caution in gastro-esophageal
reflux disease, diarrhea, ulcerative colitis,
autonomic neuropathy, acute myocardial infarction,
hypertension, conditions characterized by tachycardia
(including hyperthyroidism, cardiac insufficiency cardiac
surgery), pyrexia, and in individuals susceptible to angle-closure
glaucoma[7]

16. Side effects
constipation, transient bradycardia (followed by tachycardia,
palpitation and arrhythmias), reduced bronchial
secretions, urinary urgency and retention, dilatation of
the pupils with loss of accommodation, photophobia,
Dry mouth, flushing and dryness of the skin. Side-effects
that occur occasionally include confusion (particularly
in the elderly), nausea, vomiting, and giddiness; very
rarely, angle-closure glaucoma may occur.[7]
Interaction with
food

Ethanol [6]


BNF advisory label

NA

When to
discontinue
medication

As mentioned in prescription

When to report the
doctor / pharmacist
In case of any problem
Interaction with any
other medication
Ethanol,Benztropine,codeine,nefopam,glyceryl nitrate,MAOIs or
tricyclics,Antazoline,diphenhydramine,azelastin,bromphenaramine
,carbinoxamine,Haloperidol ,clozapine,Digoxin,Chlordiazepoxide
Cinitapride,Metclopramide [7]

What to do when
the dose is missed

Take the missed dose as soon as you remember. However, if it is almost time
for your next dose, skip the missed dose and take only the next regularly
scheduled dose. Do not take a double dose of this medication.[6]

17. AVAILABLE BRANDS
Sr.
#
Brands Dosage
form
Strength Mfg. by Price
(packaging)
Available at
visited store
1. Motilex Tablet 25mcg Ferozsons
laboratoies Ltd.
41.60
(10x10)
NA
2. Orbatropin Eye drops 1% w/v
15ml
7.5ml
Zafa
pharmaceutical
laboratories
20.25
(15ml)
13.0(7.5ml)
NA
3. Opth-atropine Eye drops 1% w/v
10ml
Opth –pharms
(pvt) ltd.
22.00
(10ml0
NA
4. Lomotil Tablets 25mcg Searle pakistan
pvt ltd
235.76
(500s)
NA
5. Gotil Tablets 0 Getz pharma
pakistan pvt.ltd
214
(25x20s)
NA
6. Dipotil Tablets 25mcg Unexo labs
(PVT) ltd
40.0
(10x10s)
NA
7. Elitopine Injection 1mg/ml Elite pharma 158.81
(1mlx100s)
NA
8. Atrosol Injections 1mg/ml Indus pharma
(PVT) LTD.
187.0
(10s) (maximum
price)
NA
9. Atropine
sulphate
Eye drops 1% w/v Shifa
laborateries
(PVT) LTD
NA
10. Atropisole Eye drops 1% w/v Lahore chemical
and
pharmaceutical
works (PVT) LTD
53.35
(10ml)
NA
11. Atridol Tablets 25mcg Global
pharmaceuticals
190.0
(20x250s)
NA

18. 1. Goodman and Gillman manual of pharmacology and therapeutics 2008 pg 130
2. Martindale-The complete refrence book 36
th
edition pg 1219-1221
3. http://www.druginfosys.com/Drug.aspx?drugCode=64&drugName=atropine&type=1
4. Basic and clinical pharmacology 12
th
edition by Katzung pg ,115-124
Basic and clinical pharmacology 11
th
edition by Katzung pg 11,132,140
5. Essentials of pharmacology by K.D Tripathi pg 99,
6. Drugs.com
7. BNF 68thedition pg91, 902, 48
8. BNF for children 2011-2012 pg524, 635, 636
9.pharmaguide and Pharmapedia
10. Medscap
11. http://www.pdr.net
12.http://www.seslhd.health.nsw.gov.au/RHW/Newborn_Care/Guidelines/Medication/pdf/
Atropine 600m
13.http://www.drugbank.ca/drugs/DB00572
14.http://www.ncbi.nlm.nih.gov/pubmed/2879005
12. Atrodiphen Tablets 25mcg Aims traders 205.00
(50x10)
NA
13. Atropine Eye drops 1% w/v
10ml
Lahore chemical
and
pharmaceutical
works pvt ltd.
24.82
(10ml)
NA
14. Litropine Eye
ointment
1% w/v Neo medix 70.93
(5g)
NA
15. Opta atropine


[9]
Eye drops


[9]
1% w/v

10ml
[9]
Remington
pharmaceutical
Industries
[9]

15.71
(10ml)(minimum
price)[9]
NA