Small review but sufficient for Glycopyrrplate

1. Glycopyrrolate
robinul

2. – It’s a synthetic anticholinergic drug
– Frequently used in anasthetic practice
– used as a preoperative medication in order to
reduce salivary,
– decreases acid secretion in the stomach and
so may be used for treating stomach ulcers
– Use in treating asthma and COPD

3. Important aspect of glycopyrrolate
– Glycopyrrolate does not cross the blood brain
barriers (BBB) ,,,,, due its polar (charged) structure ,,
& therefore does not exert CNS effects.
– This is unlike other commons antimuscarinics such
as atropine which are non-polar (uncharged) and can
cross the BBB .

4. – Also has very low volume of distribution (Vb)

5. Mechanism of action
– Competitive blockade of peripheral muscarinic
acetylcholine receptors .

6. Understand the mechanism !
– Five identical muscarinic receptors (M1-M5)
– Does not exhibit preference for any of muscarinic
receptors isoforms…….
– Limited to peripheral muscarinic
– Does not activate receptor,, but just occupies receptor
and preventing the action of Ach.

7. – Bind on M1,,M2,,,and less,,M3
– To understand how glycopyrrolate achieves
its clinical effects,, we must first understand
acetylcholine’s effects at various muscarinic
receptors.

8. acetylcholine’s effects at muscarinic receptors.
– All muscarinic receptors are G-coupled protein
receptors (GCPR)
– GCPR activation lead to a cascade of intercellular
second messengers
– M1 & M3 receptors are Gq GCPRs.
– M2 receptors are Gi GPCRs .

9. acetylcholine’s effects at muscarinic receptors
– M1 & M3 receptors are Gq GCPR
 Acetylcholine stimulates IP3/DAG pathway.
Generally leads to increases in
intercellular calicium
Implicated in salivatioon , sweating
mucous secretions ,smooth muscle
contraction and pupil constriction .

11. acetylcholine’s effects at muscarinic receptors.
– M2 receptors are Gi GCPRs
– Acetylcholine stimulates an inhibitory
responses leading to a decrease in AC,Camp,&
PKA activity.
– Implicated largely in cardiac declaration (vagal
responses) …

12. Mechanism of action
– Glycopyrrolate competitively blocks acetylcholine
– Resulting blocked create parasympatholytic
– Allows for dominant sympathetic activity
– No interfere on NMJ …

13. Mechanism of action

14. Now lets talk about glycopyrrolate
– Glycopyrrolate = glycopyrronium bromide
– medication of the muscarinic anticholinergic group.
– It does not cross the blood–brain barrier and consequently
has no to few central effects
– A synthetic quaternary amine
– it is available in oral and intravenous (i.v.) forms and also
inhaler .
– It was developed by Sosei and licensed to Novartis n 2005

15. So whats used for?
– In anesthesia,,,,, anesthetic premedication
agent.
– glycopyrronium injection can be used as a
preoperative medication in order to
reduce salivary

16. – In peptic ulcer
– It decreases acid secretion in the stomach
and so may be used for treating stomach
ulcers , in combination with other
medications.

17. – It has been used topically and orally to
treat hyperhidrosis, in particular, gustatory
hyperhidrosis
– DryDerm G facial cream.
For gustatory sweating and excessive sweating
of the facial region. -

18. – conjunction with neostigmine,
a neuromuscular blocking reversal agent,
to prevent neostigmine's muscarinic effects
such as bradycardia.

19. – Use in treating asthma and COPD
– Glycopyrronium inhaled
– As LAMA ,,, long acting muscarinic antagonist
– Produce bronchodilation

20. Dosage 💉💊
– Tablets: 1mg ,2mg ,
– Oral solution: 1mg/5ml
– Injectable solution (I.V)(I.M):
0.2mg/ml ..also availabale
0.4mg/2ml,,1mg/5ml (vial).
– inhaler

21. dosing
– 0.4mg/kg for antisalivation (antisailagogue
)activity and to treat intraoperative
bradycardia
– 0.2mg (1ml) for every 1mg of neostigmine
administration .

22. onset
– i.v injection : within one minute
– i.m injection: 15 to 30 minute

23. duration
– Vagal blockade persist for 2-3 hours
– Anti salivation effec persist for up to 8 hours
– T1/2 : approximate 45 min
– Corresponds with drugs elimination half-life

24. Metabolism( pharmacokinetics )
– Undergoes little metabolism
– 80% excreted unchanged via kidneys and liver

25. Anesthetic indication
– Antisailagogoue
– Prevents upper airway secretions thereby
facilitating procedures and visualization
– Given with ketamine to prevent hypersalivation
– Intraoperative bradycardia
– Given with neostigmine to counteract effects of
acetylcholine
– Potentially prevent bronchoconstriction .

26. Side effects
– glycopyrronium reduces the body's sweating ability,
– it can even cause fever , flushing and heat stroke in hot environments.
– Dry mouth …… 40% ,
– difficulty urinating,
– headaches, N/V and constipation are also observed side effects of the
medication.
– The medication also induces drowsiness or blurred vision, an effect
exacerbated by the consumption of alcohol.

27. Some social manners
The drug is too
expensive about 400$
for the brand (30 tablets)
and that may restrict it
use , because we can
combine one or more
drug to get the same
effect or better …….?
So why Novartis comp.
push the huge amount of
money for this drug !!

28. The reason is because it's fewer atropine & atropine like S/E
on Brian & NMJ and because its efficacy as in the taste for
8 weeks as in below

29. What about Lactation…..?

30. Anticholinergic agents may
suppress lactation. It is not
known whether
glycopyrrolate is excreted in
human milk.
No milk
☹️

31. What about pregnant……?
It's Category B2
Clinically the safe use
of glycopyrrolate has
not been established
Reproduction studies
in rats and rabbits did
not reveal any
teratogenic effects
drug should not be used in
pregnant women, or those likely
to become pregnant, unless the
expected benefits outweigh any
potential risk

32. Ansthetic contraindication
– Mostly relative and include:
– Hpersensitivity
– Tachycardia
– Obsructive uropathy
– Glaucoma