Pharmacology

• Autonomic nervous system

Dr Ankit Kumar (MD, DM)

4
Lecture No.- 3
4
1 Cholinergic drugs: Directly acting

2 Myasthenia gravis

3 Carbamates and Organophosphate poisoning

 Myasthenia gravis

muscle weakness

Autoimmune Disease

Nm receptor
against

- 111 Block.
⑦
Tach Mm

Auto-Antibodies Skeletal

muscle
paints
symptomatic

Contract Paralysis

(weakness)
which Muscle : Eyes (ocular M G)

involved

Limb muscle

LAST: 'Ing Resp. paralysis

symptomatic Ht: improve weakness ' (TA)

TREAT ment:

Definiture Yt: Immunosuphsant (it. Antibody)

prod".
① Symptomatic Tlt

ATROPINE
NEOSTIG Mine (QI D) +
DOC

or
ATROPINE
ORAL PYRIDOSTIG MINE (OD) +

(Anti CHE → Mach)

shortest acting
? EDROPHONIUM (TEMSILON)

→ Not used for 7 It of MG Q

→ 1¥ Tension
→ Rather for Diagnosis of MG

Test
 9 Ach briefly
EDROPHONIUM

-
oral, ing.

improvement in Muscle weakness

Tension Test

V
{ symptoms will reduce (Amelioration
Ameliorative test

for MG

FALSE Positive # LAMBERT EATON

DRAIN BACK
syndrome
 ✗
Myasthenia gravis
Mm

Mat@Cats contract

defect → Lambert eaton synd.

like Antibody
Block Nm receptor
2 TUBO CURARE

Dangerous worsening of weakness

"Provocative Test for Myasthenia gravis"

Test is NOT

used
 EDRophonium ⇒ Also used to Differentiate between

VS Cholinergic crisis.
Myasthenic crisis

taking Meostigmine.
MG

Cholinergic
asthenic
crisis

MY crisis
over treatment
under treatment

excess Antibody (flaccid) excess Ack (spastic paralysis

paralysis

°
ED Roshonium : O

Mach)
IN Orsening
Im drovement
 DEFINITIVE TIE : Immunosuppressant

→ Remove Auto-Antibodies.

Methyl Prednisone FASTEST

DOC
Induction
or } corticosteroid. →
Acting

Prednisone Corticosteroid

Azathioprine
effect
TAPER
SLO IN
+

Take> 1 month
Azathioprine
Maintenance
to produce

(or 6 mercaptopurine) - effect

80%
Adv: STEROID sparing effect
permanently cured

(do not produce Cushing syndromey

 If no improvement

SURGERY • Thymectomy
2
① STEROID Refractory cases

Remove thymus
DOC CYCLOSPORIN or Tacrolimus
☒ source of Antibody prod"

no

Tymoma
✓ Do: associated
Add: Cyclophosphamide

Steroid Resistant cases

MYCOPH ENOLATE 2

RITUXIMAB.
✗ E: Ocular myasthenia gravis (only)

(initial stages)

→ no functional Disability
 otherwise: life Long

immunosupressed

Tension

ENSILON Test After Tension

Test
Test
for Diagnosis
(EDrophonium)

improvement
ptosis

My aesthenig

gravis
 CASE Scenario

E Resp. paralyses.
A 35 yr old female presented to emergency
*

She was suffering from myasthenia gravis !.

7
High Amount ☒ 00 n Putsme

YsgI
Anti sods
¥- mechanical
symptomatic 7) t
ing. NEO Stigmine + Atropine
ventilation

? Plasma exchange (Plasm apheresis)

l
Remove Antiboda

Ig (intravenous Ig
2

o neutralize auto-Antibodies

DOC
 Drugs avoided in myasthenia
Block Nm receptor.

3
 Irreversible Anti-CHE
OP

CARBAMATES ORGANOPHOSPHATES

*
CARBARYL INSEUTUDE, MALATHION , PARATHION, SULTHION

DYFLOZ, TIKI. DIAZ/MOM

ALDI CARI
FARMERS

PROPUXUR CHLORPYRIFOS.*

OP
BAYGON. NERVE GAS
H

INARS
TABUN Q
FARMERS → Poisoning
- sarin &

• ACCIDENTAL
SOMAN °
• sociabae}
• HOMICIDAL.
 carbamate & OP solsoning

: > ACHE
PACHE
Inhibit cholinesterase
Irreversible Antiche :

PLASMA.

M Ach

+ RED Tears
DUMBBELLS

,×nh at RBC
MIOSIS (pinpoint pupil)
Esterase

HEMOLYSIS
: Resp paralys > SHOCK
MC death
 Carbamate and OP poisoning or

nature!
> Mainly by HISTORY & Clinical
Diagnosis

•c/f
Activity of Psuedo cholinesterase & RBC esterase
LAB Test

Reduced
N ff
e
Mechanism:

Diagnosis:
s e
e
 CA

Choline-Esterase Enzyme Degrdes Ach

9
OP

Acetyl Break to
0- Iteratec
ESTERATIC

cholne - site 0
N E 1 Tacrine
(HYDR oysis

11
"
: Attachment Anionic
Anionic site
CARB Amate

• OP → Block Esteratic site • Oximes

• Carbamate → Block Both Esteratec + Anionic site

• Tacrine and Edrophonium → Block Anionic site

 OP poisoning is more Dangerous to →
AGEING of

enzyme

of p enzyme is
Esteratic
irreversibly

Blocked

slowly organic
* of OP poisoning → continues (LATE stage)

group: separate

from phosphate

cannot can never

remove

Phosphate Reactivate this enzyme

 0
Treatment

OP poisoning Carbamate poisoning

DOC if v ATROPINE@ DOC in Atropine@

C) I OXIMEI (not gwen

')
Add: OXIMES

Oximes → only in → OP.

C) I → CARBA mate
REASON Anti cholinesterase ✗ CHE enzyme Reactivate

Oximes

9 Ach (Dumbbells)

Atropine
Block Receptor
 ✓ carbamate

• Atropine ⇒ overall DOC: Lifesaving drug

✓ OP

: Block Ach receptor.

if u Arosine 2mg 1kg repetitive injection

: Ahooine effect comes

Ti Atropinization Occurs

(opposite of umEbelb)
#

• Oximes MYDRIASIS.
1
signs of

TACHYCARDIA
2

Apopinization Constipaton: Reduce Bowel sound.

3 Definite sign

Dryness of Respiratory (bayern ⇒

4

Stop Atropine ing.

 OXIMES

MOA: CHOLINE ESTERASE REACTIVATORS

CHE → degrade Ach

* Reactuiale

in PRALLIDONME (PAM) ⇒ ② used

OBID OXIME - Longest

Also I
Cross BBB
DI ACYL MONOXIME (DAM) →
 Oxime-OP

MOA of oximes
separate

Oximes attach to Anionic site

OP
Esteratic

Oximes

Remove OP from Esterate sue

Anionic

* Oximes ⇒ only in EARLY OP poising

1
↳ Not effective in AGEING enzyme
CHE enzyme

* oximes ⇒ not effective in carbamate poisoning.

Reason: carbamate poisoning → Anionic site is Already blocked

2
Chronic OP poisoning ✗ Imes

✓ OP C)I CARB Amati ✗ ✗

in early case

not in AGEING of enzyme

X
Chronic OP poisoning

industrial workers : insecticides/ pesticides factories.

* Long term → Low dose exposure → for many years.

Nerve Demyelination /Neurodenergation.

Permanent & Irreversible

* NO CURE

r
 Always
READ YOUR TONIGHT

<

Thank You