4. Sympathicus Parasympathicus
mydrasis myosis
Inhibition of salivation Stimulation of salivation
Bronchodilation, secretion inhibition Bronchoconstriction, secretion of bronchial
glands
Tachycardia, ↑MV , ↑BP Bradycardia
Glyconeogenesis, glycoogenolysis Glycogen synthesis
↑ sphyincter tone in GIT, inhibition of peristalsis HCl secretion, stimulation of peristalsis, ↓
sphincter tone
Stimulation of adrenal medulla Inhibition of adrenal medulla
Relaxation of the bladder, ↑ sphyncter tone of
the bladder
Contraction of the smooth muscles of the
bladder, ↓ sphyncter tone of the bladder
Ejaculation, vaginal contractions Erection, sexual arousal
5.
6.
7.
8. Cholinergic receptors
Muscarinic receptors Nicotinic
• Ionotropic
• Excitatory
• NM: muscle type
• NN: nervous type
• Metabotropic
• Excitatory i inhibitory
• M1, M2, M3, M4, M5
9. Muscarinic receptors
M2, M4
• Gi
M1, M3, M5
• Gq
G
protein
Receptor Signal pathway
Gi Alpha2
adrenergic,
muscarinic
M2 i M4,
opioid
Decrease in cAMP, K
channels opening,
inhibition
Gq muscarinic
M1 i M3,
alpha1
adrenergic,
V1
vazopressin
PLC – IP3 i DAG,
increase in
intracellular Ca2+,
excitation
13. Pharmacology of nitric oxide (NO)
EDRF (NO) discovery 1980–1987.
Originate from L-arginine under cathalic
influence of NO-synthase.
Sodium-nitroprusside reacts with physiologic
sulphhydryl groups and releases NO
NO activate guanylate cyclase and cyclic GMP
sinthesis (it can be inhebited by methylen
blue).
NO can be inactivated by free oxygen radicals.
14. Direct cholinergic drugs
pilocarpine, muscarine
• Natural origin: Pilocarpus jaborandi, Amanita muscaria
• Pilocarpine 1%, eyedrops (myosis, ↓IOP)
TROVANJE GLJIVAMA:
Amanita muscaria:
Symptoms of poisoning appear in 15 to 30 min, it can
be stopped by atropine.
Amanita phalloides, Amanita virosa, Galerina
automnalis i Galerina marginata
Symptoms of poisoning appear in 6 to 12 hours. Liver
and kidney damage. Atropine is not efficient,
Hemodialysis!
15. Indirect cholinergic drugs or
anticholinesterase supstances
Reversible
• Short acting
• edrophonium (2-10 min) (dij –
Myasthenia gravis)
• Carbamate: enzyme carbamylation
(30 min- 2h), spontaneous
hydrolysis
• neostigmine (polar, N Rc, My g,
↑GIT and bladder tone, antagonist
of NMJR)
• piridostigmine,
• fizostigmine (N and M receptors,
CNS, long acting, atropine
poisoning)
• Alzheimer’s desease (donepezil,
galantamine, rivastigmine)
Irreversible
• Long acting (insekticides
and nerve agents)
• Organophosphates, organic
derivates of phosphoric
acids
• They phosphorilate
enzyme, >500h aging of
enzyme
• Insecticides: paraoxon,
malation
• Nervous agents: sarin,
tabun, soman, VX
16. Regeneration of ACH-esterase
• Oxime drugs can
regenerate enzyme If
they are given on time
• Nukleophilic agents
(pralidoxime) bind to
active place on
enzyme
• If the complex
“poison-enzyme” is
aged, oximes do nor
have any effect
