2. ANS drugs Flashcards
Choline enters from ECF by sodium-dependent membrane carrier( blocked by
hemicholinium
Acetylcholine(Ach) is transported from cytoplasm to storage vesicles by antiporter(to be blocked by
vesamicol
ACh release can be blocked by
botulinum toxin
Dopamine is transported into vesicle by high-affinity carrier mechanism(inhibited by
reserpine
Release of norepinephrine can be blocked by
guanethidine and bretylium
Reuptake 1of NE is the most important mechanism for termination which can be blocked by
cocaine and tricyclic antidepressants
Cholinomimetic drugs divided into
Divided into: cholinoceptor-activating(direct) and cholinesterase inhibiting drugs(indirect)
Direct-acting drugs can be divided on the basis of chemical structure into:
Esters of choline, and
Alkaloids
Esters of choline:
acetylcholine, methacholine, carbachol, bethanechol
ACh has virtually no therapeutic applications because it
is hydrolyzed rapidly by AChE and pseudocholinesterases and diffuseness of its actions
Alkaloids:
muscarine, pilocarpine, nicotine, and lobeline
Esters of choline are
hydrophillic or hydrophobic
hydrophillic so not absorbed rapidly
Tertiary alkaloids are well absorbed from most sites of administration except
muscarine
ACh released from activation of parasympathetic NS can activate:
1) muscarinic receptors on effector organs,
2) interact with muscarinic receptors on nerve terminals to inhibit release of NTs
3) ACh can also activate nicotinic receptors
organ system effects og cholinomimetics
eye - miosis/ contaction which facilitate flow of aqueous humour
CVS- decrease in heart rate direct effect
increase reflex effect
decrease peripheral resistance
respa- broncho constriction
GIT - increased motility
GUT - increase voiding
Indirect-acting cholinomimetics types
1) Simple alcohols bearing quaternary ammonium group e.g. edrophonium
2) Carbamic acid esters of alcohols bearing
tertiary or quaternary ammonium groups e.g. physostigmine, neostigmine, pyridostigmine, ambenonium…)
3) Organic derivatives of phosphoric acid (organophosphates) e.g. isoflurophate, echothiophate,malathion, parathion,sarin,tabun…)
based on absorption best to worst
physostigmine well absorbed
organophosphates except echthiophate well absorbed
Quaternary amines poorly absorbed
Binding to the active site of the enzyme is
reversible for edrophonium and carbamic acid esters of alcohols bearing tertiary or Quaternary ammonium compounds(reversible AChE inhibitors)
irreversible for organophosphates
The process termed as aging
(breaking of one of oxygen-phosphorus bonds of the inhibitor) further strengthens the phosphorus-enzyme bond
antidote for aging or organophosphate poisoning
oxime regenerators or cholinesterase regenerators
split enzyme phosphate bond before aging
duration of action shortest to longest
edrophonium short
organophospahte long
clinical use
eye
git
gut
skeletal
anti muscarnic drug intoxication
CNS
treatment of glaucoma open angle
post op ileus congenital megacolon
bethanecol
urine retention
bethanechol and neostigmine
myastenia gravis- edrophonium for diagnosis
-carvamic acid estres for treatment
physostigmine
alzheimers
Cholinoceptor antagonists are divided into:
muscarinic, and
nicotinic antagonists
muscarnic antagonists divided into
teritiary ammonium and quaternary ammonium cpds
tertiary amines include
atropine, scopolamine, dicyclomine, pirenzepine, benztropine,
Quaternary ammonium agents:
propantheline, glycopyrrolate, ipratropium, tiotropium….
Tertiary amines or quats well absorbed from the GIT and conjuctival membranes
teritiary
Mechanism of action of anti muscarnics
atropine causes reversible blockade of the actions of ACh at muscarinic receptors
They compete for the common binding site
Atropine does not distinguish between sub types of muscarinic receptors
…………..exhibit relative selectivity
pirenzepine for M1
organ system effects
eye
cvs
respa
git
gut
sweat glands
CNS
eye mydriasis and cycloplegia
cvs tachycardia and block vasodilation
respa bronco dilation
git reduced motilty and secretion
gut relaxed detrusor
sweat glands no sweat atropine fever
cns sedative effect
clinical use
cns
eye
git
cvs
respa
gut
cns
parkinsons -benz and trihex
motion sickness- scopolamine
eye
measuring refractive error - tropicamide
git
treat pud and diarrhea
cvs
treat bradycardia
respa
treat asthma - ipratropine and tiotro
Gut
treat urinary urgency
Nicotinic rec. antagonists are divided into:
Ganglion blockers
Neuromuscular blockers
Ganglion blockers include
hexamethonium, mecamylamine, trimethaphan
organ system effects
cns
cvs
eye
git
gut
sweat gland
cns
mecamylamine cross bbb and cause sedation
cvs
tachycardia
reduce bp
eye
mydryasis and cycloplegia
git
reduced motility
gut
urine retention
impaired sex function
sweat gland
ihibited
therapeutic use of gang. blockers
limited
used for short term bp lowering
2 types of NM blockers
depolarizing and non depolarizing
non depolarizing based on time effective
long term
tubucurarine
pancuronium
dexacurium
intermediate
vecucorium
atracorium
short
mivacorium
depolarizing blockers
succinylcholine
decamethonium
3 types of sympatomimetic drugs
direct
indirect
mixed
direct sympatomimetics
epinephrine,
norepinephrine,
phenylephrine.
Isoproterenol,
salbutamol,
clonidine,.
indirect symp mimetics
amphetamine
tyramine
Mixed-acting
ephedrine
based on selectivity
alpha 1 selective
phenylephrine,methoxamine
Alpha2 selective: ..
clonidine, methylnorepinephrine
Beta1 selective:
dobutamine
Beta2 selective:
albuterol(salbutamol), terbutaline, salmeterol..
organ system effect
cvs
eye
respa
git
gut
exocrine glands
metabolism
cns
cvs
tachycardia
increase bp
alpha 1 and 2 vasoconstrict
b2 vasodilate
eye
mydriasis
respa
bronchodilate
git
decrease motility
gut
yterus alpha and beta 1 relax’bladder and sphinicter retention
Adrenoceptor blocking drugs divided into
Alpha rec antagonists- block alpha
Beta rec. antagonists-block beta
Alpha rec antagonists divided into
based on selectivity
Alpha1 selective blockers: prazosin, doxazosin, terazosin, tamsulosin
Alpha2 selective blockers: yohimbine
non selective
phentolamine, phenoxybenzamine
Alpha1 antagonists are given
orally
Prazosin is the prototype
Doxazosin and terazosin are congeners of prazosin
have higher bioavailability and longer half-lives
Beta receptor antagonists divided based on selectivity
Non-selective antagonists: propranolol, nadolol, pindolol, timolol, sotalol,labetalol,etc
Beta1 selective antagonists: metoprolol(prototype), acebutolol, atenolol, betaxolol, bisoprolol, celiprolol,esmolol
ABEAM
partial agonists activity: acebutolol, celiprolol, pindolol,etc
all beta blockers are reversible or irreversible
reversible
