Lecture 1 (Drugs Acting on Autonomic Ganglia)
-
Upload
priyal-shah -
Category
Documents
-
view
228 -
download
1
Transcript of Lecture 1 (Drugs Acting on Autonomic Ganglia)
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
1/32
Drugs that affectsneurotransmitter Release,
Synthesis or Uptake
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
2/32
OBJECTIVE S
Identify different types of drugs thatinterefer with synthesis, storage or uptake of NAUnderstand the mechanism of actionof :E -methyldopa
ReserpineGuanethidine
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
3/32
The drugs in this group block the adrenergic
neurons, by interference with NA release,storage, synthesis or alter the uptake into theadrenergic nerve.
They could be classified into:
Drugs that affect NA synthesis:(E -methyldopa)
Drugs that affect NA storage:
(Reserpine)Adrenergic neuron blockers:(Guanethidine)
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
4/32
Drugs that affect NA synthesisE -methyldopa
It is a dopa decarboxylase inhibitor.It inhibits NA biosynthesis.It is metabolized to E - methyl NA, whichcan be stored in the sympathetic nerveendings, therefore, displacing NA andacting as a false transmitter.E -
methyl NA stimulates presynapticE
2-
receptors in brain leading to inhibition of sympathetic outflow.
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
5/32
USES:
Treatment of hypertension
Contraindications:Pheochromocytoma
Active liver diseases
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
6/32
Drugs that affect NA storage:Reserpine:
It blocks the magnesium/ATP -dependent transport of biogenicamines from the cytoplasm into thestorage vesicles in the adrenergicnerves.This causes an ultimate depletion of
NA levels in the adrenergic neurons.
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
7/32
The amine -depleting action of reserpine results in:
Sedation and tranquilizing action bydepleting catecholamines and 5 -H Tstores in the brain.H ypotension and bradycardia
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
8/32
The rap eu tic u s e s: H ypertension (in combination with other drugs) except in case of phaeochromocytoma
Sid e effe cts:- Postural hypotension, Failure of ejaculation ,
Diarrhea, Nasal congestion, Miosisweight gain, activations of peptic ulcer, CNS
effects .
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
9/32
Adrenergic neuron blockers:Guanethidine:
Guanethidine inhibits the response of adrenergic nerve to stimulation or toindirectly acting sympathomimeticamines.
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
10/32
GUAN ETHI D I N E
Inhibit uptake
InhibitRelease
Storedinsteadof NA
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
11/32
M e c h anism o f action:
Guanethidine acts by blocking therelease of stored NA and also inhibitsthe uptake of NA.
Guanethidine is taken up by adrenergicnerves by the same mechanismsinvolved in NA uptake (uptake 1).
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
12/32
M e c h anism o f action:
Subsequently, it accumulates in thestorage granules and displaces NA,thus producing a transient increase in
blood pressure.Furthermore, it prevents further release of NA in response to neuronal depolarization
(leading to prolonged fall in blood pressure).
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
13/32
The adrenergic receptors are notblocked and therefore the drug does
not antagonize the circulatingcatecholamine but may potentiatetheir effects as it preventing theuptake.
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
14/32
The rap eu tic u s e s: Treatment of severe hypertensionexcept in case of phaeochromocytoma
Sid e effe cts:Postural hypotension, Diarrhea,
Miosis, Nasal congestion, Failure of ejaculation
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
15/32
Drugs Acting O nDrugs Acting O n
Autonomic GangliaAutonomic Ganglia
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
16/32
Ov er v iew
Review ganglionic transmission
Definition and Classification Ganglionic Stimulants Ganglionic Blockers
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
17/32
Ganglionic T ransmission
Primary neurotransmitter at allganglia and the adrenal medulla is
Ach
Receptor mediating the effects of Ach is nicotinic receptor
ACh binding results in an increased
permeability to Na+ (mainly) resultingin an EPSP
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
18/32
Autonomic Ganglia
ACH
Nn
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
19/32
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
20/32
Ganglion Stimulants
Stimulates nicotinic receptors insympathetic and parasympatheticganglia.
Nicotine (low concentration)Tetramethylammonium (TMA)Dimethylphenylpiperazinium (DMPP)
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
21/32
N ICOTI N E
Stimulates at low dosesStimulates then blocks at high doses
Clinical uses: restricted to nicotinedependence (i.e. nicotine patches)
Tolerance developed after repeatedsmall doses of nicotine
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
22/32
Pharma cologic al a ction:
It acts on:Sympathetic & parasympathetic ganglia
Nicotinic receptors of muscle (Nm)
In larger doses, the initial stimulation isfollowed very rapidly by depolarizationblockade
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
23/32
Cardiovascular system:
Small dose; increased H R,vasoconstriction (stimulation of sympathetic ganglia).
Large dose; initially an increase then adecrease in H R, vasodilation (ganglionicblockade)
Similar to sympathetic stimulation
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
24/32
Gastrointestinal tract actions :
(Parasympathetic stimulation)Increased tone and motility of the intestine.
Central nervous systemVomiting
Antidiuretic effectIncreased drive to respiration
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
25/32
Ganglion Blockers
Depolarizing Non-Depolarizing
Competitive Non-Competitive
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
26/32
Non-Depolarizing ganglion block
Competitive ganglion blocker:Mechanism of action:
No initial stimulation on Nn
receptor
Compete with acetylcholine for N nreceptor in the autonomic ganglia.
It blocks both sympathetic andparasympathetic ganglia
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
27/32
Eff ect will always appear to be
opposite to the predominate ANS tone
Ganglionic blockade will alwayslower blood pressure (why?)
At rest, PS tone predominates in organs andglands jointly innervated by PS and S f ibers;
the e ff ect o f blockade looks like mildsympathetic activation
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
28/32
Ex amples o f competitive ganglion
blockers:Te tra e t hyl ammoni u m.
M e cam yl amin e s
P e mpidin e
T rim e tap h an
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
29/32
N on-competitive Ganglion
BLOCKERS:HEXAM T HONIUM
Blocks the response of acetylcholine at theautonomic ganglia
Does not depolarize or stimulate the ganglion
It blocks the associated ion channels with thereceptor, while the receptor was opened.
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
30/32
Th erapeutic Uses:
Use of the ganglion blockers isinfrequent because more selectiveautonomic blocking agents areavailable.
Mecamylamine is being studied for possible use in reducing nicotine
craving in patients attempting to quitsmoking.
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
31/32
Trimethaphan is occasionally usedin the treatment of hypertensiveemergencies and dissecting aorticaneurysm to produce controlled
hypotension.Electroconvulsive therapy.
-
8/8/2019 Lecture 1 (Drugs Acting on Autonomic Ganglia)
32/32
G ang l ionic b l ock e rs: sid e effe cts
Orthostatic hypotension
Blurred vision
Urinary retention, constipation
Sexual dysfunction