Autonomic Pharmacology

Front 1

Hemicholinium

Back 1

-Blocks the action of the Na+ dependent membrane carrier that transports choline
-there is a decrease in ACh synthesis and ultimately decreased ACh release

Front 2

Vesamicol

Back 2

inhibits ACh antiporter resulting in a decrease in ACh

Front 3

Botulinum toxin (BOTOX)

Back 3

-blocks the action of vesicular associated membrane proteins and synaptosome associated proteins (SNAPs)
-This prevents vesicle fusion and inhibits ACh release

Front 4

Metyrosine

Back 4

-inhibits tyrosine hydoxylase blocking catecholamine synthesis and adrenergic neurotransmission

Front 5

Reserpine

Back 5

-inhibits a catecholamine carrier that transports dopamine (DA) and norepinephrine (NE)
-causes DA and NE to accumulate and then degredation by MAO.
-decreases chatecholamine and synaptic transmission

Front 6

bretylium

Back 6

-increases NE release
-blocks fusion of vesicles which result in exoctosis of NE

Front 7

guanethidine

Back 7

-increases NE release
-blocks fusion of vesicles which result in exoctosis of NE

Front 8

How are the actions of ACh terminated?

Back 8

by acteylocholinesterase (AChE)

Front 9

list 4 AChE inhibititors?

Back 9

Malathion, Edophonium, Pesticides and chemical warfare

Front 10

M1

Back 10

-located in nerves and glands
-stimulatory, IP3/DAG
-Increases gland secretion

Front 11

M2

Back 11

-located in heart, nerve terminals smooth muscle
-inhibitory, decreases AC
-Slows heart rate/force of contraction (atria SA node). Decrease in contractile force of ventricle

Front 12

Mechanism of M1?

Back 12

-increases Ca+2 intracell
-activate PKC

Front 13

Mechanisms of M2

Back 13

-decreases cAMP
-decreases Ca+2 intracell
-increases K+ channels

Front 14

M3

Back 14

-located in the glands, smooth muscle and endothelium
-stimulatory, IP3/DAG
-secretion and contraction of smooth muscle; Relax sphincters in GI/bladder, release of NO from vascular endothelium

Front 15

mechanisms of M3

Back 15

-increases Ca+2 activate PKC

Front 16

How do muscarinic agonist effect the eye?

Back 16

they decrease intraocular pressure

Front 17

What are the some of the effects of muscarinic agonists on the cardiovascular system? How is this altered?

Back 17

-Vasodilation, decreased heart rate and reduced atrial contractility
-reflex arcs will cause tachycardia

Front 18

what is the NET effect of muscarinic agonism on heart rate dependent on?

Back 18

-on the local agonist concentration in the heart and vasculature and the amount of reflex activity

Front 19

Innervation of blood vessels

Back 19

-NO parasymp.
-circulating muscarinic agonists cause vasodilation when acting on M3 receptors in endothelial cells
-NO is produced and causes relaxation

Front 20

What do muscarinic agonists cause in vessels without endothelium?

Back 20

-constriction through direct activation of muscarinic receptors present on the smooth muscle

Front 21

Effect of muscarinic agonism (M3) on the tracheobronchial mucosa?

Back 21

-bronchoconstriction and increased secretion from mucosa

Front 22

What type of drug is contraindicated in asthma pts?

Back 22

-cholinergic agonists

Front 23

muscarinic agonists effect on the GI tract?

Back 23

-increase secretory and motor activity

Front 24

muscarinic agonists effect on the genitourinary tract?

Back 24

-increased voiding

Front 25

Muscarinic over activation?

Back 25

Diarrhea
Uriniation
Miosis
Bradycardia, Brochoconstriction
Emesis
Lacrimation
Salvation, Sweating

Front 26

Nicotinic over activation?

Back 26

Muscle weakness or fasciculations
Adrenal Medulla (increased activation)
Tachycardia
Camping of skeletal muscle
Hypertension

Front 27

Contraindications of Esters of choline

Back 27

Hyperthyoidisms, asthma, coronary artery disease, acid-peptic disorders, obstructive urinary retention

Front 28

Actylocholine (Miochol)

Back 28

-High IV doses only
-ocular surgery
-sweat spot test for autonomic neuropathy in diebetic pt

Front 29

Methacholine (Provacholine)

Back 29

-longer lasting ACh more resistant to cholinesterase
-used to provoke bronchoconstriction in the diagnosis of bronchial airway hypersensitivity

Front 30

list the esters of choline?

Back 30

-ACh (michol)
-Methacholine
-Bethanecol
-Carbachol

Front 31

Describe the properties of the esters of choline?

Back 31

-they all contain permanently charged ammonium groups (do not cross the blood brain barrier)

Front 32

system adverse effects of the choline esters?

Back 32

-nausea, vomiting, abdominal pain, flushing, sweating, salivation, lacrimation, rhinorrhea,eructation, diarrhea, urinary frequency, headache, difficulty in visual accomodation, bradycardia, peripheral vasodilation leadingto hypotension and bronchoconstriction

Front 33

Desribe the cholinesterase sensitivity of the choline esters?

Back 33

ACh = highly sensitive
Methachoine = slightly sensitive
Bethanecol and Carbachol are resistant

Front 34

List the alkaloids?

Back 34

-Muscarine
-Pilocarpine (Salagen or Pilocar)
-Nicotine
-Varenchline (Chantix)

Front 35

Muscarine

Back 35

-isolated from the mushroom Amanita muscaria. Original agent used in development
-no clinical uses

Front 36

Main uses of pilocarpine?

Back 36

-topical; eye = miosis and accommodation
-treats open angle glaucoma, reduces intra-occular pressure
-reverses sympathomimetic mydriatics
-reverse mydratic actions of atrophine and break adhesions between iris and lens
-used to treat xerostomia

Front 37

Contrainications for pilocarpine?

Back 37

-do not use for glaucoma is IOP is higher than 45 mmHg
-at this pressure a mitotic can reduce the angle further and worsen the attack

Front 38

Side effects of pilocarpine?

Back 38

-eye: myopia, blurred vision, ciliary body spasm.
-systemically: sweating, excess salivation etc., cardiovascular effects include sinus tachycardia and hypertension. Overdose can produce bradycardia, AV block

Front 39

properties of pilocarpine

Back 39

-tertiary amine (not charged) crosses the BBB
-longer acting than choline esters but not as potent
-parasympathomimetic with primarily muscarinic effects of Ach
-particularily active on the eye and sweat glands

Front 40

Where is nicotine specific to?

Back 40

-nicotinic receptors located at all all autonomic ganglia (including adrenal medulla), skeletal muscle and CNS

Front 41

How does nicotine effect the receptors?

Back 41

-activates and inhibits acetylcholine receptors
-First they activate receptors then they become desensitized which causes a ganglionic blockade and flaccid paralysis of muscle

Front 42

effects of nicotine?

Back 42

-increase heart rate and BP (symp stimulation)
-simulates secretion of E at the adrenal medulla
-increase GI tone and motility (para)

Front 43

side effects of nicotine?

Back 43

-cholinergic nausea, vomiting, dizziness, diarrhea, weakness and rapid heartbeat

Front 44

Varenecline (Chantix)

Back 44

-Partial agonist at neuronal nicotinic receptors
-stimulates receptors in brain and can block the actions of nicotine at the same time.

Front 45

side effects of Varenecline (Chantix)?

Back 45

-changes in behavior, hostility, agitation, depressed mood, suicidal thought ans attempted suicide

Front 46

how do in-direct acting chilinergic agonists work?

Back 46

inhibit acetylocholinesterase (anti-cholinesterases) and thus increasing the duration of action of ACh

Front 47

3 groups of in-direct acting cholinergic agents

Back 47

1. simple alcohols
2. Carbamic acid esters
3. organic derivatives of phosphoric acid

Front 48

properties of the 3 chemical groups of in-direct acting cholinergic agents?

Back 48

1. simple alcohols
-reversible
-acts for short periods 5-15 min
2. Carbamic acid esters
-reversible not lipophilic
-acts for longer periods 30min-6hrs
3. organic derivatives of phosphoric acid
-irreversible lipophilic
-hundreds of hrs

Front 49

Endophonium (Tensilon)

Back 49

-Diagnosis of Myasthenia and evaluating efficacy of myasthenia therapies

Front 50

List the Reversible anticholinesterases

Back 50

-Edrophonium
-Physostigmine salicylate (antilirium)
-Neostigmine
-Donepezil
-Tacrine
-Galantamine
-Pyridostigmine
-Ambenonium
-Demecarium
-Carbaryl

(D3 CAT PEGN)

Front 51

Descibe the diagnosis test with endophonium?

Back 51

Positive (increase in m. strength) = pt has myasthenia Gravis

Negative (decrease in m. strength) = pt has cholinergic crisis (overacting of all cholinergic systems) Use atropine to teat.

Front 52

Physostigime

Back 52

-30min to 6hrs
-opthalmic solution causes miosis, accomodation and a decrease in intra-ocular pressure

Front 53

Neostogmine

Back 53

-.5-2hrs
-myasthenia gravis (alleviates postperopterative urinary retention and paralytic ileus)
-anethesia (reverse the neuromuscular blockade)
-lower IOP to manage glaucoma

Front 54

structure/function of muscarinic antagonists?

Back 54

tertiary amines (atropine etc)
-well absorbed in gut, conjunctival membrane, systemic distribution including CNS

quaternary amines (ipratropium)
-not readily absorbed

Front 55

Mechanisms of antimuscarinic agents?

Back 55

-competitive antagonist at muscarinic receptors
-block actions of parasympathetic system

Front 56

These agents are useful in treating parkinson's disease because they decrease cholinergic activity in the basal ganglia and striatum

Back 56

-Antimuscarinic agents

Front 57

Adverse effects of antimuscarinic agents in the eye?

Back 57

-can precipitate acute glaucoma in a pt with a narrow anterior chamber angle
-Cycloplegia
-dry eye