Cholinergic Drugs

Front 1

Acetylcholine- Use, Contraindication

Back 1

Use: glaucoma
Contraindication: asthma, bradycardia, peptic ulcer disease, weakened bladder, urinary or intestinal obstruction

Front 2

At what spinal levels to sympathetic preganglionic fibers emerge? Are preganglionic fibers long or short?

Back 2

1. C8-L3
2. Sympathetic preganglionic fibers are short and synapse on the sympathetic chain ganglion

Front 3

What NT do preganglionic fibers release onto receptors of the post ganglionic neurons? What type of receptors receive these signals?

Back 3

Ach released, onto nicotinic receptors. This is the preganglionic NT released in both the sympathetic and parasympathetic system.

Front 4

What is the NT released from the post synaptic fibers in the sympathetic system? What type of receptors does this NT act on? What are the two major exceptions to this rule?

Back 4

1. NE 2. adrenergic receptors--alpha1, alpha 2, beta 1, and beta 2
3. Sweat glands where post gang neurons release Ach on muscarinic receptors and adrenal medulla where Ach released onto nicotinic receptors (stimulation of nicotinic receptors causes release of epinephrine into the blood stream)

Front 5

What NT is used at the NMJ in the somatic nervous system? What kind of receptor does this NT act on?

Back 5

1. Ach 2. Nicotinic receptor

Front 6

What is the main NT released from post ganglionic parasympathetic fibers? What type of receptor does this NT act on?

Back 6

Ach onto muscarinic receptors

Front 7

Beta 1 adrenergic receptors are found mainly in what organs? What type of response do these receptors mediate?

Back 7

- Beta 1 found mainly in heart, kidney, and brain. In the heart they mediate increased force and rate of contraction, and in kidney they mediate renin secretion

Front 8

Beta 2 adrenergic receptors are found mainly in what organs? What type of response do these receptors mediate?

Back 8

- Beta 2 mainly found in the airways, blood vessels of skeletal muscle and in the uterus of pregnant females. Beta 2 receptors mediate smooth muscle relaxation

Front 9

Alpha 1 adrenergic recptors are found in which organs? What response do these receptors mediate?

Back 9

- Alpha 1 found in blood vessels, urinary sphincters, eye-- they mediate smooth muscle contraction

Front 10

Most organs recieve dual input from both sympathetic and parasympathetic nervous systems, in some organs and tissues the sympathetic nervous system predominates, which organs are these?

Back 10

- Adrenal medulla, spleen capsule, pilomotor muscles, and blood vessels of skin and skeletal muscle

Front 11

What are the sympathetic responses in the eye? Which receptors mediate these responses?

Back 11

Alpha 1-- pupillary dilation (mydriasis)
Beta 2-- ciliary aqueous humor production

Front 12

What is the parasympathetic response in the eye?

Back 12

- Pupillary constriction (miosis), contraction of ciliary muscle (accommodation of near vision), decrease intraocular pressure

Front 13

What is the sympathetic mediated response of the secretory glands and organs?

Back 13

Drying mediated by alpha 1 and alpha 2. Beta 2 mediates increased respiratory secretions

Front 14

What is the parasympathetic mediated response of the secretory glands and organs?

Back 14

Increased secretion

Front 15

What is the sympathetic response in the heart?

Back 15

Beta 1 and Beta 2--- increased rate, contractility, automaticity, and conduction velocity

Front 16

What is the parasympathetic response in the heart?

Back 16

Decreased rate, contractility, automaticity, and conduction velocity

Front 17

What is the sympathetic response in the blood vessels of mucosa, skin, and splanchnic beds?

Back 17

Constriction mediated by alpha 1 and alpha 2 receptors

Front 18

What is the parasympathetic response of blood vessels of mucosa, skin, and splanchnic beds?

Back 18

Dilation

Front 19

What is the sympathetic response of the blood vessels of skeletal muscle?

Back 19

Dilation mediated by beta 2

Front 20

What is the parasympathetic response of blood vessels in the skeletal muscle?

Back 20

Dilation

Front 21

What is the sympathetic response of airways?

Back 21

Relaxation mediated by beta 2

Front 22

What is the parasympathetic response of the airways?

Back 22

Constriction (some asthma drugs work by blocking this response)

Front 23

What is the sympathetic response of the GI tract?

Back 23

Relaxtion, and decreased motility

Front 24

What is the parasympathetic response of the GI tract?

Back 24

Increased motility, and increased spasms (some IBS drugs are muscarinic antagonists)

Front 25

What is the sympathetic response of the bladder? What is the sympathetic response of the urinary sphincter and prostate?

Back 25

Relaxation of bladder mediated by beta 2. Contraction of the urinary sphincter and prostate mediated by alpha 1

Front 26

What is the parasympathetic response of bladder? What is the urinary sphincter response?

Back 26

Constriction of bladder. Relaxation of urinary sphincter.

Front 27

What is the sympathetic response of kidney JG cells?

Back 27

Increased renin secretion mediated by beta 1 receptors (part of the way beta blockers work for htn)

Front 28

What is the sympathetic response of the uterus?

Back 28

Alpha 1 mediates contraction while beta 2 mediates relaxation

Front 29

What is the sympathetic response of the male sex organ?

Back 29

Ejaculation mediated by alpha 1

Front 30

What is the parasympathetic response of the male sex organ?

Back 30

Erection

Front 31

What is the symp response of the liver and fat cells? What is the sympathetic pilomotor response? What is the sympathetic sweat gland response?

Back 31

Increased glucose output and increase fatty acid out put. COntraction of pilomotor muscles by alpha 1, and increased secretion by sweat glands via muscarinic receptors

Front 32

What is the difference between the effects of sympathomimetic drugs and those of antimuscarinic drugs in the heart?

Back 32

Parasympathetics mainly innervate the nodes and to a much lesser extent the ventricles while the sympathetics innervate both nodes and ventricles. Thus a sympathomimetic drug will greatly increase both RATE and CONTRACTILITY (so rapid strong pulse) while an antimuscarinic agent will increase RATE but NOT CONTRACTILITY (so rapid weak pulse)

Front 33

What is the effect of parasympathetic innervation of the eye?

Back 33

Contraction of pupillary sphincter and ciliary muscle-- allowing for accomodation. Also contraction of ciliary muscle allows outflow of aqueous humor into the canal of Schlem and lowers intraocular pressure. (think about muscarinic antagonist side effects)

Front 34

Ach stimulates muscarinic receptors with what type of kinetics?

Back 34

Classic dose concentration response

Front 35

What happens at high concentrations of Ach in nicotinic receptors?

Back 35

Desensitizes nicotinic receptors leading to ganglionic blockade or muscle paralysis

Front 36

Ach or muscarinic agonists have what effect on the heart?

Back 36

They slow the rate of the heart by affecting the SA nodes and atrium, but not the contractility b.c no muscarinic receptors in the ventricles

Front 37

Ach or muscarinic agonists have what effect on blood vessles?

Back 37

Although not much parasympathetic innervation of blood vessels, muscarinic receptors are still present and if Ach agonists injected into the blood stream can cause NO mediated vasodilation and decrease bp. Also will cause erection

Front 38

Cholinergic neurons innervate the airway and Ach.muscarinic agonists will cause ____ and ____ respiratory secretions. Subsequently, what types of drugs may be used to treat asthma, what drugs are contraindicated?

Back 38

1. bronchoconstriction
2. increase respiratory secretions
Thus muscarinic antagonists such as ipratropium & triatropim are used and muscarinic agonists and cholinesterase inhibitors can aggravate asthma

Front 39

High dose treatments at the NMJ of cholinesterase inhibitors would have what effect on the nicotinic receptors present?

Back 39

With high dose of cholinesterase inhibitors xs Ach will accumulate at the NMJ leading to desensitization and muscle paralysis

Front 40

Direct Acting Muscarinic Agonists, Use

Back 40

Ach, carbachol, methacholine, bethanechol, pliocarpine, muscarine
Use: Increased GI motility and secretion, decreased heart rate, decreased bp due to decreased CO, bladder contraction and urinary sphincter relaxation, miosis (accomodation) and decreased intraocular pressure, stimulation of secretions

Front 41

Adverse effects of Direct Acting Muscarinic Agonists, Contraindications, Precautions

Back 41

Hypotension, bradychardia, bronchoconstriction, diarrhea, cramping, urinary incontinence, xs sweating, salivation
Contraindications: asthma, bradycardia, hypotension, vasomotor instability, peptic ulcer disease, hyperthyroidism, weakened smooth muscle of the bladder (such as after surgery), urinary or intestinal obstruction
Precaution: direct acting muscarinic agonists should never be given IV or IM, they should only be given subcutaneously, orally, or topically

Front 42

Bethanechol- Use, Class, MOA

Back 42

Use: promote GI motility, urinary retention treatment, Class: Direct acting muscarinic agonist
MOA: direct muscarinic agonsit that has little effect on nicotinic receptors

Front 43

Pilocarpine-Use, Class

Back 43

Use: glaucoma treatment, salivary gland dysfunction treatment Class: Direct acting muscarinic agonist

Front 44

Carbachol- Use, Class

Back 44

Use: Glaucoma treatment
Class: Direct Acting Muscarinic Agonist

Front 45

Metacholine- Use, Class, MOA

Back 45

Use: pulmonary function testing in asthmatics (i.e. metacholine will cause bronchoconstriction), thus must be very careful b/c can cause asthma attack
Class: Direct acting muscarinic agonist
MOA: ach analog that has little effect on nicotinic receptors

Front 46

Muscarine- Use, Class, Adverse Effects

Back 46

Use: natural prod found in mushrooms, not used medically
Adverse effects: bronchospasms, hyper GI motility, nausea, salivation, lacrimation (can be treated with atropine)
Class: Direct muscarinic agonist

Front 47

Cholinesterase inhibitors -- reversible

Back 47

Edrophonium, physostigmine, neostigmine, pyridostigmine, rivastigmine, donepezil, carbamate insecticides, tetrahydroaminoacridine, galamtamine

Front 48

Choliesterase inhibitors-- irreversible

Back 48

DFP, organophosphate insecticides (parathion, malathion), nerve gas in chemical warfae (Sarin)

Front 49

Cholinesterase reactivator

Back 49

Pralidoxime

Front 50

Cholinesterase inhibitor- Tox

Back 50

1. SLUDGE (salivation, lacrimation, urination, defecation, GI distress, emesis).
2. skeletal muscle fasciculations followed by paralysis--WHICH DIFFERENTIATES THIS FROM direct cholinergic stimulation
3. bradycardia, hypotension, shock
4. severe miosis
5. CNS stimulation and seizures followed by coma.
6. Chronic exposure to some cholinesterase inhibitors has been associated with demyelination of axons and various neuropathies.

Front 51

Treatment of cholinesterase inhibitor poisoning

Back 51

High IV dose of atropine, administer pralidoxime to reactivate enzyme (which removes phosphate group off cholinesterase inhibitor and reactivates acetycholiesterase)

Front 52

Edrophonium- Use, PK, Class

Back 52

Use: diagnostic of myasthenia gravis, and also to diagnose over use of cholinesterase inhibitors
PK: SHORT ACTING reversible cholinesterase inhibitor- which is why it is helpful in diagnostic circumstances, is quaternary ammonium compound-- meaning it cannot enter the CNS
Class: Reversible cholinestersae inhibitor

Front 53

Physostigmine- Use, Class

Back 53

Use:treatment for poisoning with antimuscarinic drugs-- i.e. atropine. Physostigmine can cross the BBB b/c is non quaternary ammonium
Class: reversible Cholinesterase inhibitor

Front 54

Neostigmine- Use, Class, PK

Back 54

Use: Myasthenia Gravis, Class: reversible cholinestrase inhibitors
PK: quaternary ammonium--does not get into the CNS, longer acting than edrophonium

Front 55

Pyridostigmine- Use, Class, PK

Back 55

Use: Myasthenia Gravis, pre exposure antidotal for military
Class: reversible cholinesterase inhibitor. PK: quarternary ammonium which cannot cross BBB

Front 56

Rivastigmine- Use, Class

Back 56

Use: Alzheimers disease Class: reversible cholinesterase inhibitor
- tetrahydroaminoacridine (although not used any longer b.c of hepatotoxicity) and galantamine have also been used for alzheimers

Front 57

Donepezil- Use, Class

Back 57

Use: Alzheimers disease Class: reversible cholinesterase inhibitor

Front 58

Ecothiophate- Use, Class

Back 58

Use: glaucoma, Class: reversible cholinesterase inhibitor

Front 59

Cholinesterase inhibitors are used generally to treat ____ of the bladder

Back 59

- atony, i.e. urine retention and paralytic ileus

Front 60

Cabaryl insecticide poisioning, treatment

Back 60

- carbamate insecticides are reversible cholinesterase inhibitors
- treatment with atropine, pralidoxime is not helpful (b/c carbaryl is reversible cholinesterase inhibitor)

Front 61

Sarin-- DFP-- nerve gas, Class, Treatment

Back 61

irreversible cholinesterase inhibitor, treat with atropine and pralidoxime, DFP used to treat glaucoma

Front 62

Sildenafil, Vardenafil, Tadalafil- MOA, Use, Tox/Side effects, PK, Drug Interactions

Back 62

- MOA: Inhibit cGMP phosphodiesterase--Ach released during arousal, which causes NO release in endothelium, NO activates G-cyclase which produces cGMP which causes vasodilation. Phosphodiesterase breaks down cGMP, - nafil drugs act by inhibit PDE so that vasodilation happens for longer
Use: ED
Tox/Side Effects:PDE 5 found in highest concentrations in corpus cavernosum, but at lower levels throughout the body so some general vasodilation may occur which will cause hypotension and a compensatory INCREASE in heart rate, visual disturbances (blue/green color disturbances), auditory disturbances
PK: oral, tadalafil has much longer half life than others, metabolized by CYP3A4
Drug interactions:1. CYP3A4 metabolization pathway--erythromycin, ketacoaxole, cimetidine, and others 2l vasodilators, 3, sympathomimetics

Front 63

Botulinium Toxin-- MOA, treatment, Dose

Back 63

MOA: toxin prevents release of Ach from nerve endings in both autonomic nerve endings and at the NMJ (results in paralysis)
Treatment: symptomatic support--respiratory function
Dose: very small doses can be fatal-- used for opthamologic disorders, wrinkles, dystonia, xs sweating

Front 64

Anticholinergic drugs, MOA, contraindications, side effects/tox

Back 64

1. *atropine (AKA hyoscyamine and analogs)
2. *scopolamine (AKA hyoscine and analogs)
3. *dicyclomine (Bentyl)
4. *propantheline
5. *glycopyrrolate (Robinul)
6. *ipratropium (Atrovent)
7. *tiatropium (Spiriva)
8. *benztropine (Cogentin)
9. *trihexyphenidyl (Artane)
10. *tolterodine (Detrol)
11. *oxybutynin (Ditropan)
12. *solifenacin (Vesicare)
13. *tropicamide (Mydriacyl)
14. fesoterodine (Toviaz)
15. cyclopentolate (Cyclogyl)
16. others

MOA: act as competitive antagonists at muscarinic receptors

Contraindications: Glaucoma (esp narrow angle), prostatic hypertrophy, CV instability, severe ulcerative colitis

Side effects, Tox: Dry mouth, dry hot skin, constipation, urine retention, visual disturbances, CNS effects

Front 65

Acute poisioning by anticholinergic drugs, treatment

Back 65

a. dry, hot skin and hyperthermia
b. severe mydriasis, blurring of vision, photophobia
c. CNS stimulation - agitation, hallucinations, seizures progressing to coma and death
d. cessation of GI motility (no bowel sounds)
e. weak, rapid pulse, tachycardia and arrhythmias
Treatment: physostigmine or other cholinesterase inhibitor, benzodiazepines for seizure treatment

Front 66

Atropine, homatropine- Use, MOA, class

Back 66

- class: anti muscarinic agent
MOA: competitively binds muscarinic receptor
Use: heart- treat myocardial infarct (if these is increased vagal tone and low CO) by causing tachycardia and increasing CO- will result in WEAK rapid pulse (b/c ventricles not responsive to muscarinics as much as sympathomimetics)

Blood vessels-- not much though will reverses hypotensive actions of Ach. muscarinic agonists, causes cutaneous vasodilation and flushing of the skin
Eye: Cuases mydriasis (pupillary dilation), cycloplegia (paralysis of accomodation), and increased intraocular presssure
GI: inhibitory on motility and tone-- could be used to reduce gastric acid secretions but need too high a dose to be useful
UT-urinary retention-- atropine will relax the body of the bladder, while contracting the sphincter
Sweat glands--blocks muscarinic receptors so inhibits sweating and increases temperature of body
Salivary glands: atropine inhibits secretion of saliva--leading to dry mouth
Respiratory tract: dry respiratory secretion and bronchodilation
CNS: atropine has both depressant (at low concentrations) and stimulatory (at high conccentrations) effects in the CNS

Front 67

Main use of atropine

Back 67

1. preop med to reduce secretione and block vagal reflexs of the heart, cardiac stimulant for certain MIs, antidote for poisioning with cholinesterase inhibitors or muscarinic agonists, to dry resp secretions, as a mydriatic agent or cycloplegic agent, as antispasmodic treatment for IBS or biliary colic

Front 68

Scopalamine and methscopalamine--Use, Class/MOA, PK

Back 68

Use: sim to atropine, except more of a CNS depressant than atropine, orally used and as a transderm patch for motion sickness and vertigo ass. with stimulation of inner ear
PK: methscopolamine is quaternary analog that does not cross BBB
MOA: competitively binds to muscarinic receptors

Front 69

Dicyclomine- PK, Use, Class/MOA

Back 69

PK: NON quarternary antimuscarinic agent
Use: widely used as intestinal antispasmodic to treat IBS
MOA: competitively binds muscarinic receptors

Front 70

Propantheline- Use, MOA/Class, PK

Back 70

Use: antspasmodic in IBS
MOA: competitively binds to muscarinic receptors
PK: quarternary compd--few CNS effects

Front 71

Glycopyrrolate- Use, MOA/Class, PK

Back 71

Use: general anti muscarinic agent, used in anesthisiology preop to dry resp secretions and inhibit vagal reflexs
MOA: quaternary compd- no CNS effects

Front 72

Ipratropium or tiatropium- Use, MOA/Class, PK

Back 72

Use: asthma and COPD
MOA: competitively binds to muscarinic receptors
PK: quarternary salts, administered by inhalation, have few systemic effects (tiatropium has longer half life)

Front 73

Benzotropine and trihexyphenidul- Use, MOA/Class

Back 73

Use: centreally acting antimuscarinic agents for treating PARKINSONS
MOA: competitively binds muscarinic receptors

Front 74

Tropicamide: Use. Class/MOA

Back 74

Use: dilation of the pupil during optho exam
Class/MOA: competitively binds muscarinic receptors

Front 75

Neuromuscular blocking drugs-- Nondepolarizing-MOA, Use, Drug used for reversal of effects

Back 75

Use: cause paralysis of skeletal muscle, MAIN DRUG -- Pancuronium
MOA: competitive blocking of muscarinic receptors
Drug used to reverse pancuroniums effects-- cholinesterase inhibitors such as neostigmine or pyridostigmine

- When Cholinesterase inhibitors such as neostigmine or pyridostigmine are used to reverse neuromuscular blockade, unwanted side effects such as bradycardia and bronchoconstriction can occur at muscarinic sites. These side effects can be blocked by muscarinic antagonists such as atropine or glycopyrrolate.

Front 76

Neuromuscular blocking drugs-Depolarizing-MOA, Use, Drug used for reversal of effects

Back 76

- Use: initally stimulated receptors to cause fasiculations dfollowed by relaxation and paralysis
MOA: competitive blocking of muscarinic receptors
- Cholinesterase inhibitors such as neostigmine, pyridostigmine cannot be used to overcome effects
- When Cholinesterase inhibitors such as neostigmine or pyridostigmine are used to reverse neuromuscular blockade, unwanted side effects such as bradycardia and bronchoconstriction can occur at muscarinic sites. These side effects can be blocked by muscarinic antagonists such as atropine or glycopyrrolate.