Ans Pharmacology

Front 1

Name the 6 mechanisms by which a drug can act as an agonist and alter neurotransmission in the ANS (and drug examples for each mechanism!)

Back 1

1. Drug can act as a precursor for the synthesis of a neurotransmitter (e.g. L-Dopa for Dopamine)
2. Drug can stimulate the release of neurotransmitter into the synaptic cleft (e.g. black widow spider venom for ACh)
3. Drug can directly stimulate postsynaptic receptors (e.g. nicotine and muscarine for Ach)
4. Drug blocks autoreceptors (e.g. clonidine for NE)
5. Drug blocks reuptake of the neurotransmitter into the presynaptic terminal (e.g. cocaine blocks reuptake of NE)
6. Drug inactivates acetylcholinesterase, meaning there is less breakdown of the neurotransmitter in the synaptic cleft (e.g. physostigmine for ACh)

Front 2

Name the 5 mechanisms by which a drug can act as an antagonist and alter neurotransmission in the ANS (and drug examples for each mechanism!)

Back 2

1. Drug inactivates synthetic enzyme, and inhibits synthesis of NT (e.g. PCPA for serotonin)
2. Drug prevents storage of neurotransmitter in vesicles (e.g. reserpine for monoamines)
3. Drug inhibits release of the neurotransmitter (e.g. botulism toxin for ACh)
4. Drug directly blocks postsynaptic receptors (e.g. curare, atropine for ACh)
5. Drug stimulates autoreceptors (e.g. apomorphine for dopamine)

Front 3

What is the difference between a direct and an indirect agonist?

Back 3

Both direct and indirect agonists increase the action of the exogenous neurotransmitter. A direct agonist binds to and activates the receptor, whereas an indirect agonist increases the action of the NT by increasing a secondary messenger action, decreasing degradation, etc.

Front 4

What is the difference between a direct and an indirect antagonist?

Back 4

Both direct and indirect antagonists decrease the action of the NT. Direct antagonists directly inhibit the NT binding to the receptor (via competitive inhibition). Indirect antagonists decrease the availability of the neurotransmitter.

Front 5

Drug to know: Amphetamine/ Methamphetamine

Back 5

Sympathomimetic.
Indirect Agonist.
Acts by stimulating the release of norepinephrine at the presynaptic cleft.
Overdose can result in tremors, agitation, hypertension, tachycardia, arrythmia, fever.
This is why Sudafed is behind the counter.

Front 6

Drug to know: Cocaine

Back 6

Sympathomimetic.
Indirect agonist.
Works by blocking the reuptake of norepinephrine into the presynaptic membrane.

Front 7

Drug to know: Phenylephrine

Back 7

Sympathomimetic.
Direct agonist.
Works by stimulating the alpha 1 receptors on the postsynaptic membrane.
Used as a nasal decongestant to cause vasoconstriction and prevent secretions. If overdosed, will cause hypertension, vasospasm, appetite suppression and mydriasis.

Front 8

Drug to know: Albuterol

Back 8

Sympathomimetic.
Direct agonist.
Works by stimulating the beta 2 receptors on the postsynaptic membrane.
Used in cases of asthma to cause bronchodilation. If overdosed, will cause profound hypotension followed by reflex tachycardia.

Front 9

Drug to know: Prazocin

Back 9

Sympatholytic.
Direct antagonist.
Works by inhibiting the alpha 1 receptors on the postsynaptic membrane.
Used to treat hypertension.
Overdose will result in hypotension, bradycardia.

Front 10

Drug to know: Atenolol

Back 10

Sympatholytic.
Direct antagonist.
Works by inhibiting the beta 1 receptors on the postsynaptic membrane.
Causes attenuated cardiac response: decreased contractile force/rate of the heart.
Use in cases of hypertension, congestive heart failure, cardiac arrest. Overdose will cause hypotension, bradycardia.

Front 11

What would alpha agonists be considered (in the mimetic vs. lytic showdown)? What do they cause? When would you use them, and what are some examples (that we have to know) of alpha agonist drugs?

Back 11

Alpha agonists are considered sympathomimetics. Alpha 1 agonists specifically cause vasoconstriction (because the vasculature primarily has alpha 1 receptors). They would be indicated for use in cases of anaphylaxis (because you have systemic vasodilation), hypotension and shock, to control hemorrhage in superficial surgery, to contain local anesthetics (by blocking diffusion of anesthetic into the bloodflow), as a nasal decongestant, or in cases of urinary incontinence (to keep the sphincter tight). Examples we need to know: epinephrine, norepinephrine.

Front 12

What would beta agonists be considered (in the mimetic vs. lytic showdown)? What are the two types of beta agonists, and what do they cause? When would you use them?

Back 12

Beta agonists are considered sympathomimetics. Two types of beta agonists:
1. Nonspecific beta agonists: cause cardiac stimulation. Use them for bradycardia, AV block, cardiac arrest, heart failure)
2. Beta 2 agonists: cause bronchial relaxation. Use in cases of asthma attacks.

Front 13

Drug to know: Epinephrine

Back 13

Sympathomimetic.
Beta 1, Beta 2 > Alpha 1 agonist
Causes cardiac stimulation, vasoconstriction.
Use in cases of anaphylaxis, to control hemorrhage in superficial surgery, contain local anesthetics.

Front 14

Drug to know: Norepinephrine

Back 14

Sympathomimetic.
Alpha 1 Beta 1 agonist.
Causes vasoconstriction, cardiac stimulation, mydriasis, increased peripheral and systemic arterial blood pressure.
Use in cases of hypotension and shock.
Overdose will cause hypertension, tachycardia.

Front 15

Drug to know: Isoproterenol

Back 15

Sympathomimetic.
Beta 1, beta 2 agonist.
Will cause cardiac stimulation, relax smooth muscle.
Use in cases of bradycardia, AV block.

Front 16

Drug to know: Dopamine

Back 16

Sympathomimetic.
Nonselective beta agonist.
Use in cases of cardiac arrest, congestive heart failure.

Front 17

What are alpha 1 antagonists considered? What do they do, what are they used for, and what are some examples of drugs?

Back 17

Alpha 1 antagonists are sympatholytics. They cause vasodilation, and would thus be used in cases of hypertension. Two examples: Prazosin, Phenoxybenzamine.

Front 18

What are alpha 2 antagonists considered? What do they do and what are they used for?

Back 18

Alpha 2 antagonists are sympathomimetics. They increase sympathetic outflow, and could be used as reversal for tranquilizers (e.g. yohimbine)

Front 19

uWhat are beta antagonists? What are the two types, what do they do, and when would they be used?

Back 19

Beta antagonists are sympatholytics. There are two types: nonspecific beta blockers (used in cases of hypertension- e.g. propranolol, sotalol), and specific beta 1 antagonists- these would be used to create an attenuated cardiac response. They would be used in cases of cardiac arrest, congestive heart failure, and hypertension (drug example: atenolol)

Front 20

Drug to know: Phenoxybenzamine

Back 20

Sympatholytic.
Alpha 1 antagonist.
Causes vasodilation, myosis.
Used in cases of hypertension, also used in treatment of pheochromocytoma.
Overdose will cause hypotension, bradycardia.

Front 21

Drug to know: Propranolol

Back 21

Sympatholytic.
Non-selective beta antagonist (aka beta blocker).
Will result in decreased contractile force/rate of the heart.
Use in cases of hypertension, albuterol toxicity.
Overdose will cause hypotension, bradycardia.

Front 22

Drug to know: Sotalol

Back 22

Sympatholytic.
Non-selective beta blocker.
Acts by decreasing contractile force/rate of the heart.
Use in cases of hypertension. Overdose will cause hypotension, bradycardia.

Front 23

Drug to know: Nicotine

Back 23

Parasympathomimetic.
Direct nicotinic agonist.
Will result in increased parasympathetic stimulation.
Overdose will result in:
initially: vomiting, excitement, tremors/convulsions

ultimately: muscular weakness, tremors, nausea, vmoiting, ataxia, tachypnea, tachycardia, hypertension, mydriasis, respiratory distress

Front 24

Drug to know: Carbachol

Back 24

Parasympathomimetic.
Direct muscarinic agonist.
Results in increased secretions, miosis.
Overdose will result in DUMBELS.

Front 25

Drug to know: Bethanechol

Back 25

Parasympathomimetic.
Direct muscarinic agonist.
Causes smooth muscle contraction- increases GI tone and peristalsis, decreases bladder capacity, relaxes external sphincter muscle.
Use in cases of GI stasis, urinary retention (in absence of blockage).
Overdose will result in DUMBELS.

Front 26

Drug to know: Pilocarpine

Back 26

Parasympathomimetic.
Muscarinic agonist.
Causes contraction of iris sphincter muscle, allowing drainage of aqueous humor (decreasing intraocular pressure).
Used for glaucoma.
Overdose will result in DUMBELS.

Front 27

Drug to know: Physostigmine

Back 27

Parasympathomimetic.
Cholinesterase inhibitor.
Increases amount of ACh in synaptic cleft. Causes contraction of iris sphincter muscle (decreasing intraocular pressure), smooth muscle contraction, increased secretions.
Used in cases of glaucoma, GI stasis, urinary retention, myasthenia gravis.
Overdose will cause DUMBELS.

Front 28

Drug to know: Edrophonium

Back 28

Parasympathomimetic.
Cholinesterase inhibitor.
Increases amount of ACh in synaptic cleft, allowing more to bind to ACh receptors at neuromuscular junction.
Used for treatment of myasthenia gravis.
Overdose will result in DUMBELS.

Front 29

Drug to know: Demecarium bromide

Back 29

Parasympathomimetic.
Cholinesterase inhibitor.
Increases amount of ACh in synaptic cleft. Causes contraction of iris sphincter muscle (decreasing intraocular pressure), smooth muscle contraction, increased secretions.
Used in cases of glaucoma. Can be used in preventative management in dogs after diagnosis of primary glaucoma in other eye.
Overdose will cause DUMBELS.

Front 30

Drug to know: Tubocurarine

Back 30

Parasympatholytic.
Nicotinic antagonist.
Blocks nicotinic receptors at neuromuscular junction. Results in decreased muscle contraction.
This is a toxin.

Front 31

Drug to know: Atropine

Back 31

Parasympatholytic.
Muscarinic antagonist.
Causes mydriasis, smooth muscle relaxation, decreased secretions.
Used as a pre-anesthetic medication (to dry secretions),

Front 32

Drug to know: Tropicamide

Back 32

Parasympatholytic.
Muscarinic antagonist.
Causes mydriasis, smooth muscle relaxation, decreased secretions. Used in opthamology.

Front 33

Drug to know: Pilocarpine

Back 33

Parasympathomimetic.
Muscarinic agonist. Causes contraction of iris sphincter muscle, allows drainage of aqueous humor, increased secretions. Decreases intraocular pressure.
Used for treatment of glaucoma.
Overdose will cause DUMBELS.

Front 34

Drug to know: Ecothiophate

Back 34

Parasympathomimetic.
Cholinesterase inhibitor.
Causes contraction of iris sphincter muscle, allows for drainage of aqueous humor, smooth muscle contraction.
Used for treatment of glaucoma.
Overdose will cause DUMBELS.

Front 35

Drug to know: Atropine

Back 35

Parasympatholytic.
Muscarinic antagonist (long acting).
Used to produce mydriasis, as a pre-anesthetic medication (to reduce secretions, to treat drug-induced bradycardia during sx), as a treatment for organophosphate toxicity.
Overdose will cause fever, tachycardia, mydriasis, dry mouth, thirst, urinary retention, respiratory paralysis.

Front 36

What are some clinical uses for sympathomimetics?

Back 36

To cause:
Vasoconstriction
Cardiac stimulation
Bronchial relaxation

Front 37

What are some clinical uses for sympatholytics?

Back 37

To cause:
Vasodilation
Decrease sympathetic outflow
Attenuated cardiac response

Front 38

What are some clinical uses of parasympathomimetics?

Back 38

In the treatment of:
glaucoma
GI stasis and urinary retention (in absence of muscle fatigue)
Myasthenia gravis

Front 39

What are some clinical uses of parasympatholytics?

Back 39

Used to:
Dilate pupil (produce mydriasis)
As a pre-anesthetic medication (to reduce secretions, combat drug induced bradycardia during sx)
To decrease GI hypermotility/spasms of GI/urinary tract
As an antiemetic
To treat urinary incontinence
In the treatment of organophosphate toxicity

Front 40

What are the primary receptors on cardiac muscle?

Back 40

Beta 1

Front 41

What are some of the symptoms of intoxication with a muscarinic agonist? What is one example of a toxin that is a muscarinic agonist?

Back 41

Diarrhea
Urination
Miosis
Bronchospasm
Emesis
Urination
Lacrimation
Salivation
Examples: muscarine, from Amanita mushrooms

Front 42

What are some of the symptoms of intoxication with a muscarinic antagonist? What is one example of a drug that, when overdosed, will produce these symptoms?

Back 42

Fever, tachycardia, dilated pupils, dry mouth (and increased thirst), urinary retention, respiratory paralysis, death
"Blind as a bat, mad as a hatter, red as a beet, dry as a bone, hot as hell"
Example: Atropine

Front 43

What are some of the symptoms of intoxication with a nicotinic agonist? What is one example of a toxin that is a nicotinic agonist?

Back 43

With low dose or initially after a high dose: Vomiting, excitement, tremors or convulsions
Ultimately after a high dose: muscular weakness, tremors, nausea, vomiting, ataxia, tachycardia, tachypnea, hypertension, mydriasis, respiratory distress
Example: Nicotine

Front 44

What are some examples of intoxication with an acetylcholinesterase inhibitor? What clinical signs will these cause?

Back 44

Organophosphorus pesticides (OPs)- irreversible AChE inhibitors
Carbamate pesticides- reversible AChE inhibitors
Intoxication with these agents will cause BOTH muscarinic and nicotinic signs (DUMBELS + muscle tremors)

Front 45

What is the the mechanism of action of the botulinum toxin? What are the symptoms of botulism intoxication?

Back 45

It is an indirect acting toxin that blocks the presynaptic release of ACh. The toxin binds to the vesicle protein and prevents docking of the vesicles to the plasma membrane. There are a number of different botulinum toxin compounds that attack different aspects of the many proteins necessary to have vesicle-membrane fusion and exocytosis.
Symptoms of intoxication with botulinum toxin: Flaccid paralysis, resulting in death in 3-10 days

Front 46

What is the mechanism of action of theobromine (chocolate) intoxication? What are the clinical signs?

Back 46

Theobromine is a sympathomimetic that inhibits phosphodiesterase (thus prolonging beta receptor signaling).
Clinical signs include hypertension, hyperexcitability, tachycardia, tremors, mydriasis, and head-bobbing.

Front 47

What are the treatment for an acute cholinergic crisis brought on by cholinesterase inhibitor intoxication?

Back 47

1. Decontamination of skin (only effective when it is performed within minutes to hours of exposure)
2. Atropine- noncompetitive antagonist of muscarinic receptors. Has no effect on nicotinic signs (muscle weakness) or respiratory failure.
3. Pralidoxime (2-PAM)- reactivates cholinesterase enzymes. Only effective if enzyme has not aged! Used in conjunction with atropine. Very expensive, used more for OP intox than for carbamate toxicity.
4. Enhancement of elimination (activated charcoal)- effectiveness is not clearly established.

Avoid parasympathomimetic agents and antihistamines. CNS depressants may increase likelihood of respiratory distress. Maintain respiratory and cardiac function, and administer fluids to prevent severe dehydration.

For OP intoxication, M3 selective antagonists should be used as well, because OPs inhibit M2 receptors on parasympathetic nerves in the lungs and cause airway hyperreactivity at doses that do not inhibit AChE. You've still resulted in a net increase of ACh at the synaptic cleft. M3 selective antagonists will help decrease the amount of signaling in the airways and prevent hyperreactivity.

Front 48

Name 5 drugs we have learned to treat hypertension.

Back 48

You want sympatholytic drugs to treat hypertension.
- Prazosin (alpha 1 antagonist, causes vasodilation)
- Phenoxybenzamine (alpha 1 antagonist, causes vasodilation)
- Propanolol (non-selective beta blocker, acts on the kidney to decrease renin production, which is a vasoconstrictor)
- Sotalol (non-selective beta blocker, acts on the kidney to decrease renin production, which is a vasoconstrictor)
- Atenolol (beta 1 antagonist, causes attenuated cardiac response)

Front 49

Name 1 drug we have learned to treat hypotension.

Back 49

Norepinephrine (sympathomimetic, alpha 1 beta 1 agonist, causes vasoconstriction)

Front 50

What 2 drugs have we learned to treat congestive heart failure?

Back 50

Dopamine- Sympathomimetic, beta agonist, causes cardiac stimulation.
Atenolol- Sympatholytic, beta 1 antagonist, causes attenuated cardiac response. Slows the heart down, allows the ventricles to fill- contraindicated in unstable patients.

Front 51

Name 4 drugs we've learned about to treat glaucoma.

Back 51

All are parasympathomimetic drugs.
Pilocarpine- Muscarinic agonist, lowers intraocular pressure
Physostigmine- cholinesterase inhibitor, causes contraction of iris sphincter muscle, decreasing intraocular pressure.
Ecothiophate- cholinesterase inhibitor
Demecarium bromide- cholinesterase inhibitor