Veterinary Pharmacology 2

Front 1

Define “Sympathomimetic” and where do they act?

Back 1

Action similar to stimulation of sympathetic nervous system; act in postganglionic sympathetic nerve endings

Front 2

Define “Parasympathomimetic” and where do the act?

Back 2

Action similar to stimulation of parasympathetic nervous system; act in postganglionic parasympathetic nerve endings

Front 3

Define Sympatholytic

Back 3

Block action of sympathetic NS.

Front 4

Define Parasympatholytic

Back 4

Block action of parasympathetic NS

Front 5

What region of the spinal cord does the sympathetic NS branch off of?

Back 5

Thoracolumbar

Front 6

What region of the spinal cord does the parasympathetic NS branch off of?

Back 6

Craniosacral

Front 7

Define adrenergic.

Back 7

Action or site mediated by epinephrine or NE.

Front 8

Define cholinergic.

Back 8

Action or site mediated by acetylcholine.

Front 9

Where are β1 receptors found? Β2 receptors?

Back 9

β1 – Heart, β2 – Most tissues except the heart

Front 10

Tell whether stimulation of the following receptors causes smooth muscle contraction or relaxation:
Acetylcholine receptors
α1 adrenergic receptors
β1 adrenergic receptors

Back 10

Acetylcholine receptors - Contraction
α1 adrenergic receptors - Contraction
β1 adrenergic receptors - Relaxation

Front 11

True or False: Most organs have a predominant parasympathetic tone.

Back 11

True

Front 12

Which tissues have a predominant sympathetic tone?

Back 12

Arterioles, veins, sweat glands

Front 13

Determine the location, presynaptic or postsynaptic, of the following receptors:
- Alpha 1:
- Alpha 2:
- Beta 1:
- Beta 2:

Back 13

- Alpha 1: postsynaptic
- Alpha 2: presynaptic
- Beta 1: postsynaptic
- Beta 2: postsynaptic

Front 14

Describe the difference between Beta 1 and Beta 2 receptors in terms of their response to Norepinephrine and Epinephrine

Back 14

- Beta 1 receptors’ response to epinephrine is greater than or equal to norepinephrine
- Beta 2 receptors’ response to epinephrine is greater than norepinephrine (responds primarily to epinephrine).
- Beta 1 receptors are found primarily in the heart. Beta 2 receptors are found everywhere else.

Front 15

Determine the selectivity of the neurotransmitters and their receptors:
Norepinephrine α1
Epinephrine β1
Isoproterenol β2

Back 15

NE: α1, β1
Epi: α1, β1, β2
Iso: β1, β2

Front 16

Describe the effects of the sympathetic and parasympathetic nervous system on cardiac function.

Back 16

- Sympathetic stimulation increases cardiac output
- Parasympathetic stimulation decreases cardiac output

Front 17

What mechanism controls the reflex control of heart rate with the administration of norepiniephrine?

Back 17

- The norepinephrine causes a sharp increase in blood pressure through stimulation of the alpha receptors which contracts smooth muscle and raises peripheral resistance.
- The baroreceptors in the carotid sinus sense the increased pressure and the vagus nerve responds with release of ACh to the sinoatrial node to slow the heart rate.

Front 18

Why do renal arteries have a high concentration of alpha receptors?

Back 18

- Alpha receptors respond to epinephrine and norepinephrine by constricting smooth muscles.
- In the case of the renal arteries, the high concentration of α-1 receptors allows them to respond to the NT released with shock and rapidly decrease renal blood flow to shunt the blood to the major organs.

Front 19

Name three indirect sympathomimetics and their site of action.

Back 19

- Tyramine: displaces neurotransmitter vesicle (NE)
- Cocaine and tricyclic antidepressants: blocks reuptake of the neurotransmitter to increase the NT concentration in the synaptic cleft
- Caffeine, Aminophylline, Theophylline: Phosphodiesterase inhibitor

Front 20

Define “epinephrine reversal”. What is epinephrine reversal’s effect on blood pressure?

Back 20

This occurs in any animal when you give epinephrine in the presence of an α blocker.
When you give E in the presence of an α blocker, its effects essentially become the same as if you gave only Isoproterenol, thus decreasing BP but getting a large increase in cardiac output. “The pharmacological response is that of the unoccupied receptor.”

Front 21

What are the 3 modes of action for adrenergic stimulants? Give a drug example of each.

Back 21

Direct- direct interaction of adrenergic with specific receptors (Ex. Epinephrine, Dopamine, Norepinephrine, phenylephrine)
Indirect- adrenergic stimulates the release of neurotransmitters (Ex. amphetamines)
Mixed- adrenergic stimulant involves both direct and indirect modes (Ex. Ephedrine, caffeine, phenylpropanolamine)

Front 22

If a sympathomimetic drug cannot be broken down by monamine oxidase (MAO) what happens to it? What is this called?

Back 22

If a drug cannot be broken down by MAO, then these stimulants get stored where neurotransmitters are stored, effectively forcing the neurotransmitter to be released. These are called indirect acting adrenergic stimulants.

Front 23

Give an example of an MAO inhibitor.

Back 23

Anipryl (he’s mentioned this like 8 times in class)

Front 24

Name 7 clinical uses for adrenergic agents.

Back 24

Shock, asthma, arrhythmias, hypotension, hemostasis (local), anesthesia (prolonged local), nasal congestion.

Front 25

What are the 3 different names for drugs that inhibit sympathetic responses?

Back 25

Anti-adrenergic, adrenolytic, sympatholytic agents

Front 26

What is the effect of epinephrine on BP in the presence of a β2-blocker?

Back 26

Epinephrine will have the same effects as norepinephrine at equivalent doses.

Front 27

Which α-antagonists we discussed in class is reversible and which is irreversible?

Back 27

Phentolamine- reversible α-blocker
Phenoxybenzamine- irreversible α-blocker

Front 28

Epinephrine is commonly added to local anesthetic agents, such as lidocaine. Why?

Back 28

It increases the local duration of the anesthetic by decreasing blood flow to the area.

Front 29

Intravenous infusion of phenylephrine results in a decrease in heart rate. Why?

Back 29

It indirectly activates the baroreceptors reflex.

Front 30

How does aminophylline produce its pharmacological action?

Back 30

By inhibiting cAMP Phosphodiesterase

Front 31

Why is phenylephrine a good drug to use when you have a runny nose?

Back 31

When you squirt it into your nose, it stimulates the α-receptors on the SQ vessels, decreasing blood flow to the inflamed mucous membranes thus decreasing secretions.

Front 32

Which drug would you use to treat urinary incontinence in middle age to older female dogs? Why does the urine dribbling occur?

Back 32

Phenylpropanolamine (PPA)
The dribbling is due to a decreased sphincter tone.

Front 33

Why are β-agonists not good to be used for a long term treatment of asthma-like conditions?

Back 33

β-receptors can be desensitized and down regulated with chronic stimulation

Front 34

What is the major fate of norepinephrine that is released into the synaptic cleft?

Back 34

It is recycled into the presynaptic nerve terminal.

Front 35

What happens to the blood pressure of a patient when they are given them a beta receptor agonist?

Back 35

bp goes down

Front 36

What is the most common alpha blocker given to animals as a pre-anesthetic medication?

Back 36

Acepromazine

Front 37

True or False. Acetylcholine is the neurotransmitter at both pre and post ganglionic parasympathetic neurons.

Back 37

True

Front 38

True or False. Atropine is a muscarinic agonist.

Back 38

False. Atropine is a muscarinic antagonist

Front 39

Sympatholytic agents are used primarily as pre-anesthetic agents. What other clinical uses are there for sympatholytic agents?

Back 39

a. Control of cardiac arrhythmias
b. Tranquilization
c. Pheochromocytoma (neuroendocrine tumor of the medulla of the adrenal glands that secretes catecholamines)

Front 40

Which cranial nerve in the parasympathetic nervous system innervates the ciliary muscles of the eye?

Back 40

Cranial nerve III-oculomotor nerve

Front 41

Parasympathetic outflow exits the spinal cord from the cranial / sacral outflows and innervates most of the organs of the body with ________ _____ ganglionic and ________ _____ ganglionic fibers.
a. Short pre / long post
b. Long pre / short post
c. Dorsal root / ventral root
d. None of the above

Back 41

b. Long pre / short post

Front 42

The parasympathetic nervous system uses pre-ganglionic nicotinic cholinergic receptors. What are the parasympathetic post ganglionic receptors?

Back 42

muscarinic cholinergic receptors

Front 43

__________ is one of the fastest enzymes in the body and hydrolyzes approx. 100,000 molecules per minute.

Back 43

Acetylcholine Esterase

Front 44

When administering a low dose of acetylcholine (10 micrograms/kg) one gets bradycardia and transitory hypotension. When the dose is increased 10 fold and is readministered, one gets tachycardia and hypertension. What is the reason for the paradoxical effect at the higher dose?
a. At higher doses, ACh competes for muscarinic sites and blocks the endogenous neurotransmitters that maintain tone on smooth muscle.
b. At higher doses, ACh stimulates sympathetic nicotinic ganglionic receptors
c. At higher doses, ACh stimulates parasympathetic nicotinic ganglionic receptors
d. At lower doses, ACh stimulates sympathetic muscarinic receptors
e. ACh feeds back on sympathetic presynaptic muscarinic receptors and increases the amount of NE release.

Back 44

b. At higher doses, ACh stimulates sympathetic nicotinic ganglionic receptors

Front 45

Which of the following is not affected by parasympathetic stimulation?
a. Heart
b. Eye
c. Bladder
d. Bronchioles
e. All of the above are affected
f. None of the above are affected

Back 45

e. All of the above are affected

Front 46

What 3 systems work in concert to control the urinary bladder?

Back 46

a. Parasympathetic control
b. Sympathetic control
c. Voluntary control

Front 47

Which statement about the urinary bladder is false?
a. The bladder sphincter contains smooth muscle
b. The bladder sphincter contains voluntary muscle
c. Storage phase is under both sympathetic and parasympathetic control.
d. Emptying phase is under parasympathetic control
e. All the above statements are true

Back 47

c. Storage phase is under both sympathetic and parasympathetic control. (false-only sympathetic control)

Front 48

Explain the difference between direct and indirect acting parasympathomimetic agents.

Back 48

Direct- agents directly combine with the cholinergic receptor
Indirect- agents inhibit acetylcholinesterase (AChE)

Front 49

What are the 2 different classes of direct acting parasympathomimetic agents, and what are examples of each?

Back 49

Choline esters- methacholine, carbacol, bethanechol (and acetylcholine of course)
Plant alkyloids- pilocarpine, arecoline

Front 50

Give the order of susceptibility of choline esters to cholinesterases from most reactive to least reactive:
Carbachol, methacholine, acetylcholine, bethanechol

Back 50

Acetylcholine>methacholine>carbachol=bethanechol
(Table 5-2 in lecture)

Front 51

Give the order of reactivity of choline esters for nicotinic receptors from most reactive to least reactive:
Carbachol, methacholine, acetylcholine, bethanechol

Back 51

Carbachol>acetylcholine>methacholine>bethanechol

Front 52

Which choline ester would you want to use if you needed to induce PNS effects in the cardiovascular system, the GI system, and the eye?

Back 52

CV- methacholine
GI- barbachol/bethanechol
Eye- carbachol/bethanechol

Front 53

What are the two forms of AChE?

Back 53

Acetylcholinesterase – true form- found in RBC, nerve terminals (including NMJ of skeletal muscle)
Butyrulcholinesterase – “pseudo” form- found in plasma, and other tissues like liver and intestine

Front 54

What is the function of AChE?

Back 54

It breaks down Ach into an into choline and acetic acid

Front 55

Give 3 examples of AChE inhibitors and tell if they are reversible or irreversible inhibitors.

Back 55

Reversible: Edrophonium, neostigmine, physostigmine,
Irreversible: organophosphates and alkylphosphates; Diisopropyl fluorophosphates(DFP, irreversible for the life of the enzyme, 80-120 days), tetraethyl pyrophosphate, parathion, malthion, dichlorous, parameter

Front 56

In what type of commercial product is DFP usually found? What drug is used to treat severe DFP toxicosis? How does it work?

Back 56

DFP is an organophosphate usually found in bait- like slug, gopher, etc.
To treat severe DFP toxicosis, use pralidoxime (2PAM).
2PAM binds to the phosphorylated form of the enzyme at the active site. This causes a bond to form and the oxime phosphate dissociates leaving active AChE.

Front 57

If an animal is exposed to OP, what cholinergic receptors are activated? What would you treat it with?

Back 57

Since dose dependent, a smaller amount of OP will only activate the muscarinic receptors. The clinical signs of this are SLUD- salivation, lacrimation, urination, and defecation. (A case like this, treating with atropine would be sufficient.) If a significant amount of OP is ingested, muscarinic and nicotinic receptors are activated, then you’ll see CNS signs/full body twitching. (This case would treat with atropine and 2PAM)

Front 58

What are clinical uses of cholinergic agents?

Back 58

GI disorders, urinary retention, ophthalmic uses, skeletal muscle (Myasthenia gravis), anthelmintics.

Front 59

What is the function of parasympatholytic agents? What are 3 common drug examples?

Back 59

To block the action of ACh at muscarinic sites- smooth muscle and glandular. Atropine, glycopyrrolate, scopolamine.

Front 60

What are clinical uses of anticholinergic agents?

Back 60

Preanesthesia, decrease hyperperistalsis, antiemetics, dilate pupils, organophosphate toxicity, relief of urinary tract spasms, urinary incontinence.

Front 61

What is the major mechanism by which ACh is inactivated at the preganglionic nicotinic site?

Back 61

Hydrolysis by AChE.

Front 62

Which of the following choline esters are rapidly metabolized by butrylcholinesterase (“pseudocholinesterase”)? Acetylcholine, bethanechol, methacholine, succinylcholine, carbechol.

Back 62

acetylcholine

Front 63

Although many of the cholinomimetics appear to produce similar actions on the body, bethanechol is noteable due to its comparable lack of ___________ action?

Back 63

nicotinic

Front 64

A common sx 3rd year students perform is gut anastamosis. A complication can be GI stasis of the gut. Which of the following drugs would you consider to use post-op if normal gut function does not return? Atropine, nicotine, muscarine, bethanechol, acetylcholine

Back 64

bethanechol

Front 65

Most likely the drug acetylcholine won’t be used in a clinical setting; you will use an ACh derivative. Why is this?

Back 65

It has too short of a half life (5 mins).

Front 66

A dog presents to you in a clinic with what you think is Myasthenia gravis. What is a cheap way to test for this disease?

Back 66

Assess the dog’s response to a test dose of Tensilon, which blocks AChE function.

Front 67

Name 4 clinical indications for the use of diuretic

Back 67

Hypertension, Edema (congestive heart failure, exercise induced pulmonary hemorrhage), urinary excretion of toxic substances (overdose), regulation of cerebrospinal and intraocular pressure

Front 68

What are three main cellular mechanisms of electrolyte transport utilized by the kidney nephron and give an example of electrolytes that utilize each one?

Back 68

ATP active transport (Na in the proximal tubule)
Cotransport/Symport (Cl is active in ascending loop of Henle and ions travel with it)
Antiport (proximal and distal tubule, K+ and H+ exchange)

Front 69

Where is the diuretic mannitol effective? What kind of diuretic is it?

Back 69

Mannitol works along the entire length of the tubule. It is an osmotic diuretic – which means that it is highly effective but must maintain sufficiently high glomerular filtrations rates and has the potential to cause hyponatremia.

Front 70

Where would a carbonic anhydrase inhibitor be effective? What is its mechanism of action?

Back 70

Cytoplasm and brush border of tubular cells. It decreases bicarbonate HCO3 reabsorption, H+ secretion, and Na+ reabsorption and causes a corresponding increase.

Front 71

What region of the Loop of Henle would be affected by a “Loop Diuretic?” What is its mechanism of action?

Back 71

The ascending loop of Henle – it inhibits the reabsorption of Cl which through symport mechanisms inhibits Na+, which carries water with it through the tubule

Front 72

Where would aldosterone exert its action?

Back 72

Collecting ducts.

Front 73

What is special about a loop diuretic as compared to all other diuretics?

Back 73

It is still effective in cases of low GFR

Front 74

What are 4 important toxicities associated with loop diuretics?

Back 74

• Changes in electrolyte balance.
• Ototoxicity with ethcrynic acid (rare)  do not use loop diuretics with aminoglycosides!
• Competition for plasma protein binding sites  be careful with other protein bound drugs that have narrow therapeutic indices (warfarin)
• NOT approved for use in food animals!

Front 75

True or False: Aldosterone antagonists are competitive inhibitors that greatly increase the Na+/K+ ratio (Potassium sparing).

Back 75

True
Remember however that they are only effective in the presence of aldosterone.

Front 76

True or False: Thiazides are often used in combination with carbonic anhydrase inhibitors in order to prevent potassium loss/ hyperkalemic toxicity.

Back 76

False
Thiazides are used in combination with aldosterone antagonists – prevents potassium loss from the thiazides and hyperkalemic toxicity from aldosterone antagonists.