Vmd414B: Veterinary Pharmacology, Exam Ii

Front 1

What are 3 classes of autocoids? Give 2 examples of each.

Back 1

1. Amines- histamine (from histidine) and serotonin (from tryptophan)
2. Lipids (eicosanoids)- prostaglandins, leukotrienes, thromboxanes, prostacyclins
3. Polypeptides- bradykinin, angiotensin, kallidin, substance p

Front 2

Name a parenteral anticoagulant.

Back 2

Heparin

Front 3

Describe the action and effect of Heparin

Back 3

inactivation of clotting factors
prevents venous thrombosis

Front 4

Name an oral anticoagulant

Back 4

Warfarin

Front 5

Describe the action and effect of warfarin

Back 5

It decreases synthesis of clotting factors, preventing venous thrombosis

Front 6

Name an antiplatelet drug

Back 6

Aspirin

Front 7

Describe the action and effect of aspirin.

Back 7

Decreases platelet aggregation and prevents arterial thrombosis.

Front 8

Name a thrombolytic drug

Back 8

Streptokinase

Front 9

Describe the action and effect of streptokinase

Back 9

It causes fibrinolysis, and breaks down thrombi.

Front 10

Name 4 products of COX 1, and give as many functions of each as you can.

Back 10

PGE2: GI protectant
PGI2: decreased platelet function, increased blood flow, increased RBF
TXA2: increased platelet function, lower blood flow
Prostacylcin: antithrombogenic in endothelium, cytoprotective in gastric mucosa

Front 11

List four side effects, generally, of nonselective Cox inhibitors. Also give 2 side effects specific to particular nonselective COX inhibitors.

Back 11

-Inhibit cytoprotective PGs->ulcer
-inhibit platelet function
-impair renal, cardiac function
-mask pain

Phenylbutazone can cause blood dyscrasias
Acetaminophen is hepatotoxic

Front 12

List 2 mechanisms NSAIDS cause Gi injury

Back 12

1. topical- weak acids are not ionized at gastric pH, diffuse, get ion-trapped. Also lower hydrophobicity of mucus.

2. systemic- prevent formation of protective PGs.

Hint 12

systemic effect on hormone production, direct effect

Front 13

How is aspirin (salilcylic acid) unique in its effects?

Back 13

It is irreversible- acetylates arachidonic acid so it won't fit into the enzyme binding site.

Front 14

Is COX II selectivity consistent across species? Give THREE examples to support your answer.

Back 14

1. Carbuprofen selective in dogs (maybe), not in humans.
2. Ketoprofen high risk in humans, safe in most animals.
3. Aspirin causes GI complication in dogs.

Front 15

Give functions of PGE2

Back 15

1. Most commonly vasodilator of blood vessels, but is an important vasoconstrictor in some vascular smooth muscle (apparently.)
2. Induces fever (CNS)
3. Inhibit gastric acid secretion, increase mucous secretion
4. Increase ACTH, GH, prolactin, gonadotropins.
5. Insulin-like effects on carbohydrate mets, increase lipolysis

Front 16

What are the effects of Misoprostol? (What is it?)

Back 16

Analogue of PGE1.
Inhibits GI Acid, increases mucous
cytoprotective (counter NSAIDs)

Front 17

What does Omeprozole do?

Back 17

It's a proton-pump inhibitor, prevents gastric ulcers.

Front 18

What is the effect of H2 receptor antagonists?

Back 18

prevent duodenal ulcers, NOT gastric!

Front 19

What happens when you combine NSAIDs and corticosteroids?

Back 19

GI risk doubles
Death risk 10x NSAIDs alone!

Front 20

Considering the duration of effect of NSAIDs, what is important to keep in mind?

Back 20

Not necessarily related to clearance! Aspirin is irreversible, others are time-dependent.

Front 21

Name 7 classes of NSAIDS, and a representative of each class

Back 21

Salicylates- Aspirin
Para-aminophenols- acetaminophen
Pyrazolons- dypyrone, phenylbutazone
Propionic acid- ketoprofen, flurbiprofen
Acetic Acid- Indomethacin, etodolac
Enolic Acid- piroxicam, meloxicam
Fenamates- mefenamic acid, flufenamic acid, tolfenamic acid, meclofenamic acid

Front 22

Concerning Saliclylic Acid/ASPRIN:
-therapeutic range?
-2 uses
-T1/2?

Back 22

NARROW range
Analgesic/anti-inflammatory
prevent thromboembolism, arthritis

Short t1/2 in horses, long in dogs, cats.

Front 23

Concerning ACETAMINOPHEN/tylenol
-which of the following can you use it for:analgesic, antipyretic, anti-inflammatory?
-commonly used with what for analgesis?
-cats?

Back 23

good analgesiz/antipyretic.
*poor anti-inflammatory
-used w/ codeine for analgesis
-CATS HAVE POOR PHASE II metabolism=toxicity

Front 24

Concerning PHENYLBUTAZONE:
species?
Class?
Administration?
Side-effects in dogs, horses, man?

Back 24

-V. common in HORSES
rare in dogs, banne din food animals.
-a pyrazolon derivative
-ALKALINIC, NO IM. Give IV or PO
-Dogs: ulcers
-horses: ulcers, renal papillary necrosis
-humans: agranulocytosis, blood dyscrasias (careful when handling!)

Front 25

Concerning INDOMETHACIN:
-trade name
-selectivity/potency
-side effect
-drug class

Back 25

Indocin- NONselective, VERY potent,-ULCERS
-acetic acid dcerivative

Front 26

Concerning ETODOLAC:
-trade name?
-selectivity?
-side effects?
-frequency of administration?

Back 26

EtoGesic
COX-2 selective
SID
Low side effects

Front 27

Concerning ARQUEL (tm)
-species?
-general class of drug
-rate of onset of action
-oral availability?

Back 27

fenamate
-slow onset, given daily
-horses
-good oral availability

Front 28

Concerning KETOPROFEN:
name the class

Back 28

propionic acid derivative (like ibuprofen, flurbiprofen)

Front 29

Concerning NAPROXEN:
-give 1 human drug
-give name of horse drug
-half life?

Back 29

aleve
equiproxen
Long- 14-16 hours

Front 30

Concerning KETOPROFEN
-give a trade name
-species?
-rate of clearance/organ?
-half life?

Back 30

ketofen
-horses
-metabolized, secreted (liver, kidney)
-rapid clearance
-short half-life

Front 31

Concerning CARPROFEN
-drug class?
-trade name?
-selectivity in dogs?
-side effect (BREED?)

Back 31

RIMADYL
COX-2
a proprionic acid derivative
acute hepatic tox (within 203 wks of therapy), in LABS (maybe false correlation?)

Front 32

Considering PIROXICAM
-common use
-side effect

Back 32

inflammation from arthritis (rheumatoid, osteo)
-ULCERS, consider prophylaxis (ie, misoprostol, a PGE1 analogue)

Front 33

MELOXICAM
-selectivity?
-species?
-trade name?

Back 33

COX-2
dogs- Metacam

Front 34

Name 3 expensive COX-2 inhibitors (one is not yet commercially available). What is the class?

Back 34

Deramaxx TM (deracoxib)
previcox TM and equioxx TM (firocoxib)
Robenacoxib

-Diaryl substituted pyrazoles

Front 35

NALBUMETONE:
-uses?
-Selective?

Back 35

rheumatoid and refractory osteoarthritis
-COX-2 or else not abosrbed in stomach.

Front 36

TEPOXALIN (Zubrin TM)
-mechanism?
-unique:

Back 36

COX/LOX dual inhibitor
-dissolves V RAPIDLY

Front 37

FLUNIXIN MEGLUMINE:
species?
use?

Back 37

HORSES, dogs w/ caution, food animals
-relief of visceral pain
-BLUNT ENDOTOXIN EFFECTS

Front 38

Mineralocorticoids result in what two changes in mineral balance?

Back 38

enhanced sodium reabsorption
higher level of potassium excretion

Front 39

What affect does aldosterone have on extracellular fluid volume and GFR?

Back 39

increased extracell water, higher GFR

Front 40

Name the glucocorticoids found int:
horses, humans
pigs, dogs
Rabbits, mice, rats
Ruminants

Back 40

pigs, dogs, horses, humans: cortisol (=hydrocortisone)
rabbits, mice, rats: corticosterone
both: ruminants

Front 41

name a synthetic glucocorticoid

Back 41

dexamethasone

Front 42

Describe the circulating properties of glucocorticoids

Back 42

75% bound to transcortin
10-15% bound to albumin, loosely
10-15% free, accounts for effects. (As used up, more becomes free first from albumin.)

Hint 42

Some is free, there are 2 proteins it's bound to.

Front 43

Half-life of cortisol?
where/how is it excreted?
metabolism

Back 43

2 hours
glucuronic acid and sulfate conjugates in urine. (Urine 75% feces 25%)
Metabolism- LIVER MICROSOMES, which means upregulates its own metabolism.

Front 44

list 3 sites of manipulation for synthetic glucocorticoids

Back 44

methyl group on c16 minimized MINERALcorticoid activity
-halides at C9 enhances both mineral and glucocorticoid actions
-methyl group on C-6 prolongs half-life

Front 45

Describe the principles of GC therapy

Back 45

SINGLE LARGE DOSE for short-term treatment- up to a week.
Prolonged periods, use the minimally effective dose; only use long-term in life-threatening cases.

Front 46

Describe the effects of GCs on GNG and peripheral glucose use (2 principles, at least 3 efffects.)

Back 46

-increases GNG
-Decreases peripheral glucose

-increased central glycogen storage
-hyperglycemia, glucosuria
(manage w/ insulin or low carb diet.)

Front 47

K+, Ca+, N2 and P are lost from which tissues with GCs, and what is their effect?

Back 47

K+ loss: muscular weaknes, wasting
Ca, N, P- osteoporosis (inhibit osteoblasts.)

Front 48

PTH and PTHrP cause what?

Back 48

increase Calcium levels; increased production of PTH in response to hypoclacemia. PTH stimulates osteoclasts->bone degradation.

Front 49

An absence of GCs in the cardiovascular system leads to (name 3 problems)

Back 49

increased cap permeability
inadequate vasomotor tone
smaller cardiac size/output

Front 50

What is a product of PLA2?
What do GCs do to PLA2 levels?
Name an important related enzyme and the effect GCs have on it

Back 50

arachidonic acid->inflammatory intermediates (COX-II)
reduce them
INHIBITS COXII Expression, and PG/leukotriene synth.

Front 51

2 cells w/ decreased levels in response to GC?
Another cell has decreased function w/ GC: which?

Back 51

eo, lympho apoptosis
macrophage crappiness

Front 52

Name 2 immunosuppressive cytokines, hormones, or enzymes increased in presence of GC

Back 52

IL-10, lipocortin-1**, neutral endopeptidase are increased.

Front 53

How do you avoid withdrawal problems with GC use?

Back 53

large doses every 2-3 days instead of constant (so ACTH is still stimulated) or combine with ACTH therapy.

Front 54

Give at least 5 uses for GCs therapeutically

Back 54

otitis externa/subconjunctival inflammation of eyes
hypovolemic shock
bovine ketosis
labor induction (deprive uterus of normal source for progesterone)
immunosuppressant- arthritis
addison's

Front 55

Name 3-4 adrenal cortex antagonists, and explain the importance of one in particular

Back 55

op-DDD: SUPPRESSES CORTICAL ACTIVITY, irreversibly destroying the cortex.

amphenone blocks a path in GC synthesis
Metyrapone blocks cortisol (not corticosterone)
Aminoglutethimidine blocks step in GC (cholesterol->pregnenolone)

Hint 55

the AMA opposes o,p,DDD

Front 56

Describe at least 4 steps connecting platelet activation with TXA2 production/shape change.

Back 56

(1)Activation of platelet->activation of PLA2, which (2) converts phospholipids to arachidonic acid.(3) COX converts AA to PGH2, PGG2 (4) thromboxane synthetase makes TXA2 (out of PGH2??)

Front 57

How do corticosteroids inhibit arachidonic acid?

Back 57

They inhibit PLA2.

Front 58

What's the difference between the intrinsic phase and the extrinsic phase?

Back 58

intrinsic: all factors within the blood vessel. (Collagen exposure activates XII->XI->IX->X)

extrinsic:outisde vessels: TISSUE FACTOR (combines with factor VIIa to activate X)

Front 59

What is the endogenous fibrinolytic factor in its active and inactive form (2 names.)

name 3 things that can activate it

Back 59

plasminogen (inactive), plasmin

extrinsic: t-PA, urokinase
intrinsic: factor XIIa, HMWK, kallikrein
Exogenous: streptokinase

Front 60

Is it better to use thromboplastin SC/SQ, IM, IV, PO, or topically?

Back 60

DON'T EVER FRIGGIN GIVE IT SYSTEMICALLY UNLESS YOU ARE SICK OF CARRYING YOUR VETERINARY LICENSE AROUND. It's, um, a pretty good coagulant, why don't we just keep it for topical use.

Front 61

What's the advantage of using gelatin sponge as a hemostatic?

Back 61

non-antigenic, absorbed in 4-6 weeks.

Front 62

Name 3 general systemic hemostatics. (Okay, two are sort of the same BUT TECHNICALLY THEY'RE DIFFERENT OKAY?)

Back 62

fresh whole blood, plasma, vitamin K hemostatics.

Front 63

Name a vitamin essential for production/formation of prothrombin and VII, IX, and X

Back 63

Vitamin K

Front 64

Name a systemic hemostatic specific for heparin-induced hemorrhage, and describe its action.

Back 64

protamine sulfate is strongly basic and combines with heparin, which is strongly acidic, to form a stable salt.

Front 65

What is the effect of heparin on coagulation? Give one important complex it binds.

Back 65

Binds to basic enzymes involved in coagulation (eg thrombin, prothrombin, thromboplastin, Factor IIa, etc.). It is an anticoagulant. (Binds the ATIII-Thrombin complex, then leaves to go bind another ATIII-thrombin complex.)

Front 66

Which is best route (of these options) for heparin administration, parenteral, IV, IM? What is another good option?
What is the half-life?

Back 66

DON'T give IM
IV or DEEP s.c.
1-5 hours

Front 67

Name an anticoagulant that can be used during pregnancy, and why?

Back 67

Heparin- does not cross placental barrier

Front 68

Where is heparin metabolized, secreted?

Back 68

liver- heparinase.
20% secreted in urine.

Front 69

Suppose heparin causes hemorrhage, or you stupidly gave it to a patient with mild internal bleeding or cerebral hemorrhage-- what is a good antidote?

Back 69

protamine sulfate

Front 70

Name 2 systemic anticoagulants that can be given ORALLY, and their mechanism of action. Which is absorbed slowly and incompletely, and which is absorbed rapidly and completely?

Back 70

Warfarin (well-absorbed), bis-hydroxycoumarin

Compet. ant of vitamin K- prevent prothrombin, VII, IX, X formation.

Front 71

How quickly will courmarins take effect?
What chemical do they resemble?
Rate of absorption and clearance?
Cross placenta?y/n

Back 71

latent period of 24-48 hours.
vitamin-K analogues
Rapid absorption (on albumin), slow clearance (36 hours)
DOES cross placenta, NOT for pregnancies.

Front 72

What is a contraindication with warfarin or coumarines

Back 72

bleeding of any kind!

Front 73

Name 4 elements of treatment for warfarin toxicity.

Back 73

sedation, O2 therapy, blood trsnsfusion, slow IV infusion of vitamin K

Front 74

name 2 coumarins

Back 74

warfarin, dicumarol (maybe bishydroxycoumarin)

Front 75

Name two inhibitors of fibrinolysis

Back 75

aminocaproic acid, aprotinin

Front 76

Name 3 exogenously administered fibrinolytics

Back 76

streptokinase, urokinase, tPA (tissue plasminogen activator)

Front 77

Name three preparations used to lyse clots:

Back 77

Aletplase, which is recombinant tPA (Activase TM)
Streptokinase (such as Kabikinase TM, and streptase TM)
Urokinase (Abbokinase TM)

Front 78

Describe 2 txts for an underactive fibrinolytic system

Back 78

Fibrinolysin (Thrombolysin TM)- proteolysis of fibrinogen/dibrin, dissolves clots. (NOT used in cerebral, coronary vessels.)
Streptokinase-streptodornase (Varidase TM)
-TOPICAL, dissolve clots in 30 min-12 h

Front 79

Name 4 antiplatelet drugs

How do they work?

Back 79

Aspirin, dipyridamole, sulfinpyrazone, ticlopidine

COX inhibitors- no TXA2, a pg that inhibits platelet aggregation.

Front 80

TX for DIC?

3 tests for DIC?

Back 80

-plasma, platelet substitution
-anticoagulants (heparin)

D-Dimer, FDPs, platelet count.

Front 81

name 2 vitamin K preparations

Back 81

menadione, phytonadione

Front 82

What antibiotic drugs would inhibit absorption of vitamin K from the GI tract of a bird?

Back 82

salicylic acid and sulfonamides (for coccidiosis)