Exam 1 Pharm II Flashcards
1
Q
4 Types of drugs that act on the blood
A
(1) Antianemic
(2) Colony Stimulating Factors (CSF)
(3) Drugs affecting hemostasis - pro and anti
(4) Drugs to Treat thromboembolism in cats
2
Q
4 Classifications of Anemia that require Antianemic Drugs
A
1. Microcytic (hypochrome) anemia = Fe and Cu
2. Macrocytic (megaloblastic) anemia - cobalt
- Normocytic anemiadue to CRF or bone marrow suppression - EPO, iron, anabolic steroids
4. Immune- mediated hemolytic anemia (IMHA) - supportive, blood transfusion, Immunosuppresives, IV gamma globulin
3
Q
Iron preparations
A
Classification: Anti-anemic
MOA: component of heme
Use: Microcytic (hypochromic) anemia in DOGs and PIGLETs
Problems: heavy metal issues (toxic, irritation, estringent), carbohydrates added to parental preparations causes histamine release, SQ & IM administration causes yellow discoloration
ADME: Oral (stable use- less irritating) or Parental (emergency use) divalent is better than trivalent requires carrier protein (epotherotin) to move through body no excretion method- be careful with dose
4
Q
Copper Preparation
Copper Sulfate & Copper Glycinate
A
- Classification: Anti-anemic
- MOA:
- (1) involved in Fe absorption and metabolism
- (2) component of cytochrome oxidase
- Use: Microcytic (hypochromic) anemia in DOGs and PIGLETs
- Problems: heavy metal issues
- ADME:
- –Copper Sulfate= Oral
- – Copper Glycinate = SC or IM
5
Q
Cobalt
A
Classification: Antianemic
Use: Macrocytic (megaloblastic) anemia in RUMINANTs
6
Q
Erythropoeitin, EPO (Epogen)
A
- Classification: Antianemic
- MOA:
- (1) replacement of reduced EPO due to decreased renal production
- (2) bone marrow stimulation of RBC precursor
- Use: Anemia due to CRF or bone marrow suppression
- Problems: vasoconstriction, allergic reaction
- ADME: inject 2x a week, made by recombination DNA technology ( Dog and human available?)
7
Q
How do you treat immune-mediated hemolytic anemia?
A
(1) Supportive Therapy = fluids, acid-base balance, organ perfusion
(2) Blood transfusion
(3) Immunosuppresives -
- — GLucocorticoids (prednisone, presnisolone)
- — Cytotocic drugs (cyclophosphamide, azathioprine)
- –Danazol
- —Cytosporin A
(4) Intravenous gamma globulin
8
Q
What are the problems associated with heavy metals (such as Iron and Cooper)?
A
Heavy Metals are:
- –very potent & toxic
- – large doses cause GI irritation (ulcers, nausea, diarrhea)
- –estringent–> precipitate proteins –> constipation
- – animals lack removal mechanisms
can provide chelating agents as antidotes (bind to metal to form water soluble and easily excreted complex that is less toxic)
9
Q
Colony Stimulating Factor
Filgrastin (G-CSF) vs Sargramostim (GM-CSF)
A
- Classification: drugs acting on the blood
- MOA: stimulate maturation, differentiation and proliferation of proginator cells
- (a) G-CSF stimulates neutrophils
- (b) GM- CSF stimulates myeloid precursor to increase neutrophils, eosinophils, basophils, erythocytes and macrophages
- Use: prevent and treat neutropenia induced by anti-cancer chemotherapy
- Problems: Bone pain & Sargramostim causes fever and cardiopulmonary toxicity
- ADME: injectable
10
Q
Filgrastin (G-CSF)
A
- G-CSF stimulates neutrophils
- Use: prevent and treat neutropenia induced by anti-cancer chemotherapy
- Problems: Bone pain
- ADME: injectable
11
Q
Sargramostim (GM-CSF)
A
- Sargramostim (GM- CSF) stimulates myeloid precursor to increase neutrophils, eosinophils, basophils, erythocytes and macrophages
- Use: prevent and treat neutropenia induced by anti-cancer chemotherapy
- Problems: Bone pain & Sargramostim causes fever and cardiopulmonary toxicity
- ADME: injectable
12
Q
What are the 2 Groups of Hemostatic Drugs
A
Local (Styptics) and Systemic
13
Q
Local Hemostatics (Styptics)
A
For topical use only (thrombus is used systemically)
- (1) Vasoconstrictors - epinephrine
- (2) Astringents - tannic acid & ferric chloride – precipitated proteins form crust/seal over injured vessel
- (3) Surgical- oxidized cellulose, gelatin sponge, collagen
- (4) Physiological - Thromboplastin, thrombin, fibrinogen, fibrin foam
14
Q
what drug is a Vasocontrictive local hemostatic?
A
Epinephrine
15
Q
What two drugs are Astringent Local Hemostatics? How do they work?
A
tannic acid (in coffee and tea) & ferric chloride
– precipitated proteins form crust/seal over injured vessel
(ferric= local/topical, ferous= systemic)
16
Q
What drug is a Surgical Local Hemostatics?
A
oxidized cellulose gelatin sponge collagen
17
Q
Physiological Local Hemostatics
A
Thromboplastin
thrombin
fibrinogen
fibrin foam
18
Q
What is Benzocaine? What product is it in
A
local anesthetic in Clot-it- PLUS Ester
(most amides have “i” before -caine)
19
Q
What are the 5 systemic hemostatics?
A
- Clotting factors- can be used in ANY type of hemorrage - in blood transfusions & fresh frozen plasma (FFP)
- Vitamin K for warfarins
- Protamine sulfate – for heprin bleeding
- Aminocaproic acid – for thrombolytic agent bleeding
- Desmopressin (DDAVP) – for vWF disease ( and ADH/Vasopressin analog)
20
Q
Vitamin K- classification, MOA, Use, ADME?
A
Classification: Systemic Hemostatics
- (a) *Vitamin K1 (phytonadione) from plants *
- (b) Vitamine K2 (menaquinone) formed by bacteria in the GI tract - not available as drug
- (c) Vitamin K3 (menadione) synthetic - DO NOT USE IN HORSES
MOA: active/reduced K1 is a co-factor for carboxylase enzyme that is required to activate precursors of factors 2, 7, 9 & 10 (PIVKA) in the liver
Use:
- (1) antidote to warfarins (both 1st and 2nd genration)
- (2) treatment of spoiled sweet clover poisening in cattle (releases glycosides that act similar to warfarin)
- (3) Treatment of rare vitamin K deficiency in ulcerative colitis and liver cirrhosis (abundant in diet and thus must have alteration in K ADME)
- (4) treat epistasis in dogs Problems: K3 causes renal failure in horses, slow onset, IV–> hypersensitivity
ADME: slow onset (24 hours) due to mechanism acting on precursors
- –oral (K-Caps)
- – Prenterally - IV, SC, IM –
- fat soluble and widely distributed
21
Q
Protamine sulfate- classification, MOA, Use, ADME?
A
Protamine sulfate
- Classification: Systemic hemostatic
- MOA: highly basic drug that binds with acidic heparin to form a inactive salt (=Chemical antagonism)
- Use: antidote for heparin Problems: overdose has anticoagulant effect
- ADME: give slow IV
22
Q
Aminocaproic acid- classification, MOA, 3 uses?
A
Classification: Systemic hemostatic
MOA: inhibits conversion of plasminogen to plasmin
Use:
- (1) antagonism of thrombolytic agent
- (2) treatment of hyperfibrinolysis hemorrhage
- (3) treatment of degenerative myelopathy in German shepards by antiprotease activity
23
Q
Desmopressin (DDAVP) - classification, MOA, Use
A
Classification: Systemic hemostatic
MOA: increases VWF levels for two hours in dogs by causing release from endothelial cells and macrophages.
- vWF is important for adherance of platelets to an injured vessel, platelet aggregation, & stabalizing factor 8
Use:
- (1) control bleeding in dogs with vWF disease
- (2) surgery in dogs with vWF disease
- (3) in blood donor dogs with vWF disease ProblemsL short duration (2 hours)
24
Q
3 types of Antithrombotic drugs
A
- Anticoagulants (heparin and warfarin)
- Thrombolytics
- Antiplatelet drugs
25
**Heparin**
classification, MOA, use, PK problems?
Classification: Anticoagulant antithrombotic
MOA: activates anti-thrombin III resulting in :
* (1) inhibition of thrombin
* (2) inhibition of activated coagulation factors 9, 10, 11 & 12 in the liver
Pharmacokinetics:
* Give IV (not absorbed orally, SC is slow, and should not be used IM)
* Fast onset and short duration
* give as IV infusion or IV intermittent
* Rapid metabolism in liver
* Does NOT cross the placenta or enter milk
Use: anticoagulant of choice in pregnant animals
* (1) treat acute thromboembolism
* (2) anticoagulant in-vitro
Problems: narrow safety margins, \*\*bleeding\*\*, cause allergies.
* Low molecular weight heparins (LMWHs) are less antigenic and less likely to cause allergies BUT are more $$$$
* Treat toxicities with protamine sulfate, blood transfusion or fresh frozen plasma (FFP)
26
Warfarin
_Classification_: Anticoagulants
_MOA_: inhibits vitamin K epoxide reductase --\> depletion of redued vitamin K --\> less carboxylation--\> inhibition of prothrombin (expires first) and coagulation factors 7, 9 & 10
_PK_:
* ORAL, Slow onset (2 days) - because have to deplete existing coagulation factors.
* Slow absorption (2 hours).
* Widely distributed. Crosses placenta & milk.
* Long duration 2-5 days (due to high plasma protein binding- 99% of albumin).
* Metabolized by the liver microsomal enzymes (altered by enzyme induction/inhibition).
_Use_: long term prevention in thromboembolic diseases (too slow for acute thromboembolism), Rodenticide
_Problems:_ narrow safety margin, bleeding, teratogen (bone defects), Drug interactions (weakly bound to plasma proteins, easily displaced), crosses placenta.
Antidote: Vitamin K (slow onset) and blood/plasma transfusion (acute replacement of clotting factors)
27
Drugs that increase warfarin effect
* --Phenylbutazonee, salicylates
* --Heparin
* --Chloramphenicol
* --Sulfonamides and broad-spectrum antibiotics (displacement & inhibit intestinal flora production of vitamin K)
* --anabolic steroids- increase binding affinity to receptors
28
Drugs that decrease warfarin effect
enzyme inducers (phenobarbitol)
29
What are **STREPTOKINASE, UROKINASE, TPA, & ANISTREPLASE** all an example of?
What is their MOA? Use? Problems? Antidote?
_Classification_: **Thrombolytic agents**
_MOA_: activates conversion of **plasminogen to plasmin** (breaks down clots/**fibrinolysis**)
--**tPA is clot-specific** at low therapeutic doses by binding to plasminogen bound to fibrin
_Use_: **Acute** thromboembolic disorders, tPA is used in opthalmology
_Problems_: narrow safety margin (monitor for 48 hours), **bleeding**, allergy
**_Antidote_: Aminocaproic acids** (prevents conversion)
30
Which drugs are Anti-platelet drugs?
Asprin
Dipyridamole
Abciximab
Lepirudin
Clopidogrel
31
Asprin
_Classification_: Anti-platelet Drug
_MOA_:
* Low does --| Cox inhibit synthesis of thromboxane A2 (TXA2) by **irreversibly** (For whole lifespan of the platelet) inhibiting cyclooxygenase. Also --| PGI2 (antiaggregant).
* TXA2 is the main proaggregant
* Action behinds to cyclooxygenase irreversibly, called **“Acetylation”**
* Non-selective COX inhibitor --\> side effects by blocking protective PGE
_Problems_: ulceration & bleeding.
_Clinical Uses_
* **Low doses** of aspirin are used in **prevention of thrombotic disorder**
* Low doses \> large doses
* Large doses inhibit the proaggregant activity (TXA2) and also the antiaggregant activity (PGI2), which will decrease the effect.
32
Dipyridamole
_Classification_: Antiplatelet
_MOA_: Inhibits enzyme that breaks down cAMP (Phosphodiesterase) and causes an increase in cAMP ( Which --I aggregation)
33
Abciximab
_Classification_: Antiplatelet (human)
_MOA_:block receptor that links platelets together by fibrinogen (GPIIb/IIIa receptor)
34
Lepirudin
Classification: antiplatelet
MOA: Binds to thrombin
35
Clopidogrel
_Classification_: anti-platelet
_MOA_: inhibit binding of pro-aggretive ADP
36
What is the definition of a Diuretic?
Diuretics are drugs that increase the rate of urine floe or increase urine volume
They also increase the rate of Na excretion, usually as NaCl in water
37
What are Diuretics Classified as?
Caridovascular
Physiological
---
Osmotic diuretics
Loop/high ceiling diuretics
Thiazide diuretics
Potassium-sparing diuretics
Carbonic anhydrade inhibitors (used to treat glucoma)
38
What are examples of Cardiovascular Diuretics? How do they work?
Cardiovascular Diuretics: Digitalis (**digoxin)**, Phosphodiesterase inhibitors (Aminophylline, inamrinone, Milrionone)
MOA: Positive ionotrophs that increase the GFR.
Use: treatment of edema associated with congested heart failure.
Not diuretic if also cause vasoconstriction as well as increase heart contractivity.
39
What are physiological diuretics? how do they work?
**(1) WATER!**
MOA: inhibit ADH production (which acts on DCT and collecting duct)
Use: compensate chronic interstitial nephritis in dogs
**(2) Sodium Chloride**
Use: urolithiasis in sheep, calves and cats.
40
What are 4 examples of Osmotic diuretics? MOA? PK? Use?
_Osmotic Diuretics_: **Mannitol\*** (action depends on route of administration), urea, glycerin, Isosorbide.
_MOA_: osmotically draw water into tubules.
* Acts on loop of Henles and PCT
* Has very insignificant interferance on Na, K, Ca, Mg, Cl, Bicarb and phosphate
* Increases renal blood flow (use in oliguric renal failure
* Stays in the blood or interstitium (contraindicated in generalized edema)
_Use:_
* Local edema in cerebral edema & acute glaucoma.
* Treat acute renal failure
* Mobilization of edema fluid
* Drug overdose/ toxicity ( because weak diuretic, does not alter electrolyes and increases renal perfusion)
_PK_:
* Mannitol = IV (oral is a laxative), not metabolized, eliminated rapidly
* Urea= IV
* Glycerin and isosorbide= ORAL
41
List the effectiveness of diuretics from most to least? What are the relative precentages?
Most effective= 25% = Loop diuretics
5%= Thiazide diuretics (act on early DCT)
2%= Potassium Sparing (act on late DCT and CD)
42
What are examples of Loop or High ceiling diuretics?
Furosemide
Bumetanide
Ethacrynic acid
43
What is the MOA of Loop or High Ceiling Diuretics?
Furosemide, Bumetanide, Ethacrynic acid
_MOA_:
* **_Inhibit Na-K-Cl symporter_** on the luminal membrane of the aLOH (Most effective, block 25% of Na reabsortion)
* Results in inhibition of **paracellular** reabsorption of Na, Ca, and Mg
* Negative luminal transmembrane potential in the DCT and collecting duct facilitates K excretion (principal calls) and H secretion (a cells) --\> hypokalemia and systemic acidosis
* Stimulates RAAS --\> hypokalemia and systemic acidosis
* Increases total renal blood flow (may involve PG)
* Increases systemic venous capacitance (vasodilating) via PG
44
What are therapeutic uses of Loop diuretics?
Loop diuretics= Furosemide, Bumetanide, Ethacrynice acid
_Uses_:
* Generalized and localized edema
* Treat hyperkalemia (if combined with isotonic saline)
* Used in acute renal failure patients
* Treat increased IOP and udder edema
* Treat exercise-induced pulmonary hemmorage in horses = Furosemide only
* Drug overdose (be careful of hypovolemia)
* Treat life-threatening hypernatremia (combined with hypertonic saline)
* Treat edema of nephrotic syndrome
45
What are the adverse effects of Loop Diuretics?
Loop diuretics= Furosemide, Bumetanide, Ethacrynice acid
Uses:
* Ototoxicity- due to electrolyte inbalance in the inner ear fluid
* Hypokalemia\*\*
* HypoMg
* Hypovolemia
* Hypotension & arrhythmia
* Hyperglycemia (only issue in diabetes)
* Hyperuricemia (in human gout patients)
* Hypersensitivity in patients with sulfonamide allergy
46
How do you give furosemide? What are its pharmacokinetics?
IV or Oral
Rapid onset, short duration
partly metabolized by conjugation
actively secreted in urine by organic acid transportes
47
**Spironolactone**
**_Spironolactone_**
_Classification_: Potassium-Sparing Diuretic
_MOA_: Competitively **block aldosterone binding** to aldosterone/mineralcorticoid receptors in the **late DCT and collecting duct**
* Results in exretion of NaCl and retention of K & H
* Diuretic effect depends on the endogneous levels of aldosterone
* Mild diuretic because only 2% of Na reabsorption occurs in the late DCT to collecting duct
_Use_:
1. mild diuretic (use with other diuretics in heart failure)
2. Treatment of primary and secondary hyperaldosteronism
_Problems_
* Hyperkalemia
* Systemic acidosis
* Reproductive issues (acts on androgen and progesterone receptors)
_PK_:
* Oral
* prodrug
* highly plasma protein bound
* slow onset (2-3 days) and long duration
48
**Triamterene & Amiloride**
**_Triamterene & Amiloride_**
_Classification_: potassium-sparing diuretic
_MOA_: **Block Na channels** on the luminal membran eof the **principal cells of the late DCT and collecting duct.**
* Excretion of Na, diuresis and retention of H & K
_Use_:
* Treatment of hypokalemia and hypomagnesemia
* very week diuretic, occasionally used in edematous disorders and hypertensio
_Problems_: Hyperkalemia & Systemic acidosis
_PK_: Oral
49
Acetazolamide
Methazolamide
Dorzolamide, Brinzolamide
**_Acetazolamide, Methazolamide, Dorzolamide, Brinzolamide_**
_Classification_: Carbonic anhydrase inhibitors (CAI's)
_MOA_: reversible inhibition of carbonic anhydrase (which inhibits the exchange of H for Na in the PCT (primary site) and Collecting duct (secondary site)
* **Lower intraocular pressure (IOP) by inhibiting CA in the eye --\> decrease formation of aqueous humor**
_Use_:
* Treatment of **chronic glaucoma** (topical dorzolamide is best)
* Acetazolamid for udder edema
_Problems_
* Systemic acidosis (vomit, diarrhea, hyperventilation, PU/PD, prutitus of paws)
* Hypokalemia
* Hyperglycemis
_PK_:
* Acetazolamide = oral
* onset is 30 minutes, duration 4-6 hours in small animals
* eliminated by kidney - actively excreted in urine bt organic acid secretory mechanism
* Dorzolamide= opthamlic topical
* less systemic acidosis
50
ADH (vasopressin)
Stims reabsorption of water in the DCT and collecting duct
Results in decrease ECF osmolarity and increase water in the ECF
Natural= pitressin = used IM/IV for 1 hour to differentiate central from peripheral diabetes insipidus (DI)
Synthetic= Desmopressin (DDAVP)= more potent, longer duration= drug of choice to treat central DI in cats and dogs
51
What are your drugs of choice for diabetes insipidus?
Central = Desmopressin
Nephrogenic = Thiazide Diuretics
52
What is oliguric renal failure and how can you treat it (3 drugs)?
Acute renal failure
Treat with Mannitol, furosemide and dopamine
53
What drug will you use to treat an **incomplete AV block?**
ATROPINE
54
What drug do you use to treat a complete AV block?
Epinephrine!
Low dose acting on B2, high dose acting on a2
55
List the Beta-1 agonist in order of potency
Most potent=Isoproterenol
epinephrine
norepinephrine
Least potent= dopamine
56
Norepinephrine
Acts on alpha-1 and beta-1 (with no counteracting beta-2)
Not commonly used due to too much vasoconstriction that is more likely to cause a reflex bradycardia than epinephrine
57
What are non-drug therapies you can use for congested heart failure
Restrict Salt
Restrict Exercise
58
What drugs can you use to treat CHF?
Positive Inotrophic drugs
Vasodilators
Inodilators
Diuretics
B-Blockers
PImobendan is the drug of choice for CHF
59
What is the MOA of Digitalis glycosides?
**Block Na/K ATPase** --\> increase Na available for exchange for Ca --\> **Increase intracellular Ca** --\> positive inotrophic
Increases the mechanical efficency of heart & slows heart down by allowing the parasympathetic system to predominate (?)- things he said
60
What is significant of Digitalis glycosides undergoing **enterohepatic recycline**?
Prolongs duration of action
61
What are Inodilators?
Inodilatos are both vasodilators and increase cardiac output
Include:
Phosphodiesterase inhibitors (Amrinone & Milrinone) - use in emergency
**Pimobendan** - used in CHF in dogs-increases sensitivity to Ca & causes mixed vasodilation
62
What is so great about using **Spironolactone** in CHF?
blocks aldosterone (which is elevated in CHF)
K-sparring diuretics-thus will correct the decrease K
63
Which are better to use in CHF?
a. Non-selective B Blockers (Carvedilol)
b. Selective B-Blockers (Metoprolol & atenolol)
Selective B Blockers (Metoprolol & atenolol)
You maintain your B2 function --\> more vasodilation, bronchodilation, less hypoglycemia
B1 is used in CHF because it prevents the RAAS which decreases angiotensive II and aldosterone
64
**Carvedilol**
Carvedilol
Classification: **B- Blocker**
Use: Treat CHF due to **dilated cardiomyopathy** to blunt the harmful effects of the SNS on the heart
MOA:
(1) **nonselective B blocker** and a1 blocker (prevents RAAS & vasodilator)
(2) antioxidant
(3) inhibits endothelin release
65
How does nebulization of ethanol (20%) help severe cases of CHF?
Prevents foaming
66
What is the drug of choice for atrial fibrillation in equines?
Quinidine
67
What is the MOA of Class I antiarrythmic drugs?
**Class I= block volatge sensitive Na channels**
_IA_: prolongs AP = Quinidine & Procainamide
_IB_: shortern AP= Lidocaine, Phenytoin, Mexiletin
_IC:_ no effect on AP= flecainide
68
What is the drug of choice for **ventricular arrythmias** in **DOG**s?
**Lidocaine-IV Only**
Lidocaine can also be used to treat digitalis induced arrhythmias (with Phenytoin)
69
What drugs can you use to treat digitalis induced arrythmias?
Lidocaine
**Phenytoin** = DOGs only
70
What is great about **mexiletin**?
It is similar to lidocaine, but can be **given ORALLY**
Lidocaine has a very high first pass effect and thus can only be given IV
Both are Class IB Antiarrythmic drugs
71
What is the drug of choice for supraventricular and ventricular arrythmias in CATS?
**Propranolol** ( **B blocker**- Class II antiarrythmic)
Also effective if induced by hyperthyroidism
72
Why are B-blockers effective to treat cats with hyperthyroidism?
They block B1
B1 is upregulated in hyperthyroidism --\> tachyarrythmias and tachycardia
73
What are Class III (K-channel blockers) anti-arrythmias useful for?
Refractory ventricular arrythmias
Includes Bretylium, Amiodarone and Sotalol
74
What are Class IV antiarrythmic drugs?
Class IV= **Ca channel blockers**
Only **Verapamil and Diltiazem** are anti-arrythmic
Work **ONLY for supraventricular tachyarrythmias** (Ca channels are not within the ventricle)
Also used for Myocardial hypertrophy
75
What is the drug of choice for **dogs with supraventricular tachyarrythmias** (atrial tachycardia, atrial flutter, atrial fibrillation)?
Digoxin
76
What is the drug group of choice for **cats with supraventricular and/or ventricular tachyarrythmias**?
**B- Blockers (Propranolol)**
May or may not be due to hyperthyroidism
77
What is the drug of choice for cardiac asystole (aka cardiac resuscitation)?
Epinephrine
(aso used for COMPLETE AV block)
78
Drug of choice for treating dogs with CHF?
**Pimobendan**
Classification: Inodialtor
MOA: sensitizes heart to Ca by enhancing interaction b/w Ca and troponin C
**should NOT be used in conditions where an increase of cardiac output is not possible**
79
Vasoconstrictors
Used in **vasodilatory shock, as nasal decongestion,** and in severe hypotensive shock
**_Nonselective a-‐agonists_**
? Epinephrine
? Norepinephrine
**_? Selective a1-‐agonist_**
? Phenylephrine
**_? Direct and indirect sympathomimetics_**
? Ephedrine, pseudoephedrine, phenylpropanolamine(PPA)
Given orally. Tolerance is an issue.
**_High dose Dopamine_**
**_Vasopressin_**
80
Sympatholytic Vasodilators
**_? Nonselective a-‐blockers_**
? Phentolamine & ? Phenoxybenzamine
**_? Selective a1-‐blocker_**
? Prazosin
**_? Presynaptic a2-‐agonist_**
? Clonidine
**_? Nonselective B-‐blockers_**
? Propanolol
**_? Selective B1-‐blockers_**
? Atenolol
**_? B and a1-‐blocker_**
Carvedilol
81
ACE Inhibitors
Captopril, **Enalapril**, Benazepril, Lisinopril
_MOA:_ by inhibiting ACE they reduce actions of angiotensin II and aldoserone
_Use_:
* **CHF**
* **Hypertension** (= Drug of choice for systemic hypertension in dogs)
* **Progressive renal failure** - improve renal perfusion from internal mechanisms
_Problems_:
* Hypotension
* May lower GFR
* Ideopathic glomerular disease
82
Losartan
Angiotensin II antagonist
MOA: Competitive antagonist of angiotensin II receptors
83
Direct- Accting Vasodilators (2)
**_Hydralazine_**- arterial vasodilator
? MOA: Increases local concentrations of PGI2/block Ca influx
**_? Nitrates_****-** low dose on veins, high dose on arteries
(Sodium nitroprusside, Nitroglycerin, Isosorbide dinitrate)
? MOA: Formation of the reactive radical nitric oxide? Only used in emergencies because of their potent vasodilatory effect
84
Calcium Channel Blockers
Verapamil, Diltiazem, Amlodipine, Nifedipine
_? MOA_: Inhibit influx of extracellular calcium across myocardial and smooth muscle cell membranes.
_? Effects_: ?
* Negative intotrope, ?
* Negative chronotrope, ?
* Increased O2 delivery to myocardial tissue, ?
* Decreased afterload (due to vasodilatory effect)
_Use_:
* Class IV Antiarrhythmic
* Antihypertensive- Amlodipine is drug of choice in cats (unless due to hyperthyroidism)
* Myocardial hypertrophy - Diltiazem is drug of choice in cats
* Antianginal
85
What is the first line antihypertensive drug in cats?
**Amlodipine** (Ca channel blocker)
UNLESS caused by hyperthyroidism (then use B-Blockers)
(Dogs = Ace inhibitors)
86
What are the drugs of choice for myocardial hypertrophy?
**Diltiazem**
(Benzodiazapine- Ca Channel Blockers)
-and-
B Blockers
87
How do you treat normal and emergency hypertension?
_Normal cases_:
? Diuretics
? Beta
blockers
? Vasodilators
? Caclium Channel Blockers
_? Emergency_:
**? Hydralazine or sodium nitroprusside IV**?Propanolol or acepromazine IV
**Phemtolamine IV**? Oral calcium channel blockers, prazosin or ACE inhibitors
? _Pheochromocytoma-‐induced_
**? Phenoxybenzamine**
88
What is the drug of choice for pheochromocytoma induced hypertension?
**Phenoxybenzamine**
89
Drug of choice for CHF?
Pimobenden
90
Which of the following is NOT a use for Ca Channel Blockers?
A. Posi;ve Inotrope
B. Treatment of CHF
C. Antiarrhythmic
D. Antihypertensive
E. Treatment of myocardial hypertrophy
B. Treatment of CHF
91
Which of the following drugs could be used to treat a subventricular tachyarrythmia?
A. Digoxin
B. Captopril
C. Lidocaine
D. Diltiazem
E. Epinephrine
C. Lidocaine
92
Which if the following drug would be the first choice antihypertensive drug in hyperthyroid cat?
A. Furosemide
B. Captopril
C. Amlodipine
D. Propanolol
E. Diltiazem
D. Propanolol
93
Who produces T4?
100% the thyroid gland
94
Who produces T3?
20% thyroid gland
80% liver kidney and muscle tissue by deiodinating T4 into T3
95
T4 and T3 are _____ plamsa bound
99% plasma bound
Only 1% 'free'
96
What is the thyroids function?
ALOT (dont have to memorize all of them)
97
How do you treat **Hypo**thyroidism?
Replace the hormone!
**Levothyroxine (T4)** \> T3
98
What are the difference between Liothyronine and Levothyroxine?
99
Why do you use L4 over L3to treat hypothyroidism?
L4 allows **intracellular autoregulation**, providing only L3 to cells as they have a need for it
T4 has a **longer half-life,** which makes its **easier to dose** (SID to BID)
The higher potency of L3 puts the animal at greater risk of thyrotoxicosis
100
Levothyroxine Sodiume (Soloxine)
Levothyroxine Sodiume (Soloxine)
* **Oral** tablet (scored)
* 0.02 mg/kg PO BID, 0.5 mg/ m^2
* should try not to give \>0.8 mg BID
* Should monitor peak plasma concentration 4-12 hours post dose (very high variation of half-life)
* **check thyroid levels after 4-8 weeks**
* Problems (chronic \> acute) = **thyrotoxicosis** usually due to chronic overdose
* Not all formulations are equal (but not always a big deal)
* In **dogs over 50 lbs, use the body surface area to calculate the dose (0.5 mg/m^2)**
* **Injectable** **_ONLY_ for Myzedema Coma** -rare- also warm patient, provide respiratory and fluid support
101
What drug should you use for a Myxedema Coma?
**Injectable** Levothyroxine sodium
(this is the only condition you use the injectable form of this drug)
Also warm patient and provide fluid/electrolyte and respiratory support
102
What are the clinical signs of Thyrotoxicosis?
Thyrotoxicosis – **vomiting/diarrhea, tachycardia, tachypnea, weight loss, hyperactivity, hypertension**
Should recheck dose/weight (maybe try calculating by surface are in large dog) and decrease the dose.
Thyrotoxicosis is usually due to chronic overdose
103
What AED will NOT interfere with thryoid testing?
**Levetiracetam or Potassium Bromide (KBr)**
One that do: Phenobarbital, Zonisamide
104
Which drugs interfere with thyroid testing?
105
What care common causes of hyperthyroidism in cats?
**\*\*\*Functional adenomatous hyperplasia \*\*\*\***
Less commonly thyroid adenomas
Uncommonly thyroid carcinomas
106
What are common causes of hyperthyroidism in dogs?
Iatrogenic or functional neoplasia
107
What are the three best treatment options for hyperthyroidism?
1. **Radioactive iodine (I-131)**
2. **Antithyroid drugs** (Thioureylenes, Iodides, Iodinated contrast agents)
3. **Diet (Hill's y/d)**
Surgical thyoidectomy and intrathyroid injection of ethanol are not commonly used. Risky and other options are better.
108
Radioactive Iodine Therapy
Drug to **Treat Hyperthyroidism** (also thyroid carcinoma)
_MOA_: selectively **destroys thyoid tissue**
_Pros_: single injection, **permanent cure**, no anesthesia, **safe,** usually dont have to supplement thyroid hormone after.
_Cons_: **isolation** for 1-4 weeks, permanent (issue if kidney disease), **expensive**. If animal dies, it remains radioactive for months/years
_PK_: single injections, **eliminated in urine**
109
Methimazole
Treats **Hyperthyroidism** (_drug_ of choice) - **Felimazole/** Tapazole
_MOA_: **inhibits synthesis of thyroid hormone** by inhibiting organification and coupling. Lowers T4, but T3 is normal due to autoregulation mechanism in the tissue
_PK_: good **oral** availability, can be compounded to **transdermal paste** (does NOT prevent adverse effects)
_Cons_:
* **monitor T4 levels** adter 2-4 weeks (in cats, time of day does not matter)
* **common (10-15%) side effects** (vomiting, anorezia, depression, hematology changes)
* rare **idiosyncratic reactions** (facial excoriations, hepatopathy, bleeding, agranulocytosis, bleeding, thrombocytopenia)
110
Carbimazole (Vidalta)
Treats **Hyperthyroidism**
_MOA_: **converted in body into Methimazole** (=inhibits synthesis of thyroid hormones)
Long acting formula - **UK/Aus only**
111
Propylthiouracil (PTU)
Treat **Hyperthyroidism**
## Footnote
**Inhibits conversion of T4 to T3 in tissue**
112
What drugs should you use for hyperthyroidism if mehtimazole, radioactive iodine, and diet are NOT options?
**Iodines & Iodinated radiographic contrast agents**
Not first-line drugs due to transient effects and efficacy.
_Iodides_: Lugol's solution, Potassium/Na iodide
* Inhibit thyroid hormone organification & Inhibit preformed hormone secretion. May inhibit binding of iodine
_Iodinated radiographic contrast agents_: Ipodate (Oragrafin®), Iopanoic Acid
* Inhibit the conversion of T4 to T3 in peripheral tissues
* Monitor T3 levels (T4 may not change)
113
**Hill's Y/D Diet**
Treats **Hyperthyroidism**
_MOA_: **Restricts dietary iodine** --\> reduces T4/T3
_Pros_: does not cause hypothyroidism
_Cons_: has be fed **_exclusively_** (indoors, no treats etc.). Still have to monitor T4 levels
In multi-cat house hold, you should supplement non-hyperthyroids cats 1 tablespoon of normal food.
114
What are the kidneys, guy, and bones roles in calcium metabolism?
Bone – storage pool for calcium, can be mobilized
Kidney – resorption or excretion of calcium. Converts vitamin D2 to calcitriol (=PTH minion)
GIT – absorption (or not) of dietary calcium
115
What are 3 top causes of hypocalcemia? What are less significant causes?
```
Parturient paresis (“milk fever”) in cattle and sheep
Parturient eclampsia in lactating bitches
Primary hypoparathyroidism (canines)
```
_ALSO_: Contamination of EDTA will cause decrease Ca levels, as well as increased K.
_Other causes_: With hypomagnesemia or mastitis (cattle), Pancreatitis (cats), Sepsis (horses), Acute/chronic renal disease (variable), Iatrogenic
116
What are clinical signs of hypocalcemia?
May be medical emergency!
## Footnote
Hyperesthesia, muscle tremors, muscle fasciculations or tetany
Progression to flaccid paralysis (cattle)
Seizures
Hyperthermia, bradycardia
Pawing/rubbing at face (dogs/cats)
117
What are you two overal treatment goals for hypocalcemia?
(1) **Correct calcium deficit** - short term, for transient issues (increase need), provide oral or parenteral Ca supplementation
(2) **Correct underlying problem** - long term, provide oral vitamin D therapy
118
Which parenteral calcium can you ONLY give IV?
Ca Chloride
119
Which Parenteral Ca can you possibly give IM?
**Ca (Boro) Gluconate**
Should be diluted forms only, it can be caustic to tissues
120
What are two concerns you should have when giving patenteral calcium to rapidly correct hypocalcemia?
1. Monitoring for arrythmias/cardiac arrest (if give too rapidly)
2. Can precipitate with bicarbonate, acetate, or lactate
121
Oral calcium requires the _______ to be able to absorb the calcium.
gut
122
What is a benefit of using oral Ca Gluconate/Lactate?
tablets have a small quantity of element (90-130 mg/g) and thus ideal for smaller patients
123
What is good and bad about oral Ca Carbonate?
good= 400 mg/g - better for larger animals
Bad= may cause alkalosis
124
What is an issue with Ca Chloride?
It is acidic, thus more likely to cause GI irritation
125
Ca Acetate can be used to...
bind dietary phosphorus/phosphate binder
(but Aluminum is more common)
126
Ca propriote is used in which species as a food supplement?
Cattle (250 mg/g)
127
What is the most recomended form of Oral calcium to use?
Ca Carbonate
128
How does long term use of Vitamin D help with hypocalcemia?
Increase intestinal absorption of calcium/phosphorus
Increase renal tubular re-absoption of calcium/phos
Increase mineral bone resorption
129
Which form of Vitamin D supplement is most commonly used?
1. Ergocalciferol (Vitamin D2)
2. Dihydrotachysterol (DHT, synthetic Vit D2 analog)
3. Calcitriol (1,25-dihydroxycholecalciferol)
Calcitriol
130
What is the drug of choice for prmiary hypoparathyroidism?
Calcitriol
(also used to manage chronic renal failure)
131
Compare the followings potency and time to clinical response:
Ergocalciferol (Vitamin D2)
Dihydrotachysterol (DHT, synthetic Vit D2 analog)
Calcitriol (1,25-dihydroxycholecalciferol)
Ergocalciferol- need large dose, is slow, and needs liver& renal activation
DHT- potent, faster than ergocalciferol, NO PTH activation
Calcitriol: most potent, fastest, no renal or liver activation
132
What are your top differentials for hypercalcemia?
133
What is the most common,and often only, clinical sign of hypercalcemia?
PU/PD
134
What is most important when treating hypercalcemia?
**Treat underlying disease!!!** and maybe short term measures to correct hypercalcemia
If unknown, or untreatable, or Ca is still too high you can then provide longer term measures to manage Ca.
135
What are short term and long term treatment options of hypercalcemia?
**_Short Term_** ( supplement K, provide fluids)
1. **Saline diuresis-** Na competes for Ca tubular reabsorption
2. **Furosemide-** prevents Ca reabsorption
3. **Sodium bicarbonate**- decreasesactive Ca, short term
4. **Calcitonin** - reduces osteoclast activity
**_Long term_**
1. **Glucocorticoids** - reduces absorption and excretion, antineoplastic (may interfere with Dx)
2. **Bisphosphonates** - Inhibits osteoclast activity, $$$, side effects
3. **Plicamycin** (mithramycin)- inhibits RNA synthesis in osteoclasts, toxicity concerns
136
What should you use to treat cholecalciferol toxicity?
Calcitonin
137
What stimulates insulin secretion?
* Rise in blood glucose concentration
* GI hormones
* Amino acids and fatty acids in the GIT
* Vagal stimulation (M receptors)
* Catecholamines (β2 receptors)
138
What decreases insulin secretion?
Decrease in blood glucose concentration
Somatostatin
Catecholamines (α2 or I3 receptors)
139
What are the 4 effects of insulin in the boday?
* Storage and building- Stimulates glycogenesis, lipogenesis & protein synthesis
* Inhibits glycogenolysis, gluconeogenesis, lipolysis
* Stimulates uptake of potassium into cells
* Anabolic (especially in the fetus)
140
What is an artifactual cause of hypoglycemia?
**Leaving blood out too longs** before spinning down
**RBC continue to metabolize glucose** while in tube.
141
What are the Therapeutic considerations of **hypoglycemia** if NOT involving insulin?
Give dextrose (if severe) and Treat the underlying disease
142
What are the Therapeutic consideration of treating hypoglycemia if involving insuling? How will it differ from iatrogenic vs endogenous insulin?
_Iatrogenic_: Stop insulin/hypoglycemic agent and implement supportive care until metabolized.
_Endogenous:_ Treat the hypoglycemia, treat the underlying disease (if possible).
143
True or False
Glucagon is commonly used in treatment of hypoglycemia
**FALSE**- it is not commonly used
--------------
It has to be given IV and the liver must have glycogen stores in order for it to work
144
True or False
Dextrose is the 1st line drug to use until you figure out the underlying cause of hypoclycemis
True
\_\_\_
It can be given for acute casees at 50% dextrose solution or for mainteneance (IV) at 2.5-5% dextrose
Consideration: hyperosmolality/irritation, rising glucose stimulates insulin secretion
145
Why should you nod use 50% dextrose for maintenance?
(1) more likely to **overdose**
(2) high osmolality --\> **phebitis**
146
If you need to make a 2.5% dextrose solution for a patient. If you have a bottle of 50% dextrose on your shelf, how much do you need to add to a 1L bag of LRS to make a 2.5 % dextrose drip?
**50 mL**
(2.5% /50%) \* 1000mL = 50 mL
147
How due use dietary management to treat hypoglycemia?
_Acute_: karo syrup/corn syrup
_Chronic_: (if not severe) **Frequent, small meals of Complex carbs (**simple carbs may stimulate insulin secretion) that are Easily digestible and have Moderate fat and protein
--
commonly used in isulinomas in whivh you are unable to treat itand thus just managing it with diet and other therapy
148
_True or False_
The goal of hypoglycemia therapy is always to maintain a "normal" blood glucose
FALSE!!!
Goal of therapy is to eliminate/minimize clinical signs associated with hypoglycemia
\_\_\_\_\_\_\_\_\_
This may not mean maintaining a ‘normal’ blood glucose!
"treat the patient, not the glucose numbers
149
Will a dog with a glucose of 50 show clinical signs?
(reference interval is 76-119)
Maybe, it is more likely if acute/rapid progression
150
What is your go to drug for treating hypoglycemia?
Glucocorticoids
\_\_\_\_
Use Diazoxide, Streptozotocin or Somatostatin only if glucocorticoids are not working
151
What is the MOA of glucocorticoids (predmisone, Prednisolone) in treating hypoglycemia?
Increasing gluconeogenesis
Decreasing glucose utilization
Stimulating glucagon secretion
-----
side effects are mild at low doses (pu/pd, panting) and progressively severe as the dose is increased (immunosuppresion)
there is hepatic metabolism/activation of prednisone to prednisolone
152
Prednisone is metabolized into active prednisolone in the \_\_\_\_\_\_\_\_
liver
153
What are side effects of Diazoxide?
Hypersalivation, **_anorexia/vomitting/D_,** tachycardia, blood changes, diabetes, fluid retention (most are in humans)
\_\_\_\_\_
this drug is usually only used to treat **hypoglycemia** IF glucocorticoids and diet are no longer working.
Efficacy is iffy
154
What drug activates K channels in islet cells, switches off voltage-gated Ca channels to **inhibit insulin release**, increases glycogenolysis in the liver, and inhibits tissue/brain uptake of glucose?
**Diazoxide** (proglycem®, hyperstat IV ®)
Used to treat hypoglycemia if diet and glucocorticoids are not working
155
What somatostatin analogue is sometimes used for:
Insulinomas (dogs, ferrets)
Gastrinomas (dogs, cats)
Chlyothorax (dogs, cats)
Acromegaly (dogs)
**Octreotide**
\_\_\_\_\_
somatostatis efficacy is very iffy and should be **used as a last resort**.
MOA: inhibits release of insulin, GH, CCK, glucagon
156
What drug selectively destroys beta cells in the pancreas or metastatic sites?
**Streptozotocin (Zanosar®)**
-------
Given IV
very narrow therapeutic index (nephrotoxic, vomiting in ~30%)
Survival may not be significantly improved over other therapies - not worth the risk
157
Which two species are most likely going to get an insulinoma?
dogs and ferrets
158
What are your top two differential for hyperglycemia?
1. Physiologic hyperglycemia--Stress, postprandial, diestrus
2. Diabetes Mellitus
-------------------------------------
_Others_: Hyperadrenocorticism Pheochromocytoma Pancreatitis/Exocrine pancreatic neoplasia Some drugs/toxins (eg. amitraz) Head trauma
159
_True or False_
Type I diabetes (IDDM) is a Absolute deficiency of insulin from destruction (autoimmune) of pancreatic β cells
True!
160
_True or false_
Type II (NIDDM) diabetes is a Relative insulin deficiency and insulin resistance seen generallu in dogs
FALSE
Type II (NIDDM) diabetes is a Relative insulin deficiency and insulin resistance, **NOT generally seen in dogs**
Can be **seen in _cats, horses_ and humans**
161
True/False: Diabetes insipidus is due to an ADH deficiency
True
162
What are the 4 frequent signs of diabetes?
1. Catabolism (**muscle loss/weight loss**)
2. **Accumulation of glucose in the blood** (~180-220 mg/dL)
3. **PU/PD-** Glucose in urine causes osmotic diuresis
4. **Polyphagia-** Lack of glucose entering ‘satiety center’ of the brain leads to polyphagia
163
What are the goals of hyperglycemia therapy? (5)
Reduce hyperglycemia
Reverse catabolic effects
Reverse ketosis
Control clinical signs
Maintain patient in a mild hyperglycemic state (150- 200mg/dL)
164
Why not aim for normoglycemia in hyperglycemia therapy?
**Do not want to enter hypoglycemic state**
------
glucose fluctuates throughout the day and "at home" levels may be lower than "at vet" levels due to stress
If animal has decrease demand, or misses a meal, the medication may send them into a hypoglycemic state
hypoglycemic states signs are crude, thus owners may not notice if animal is hypoglycemic
165
What kind of diet do you want to used for a cat and a dog with diabetes?
_Canine_: **High fibe**r/Complex Carbs (Hill’s R/D or W/D, Purina DCO)
_Feline_: **Low Carb** (Hill’s M/D, Purina DM)
166
What diabetes drug decreased postprandial rise/ inhibits glucose uptake from the GI by Inhibiting alpha amylases and brush border oligo/disaccharides?
* *Acarbose (precose®)**
- ------
Not used often, NOT effective as solitary treatment
Sometimes used as an adjunct in dogs and cats
Can cause diarrhea, weight loss
167
Which Sulfonylureas is most commonly used to treat diabetes?
**Glipizide (glucotrol®)**
**\_\_\_\_**
Stimulates insulin secretion by blocking potassium channels in the beta cells, increases Ca++ and increases release of insulin
Increases tissue sensitivity to circulating insulin
REQUIRES FUNCTIONAL BETA CELLS TO WORK!!! - CAN ONLY USE IN TYPE 2 DIABETES
168
T/F: Glipizide is a oral drug that can be used for both type 1 or type 2 diabetes?
FALSE!!! REQUIRES FUNCTIONAL BETA CELLS TO WORK!!!
**CAN ONLY USE IN TYPE 2 DIABETES (NOT effective in dogs)**
* Stimulates insulin secretion by blocking potassium channels in the beta cells, increases Ca++ and increases release of insulin
* Increases tissue sensitivity to circulating insulin
169
What (mostly human) Biguanide causes Causes inhibition of hepatic glycogenolysis and increases peripheral glucose utilization?
**Metformin** (glucophage®) - limited vet studies
does NOT affect insulin secretion
170
T/F: Insulin injection are only for type 1 diabetes
False- they can be used for either type 1 or 2
171
What are the vet approved insulin product? Why are they better to use than human forms, even though the peptide is highly conserved?
**ProZinc™, Vetsulin/Caninsulin**
It is better to use due to the c**oncentration (40 IU/mL)** is easier to dose for smaller patients
Human preperations = 100 IU/mL
172
Can you use U40 insulin in U100 syringes?
NO
173
Is insulin function maintained if you shake it vigerously to reconstitute it, have it dilutes, or id it is expired?
**nope, nope, nope**
**\_\_\_\_\_\_\_\_\_\_**
You should:
Roll GENTLY to reconstitute
Avoid using diluted insulin
Pay attention to expiration date- get new bottle if close to expiration date before upping the dose
174
T/F: All insulins are pretty much the same
FALSE: there are different durations, potency and variations
175
Which insulin is most commonly used for DKA management?
**"Short acting insulin" as CRI/intermediat injection in hospital**
**Regular/crystalline/neutral insulin (Humulin®-R)**
Lispro (Humalog), aspart, glulisine
176
What is a good starting insulin type for **canines** with diabetes?
**"Intermediate acting**" insulin = Isophane (NPH), Lente, **_Vetsulin_**
--------------------------------------
**_SC only_**
Protamine (NPH) or zinc (Lente)are added to delay absorption and extend clinical effect
May not provide adequate duration for cats
177
What insulin should be used for a cat with diabetes?
"Long acting" insulin= **_Glargine_** (Lantus®)
-------
**SC only**- pH causes **microprecipitates =‘flat curve’**
178
T/F: **Levemir/Insulin detemir** has a similar potency compared to other insulins
FALSE- exception to the rule
Canine insulin receptors are 4x more sensitive than human receptors to detemir thus dose must be lower in dogs ( 0.1-0.2 IU/kg BID)
179
How do you correct a sick DKA(not eating)?
**Correct fluid/electrolyte/acid-base abnormalities**
Supplemental K+ (+/- PHOS supplementation)
IV CRU of insulin to start (Can also do intermittent IM injections)
-----
Goal is to reverse the metabolic situation - It is _not_ urgent to get the glucose down to normal
180
How do you treat a **hyperosmolar nonketotic diabetic?**
Start on fluids- do _not_ give insulin initially
Want to Treat like a DKA but the goal is to bring glucose down VERY SLOWLY
181
What type of **response** is happening in the graph? how do you treat it?
**Somogyi response**
Significant drop in blood glucose (due to too much insulin) triggers a glucagon/epinephrine response --\> Blood glucose rises very high (‘Overswing’)
TREATMENT= REDUCE DOSE
this response may give you altered readings that may make you believe you should up the dose when the dose is already way to hig
182
What is produced in the zona glomerulosa, fasiculata and reticularis of the adrenals?
183
What are the genomic and non-genomic effects of glucocorticoids?
_Genomic_ - binds to **cytoplasm** receptor to have a **slow feedback on ACTH** secretion by **down regulating ACTH's genomic expression**
_Non-genomic_ - binds to **membrane** receptors to have a **fast** (immediate/hours) feedback on ACTH secretion by **reducting ACTH release**
184
T/F: Glucocorticoids effect almost all body systems in some way but clinical signs will vary depending on if there are too high/low levels of glucocorticoids
True
---
they have to most effects on energy metabolism and water/electrolytes
185
What are clucocorticoids effects of energy metabolism?
* *Generally catabolic**= if excess--\> muscle wasting
* *Antagonistic to insulin**- Increase gluconeogenesis, lipolysis, protein catabolism
(Steroids and diabetes do NOT work well together)
186
What are glucocorticoids effects on water/electrolytes?
* *Alter calcium metabolism**- Decrease GI absorption, increase urinary excretion
* *Polyuria-** Decrease ADH secretion, increase GFR
* *Polydipsia**- central and due to polyuria
187
What effects do glucocorticoids have on hematology?
Increased PCV and RBC lifespan
Increased platelets
Increased clotting/platelet function
“Stress leukogram”- **eosinopenia**
(in addisons you will see normal to increase eosinophils)
188
Glucocorticoids can mask a febrile response by inhibiting _________ production in the thermoregulatory center
**PGE2**
189
What causes **calcinosis cutis?**
chronic excess of steroids
190
How do glucocorticoids affect the musculoskeletal system?
* **Increase osteoclast activity** /decrease osteoblast activity
* **Osteoporosis**, decreased bone growth
* Depletion of cartilage matrix
* **Inhibition of fibroblasts**
191
How do glucocorticoids affect the repro system?
* Fetal maturation
* Teratogenic (cleft palate)
* Induce abortion/parturition
* Inhibit spermatogeneiss or ovulation
192
How do glucocorticoids affect the GI and hepatic systems?
1. **GI ulcerations**
* Increased gastric acid secretion
* Decreased gastric mucus secretion
* Significant risk if concurrent use of NSAIDs!!
2. **Fatty liver**
* Increased fat absorption from GIT
* Increased fat deposition in the liver
* Alteration of liver enzymes
Does not directly affect the pancrease
193
What are glucocorticoids most commonly used for?
Anti-inflammatory (low dose) and immunosuppression (high dose)
----
Clinical uses:
Treat allergies
Suppress inflammation/fibrosis
Immunosuppression
Induction of parturition
Treatment of neoplasia
Replacement therapy (Addison’s disease)
Trauma/shock therapy (?)
Endocrine function testing (LDDS, HDDS)
Treat hypercalcemia, bovine ketosis, stimulate appetite,
adjunct to treatment of certain infectious diseases
194
What are some (7+) clinical uses of glucocorticoids?
* **Treat allergies**
* **Suppress inflammation/fibrosis** - ie if want to prevent esophageal stricture or slow liver fibrosis
* **Immunosuppression**
* Induction of parturition
* Treatment of **neoplasia**
* **Replacement therapy (Addison’s disease)**= pysiologic dose
* Trauma/shock therapy (?)- very case dependent
* Endocrine function testing (LDDS, HDDS)
* Treat hypercalcemia, bovine ketosis, *stimulate appetite, adjunct to treatment of certain infectious diseases*
195
T/F: glucocorticoids are highly protein bound
True
---------
* *Transcortin ‘corticosteroid-binding protein CBP**’ - high affinity, low capacity
* *Albumin** – low affinity, high capacity
196
Methylprednisolone, prednisone and cortisone require ________ metabolism to become active
hepatic
-----
anything that is given topically/not intended for systemic use, must be in an active form
197
What are contraindication/cautions to glucocorticoids?
**Diabetes mellitus**
Pre-existing catabolic disease
Infections (most of the time)
Corneal ulceration
Young, growing animals
Pregnancy
Wounds (that you want to heal)
**Concurrent use of NSAIDs**
Caution with underlying liver, cardiac disease, etc.
Numerous drug interactions (NSAIDs, digoxin, etc)
198
What are SHORT term side effects of glucocorticoids?
**Lab changes** - stress leukogram, hepatic enzyme increase, decrease thyroid values
## Footnote
**PU/PD/PP**
**Fetal abnormalities /abortion**
199
What are LONG term (\>1 week) side effects of glucocorticoids?
Increased susceptibility to **infection**
**Skin changes** (hyperpigmentation, thinning, alopecia)
**Collagen disease** (cruciate injury due to weakening of ligaments)
Hypertension, thromboembolic disease
Panting
Addisonian signs (w/ withdrawal – **‘iatrogenic Addison’s** due to rapid withdrawal and decrease ACTH production)
Less common: myopathy, calcinosis cutis, osteoporosis
200
What are the three "types" of doses you will use for glucocorticouds?
* *Physiologic** dose ~ 0.1-0.2 mg/kg/day
* *"Anti-inflammatory**” dose
* *Immunosuppressive”** dose ~2-4mg/kg day
201
T/F: If dosing glucocorticoids for more than a few days, you need to taper the dose before discontinuing
True!
\_\_\_\_
Can reduce dose amount or increase dose interval
The longer the time on, the slower the tapering of dose
202
if want to dose a patient with 2mg/kg of prednisone but we only have dexamethasome available, what dose would you use?
[HINT: Dex antiinflammatory potency is 30, while prednisole is 4]
0.27 mg/kg
Dex is more potent, dose need to be less
203
Which is longer acting: Prednisone or Dexamethasone?
Dexamethasone
204
T/F: Chemical form (compound) of the steroid can facilitate different routes of administration, delay onset and prolong the effect.
True
205
T/F: Salt Ester glucocorticoids are **highly soluable** and thus can be given by **IV injection**
**True**
--------
**Onset is faster** with IV, but the **duration is similar to normal**
206
T/F Insoluable esters glucocorticoids are less soluable and have a shorter duration than salt ester glucocorticoids
**FALSE**
_Insoluable esters glucocorticoids_ are less soluable and have a **LONGER** duration than salt ester glucocorticoids
**-----------**
due to the low soluability, it is absorbed slower (slow onset), and thus has a longer duration
CANNOT be used IV= opaque
207
What 2 glucocorticoids are often used for topical use?
Prednisolone and cortisol
----
must not require liver activation
Fluorination or esterification with fatty acids or cyclic acetonides to increases lipid solubility
208
Which propellant is preferred?
1. Chloroflurocarbon (CFC) = particle size 35μm
2. Hydrofluoroalkane-I34a (HFA) = particle size 1.1μm
**Hydrofluoroalkane-I34a (HFA)** = particle size 1.1μm
209
What type of glucocorticoid is commonly used? what excipient is prefered? and how much is systemically absorbed?
**Fluticasone diprioprionate** with **HFA** excipient
Systemic absorption: 0% in cats, 30% in humans
210
Which glucocorticoid is highly potent (~15x prednisolone) and has a high topical activity in the GIT but unknown/variable systemic absorption?
**Budesonide** (**_Ento_**cort®)
211
Mineralocorticoids are primarily under the control of \_\_\_\_\_\_\_\_\_\_\_\_
Angiotensin II
212
What are the two mineralocorticoids you need to know for this class?
1. **Fludrocortisone** -more potent Na retention, some anti-inflammatory, PO BID
2. **Desoxycorticosterone (DOCP**)- longer acting (q25 days), less potent
Clinical use = Addisons Disease (hypoadrenocorticism)
213
What are Fludrocortisone and Desoxycorticosterone (DOCP) used to treat?
**Typical Addisons Disease (hypoadrenocorticism)**
---
They are mineralcorticoids
214
What are the fast and late responses of mineralocorticoid administration?
```
_Fast response (minutes_)= Stimulate Na/K/ATPase & Activate Na/H exchanger
_Late response (hours/days)_- De novo synthesis of Na/K/ATPase by upregulating the nuclear receptor
```
215
What effects do mineralocorticoids have on the transport of electrolytes in the kidney?
Na+ (and water) retention
K+/H excretion
Increase ECF and GFR
216
T/F: Most ‘glucocorticoids’ have sufficient mineralocorticoid
activity to treat deficiency
FALSE
Most ‘glucocorticoids’ have **insufficient** mineralocorticoid activity to treat deficiency
217
In addison, do you need to replace the glucocorticoid, the
mineralocorticoid or both or neither?
It depends on the type.
* **Iatrogenic hypoadrenocorticism:**
* You suppressed the adrenals with exogenous steroids, *gradually wean off the steroid* and they’ll be fine.
* **‘Typical’ Addison’s:**
* Deficient in *_both_* mineralocorticoid and glucocorticoid
* *Florinef or DOCP + prednisone (physiologic doses)*
* **‘Atypical’ Addison’s:**
* Deficient in glucocorticoid ONLY
* *Prednisone* (physiologic doses) & monitor for development of mineralocorticoid deficiency
218
How do you treat Iatrogenic hypoadrenocorticism
Put back on steroid and then gradually wean off the steroid so that ACTH production can be amped back up
219
How do you treat Typical Addisons?
**Florinef or DOCP + prednisone (physiologic doses)**
**------------------**
Deficient in both mineralocorticoid and glucocorticoid
220
How do you treat atypical addisons?
**Prednisone (physiologic doses)**
Deficient in glucocorticoid ONLY
221
Which drug to treat for hyperadrenocorticism/cushings is cytotoxic to the adrenal glands (Zona fasciculata/reticularis)?
**Mitotane** (Lysodren®, o,p-DDD)
-------
It has a narrow therapeutic index - monitor with ACTH stim testing
Have to give *induction dose* followed by maintenance dosing
Overtreatment can cause primary addisons
Can treat pituitary or adrenal
222
In europe, vets will **overdose Mitotane** to make a cushings patient an addisons patient by destroying the adrenal gland. What are the pros and cons of this methos
_Pros_- Addisons is easier to treat than cushings due to a more predictable course of therapy
_Cons-_ if poor compliance, a untreated addisons patient will die, while a cushings patient will have a much milder outcome.
223
What is the most common drug used to treat hyperadrenocorticism in small animals?
**Trilostane (Vetoryl®)**
224
Which drug to **treat hyperadrenocorticism** (primarily pituitary) is a **competitive inhibitory of an enzyme of steroid synthesis** (3β-hydroxysteroid dehydrogenase) that requires **daily oral dosing?**
**Trilostane (Vetoryl®)**
-----
Can treat pituitary or adrenal
Start on low dose, then increase
Excessive dose --\> oversuppresion
Monitor with ACTH testing
225
What **drug to treat hyperthyroidism** is an **antifungal** that **inhibits cortisol synthesis and CYP450 enzymes** that requires daily oral dosing and has a **high risk of hepatotoxicity** and a **low efficacy?**
**Ketoconazole**
226
Which drug for **treating pituitary hyperadrenocorticism** is a **MAO-B inhibitor that** **increases dopamine** --\> decrease ACTH --\> **decrease cortisol?** This drug has **few side effects** and patients will "feel better: despite a specific response in HAC
**Selegiline (L-deprenyl, Anipryl®)**
227
Which drug to treat pituitary hyperadrenocorticism (pars intermedia dysfuction) in horses acts as a **dopamine agonist** --\> decrease ACTH --\> decrease cortisol?
**Pergolide (Permax®)**
---
NOT in USA
Clinical response seen after ~ 3 weeks of therapy
Anorexia (may be dose dependent)
- -----
* *Cabergoline (Dostinex®)** also dopamine agonist – has been looked at in canines
228
What sydrome do the below drugs all treat?
Hyperadrenocorticism
229
What are the two inputs/centers in the brain that contribute to appetite?
"Feeding center" and Satiety center
230
When treating anorexia/hyporexia, what is your main goal?
ID and treat the underlying cause
231
Which appetite stimulant acts on **GABA --\> inhibits the satiety center** --\> increase appetite that is more effective in **cats**?
What is its main two form? and what are some side effects?
Benzodiazepines!
------
sedation is most commonside effect
Diazepam (IV) and Midazolam (IM) are the two forms
232
T/F: Diazepam is given orally to increase appetite in cats
**FALSE!- Give IV**
**_Do NOT give orally in cats –\> idiosyncratic hepatotoxicity!_**
IM absorption is slow, incomplete and painful
233
Although the mechanism is not well understod, which very **short acting** (~15 min) **appetite stimulant** acts on **GABA and inhibits 5-HT** at sub-hypnotic doses?
**Propofol (Propoflo®)**
\_\_\_\_
CAUTION in cats: Heinz body anemia possible if treating repeatedly \>5 days
234
Which serotonin (5-HT) antagonist are you more likely to use in a cat? a dog?
* **Cat= Cyproheptadine (Periactin®)** -
* oral, 2-3 days for response, sedation, smaller tablets
* **Dog= Mirtazapine (Remeron®)**
* **** increase NE, large tablets (7.5 mg)
235
How does prednisone stimulate appetite?
Via negative feedback on CRH
236
T/F B-vitamins are most effective at stimulating an appetite if there is a B-vit deficiency
True
237
What are the two centers in the brain that control vomiting?
* **Emetic Center**-
* inputs from glossopharyngeal, vagal & sympathetic afferents
* **CRTZ**-
* sample blood from outside the BBB
* Receptors: Serotonin (5-HT), Neurokinin (NK1), Adrenergic (alpha-2), Dopamine (D2), Histamine (H1), Metabolic (toxins)
* Cats: More: α-2 and 5-HT Fewer: D2 and H1
238
How does 3% hydrogen peroxide induce emesis? What species is it contraindicated in?
**direct irritation of oropharynx/GI lining**
Dont use in **cats** --\> hemorrhagic gastritis
\_\_\_\_\_\_\_\_\_\_
Use only if no other options (ie at home)
239
Which emetic stimulates dopamine receptors? which species is it most effective in?
**Apomorphine** (Apokyn®)
More effective in **Dogs** (cat ~10%)
\_\_\_\_\_\_\_\_\_\_\_\_\_
Can give ALL routes- even conjunctival sac!
Reverse respiratory depression with **naloxone**
240
What is the reversal of Apomorphine? What does it do?
**Naloxone**
Reverses respiratory depression but **_WONT_ reverse the emetic effect**
\_\_\_\_\_\_\_\_\_
If give in the conjunctive, you can flush out the drug when you no longer need the emesis
241
Which emetic is a a-2 agonist? which species is it more effective in?
**Xylazine or Dexmedetomidine** (Rompun®, Dexdomitor®)
More effective in **CATS**= (cats have more α-2
receptors and fewer D2 receptors)
242
What drug is used to treat **old dog vestibular disease?**
**_Meclizine (Antivert®)_**
-----
**Antihistamine (H1 receptor antagonist)** that **reduced vestibular input** to the **CRTZ**
Oral, last 8-12 hours, few side effects
243
Which anti-emetic is a (1) **dopamine antagonist**, (2) **5-HT antafonist** @ high dose and has (3)**peripheral effects on GI motility**?
What can it be used for? How should it be administered?
**Metoclopramide (Reglan®)**
potent anti-emetic, **antagonizes apo-morphine induced emesis**
**CRI is best,** but can give **oral TID**
244
What types of drugs are Ondan*setron* (Zofran®) & Dola*setron* (Anzemet®)?
**POTENT Anti-emetics - Serotonin antagonist (5-HT)**
\_\_\_\_\_
Initially used for chemotherapy related nausea
More potent than metoclopramide, but more $$$
Usually given by injection but oral formula available
