Pharmacology Flashcards
1
Q
Name the 4 types of vasopressin receptors
A
V1, V2, V3, oxytocin
2
Q
Describe the tissues affected and effects of vasopressin on the V1 Rc
A
Vascular smooth muscle- vasoconstriction at high doses; vasodilation in cerebral, renal, pulmonary, and mesenteric vessels at low doses
3
Q
Describe the tissues affected and effects of vasopressin on the V2 Rc
A
renal collecting duct-increased h2o permeability
endothelial cells- release of vWF
platelets- stimulation of aggregation
vascular endothelium-vasodilation
4
Q
Describe the tissues affected and effects of vasopressin on the V3 Rc
A
Pituitary- adrenocorticotropic hormone release
5
Q
Describe the tissues affected and effects of vasopressin on the oxytocin Rc
A
Uterus, mammary glands, Gi tract, endothelium- contraction, vasodilation
6
Q
What is the half life of AVP?
A
10-35 min
7
Q
Where is arginine vasopressin synthesized and stored?
A
synthesis- hypothalamus
storage- posterior pituitary
8
Q
What are the 3 most potent stimuli for AVP release?
A
increased plasma osmolality, decreased blood pressure, decreased circulating blood volume
9
Q
What are some uncommon stimuli for AVP release?
A
pain, nausea, hypoxia, hypercarbia, pharyngeal stimulation, glycopenia, drugs/chemicals, malignant tumors, mechanical ventilation
10
Q
What are some chemicals/drugs that cause AVP release?
A
high dose opioids, histamine, glutamine, prostaglandings, angiotensin II, acetylcholine, dopamine
11
Q
T/F - drugs such as glucocorticoids, low dose opioids, atrial natriuretic factor, and GABA can cause increased AVP release?
A
False- they cause decreased release of AVP
12
Q
Name 6 causes of secondary hypertension
A
Kidney disease
Diabetes mellitus
13
Q
What are the indications for use of ACE inhibitors?
A
Reduce blood pressure in all forms of hypertension
Mitral insufficiency and congestive heart failure
Reduce proteinuria by maintaining the heparan sulfate layer of the basement membrane
14
Q
What type of receptors are vasopressin Rc’s?
A
G protein coupled Rc’s
15
Q
How (physiologically) does the V1 Rc cause vasoconstriction?
A
activation of phospholipase C and phosphoinositide pathways; activate voltage gated Ca++ channels, which increases intracellular Ca++ levels
16
Q
What are the indications for use of angiotensin II receptor blockers?
A
Used in humans for hypertension and cardiovascular disease.
Efficacy is unknown for treatment of hypertension in dogs and cats
17
Q
T/F- vasopressin causes inactivation of the potassium-ATP channels in vascular smooth muscle cells
A
True
18
Q
Vasopressin causes inactivation of the K+-ATP channels in vascular smooth muscle; how does this affect the muscle?
A
These channels (when they are open) normally cause K+ efflux-->hyperpolarization-->decreased Ca++ into cells-->vasodilation When the channels are inactivated vasodilation does not occur
19
Q
What are the indications for use of adrenergic receptor antagonists?
A
B-adrenergic blockers are used when primary antihypertensive treatment fails to produce the desired decrease in blood pressure. Also used to manage HCM and supraventricular and ventricular tachycardias
A-adrenergic antagonists used as a primary or adjunct therapy for hypertension in dogs. Also used in micturition disorders to relax the smooth muscle of the urethra. Also used in treatment of hypertension associated with pheochromocytomas
20
Q
What is the mechanism of action of angiotensin-converting enzyme (ACE) inhibitors?
A
Competitively inhibit the conversion of angiotensin I to angiotensin II resulting in systemic vasodilation
21
Q
What is the mechanism of action of aldosterone blockers and what are some examples of this type of drug?
A
Spironolactone
Blocks the effects of aldosterone on the renal distal convoluted tubule and collecting duct thereby decreasing sodium resorption and potassium excretion
22
Q
What are the indications for use of aldosterone blockers?
A
Hypertension due to its weak antidiuretic effects but also for its effects on the renin-angiotensin-aldosterone system
Used in treating hyperaldosteronism, iatrogenic steroid edema, refractory edema
23
Q
What are the adverse effects of aldosterone blockers?
A
Hyperkalemia may occur but is uncommon in the absence of kidney insufficiency or concurrent use of a beta blocker, ACE inhibitor, angiotensin II receptor blocker, or potassium supplements
24
Q
What is the mechanism of action of calcium channel blockers and what are some examples of this type of drug?
A
Amlodipine, nicardipine
They act by blocking the influx of calcium into vascular smooth muscle cells that is necessary to cause smooth muscle contraction thereby decreasing systemic vascular resistance.
They inhibit the slow transmembrane calcium influx into the cell via voltage-gated L-type calcium channels
The dihydopyridines (amlodipine etc) are the family of CCBs that primarily act on blood vessels producing arterial vasodilation.
25
T/F- platelets have V1 receptors, which can lead to thrombosis due to increased intracellular Ca++
True
26
What is the mechanism of action of the arteriolar vasodilator hydralazine?
Acts on the smooth muscle of arterioles with a mechanism that is incompletely understood
Known to act as an antioxidant, inhibiting vascular production of reactive oxygen species. It may induce arteriolar vasodilation by preventing oxidation of nitric oxide thereby lowering blood pressure
27
What are the adverse effects of hydralazine?
Three types of adverse effects in humans:
1. Reflex sympathetic activation
2. Lupus-like reaction
3. Nonspecific problems such as anorexia, nausea, vomiting, diarrhea, muscle cramps and tremor
In vet med, we see mainly reflex tachycardia, weakness and GI upset
28
Where are V2 receptors located?
basolateral membrane of the distal tubule, principal cells of cortical and medullary renal collecting duct
29
What are the indications for use of hydralazine?
Hypertension in dogs and cats (not a first line therapy)
30
In what 2 ways does AVP regulate water homeostasis?
1. regulate the fast shuttling of aquaporin 2 to the cell surface
2. stimulates synthesis of mRNA-encoding aquaporin 2
31
T/F: Most animals with nephrogenic DI have V1R mutations?
False; they have V2R mutations
32
How does the V2R activation affect coagulation?
release of plt from bone marrow, release of vWF and factor VIII from endothelial cells
33
What drug is used to release vWF and factor VIII?
DDAVP (1-deamino-8-d-arginine vasopressin)
| Note: it also causes vasodilation
34
What happens inside the cell when V3R are activated?
releases intracellular Ca2+ after activation of phospholipase C and phosphoinositol cascade
35
What is the mechanism of action of angiotensin II receptor blockers and what are some examples of this type of drug?
Arterial and venous vasodilation
Losartan, Irbesartan, Telmisartan
They displace angiotensin II from its specific angiotensin type I receptor (AT1R) antagonizing all of its known effects (vasoconstriction, sympathetic activation, aldosterone release, renal sodium resorption).
36
What are the indications for angiotensin II receptor blockers?
Used in humans for hypertension and cardiovascular disease.
Efficacy is unknown for treatment of hypertension in dogs and cats
37
What are the adverse effects of angiotensin II receptor blockers?
These drugs appear to be safe with few adverse effects.
38
What is the mechanism of action of adrenergic receptor antagonists and what are some examples of this type of drug?
B adrenergic receptor antagonists: propanolol, atenolol
MOA: blockade of renin release, reduction of heart rate and contractility, decrease in peripheral vascular resistance, reduction in central adrenergic drive
A adrenergic receptor antagonists: prazosin
MOA: blocks activation of the post-synaptic alpha 1 receptors which are normally activated by circulating or neurally released catecholamines. This results in balanced vasodilation.
39
How does activation of V3R affect the CNS?
modulator of memory, blood pressure, body temp, sleep cycles, release of pituitary hormones
40
T/F: oxytocin Rc has equal affinity for AVP & oxytocin?
TRUE
41
Should exogenous AVP be given orally? Why or why not?
No- destroyed within the GI tract
42
What is the half life of exogenous AVP?
24 min
43
How is exogenous AVP excreted?
35% tissue peptidases, 65% renal
44
What Rc does selepressin work on?
V1R agonist; in healthy dogs they have a reduced risk of coronary ischemia compared with those given AVP
45
What is desmopressin acetate?
synthetic vasopressin analog; available in IN and inject form; binds to V2R; potent antidiuretic and procoagulant activity
Can cause a dose dependent increase in plasma factor VIII and plasminogen factor
Half life is 0.4-4 hrs
46
What is tolvaptan?
V2R antagonist; has aquaretic response and reduced cardiac preload; doesnt affect sympathetic NS, renal hemodynamics or RAAS; may be beneficial in CHF
47
How does vasopressin compare to epi in a meta analysis during CPR?
is at least equivalent to epinephrine; in experimental models it improves cerebral O2 delivery and may improve chance of ROSC
48
T/F: hypovolemia or septic shock can cause a biphasic response in serum AVP levels (initially high, then depleted)?
True
49
What concentration of plasma AVP should be the goal for restoration of BP with minimal adverse effects?
AVP 20-30 pg/ml
50
What are the adverse effects of angiotensin II receptor blockers?
These drugs appear to be safe with few adverse effects.
51
What is the mechanism of action of adrenergic receptor antagonists and what are some examples of this type of drug?
B adrenergic receptor antagonists: propanolol, atenolol
MOA: blockade of renin release, reduction of heart rate and contractility, decrease in peripheral vascular resistance, reduction in central adrenergic drive
A adrenergic receptor antagonists: prazosin
MOA: blocks activation of the post-synaptic alpha 1 receptors which are normally activated by circulating or neurally released catecholamines. This results in balanced vasodilation.
52
What are the indications for adrenergic receptor antagonists?
B-adrenergic blockers are used when primary antihypertensive treatment fails to produce the desired decrease in blood pressure. Also used to manage HCM and supraventricular and ventricular tachycardias
A-adrenergic antagonists used as a primary or adjunct therapy for hypertension in dogs. Also used in micturition disorders to relax the smooth muscle of the urethra. Also used in treatment of hypertension associated with pheochromocytomas
53
What are the adverse effects of adrenergic receptor antagonists?
B-adrenergic blockers
Non-selective ones such as propanolol should not be used in cats due to bronchospasm.
May also cause hyperkalemia, bradycardia, insulin resistance, and depression
A-adrenergic antagonists
May cause hypotension nonresponsive to a-agonist therapy
54
What are some theories behind why septic shock causes lower levels of AVP?
degredation of released AVP, depletion of neurohypophyseal stores, enhanced sensitivity to AVP induced blood pressure changes, release may be inhibited by NO or high levels of norepi
55
T/F- many human papers have shown earlier weaning of catecholamines when giving vasopressin?
true
56
T/F- there have been human studies documenting decreased mortality rates in people with septic shock when giving vasopressin?
true
57
What are some adverse effects of AVP administration?
excessive coronary and splanchnic vasoconstriction, hypercoagulability, reduction in cardiac output, fatal cardiac events
58
What dose of AVP is used in dogs with refractory vasodilatory shock?
0.5 mU/kg/min IV, titrated up to achieve MAP >70 mm Hg and HR
59
How does AVP minimize blood loss from bleeding extremities?
redirects blood from skin, skeletal muscle and periphery
60
T/F- administration of AVP decreased fluid requirements and mortality in one human trauma study?
true
61
What drug is used to treat central diabetes insipidus?
DDAVP- monitor serial lytes and avoid water intoxication
62
What are some drawbacks to use of DDAVP for vWD?
expensive, short duration of activity, development of resistance
63
Name some adverse effects of AVP
contraction of bladder/gallbladder smooth muscle, increased peristalsis, decrease gastric secretions, phlebitis, skin necrosis, elevated LES, TCP, hyponatremia, anaphylaxis, abdominal pain, urticaria
64
What role might V1R antagonists play (in the future/not yet developed)? V2R?
V1R-mgmt of subarachnoid hemorrhage
| V2R- CHF
65
T/F: Most animals with nephrogenic DI have V1R mutations?
False; they have V2R mutations
66
What drug is used to release vWF and factor VIII?
DDAVP (1-deamino-8-d-arginine vasopressin)
| Note: it also causes vasodilation
67
What Rc does selepressin work on?
V1R agonist; in healthy dogs they have a reduced risk of coronary ischemia compared with those given AVP
68
What is tolvaptan?
V2R antagonist; has aquaretic response and reduced cardiac preload; doesnt affect sympathetic NS, renal hemodynamics or RAAS; may be beneficial in CHF
69
What is the mechanism of action of adrenergic receptor antagonists and what are some examples of this type of drug?
B adrenergic receptor antagonists: propanolol, atenolol
MOA: blockade of renin release, reduction of heart rate and contractility, decrease in peripheral vascular resistance, reduction in central adrenergic drive
A adrenergic receptor antagonists: prazosin
MOA: blocks activation of the post-synaptic alpha 1 receptors which are normally activated by circulating or neurally released catecholamines. This results in balanced vasodilation.
70
What is the mechanism of action of aldosterone blockers and what are some examples of this type of drug?
Spironolactone
Blocks the effects of aldosterone on the renal distal convoluted tubule and collecting duct thereby decreasing sodium resorption and potassium excretion
71
What are the indications for use of aldosterone blockers?
Hypertension due to its weak antidiuretic effects but also for its effects on the renin-angiotensin-aldosterone system
Used in treating hyperaldosteronism, iatrogenic steroid edema, refractory edema
72
What are the adverse effects of aldosterone blockers?
Hyperkalemia may occur but is uncommon in the absence of kidney insufficiency or concurrent use of a beta blocker, ACE inhibitor, angiotensin II receptor blocker, or potassium supplements
73
What is the mechanism of action of calcium channel blockers and what are some examples of this type of drug?
Amlodipine, nicardipine
They act by blocking the influx of calcium into vascular smooth muscle cells that is necessary to cause smooth muscle contraction thereby decreasing systemic vascular resistance.
They inhibit the slow transmembrane calcium influx into the cell via voltage-gated L-type calcium channels
The dihydopyridines (amlodipine etc) are the family of CCBs that primarily act on blood vessels producing arterial vasodilation.
74
What are the indications for use of calcium channel blockers?
Hypertension and hypertensive crises
| Amlodipine is the treatment of choice for hypertension in cats with chronic kidney disease
75
What are the adverse effects of calcium channel blockers?
Tachycardia, nausea, constipation, weakness
Afferent arteriolar vasodilation is greater than the efferent arteriolar vasodilation on the opposite side of the glomerulus which may result in decreased perfusion pressure with resultant decreased glomerular filtration
76
What is the mechanism of action of the arteriolar vasodilator hydralazine?
Acts on the smooth muscle of arterioles with a mechanism that is incompletely understood
77
What are the adverse effects of hydralazine?
Three types of adverse effects in humans:
1. Reflex sympathetic activation
2. Lupus-like reaction
3. Nonspecific problems such as anorexia, nausea, vomiting, diarrhea, muscle cramps and tremor
In vet med, we see mainly reflex tachycardia, weakness and GI upset
78
Name two arteriolar vasodilators
Hydralazine
| Sodium nitroprusside
79
What is the mechanism of action of the arteriolar vasodilator sodium nitroprusside?
Results in nitric oxide release, which stimulates the production of cyclic guanine monophosphate (cGMP) in the vascular smooth muscle. cGMP activates a kinase that leads to inhibition of calcium influx into the smooth muscle cell and decreased calcium-calmodulin stimulation of myosin light-chain kinase. This in turn decreases the phosphorylation of myosin light chains, which decreases smooth muscle contractions and causes vasodilation.
80
What are the indications for use of hydralazine?
Hypertension in dogs and cats (not a first line therapy)
81
What are the indications for use of sodium nitroprusside?
Hypertensive crisis
Rapid reduction of preload and afterload in acute heart failure
Controlled blood pressure reduction during surgery
82
What are the adverse effects of sodium nitroprusside?
Shock
Severe hyportension
Cyanide intoxication
83
What is the mechanism of action of fenoldopam?
Peripheral dopamine-1 agonist
| Maintains or increased renal perfusion while lowering blood pressure
84
What are the indications for use of fenoldopam?
Severe hypertension
| Hypertensive crisis
85
What are the adverse effects of fenoldopam?
Reflex tachycardia
| Increased intraocular pressure
86
How do steroids cause hypertension?
Hepatic induction of angiotensinogen leads to over activation of RAAS
87
How does hyperthyroidism lead to hypertension?
Increased cardiac output due to effect of excess thyroid hormone on cardiac muscle
88
How does renal disease cause hypertension?
Renal regulation of blood pressure is from Pressure natriuresis and RAAS. Maladaptive increase in renin increases blood volume which leads to increased venous return. Or possibly inability of kidneys to process fluids and el leads to increased venous return. Increased vasoconstrictors (endothelin, thromboxane, adrenergic stimuli) and decreased vasodilators (nitric oxide, prostacyclin) may play a role
89
How does hepatic disease cause hypertension?
Undetermined
90
What are the 4 mechanisms by which diabetes may cause hypertension?
Type I - effects on renal function (nephropathy with nephritic syndrome and glomerulosclerosis)Type II- 1. Hyperinsuliemia from insulin resistance leads to sodium and water retention and increased sympathetic activity, leads to increased PVR via changes in BV and vasoconstriction 2. Hypertrophy of VSM 2nd to mitogenic effects of insulin3. Elevated insulin leads to increased intracellular Ca which results in hyper responsive VSM contraction and increased PVR
91
How do pheos cause hypertension?
Release of epi and norepinephrine causes vasoconstriction and increased CO.
92
How does anemia cause hypertension?
Anemia leads to chronically dilated Capillary beds, when anemia resolves, overcompensation of capillary constriction happens causing increased PVR
93
How do ACEI's control hypertension?
Prevent the cleavage of AG I to AG II (AG is a very powerful vasoconstrictor, inhibition results in vasodilation). This decreases AG I and II and increases bradykinin. Also these drugs induce arterial and venous vasodilation.
94
Other than vasodilation, what are some others affects of ACE inhibitors?
Reduced plasma volume from lack of sodium retention from decreased AG II, prevention of aldosterone release which leads to deceased Na and H2O retention and decrease BV. Decreased preload and after load, reduced intra glomerular pressure and inhibition of growth factors that lead to glomerular hypertrophy and sclerosis.
95
How do ACE inhibitors reduce proteinuria?
Maintaining the heparan sulfate layer of the glomerular basement membrane
96
What are 3 benefits of benazepril?
Lowering of glomerular capillary hypertension, decreased release of extracellular matrix and collagen from mesangial and tubular cells, and reduction in degree of glomerular and interstitial fibrosis
97
What is a rare side effect of ACE inhibitors?
Dry cough induced by increased bradykinin
98
How do AG II receptor blockers such as losartan work?
Displace AG II from it's receptor ATIreceptor and possibly enhancing dopamine D1 signaling. Displacement form it's receptor antagonizes all of it's known effects and results in a dose dependent fall in PR with little change in HR or CO
99
How do beta blockers treat hypertension?
Blocks renin release, decreases HR and contractility, decrease in PVR and reduced central adrenergic drive
100
How do alpha adrenergic antagonists treat hypertension?
Selectively antagonizing alpha adrenergic receptors on systemic vessels. Prazosin acts as a competitive antagonist of postsynaptic alpha1 receptors and blocks activation of these receptors by circulating or neurally released catecholamines (which would typically cause vasoconstriction). PR falls with minimal changes in CO
101
What is eplerenone and what is it used for?
Antagonizes the aldosterone receptor- advantage over spironolactone is eplerenone does not bind to progesterone or androgen receptors like spiro. May cause hyperkalemia. Has been shown to reduce proteinuria and decrease renal fibrosis and inflammation.
102
List 5 secondary causes of hypertension
Kidney disease, Cushings, diabetes mellitus, hyperthyroidism, hepatic disease, less common: pheochromocytas, drugs (steroids, erythropoietin), chronic anemia, hyperaldosteronism, polycythemia
103
What is the MOA of maropitant?
Neuokinin-1 receptor antagonist that blocks the action of substance P in the central nervous system as well as at peripheral NK-1 receptors in the GI tract
104
What other effects can NK-1 receptor antagonists have other than as anti-emetics?
```
Anti-inflammatory
Neuroprotectant
Hepatoprotectant
Reduction of diarrhea
Reduce visceral pain
Reduce the minimum alveolar concentration of sevoflurane
Possible anti-tumor activity
```
105
What is the MOA of 5-HT3 receptor antagonists?
Competitive blockers of the serotonin receptors both peripherally (where they are responsible for intestinal vagal afferent input) and centrally (in the chemoreceptor trigger zone and medullary vomiting center)
106
What is an unusual characteristic of ondansetron in people?
It inhibits emesis and low and high dosages; however, it increases it an intermediate doses.
The same has been seen with metoclopramide in people.
107
True or False: Ondansetron has been reported to increase the efficacy of tramadol
FALSE
| It DECREASES the efficacy of tramadol
108
What is the MOA of metoclopramide?
It is a 5HT-3 receptor antagonist as well as an antidopaminergic
Weak 5HT-4 agonist
109
Why is metoclopramide potentially less effective in cats?
They have very few dopamine receptors
110
What is the MOA of promazine derivatives as anti-emetics?
They have antidopaminergic and antihistaminic effects that block the CRTZ and at higher dosages, the MVC as well
111
What are some side effects of promazine derivatives when they are used as anti-emetics?
Increased central venous pressure
Brady or tachycardia
Anti-arrhythmic qualities in the dog
CNS signs in dogs with hepatic insufficiency
112
What is aminopentamide?
It is an anticholinergic that has been used an an anti-emetic in dogs. There are cholinergic receptors in the brain involved in the vomiting center and in the upper GI tract via the vagus nerve.
It is less effective than metoclopramide, the 5-HT3 antagonists, and the NK-1 antagonists.
113
True or False: In humans steroids have been used as anti-emetics?
TRUE
| They are typically used in combination with other anti-emetics.
114
What class of drug is the most effective prokinetics in veterinary medicine?
5-HT4 serotonergic agonists such as cisapride
115
What is the MOA of cisapride?
5-HT4 serotonergic agonist
Enhances gastric emptying while increasing gastroesophageal sphincter pressure. It also enhances colonic and small intestinal motility (can be used in cats with idiopathic constipation).
It does not enhance esophageal motility as it is ineffective on striated muscle.
116
What is the MOA of cholinomimetic drugs as prokinetics?
Ranitidine and nizatidine inhibit acetylcholinesterase which results in increased gastric emptying.
Bethanechol binds to muscarinic receptors which effects motility throughout the GI tract.
117
True or False: The dose of metoclopramide needed to provide a prokinetic effect is lower than that needed for the anti-emetic effect
FALSE
| Higher doses are needed to cause prokinesis and reduce gastroesophageal reflux.
118
True or False: Misoprostol can be used to enhance colonic motility
TRUE
| It has been used in patients with non-responsive constipation.
119
What is the MOA of benzodiazepines?
facilitate the inhibitory actions of GABA, antagonism of serotonin, diminished release or turnover of Ach in CNS
Also have anxiolytic, sedative, hypnotic, skeletal muscle relaxant and anticonvulsant properties via limbic, thalamic, and hypothalmic areas of CNS
120
T/F: benzodiazepines provide some analgesia
False
121
What are the major differences between midazolam and diazepam?
Diazepam- not water soluble; formulated in a 40% propylene glycol and 10% alcohol vehicle
Midazolam- water soluble, well absorbed after IM injection, poorly bioavailable per rectum
122
T/F: midazolam should only be given through a central vein?
false- midazolam is water soluble and can be given through a peripheral vein; diazepam should be given through central vein b/c propylene glycol may cause phlebitis
123
T/F: midazolam and diazepam can also be given intranasally
true
124
what adverse effects are associated with propylene glycol toxicity in animals receiving diazepam?
metabolic acidosis, hyperosmolality, neuro abnormalities, organ dysfunction
125
what is a rare complication of oral diazepam administration in cats?
fulminant hepatic failure from acute hepatic necrosis (idiosyncratic rxn)
126
How do benzodiazepines stimulate appetite?
at low doses they bind to benzodiazepine receptors and increase the attraction to tastes, especially in cats; may begin working within a few seconds of administration
127
What is the controversy regarding use of benzodiazepines in animals with hepatic encephalopathy?
Human patients have been shown to increase arousal following flumazenil administration; there is a lack of arousal in other species including dogs and cats; improvement of HE signs has been shown in animals given the inverse agonist sarmazenil- this may be consistent with increased GABAergic activity in HE but not an increase in endogenous benzo ligands
128
what are the recommended doses for sedation and anticonvulsant therapy for midazolam and diazepam?
Diazepam:
Sedation- 0.2-0.6 mg/kg, CRI 0.1-1 mg/kg/hr
Anticonv- 0.5-1 mg/kg, CRI 0.5-1 mg/kg/hr, per rectum 2 mg/kg
Midazolam:
Sedation- 0.1-0.4 mg/kg, CRI 0.1-0.5 mg/kg/hr
Anticonv- 0.2-0.5 mg/kg, CRI 0.2-0.5 mg/kg/hr
129
T/F: flumazenil use is rarely indicated even in severe benzodiazepine overdoses if the patient is stable?
True, there is a possibility of severe adverse outcomes with flumazenil or sarmazenil use; overdose can usually be treated supportively with emetics and/or charcoal
130
What types of things do platelets interact with in order to become activated?
vWF, subendothelial collagen, other activated platelets,
131
Describe the two platelet receptors: P2Y1 and P2Y12
P2Y1: Agonism at this receptor is associated with platelet shape change and mild, reversible aggregation
P2Y12: Agonism at this receptor is associated with integrin activation and platelet granule secretion
132
What are the thienopyridines and give an example?
A class of drugs designed to interfere with ADP-induced platelet aggregation through irreversible binding to the platelet P2Y12 receptor.
Clopidogrel
133
How do the nucleoside analogues work as antiplatelet drugs?
They inhibit the effects of ADP on platelet aggregation through reversible inhibition of the P2Y12 receptor. They do not require hepatic metabolism for activation like the thienpyridines.
134
How does aspirin results in platelet inhibition?
Aspirin administration causes irreversible blockade of COX-1 which decreases arachidonic acid formation necessary to create thromboxane-A2 (which is a potent vasoconstrictor and also plays a role in the recruitment and activation of platelets)
135
How long do platelets last in circulation?
6 +/- 1 days
136
Why are cats potentially less sensitive to aspirin therapy?
They have reactive platelets that are sensitive to other agonists thereby minimizing the importance of TXA2 activation
137
Why are fibrinogen receptor antagonists potentially more effective than other antiplatelet drugs?
They target the final step in the platelet activation pathway (the expression of an active GPIIb/IIIa fibrinogen receptor). Because therapy is directed at the receptor itself variability in platelet response in minimized
138
What may be responsible for variable response to clopidogrel or other thienopyridines?
They are prodrugs that require activation in the liver by the P-450 enzymes. Variation in this enzyme system between individuals and in certain disease states may result in altered pharmacokinetics
139
Why are platelets more associated with arterial thromboembolism?
Sheer stress causes by fast-flowing arterial blood exposes platelet binding sites on vWF that increase the affinity for the platelet glycoprotein Ib receptor
140
What morphological changes are seen with platelet activation?
The activated platelet changes from a smooth discoid shape to a more ameboid shape with filopodia
141
What do the Alpha-granules of platelets contain? and the dense granules?
Alpha-granules: adhesion molecules (P selectin, vWF, thrombospondin, Integrin aIIbB3 (or GPIIb/IIIa)) and coagulation factors (V, VIII, fibrinogen)
Dense granules: smaller ions and nucleotides (Ca2+, ADP, adenosine triphosphate, serotonin, histamine)
142
What change is seen with the platelet membrane after activation?
Rearrangement of the membrane phospholipids which provides a surface that supports the formation of the complexes that activate factor X (the tenase complex) and factor II (the prothrombinase complex)
143
What is the name of classification scheme used for anti-arrhythmic drugs and what is it based on?
Vaughan Williams classification system
Groups drugs according to their major ion channel or receptor effects
144
In general, how do Class I anti-arrhythmics work?
The act by inhibiting the fast sodium channel and decreasing the slope of phase 0 of the action potential
145
What is an example of a class Ia anti-arrhythmic and what are its effects?
Procainamide
Depresses conduction velocity and prolongs the effective refractory period in many tissues including the atrial and ventricular myocardium, accessory AV pathways, and retrograde AV nodal pathways
146
True or False: Procainamide is less effective than lidocaine for terminating ventricular tachyarrhythmias in humans
FALSE
It is more effective than lidocaine
147
What are adverse effects of procainamide?
Anorexia, nausea, vomiting are seen most commonly.
In humans, rash and fever are seen immediately after use and myalgia, arthralgia, and agranulocytosis may be seen later.
In 1/3 of patients that take it longer than 6 months, systemic lupus erythematosus may be seen
148
What is an example of a class Ib anti-arrhythmic and what are its effects?
Lidocaine
It inhibits the fast sodium channel, primarily in the open state with rapid onset-offset kinetics. There is also shortening of the action potential duration.
149
In what conditions is lidocaine's sodium blocking activity enhanced?
Acidosis, increased extracellular potassium concentrations, and partially depolarized cells
150
Why are drugs that prolong AV nodal conduction given first for acute treatment of tachyarrhythmias?
Procainamide is not given first as it can enhance AV nodal conduction and worsen the ventricular response rate
151
What are adverse effects of lidocaine?
Nausea, vomiting, lethargy, tremors, seizures
152
Why are lower doses of lidocaine recommended in cats (if it is used at all)?
The incidence of adverse effects is much higher in cats, with earlier reports of bradyarrhythmias and sudden death
153
Give an example of an oral class Ib anti-arrhythmic
Mexiletine
154
Name two class Ic anti-arrhythmics
Flecainide
Propafenone
They block the fast sodium channel with greater effects as the depolarization rate increases. They are uncommonly used in veterinary medicine
155
What are class II anti-arrhythmics and how do they work?
B-adrenergic antagonists or B-Blockers
They work by:
1) Inhibiting the If current that also promotes pro-arrhythmic depolarization in damaged cardiomyocytes
2) Inhibit the inward calcium current indirectly by decreasing tissue cyclic adenosine monophosphate levels.
156
What are the effects of beta blockers?
Slowed AV nodal conduction in supraventricular tachyarrhythmias
Slow sinus nodal discharge rate in inappropriate sinus tachycardia
Suppression of ventricular tachyarrhythmias thought to be caused in some part by increased sympathetic tone
157
Give an example of a short acting injectable beta blocker
Esmolol
158
What is an example of a class III anti-arrhythmic and how do they work?
Sotalol and Amiodarone
They block the repolarizing potassium current which results in prolongation of the action potential duration and effective refractory period
159
What accounts for the pro-arrhythmic effects of class III anti-arrhythmics and in what conditions are the pro-arrhythmic effects enhanced?
They block the rapid component of the potassium current rather than the slow component making their effects more accentuated at slower heart rates (puts them at risk for early after-depolarization)
Accentuated with hypokalemia, bradycardia, intact status in females, increasing age, macrolide antibiotic therapy
160
What is unique about amiodarone in terms of its anti-arrhythmic effects?
It has the broadest spectrum and exhibits properties of all four anti-arrhythmic classes
161
Name some side effects of amiodarone?
Vomiting, anorexia, hepatopathies, and thrombocytopenia
162
What is an example of a class IV anti-arrhythmic and how do they work?
Diltiazem
They are calcium channel blockers and slow AV nodal conduction and prolong the effective refractory period of nodal tissue. This effect is most notable at faster stimulation rate and in depolarized fibers
163
What are adverse effects of class IV anti-arrhythmics?
Hypotension
| Bradyarrhythmias
164
How does digoxin work?
Digoxin binds to the Na-K-ATPase and inhibits it, this leads to increased intracellular Na, which causes the Na-Ca exchanger to move Ca into the cell to reduce intracellular Na.
Increased intracellular Ca causes increased sensitivity of the cardiac myocytes and increased contractility which leads to a decreased heart rate
165
Why is hypokalemia a risk factor for digoxin toxicity?
Digoxin binds to the Na-K-ATPase pump at the same site as potassium. When potassium is decreased, Digoxin has more readily available binding sites. This results in inhibition of the Na-K-ATPase pump which leads to increased intracellular sodium.
Increased intracellular sodium causes the Na-Ca exchanger to move calcium into the cell in order to decrease intracellular sodium. Increased intracellular calcium results in increased contractility of the heart.
This is the mechanism for why digoxin works; however, when there is less potassium we see a larger effect for the same amount of drug decreasing the therapeutic window (which is narrow to begin with
166
Name 5 things that predispose a patient to digoxin toxicity?
```
Renal dysfunction
Hypokalemia
Advancing age
Chronic lung disease
Hypothyroidism
```
167
When is magnesium indicated as an anti-arrhythmic and what are some potential adverse effects?
Indicated in torsade de points, and drug refractory ventricular tachyarrhythmias
Adverse effects: central nervous system depression, weakness, bradycardia, hypotension, hypocalcemia, QT prolongation
168
TRUE OR FALSE: Adenosine is an effective treatment for dogs with AV node dependent tachyarrhythmias
FALSE
It is ineffective at slowing AV nodal conduction in dogs
169
T/F- a recent Cochrane review reported a significant reduction in blood loss and need for blood transfusions after the use of EACA in patients undergoing major surgery?
true
170
when are antifibrinolytic drugs contraindicated?
in patients that have prothrombotic diseases- DIC, aortic thromboembolism, IMHA, Cushing's, upper urinary tract hemorrhage (obstruction can occur)
171
T/F- a recent Cochrane review found evidence for an increased incidence of thrombotic events with the use of EACA or TXA?
false
172
What is the concern re: antifibrinolytic use in cats?
can cause seizures and myocardial injury- their use is not recommended (at least use caution)
173
what is the MOA of EACA?
competitively inhibits plasminogen activation; at higher doses may directly inhibit plasmin
174
what is the half life of EACA? how is it excreted?
1-2 hrs, renal 65% and 30% hepatic metabolism then urinary excretion
175
adverse effects of EACA?
hypotension, nausea, vomiting, diarrhea, weakness, myonecrosis, rhabdomyolysis
176
MOA of tranexamic acid (TXA)?
competitive inhibitor of plasminogen activation and at higher concentrations is noncompetitive inhibitor of plasmin
Also competitively inhibits the activation of trypsinogen by enterokinases and noncompetitively inhibits trypsin and thrombin
177
half life of tranexamic acid? excreted via what route?
2-3 hours; 95% excreted unchanged in kidneys
178
T/F- tranexamic acid, TXA, is 6-10x more potent than EACA?
true
179
t/f- TXA increased mortality when given early (within 3 hours) to trauma patients with significant risks of bleeding?
false- it decreases mortality if given within 3 hours but after 3 hours increases risk of death due to bleeding
180
adverse effects of TXA?
hypotension after rapid administration, GI side effects, seizures after high doses, care in patients with renal disease
181
t/f- a recent Cochrane review did not support concerns stating that TXA causes thrombosis?
true
182
what are some other names for desmopressin acetate?
1-desamino-8-d-arginine vasopressin, DDAVP
183
what is the MOA of DDAVP?
it has no vasopressor activity (v1 receptor); it enhances antidiuretic activity and stimulation of endothelial release of factor VIII and vWF (v2 receptors); it is an altered form of vasopressin
184
what is the half life of DDAVP after IV administration?
2.5-4.4 hrs
185
t/f- the absorption of DDAVP after oral administration is reliable?
false- it is destroyed in GI tract
186
what types of veterinary patients would benefit from receiving DDAVP?
```
hemophilia A (deficiency of factor VIII), type I vWD
Does not work for type II or III vWD, uremic thrombocytopathia, congenital platelet function defects, chronic liver disease, diabetes insipidus
```
187
t/f- a recent cochrane review concluded that use of DDAVP did not reduce the need for blood transfusion in patients that do not have congenital bleeding disorders
true
188
adverse effects of DDAVP?
hypotension (rapid administration), water retention, hyponatremia, tachyphylaxis, thrombotic events, transient thrombocytopenia in dogs with type II vWD (GSP and wirehaired pointers)
189
what is the indication for use of protamine?
treatment or prevention of of bleeding due to administration of UFH or LMWH
190
MOA of protamine?
it is positively charged and combines with the negatively charged heparin, forming a protamine-heparin complex that is devoid of anticoagulant activity; it competes with ATIII for binding with heparin
191
adverse effects of protamine?
systemic hypotension (histamine release via mast cells), anaphylactic rxns (antibody and Ag-Ab complexes), severe pulmonary hypertension (complement activation and TXA2 and endothelin release), NCPE, thrombocytopenia
192
t/f- protamine dose should be doubled if some time has elapsed since administration of heparin?
false- protamine should be halved because heparin has an extremely low half life
193
what is the MOA of conjugated estrongens for shortening prolonged bleeding times?
unknown, but may increase the levels of vWF and factors VII and XII
194
what patients should be considered for treatment with conjugated estrogens?
patients with acute and subacute renal failure in combination with DDAVP
195
In what patients is recombinant factor VIIa used?
hemophilia A & B patients with antibodies against factor VIII & IX, respectively; uremia, vWD, liver disease, trauma, surgical procedures
196
what is the MOA of rFVIIa?
formation of TF-factor VIIa complex at the site of endothelial damage, which initiates coagulation & binding directly to the phospholipid membrane of activated platelets
197
what is the half life of rFVIIa?
2.7 hours
198
adverse effects of rFVIIa?
rare; thromboembolic states, type I hypersensitivity reactions
199
t/f- yunnan paiyao has been shown to markedly shorten bleeding and clotting times in experimental states in rabbits, rats, and humans?
true
200
what are some concerns about giving yunnan paiyao?
not overseen by FDA; ingredients not known; contamination with mycotoxins, heavy metals, microbial agents, pesticides
201
```
Give examples of each of the following:
alkylating agents
antibiotic chemo drugs
antimetabolites
nsaids
hormones
enzymes
platinum products
vinca alkaloids
tyrosine kinase inhibitors
```
alkylating agents - cyclophosphamide, chlorambucil, CCNU, carmustine
antibiotic chemo drugs - doxorubicin, actinomycin
antimetabolites - methotrexate, cytosine arabinoside
nsaids - piroxicam, meloxicam, deracoxib
hormones - prednisone
enzymes - L-aspariginase
platinum products - cisplatin, carboplatin
vinca alkaloids - vincristine, vinblastine
tyrosine kinase inhibitors - toceranib phosphate, masitinib
202
What is acute tumor lysis syndrome?
Complication of chemotherapy that occurs in patients with chemotherapy or radiation responsive tumors. Destruction of tumor cells leads to release of intracellular electrolytes as well as toxic by products of cell necrosis into circulation. May see renal failure, metabolic acidosis, cardiovascular collapse, vomiting, diarrhea, hyperkalemia, hyperphosphatemia, hypocalcemia, and azotemia.
203
```
When does the nadir occur for each of the following drugs?
doxorubicin
cyclophosphamide
cisplatin
carboplatin
```
doxorubicin 7-10 days
cyclophosphamide 7-10 days
cisplatin 7 and 16 days
carboplatin 11 and possibly 21 days
204
Below what neutrophil count are prophylactic antibiotics warranted?
Below 1,000 cells/ul
205
What chemotherapy drugs most commonly extravasate? What are the clinical signs and when do they occur?
Doxorubicin is the most common. Other ones that are irritating are vinca alkaloids and anthracyclines.
Clinical signs include pain, pruritus, erythema, moist dermatitis and necrosis
Signs may occur for 7-10 days with doxo, and up to 7 days with vinca alkaloids.
206
What drug can be given if doxorubicin extravasates?
Dexrazoxane
207
To what specific colitis are chemotherapy patients predisposed? What is the treatment?
Clostridial colitis
Treatment: sulfasalazine, metronidazole, ampicillin, tylosin, increased fiber content
Doxorubicin can cause hemorrhagic colitis that is responsive to metronidazole or sulfsalazine
208
Cyclophosphamide administration can result in which specific toxicity?
sterile hemorrhagic cystitis
209
What neurologic signs can be seen with each of the following drugs?
vinca alkaloids
cisplatin
5-fluorouracil
vinca alkaloids: Peripheral neuropathies such as hind limb weakness, partial paralysis, and ileus leading to abdominal pain and constipation
cisplatin: cortical blindness
5-fluorouracil: excitability, blindness, tremors, dysmetria, and death. In dogs, it can also result in excitation, seizures, and ataxia
210
What are the reported toxocities for alkylating agents?
```
Alopecia
Bone marrow suppression
Gastrointestinal toxicity
Nausea
Inappetence
Vomiting
Diarrhea
```
211
What are the reported toxocities for antibiotics that are used for chemotherapy?
```
Alopecia
Bone marrow suppression
Gastrointestinal toxicity
Nausea
Inappetence
Vomiting
Diarrhea
Necrosis, ischemia, and severe soft tissue
reaction if given perivascularly
```
212
What are the reported toxocities for antimetabolites?
```
Alopecia
Bone marrow suppression
Gastrointestinal toxicity
Nausea
Inappetence
Vomiting
Diarrhea
```
213
What are the reported toxocities for enzymes used for chemotherapy?
Anaphylaxis
214
What are the reported toxocities for platinum products?
```
Bone marrow suppression
Gastrointestinal toxicity
Inappetence
Nausea
Vomiting
Diarrhea
```
215
What are the reported toxocities for protein tyrosine kinase inhibitors
(toceranib phosphate, masitinib)?
```
Bone marrow suppression
Gastrointestinal toxicity
Inappetence
Nausea
Vomiting
Diarrhea
```
216
What are the reported toxocities for vinca alkaloids?
```
Alopecia
Bone marrow suppression
Gastrointestinal toxicity
Ileus
Peripheral neuropathies
```
217
What specific toxicity do we worry about with cisplatin?
Pulmonary edema and death in cats, nephrotoxicity in dogs
218
What specific toxicities do we worry about with doxorubicin?
Cumulative dose–related risk of
dilated cardiomyopathy in dogs, possible renal
toxicity in cats, allergic reactions in both
species, hemorrhagic colitis
219
What specific toxicity do we worry about with CCNU?
Cumulative dose–related risk of hepatotoxicity
220
What specific toxicities do we worry about with L-Asparaginase?
Pain on injection, pancreatitis,
| insulin resistance, anaphylaxis
221
How can acute tumor lysis syndome cause renal failure?
Nucleic acids released from cellular necrosis include purines, which are metabolized to uric acid. Increased levels of uric acid exacerbate metabolic acidosis and renal impairment or failure. Deposition of calcium phosphate salts in the renal tubules in addition
to the aforementioned biochemical alterations, intraluminal tubular obstruction, intravascular volume depletion, and release of malignancy-associated nephrotoxins can result in oliguric renal
failure.
222
When can we see signs of acute tumor lysis syndrome occur?
Hours to days after therapy has been administered.
223
what is the mechanism of action of beta lactam antimicrobials?
interfere with bacterial cell wall synthesis via binding to and inhibiting the transpeptidases and peptidoglycan-active enzymes (collectively referred to as penicillin-binding proteins (PBPs)
224
what is the role of penicillin binding proteins?
they catalyze the cross-linking of the glycopeptides that form the bacterial cell wall
225
t/f: beta lactams are bactericidal?
true
226
are beta lactam antimicrobials lipid soluble or insoluble?
insoluble
227
which organs do not get high concentrations of beta lactams b/c of their lack of crossing biological membranes?
testes, eyes, brain, prostate
228
how are most beta lactams excreted?
via the kidney into the urine- urine levels can be many times higher than those seen in serum
229
how are the cephalosporins classified according to Ch 176 in Hopperstein?
five generations (1-5); more gram negative specific with increasing generation among the first 3 generations
230
which types of bacteria have been known to produce a beta lactamase enzyme that inactivates the beta lactams?
staph bacteria; many gram negative rods
231
What is ESBL?
extended spectrum beta lactamase- it can hydrolyze penicillins, cephalosporins and aztreonam; many gram negative bacteria produce ESBL; it does not confer resistance to the carbapenems
232
methicillin resistant staphylococci are resistant to all beta lactam antimicrobials except ______?
the fifth generation cephalosporins
233
describe the spectrum of activity of penicillin G
gram positive, anaerobic except Staph; synergistic with aminoglycosides, drug of choice for strep, clostridial, and actinomyces infection
234
spectrum of activity of extended spectrum penicillins (amoxi and ampicillin)?
less active against gram + and anaerobic than pen G; greater effect against gram negatives
addition of beta lactamase inhibitor results in greater activity against gram negative, some gram positive anaerobes
235
spectrum of activity of antipseudomonal penicillins (ticarcillin, piperacillin)?
pseudomonas and proteus inhibition; otherwise similar to other penicillins
236
describe the activity of 1st gen cephalosporins?
cefazolin, cephalothin, cephalexin.. increased activity against some beta lactamase producing organisms; good gram positive, moderate gram negative, minimal anaerobe
237
describe the activity of 2nd gen cephalosporins?
cefoxitin, cefaclor, cefotetan, cefuroxime..... moderate gram positive, greater gram negative
238
describe the activity of 3rd gen cephalosporins?
cefotaxime, ceftriaxone, ceftiofur, cefpodoxime, cefovecin..... good gram negative, good for CNS disease
239
describe the activity of carbapenems?
broad spectrum when used as sole agent; resistance is rare
240
what is an adverse effect of the carbapenems?
nephrotoxic (imipenem >meropenem)
241
What types of bacteria are most commonly isolated from critically ill patients?
Staph pseudintermedius, other staph, E coli, Klebsiella, Pasteurella, beta hemolytic strep, Pseudomonas, Proteus, Enterobacter, Enteroccocus
242
Name a good first choice abx (empirical treatment) for Pasteurella, Strep, Actinomyces
penicillin or aminopenicillin
243
Name a good first choice abx (empirical treatment) for Enterobacgteriaceae
aminoglycosides, cephalosporins (cefotaxime, ceftazidime), ticarcillin, ampicillin-sulbactam
244
Name a good first choice abx (empirical treatment) for blood borne pathogens (Ricketssia, Ehrlichia, Hemoplasma)
doxycycline hyclate or monohydrate; fluoroquinolone as alternative
245
T/F: the treatment duration for antimicrobials should be as long as possible?
false
246
T/F: It is easier to escalate an antimicrobial rather than to de-escalate after receiving C&S results?
false- easier to de-escalate to a less expensive agent
247
In urinary tract infections, how many E coli organisms are resistant to cephalexin and enrofloxacin?
50% to cephalexin, 22% to enrofloxacin
248
Which antimicrobials are potentially effective against Pseudomonas?
fluoroquinolones, aminoglycosides, extended spectrum penicillin (ticarcillin); resistance is more likely if pt has been previously exposed to that abx
249
When you have a suspect MSRP infection, which abx may be needed?
chloramphenicol, rifampin, aminoglycosides, tetracycline
250
Diffusion of abx into tissues is usually limited by what?
Perfusion/tissue blood flow (perfusion rate-limited drug diffusion)
251
What is it called when penetration of abx into the tissue is limited by the cell's lipid membrane?
permeability rate-limited drug diffusion
252
When a drug is limited by permeability of the cell, what are the options for the drug to get into the cell?
must be lipid soluble or actively carried across the membrane to attain effective concentrations in the tissues
253
Name some examples of cells that cause permeability rate-limited drug diffusion
CNS, eye, prostate
254
T/F: modest doses of abx are often sufficient to attain high abx concentrations in renal tubules and lower urinary tract?
true; urine concentration of abx may be 100x greater than plasma concentration
255
What is a breakpoint?
The highest MIC achievable (usually a serum concentration of antimicrobial given at routine doses) that still inhibits growth of that microorganism
256
What are the three types of bacterial resistance?
1. Intrinsic: inherent feature of a microorganism that results in lack of activity of an antimicrobial drug or class of drugs. Example is pseudomonas resistance to beta lactams
2. Circumstantial: when an in vitro test predicts susceptibility but in vivo the antimicrobial lacks efficacy.
3. Acquired: change in the phenotypic characteristics of a microorganism, compared with the wild type, which confers decreased effectiveness of am antimicrobial against that microorgamism
257
Define MDR, XDR, and PDR
MDR: multidrug resistant, those not susceptible to at least one agent in three or more class of antimicrobials to which they are usually susceptible
XDR: extensively drug resistant, susceptible to only one or two classes or antimicrobials
PDR: pandrug resistant, not susceptible to all known or licensed antimicrobials
258
What is the difference between escalation and de-escalation therapy?
Escalation therapy involves selecting an antimicrobial with a narrow spectrum of activity that likely covers the pathogen causing the suspected infection
De-escalation therapy consists of the empiric administration of broad-spectrum antimicrobials aimed to cover all pathogens most frequently related to the infection
259
What is the mechanism of resistance for methicillin-resistant staphylococcus?
Acquisition of the mecA gene, which encodes an altered penicillin-binding protein, making it resistant to all beta lactams
260
For methicillin-resistant staphylococcus what is the drug of choice?
Vancomycin, or the aminoglycosides
261
What is the mechanism of resistance of enterococcus species?
Acquisition of aminoglycoside-modifying enzymes (AME) or alterations in penicillin-binding proteins (PBP5)
262
What is the drug of choice for MDR enterococcus?
It may not need to be treated if the patient is asymptomatic
If symptomatic, use either 1) combination of ampicillin and gentamicin, or 2) vancomycin
263
What are the mechanisms of acquired resistance for pseudomonas?
1. Decrease in intracellular drug entry from efflux pumps or altered membrane structure
2. Enzymes that modify or destroy antimicrobials
3. Modification of the target of the antimicrobials (DNA gyrase mutation)
264
What is the drug of choice for MDR pseudomonas?
Amikacin or a carbapenem
Combination therapy is unlikely to be effective
265
In what bacteria are extended spectrum beta lactamases most commonly found?
E. coli
Klebsiella pneumoniae
Enterobacter
266
Enterococci have a high level of intrinsic resistance to which antimicrobials?
```
cephalosporins
clindamycin
aminoglycosides
possibly fluorquinolones
TMS
```
267
Pseudomonas has a high level of intrinsic resistance to which antimicrobials?
Beta lactams (except ticarcillin, piperacillin, ceftazidime, and the carbapenems)
268
What is the MOA of dexmedetomidine?
Highly selective α2-adrenergic agonist.
Induces sedation by decreasing activity of noradrenergic neurons in the locus ceruleus in the brain stem, thereby increasing the activity of inhibitory gamma-aminobutyric acid neurons in the ventrolateral preoptic nucleus.
Twice as potent as medetomidine.
269
What are contraindications to dexmedetomidine use?
Cardiovascular disease, respiratory disorders, liver or kidney disease, shock, severe debilitation, or stress due to extreme heat, cold, or fatigue.
Has not been evaluated in dogs less than 16 weeks old and in cats less than 12 weeks old.
270
What are the side effects of dexmedetomidine?
Bradycardia, vasoconstriction, muscle tremors, transient hypertension, reduced tear production, occasional AV block, decreased respiration, hypothermia, urination, vomiting, hyperglycemia, and pain on IM injection.
Rare effects include prolonged sedation, paradoxical excitation, hypersensitivity, pulmonary edema, apnea, and death from circulatory failure.
271
Name some drug interactions with dexmedetomidine
Dose reduction may be indicated when used with anesthetics, opiates, sedatives, and hypnotics. If used with atropine or glycopyrrolate arterial blood pressure and heart may significantly increase which is not recommended.
Do not use epinephrine to reverse effects of dexmedetomidine.
Yohimbine will reverse the effects but atipamezole is preferred.
