Toxicology and Extracorporeal therapies (SACCM + Dobratz) Flashcards

Question

Over the counter urine ilicit drug screening tests are used for detection of….. What is the disadvantage?

Answer 1

- They test for: heroin, cocaine, THC, methanphetamines, PCP - Can give false positive if patient is on: opioids, trazodone, lidocaine, diphenhydramine, NSAIDS, others - Can give false negative for some THC metabolytes

Answer 2

Composition: - Medium to long chain tryglicerides (soybean oil, saffloer oil, etc) - Glycerin - Phospholypid emulsifier Metabolism: - tipically cleared by skeletal muscle, myocardium, splanchnic viscera and SC tissues where they are broken into glycerol, free fatty acids and choline to be used as energy by the tissues

Answer 3

Is the measure of the solubility of a compound between two solvents, one hydrophilic and one lipophilic

Answer 4

- Intermitent hemodialysis (IHD) - Continuous Renal Replacement therapy (CRRT) - Hemoperfusion (HF) - Total plasma exchange (TPE)

Answer 5

- Diffusion = movement of solute across semi-permeable membrane driven by transmembrane concentration membrane. - convection (aka. ultrafiltration) = movement of water and solvent drag across permeable membrane that occurs due to transmembrane pressure gradient. Convection allows for removal of middle (MW 500- to 60,000 Da) and large (MW > 60,000 Da) molecular weight solutes during dialysis

Answer 6

- IHD - Continuous Venovenous Hemodyalysis (CVVHD) --> mode or CRRT - Peritoneal dyalysis

Answer 7

- Continuous venovenous hemofiltration (CVVHF) --> mode of CRRT - SCUF

Answer 8

- Continuous venovenous hemodiafiltration (CVVHDF) | - Application of ultafiltration during IDH and PD

Answer 9

- Pore size - surface area - thickness - membrane material

Answer 10

- Rapid solute removal - Smaller molecular weight water-soluble intoxicants are removed most efficiently by IHD. - IHD + charcoal hemoperfusion (CH) allows for removal of large solutes.

Answer 11

- slow and continuous solute removal - better tolerated than IHD in hemodynamically unstable patients, however, rapid toxin removal is almost always more ideal, and when performed by an experienced RRT team, IHD rarely leads to hemodynamic instability. - better clearance of larger molecular weight solutes due to: * * diffusive and convective properties * * membranes used in CRRT are often more permeable than IHD membranes

Answer 12

solutes with a large Vd that are redistributed into the IV compartment have better clearance with CRRT compared with shorter IHD treatments

Answer 13

- Toxins with high protein binding capacity | - Toxin with large molecular weight (up to 40.000 Da)

Answer 14

- Hypocalcemia - Hypoglycemia - Thrombocytopenia * *Due to non selective properties - priming volume of commercially available CH cartridges ranges from 150 ml to 240 ml  can lead to hemodynamic instability in < 10 kg animals - CH is performed in tandem with HD to decrease or eliminate these potential side effects: blood passes through the dialyzer after contact with HF cartridge  normalization of electrolyte abnormalities. - priming the extracorporeal circuit with blood, can be considered when treating smaller patients

Answer 15

- Separates the blood into its various components either by centrifugation or filtration - The plasma component of the blood is removed and replaced with a replacement s/n: ?colloid (albumin, Hetastarch, or plasma) ? or a combination of crystalloid and colloid

Answer 16

- independent of the toxin size and protein binding - Removes the inciting toxin and toxic byproducts: * * mediators of inflammation and other endogenous substances - Ideal for treatment of intoxications shortly after ingestion and for those toxins that have a small volume of distribution (Vd), because only the blood compartment is being treated and procedures are performed over a shorter period

Answer 17

sum of all compartmental volumes that account for the total toxin distribution at an equilibrated state

Answer 18

Equal or less than the blood volume because toxin removal occurs directly from the intravascular compartment. - For toxins with a large Vd, concentration within the intravascular compartment decreases as the solute distributes between the body fluid compartments (intercompartmental equilibration

Answer 19

The characteristics of the toxin as well as the Vd | - Ex. a highly lipid-soluble, large-MW toxin with large Vd is likely to have a slower compartmental equilibration time.

Answer 20

Plasma [ ] of the intoxicant may return to a toxic level as intercompartmental equilibration occurs --> after cessation of toxin removal via ECT, as the toxin redistributes from the other compartments into the IV space ** Ex. Phenobarbital

Answer 21

The free fraction of drug increases but can re-equilibrate in tissue compartments and result in a higher Vd

Answer 22

- Low molecular weight (62Da) and non-protein binding capacity --> approx. 90 to 100% of the toxin and metabolites can be removed from circulation with a single session of IHD (with traditional medical management the toxic metabolites are not removed) - ethanol is added to the dialysate to inhibit ongoing metabolism of EG to its more toxic metabolites (conversion of glycoaldehyde by alcohol dehydrogenase)

Answer 23

small size, highly protein bound (90-95% to mostly albumin) and small Vd - Some undergo enterohepatic recirculation (diclofenac, indomethacin, sulindac, etodolac, ibuprofen, naproxen, piroxicam, meloxicam, carprofen)

Answer 24

- The high protein binding property of the drug favors the use of CH over conventional HD - in veterinary medicine, hemoperfusion is almost always performed simultaneously with HD to prevent the potential complications associated with CH. - The large extracorporeal volume needed to perform combined HD/HP limits the application for this modality to larger patients. - It is difficult to determine when a HP cartridge is saturated, although in the author’s experience this typically occurs 4 to 6 hours after the start of therapy

Answer 25

- It is an ideal toxin to remove via ECT due to it's small Vd, however it's rapid absorption and short plasma half life limit the benefit of the treatment - Has high affinity for AC

Answer 26

- when severe intoxication with long-acting barbiturates occurs, ECTs can be used to decrease hospital stay and to avoid complications such as aspiration pneumonia that can occur in severely obtunded or comatose patients - Given the large Vd, rebound of drug into the intravascular space is likely to occur after treatment with HD/HP, with resultant recurrence of clinical signs. In these situations, multiple or prolonged ECT sessions may be indicated

Answer 27

IDH - has mainly diffusion mode and a bit of convection CRRT (Prismaflex machine common in VM) - Predominantely convection - Combines up to 4 modes of diffusion and convection: **Slow coninuous untrafiltration (SCUF) (convection)--> ultrafiltrate gets discarded, hemoconcentrated blood goes back to patient **CVVH (convection)--> A a balanced electrolyte solution replaces the ultrafiltrate ** CVVHD (diffusion)--> similar to IHD but the rate is very slow **CVVHDF --> combines diffusion and convection, the grade of convection and diffusion can be adjusted independently

Answer 28

- Severe electrolyte/acid-base disturbances non responsive to medical management/ AKI (BUN >100mg/dL, creat >10mg/dL) - Fluid overload (specially when anuria/oliguria are present) - CHF - Refractory hyperkalemia - compromised patients secondary to uremic toxemia

Answer 29

TRUE. Large pores, 100 to 200 A˚in diameter, correspond to clefts in the endothelium and allow the transport of macromolecules such as albumin. They are present in very small numbers, accounting for less than 0.01% ofthe total pore surface area. Small pores, 20 to 25 A˚ in diameter, also correspond to clefts in the endothelium. They present in large numbers, representing more than 90% ofthe pore surface area, and allow the passage of low molecular weight substances such as urea. creatinine, and glucose. Ultra small pores, 4 to 6 A˚ in diameter, are aquaporin I channels found within peritoneal capillary and mesothelial cells, and transport only water

Answer 30

Ultrafiltration is the process of plasma water removal from the intravascular compartment (and ultimately from the interstitial and intracellular spaces as redistribution occurs)

Answer 31

Contraindications for PD in veterinary medicine include peritonitis, recent abdominal surgery, and hypoalbuminemia.

Answer 32

- Diffusion - Convection (Solvent drag) --> when solutes are carried along with the bulk flow of water during ultrafiltration (not very relevant in PD) - ultrafiltration --> removal of fluid (water) during PD --> desired when performing PD in animals that are overhydrated

Answer 33

- AKI, severe uremia - Toxicities where toxin is highly diffusible (EG, ethanol. Barbiturates) severe metabolic disturbances (hyperkalemia, hypercalcemia, hepatic encephalopathy) - life threatening fluid overload

Answer 34

- 1.5% dextrose. - 2.5% - 4.25%

Answer 35

Adding dextrose to lactated Ringer’s solution can make a suitable dialysate solution. Osmolality should closely approximate that of the patient, and the dextrose concentration should be at least 1.5%. Adding 30 mL of 50% glucose to 1 L of lactated Ringer’s solution will result in a 1.5% dextrose solution. - Heparin (250 to 1000 U/L) should be added to the dialysate for the first few days after catheter placement to help prevent occlusion of the catheter by fibrin deposition. This heparin is minimally absorbed by the patient’s circu- lation and is unlikely to prolong clotting times.

Answer 36

Dialysate is infused at a dosage of30 to 40 mL/kg during a 10-minute period.12,14,39,57 The dialysate is allowed to remain in the peritoneal cavity for 30 to 40 minutes (dwell time) and then is drained into a collection bag by gravity during a 20- to 30-minute period. A 90% to 100% recovery of dialysate is expected. This process is repeated continually, and the dialysate formula and dwell times are adjusted every 12 to 24 hours according to the animal’s need.

Answer 37

Although more concentrated dextrose solutions allow for effective fluid removal from the patient, these concentrates are more likely to lead to secondary peritonitis and dysfunction of the peritoneal membrane - Glucose activates the polyol pathway and the secretion of transforming growth fac- tor-b1 (TGF-b1), monocyte chemoattractant protein-1 (MCP-1), and fibronectin. in vitro data suggest that glu- cose is involved in the development of peritoneal fibrosis. Glucose is likely to be involved in the development of peritoneal neoangiogenesis. - A third mechanism by which glucose can damage the peritoneal tissue is by inducing nonenzymatic glycosylation oftissue proteins, which leads to the formation of advanced glycosylation end products (AGEs). The depo- sition ofAGEs in the vascular wall also leads to ultrafiltration failure

Answer 38

- Systemic heparinization --> IHD | - Regional citrate --> for CRRT

Answer 39

In severely uremic patients, rapid removal of uremic toxins should be avoided to prevent dialysis disequilibrium syndrome. Rapid removal of osmotically active solutes from the blood compartment creates osmotic pressure gradients between the blood, extravascular, and intracellular compartments. This gradient allows plasma water to shift from the vascular compartment and into the intracellular compartments. When this phenomenon occurs in brain tissue, sec- ondary swelling occurs and this can lead to irreversible neurologic damage or death

Answer 40

- when severe uremia is present, initial treatments must be designed to achieve slow solute removal. (CRRT?)

Answer 41

- 30-40ml/kg - In PD, precise measurements of dialysate inputs and outputs must be recorded to avoid overhydration of the patient - If fluid balance becomes positive or returning volume decreases to less than 90% of what was administered, the dialysate should be changed to encourage ultrafiltration

Answer 42

The intensive prolonged treatments required with CRRT and the need to have a dedicated and trained technical staff for the duration of the treatments make it difficult to carry out quality treatments in many veterinary practices. In addition, the cost for premade dialysate can become cost-prohibitive when high dialysate flows were required. In addition, since CRRT is not designed to be a long-term treatment modality, it is necessary to have facilities available to provide longer-term care for patients that remain dependent on RRT

Answer 43

I - considered standard of care for that condition (ex. Myastemia gravis) II - considered suppoertive therapy in combination with other therapies (ex. Amanita poisoning) III - condition in which controlled trials are limited or their results inconclusive IV - condition in which therapy appeared to be ineffective or harmful

Answer 44

- One - For most higher-molecular-weight substances, such as immunoglobulins, the efficiency of patho- logic substance removal is not increased when more than 1 or 1.5 plasma volumes are exchanged in a single treatment.

Answer 45

- Myastenia gravis - IMHA ** Although case numbers are low, the anecdotal success in these cases is promising

Answer 46

Use of TPE allowed patients that were previously crossmatch incom- patible due to severe agglutination to receive blood transfusions. likely because of a reduction in antibody load - Use of TPE allowed for successful control of disease with the same immunosuppressive protocols that had been previously unsuccessful in those patients

Answer 47

After a tissue has been damaged, arachidonic acid is released from cell membranes, precipitating a chain of events known as the arachi- donic acid cascade. Two enzyme groups metabolize arachidonic acid: the lipoxygenases (LOX) and the cyclooxygenases (COX). Products from the LOX cascade include leukotrienes and chemotactic factors. Products of the COX cascade include prostacyclin, thromboxanes, and prostaglandins.

Answer 48

Important in maintaining local blood supply to tissues

Answer 49

- Continuously produced (constitutive) prostaglandins are required for the normal function of the brain, kidneys, gastrointestinal tract, primary hemostatic system, and reproductive system. - Inducible prostaglandins are produced in response to tissue injury. They escalate the inflammatory response and increase peripheral nerve sensitization; they also have protective actions and play a role in tissue repair

Answer 50

- most COX-1–induced prostaglandins are constitutive and have homeostatic effects, some are also produced in response to tissue injury. - although many prostaglandins produced by COX-2 are inducible, there are constitutive COX-2 prostaglandins found in the brain, intestine, and kidneys in many species. COX2 appears to be constitutive in canine pyloric and duodenal mucosa and these products are important for healing of gastoduodenal ulcers

Answer 51

- Dual acting -->Aspirin, ketoprofen, tepoxalin | - COX2 selective: carprofen, meloxicam, deracoxib, firocoxib

Answer 52

- COX1 induced prostaglandins in gastric mucosa have protective effects --> mucous production and enhance local blood flow --> COX 2 is stimulated when damage to the gastric mucosa occurs and produces prostaglandins important in mucosal healing --> NSAIDS can inhibit all these - Some NSAIDs, such as aspirin, can cause direct injury to the gastric mucosa by disrupting surface phospho- lipids, allowing gastric acid to penetrate directly to the cells in the wall of the stomach

Answer 53

NSAIDs are weak acids that become lipid soluble in the highly acidic environment in the stomach. This allows them to penetrate easily into gastric cells, where they become trapped in the relatively more alkaline environment. This leads to a high local concentration of NSAIDs in the gastric mucosa and may be an explanation for adverse effects occurring in the gastrointestinal system at lower doses than in other organ systems.

Answer 54

- Inhibition of prostaglandins production by the juxtaglomerular apparatus --> inhibitis prostaglandin mediated local vasodilation of afferent arteriole in cases where GRF is decreased --> decreased renal blood flow -->AKI - Inhibition of renin release by the JGA (this process is mediated by COX1-COX2 enzymes

Answer 55

FALSE - NSAID use has been associated with an increase in liver enzymes and hepatocellular injury in some patients. This toxicity does not depend on dose or duration of treatment and therefore is classified as an idiosyncratic reaction. --> typically occurs within the first 3 weeks of administration, but can happen after months/years.

Answer 56

- COX-1 --> promotes production of TXA2 --> more platelet agregation and vasoconstriction - COX-2 --> promotes production of PGI2 (prostacyclin) --> vasodilation and inhibits platelet aggregation

Answer 57

TRUE. Platelets lack a nucleus and are unable to synthesize new COX enzymes

Answer 58

Protein-bound drugs --> other antiinflammatory agents, warfarin, phenytoin, penicil- lins, and sulfonamide antibiotics. NSAIDs can also increase plasma levels of digoxin and can decrease the efficacy of furosemide.

Answer 59

FALSE -Drugs that induce cytochrome P450 metabolic pathway in the liver (e.g., phenobarbi- tone) can increase NSAID metabolism, reducing their analgesic efficacy

Answer 60

- isostenuria can be indicative of acute renal insuficiency - casts in urine sediment can indicate renal tubular injury as an early sign of toxicity - proteinuria can indicate glomerular damage

Answer 61

In most cases of medication overdose, treatment duration depends on the half-life of the drug that has been ingested; treatment should continue until at least three half- lives have passed.

Answer 62

Metoclopramide should be avoided because this dopamine antagonist could decrease renal blood flow.

Answer 63

Papillary necrosis and interstitial nephritis

Answer 64

PGE1 analog

Answer 65

Two dogs that ingested potasium bitartrate (cream or tartar) developed acute azotemia and isostenuria, one ingested 2 tea spoon of cream of tartar, the second one ingested homemade play dough made with cream of tartar. Second dog died and necropsy revealed changes similar to the ones reported in raising toxicosis --> cortical tubular degeneration, necrosis, and mineralization, with some evidence of regeneration. - Potassium bitartrate is the salt of tartaric acid, and both potassium bitartrate and tartaric acid are uniquely present in high concentrations in grapes and tamarinds. - Interestingly, the ASPCA Animal Poison Control Center has had reports of severe vomiting and acute renal failure in dogs following large exposures to tamarinds, which are also uniquely high in tartaric acid.

Answer 66

- proximal tubular epithelial cells necrosis, edeme and tubular obstruction in the kidneys - pancreatitis - vomiting, lehtargy and hypersalivation appear within 1 to 5 days (some as soon as 1-3h) - seizures, ataxia (40% of cats)

Answer 67

- 25-60% - 53% - 30 days

Answer 68

- 50-100% | - 50%

Answer 69

only reversals for opioids, benzodiazepines and alpha-2 agonist. Other than than is supportive and sympthomatic care.

Answer 70

>20mg/kg (dogs) and 1600mg/kg IV respectively

Answer 71

257mg/kg PO / 61mg/kg IV (mice)

Answer 72

85mg/kg PO or 50mg/kg IV (dogs)

Answer 73

- Atipamezol - Yohimbine - Tolazoline **last 2 are less specific and have more side effects

Answer 74

For patients that ingest baclofen or carisoprodol, only one dose of activated charcoal with a cathartic is necessary because these drugs do not undergo enterohepatic circulation. For the remaining muscle relaxants, efficacy of multidose activated charcoal regimens has not been established

Answer 75

- Diazepam, despite also being a γ-aminobutyric acid agonist, is the drug of choice for baclofen- and carisoprodol-induced seizures - if carisoprodol has been ingested, barbiturates are not recommended for seizure control because they may compound the CNS depression

Answer 76

The prognosis for toxicity with most of these muscle relaxants in veterinary medicine is unknown. For symptomatic patients with baclofen toxicity, resolution of clinical signs may take several days in severe cases, but if adequate supportive care and monitoring are available, the prognosis is generally good

Answer 77

- Natural = codeine, morphine | - Synthetic = fentanyl, methadone, hydrocodone, hydromorphone, heroin

Answer 78

Opioid receptor activation results in inhibition of adenyl cyclase activity, activation of receptor-operated potassium currents, and suppression of voltage- gated calcium currents. These effects cause hyperpolarization of the cell membrane, decreased neurotransmitter release, and reduced pain transmission

Answer 79

- morphine-like opioid agonists - opioid antagonists - mixed agonist-antagonists - partial agonists

Answer 80

FALSE - highly lipid-soluble drugs (e.g., codeine, fentanyl, and heroin), onset of action occurs more rapidly, and the pharma- cologic effects resolve earlier. Drugs that are less lipid soluble, such as morphine, move less rapidly and therefore take longer to be effec- tive and may have a longer duration of action

Answer 81

Opioids may lead to hypoventilation and hypercapnia, which cause cerebral vasodilation and increased intracranial pressure.

Answer 82

- In the developing fetus, opiates pass more easily into the CNS because the blood-brain barrier is not fully developed. - Small amounts of opioids also are distributed into the milk of nursing mothers.

Answer 83

- Monoamide oxidase inhibitors (MOAs) --- fentanyl, meperidine, tramadol, methadone, and dextromethorphan are weak serotonin reuptake inhibitors and have been involved in serotonin toxicity reactions with MAOIs - Phanotiazines - Erythromycin - Cimetidine

Answer 84

There is a classic triad seen with opioid toxicity: CNS depression, respiratory depression, and miosis in dogs. Cats typically develop mydriasis.

Answer 85

from µ-related stimulation of the visceral nuclei of the oculomotor nuclear complex and the parasym- pathetic nerve that innervates the pupil

Answer 86

False - Opioids may alter the thermoregulatory response. Hypothermia is seen commonly in dogs, whereas hyperthermia may occur in cats

Answer 87

- reduction in responsiveness to CO2 in the brainstem respiratory center as well as the centers that regulate respiratory rhythm. - Areas of the medulla oblongata that control ventilation (nucleus tractus solitarius and nucleus ambiguus) have many opioid binding sites, and these respiratory neurons are inhibited by opioid receptor agonists.

Answer 88

by resetting the thermoregulatory center, so the animal attempts to lose heat by increasing the respiratory rate, despite a normal to low body temperature

Answer 89

when given IV , may cause histamine release leading to peripheral dilation (arterial and venous) and bradycardia. Cutaneous signs include itching, warmth, and urticaria

Answer 90

They stimulate chemoreceptor triggering zone

Answer 91

- Decreasedlower esophageal sphincter tone - Increase tone and decreased propulsive activity of small intestines - Decreased motility - lower small intestinal secretions and enhance intetsinal fluid absorption * *constipation - Morphine has been associated with spasm of sphincter of Oddi --> contraindicated in obstructive biliary or pancreatic disease

Answer 92

- At high doses, opioids may increase ureteral tone, bladder tone, and external sphincter tone, leading to urinary retention. - µ-agonist increase ADH release --> reduced urine production, increased USG

Answer 93

yes, particularly those drugs that can have delayed absorption such as loperamide and sustained-release morphine products.

Answer 94

sigma --> responsible for autonomic stimulation, dysphoria, hallucinations

Answer 95

- competitively binds opioid receptors κ, δ, and, particularly, µ. It has a greater affinity for receptors than do the agonists. - It is highly lipophilic and moves rapidly into the CNS. - usually has an onset of action of 1 to 2 minutes when given intravenously. - duration of action ~ 45 to 90 minutes. - dose for dogs and cats = 0.01 to 0.04 mg/kg. IV,, IM, SC, IO, ET - Naloxone may have a shorter duration of action than most opioids, and repeated doses or a continuous infusion may be necessary.

Answer 96

- due to reuptake inhibition of norepinephrine, serotonin and dopamine - There is stimulation of endogenous catecholamine release having direct effects in the myocardium and CNS

Answer 97

- Amphetamines - methamphetamines - serotonergic drugs - caffeine - mycotoxins - strichnine - metaldehyde - Pheochromocytoma

Answer 98

- sympathomimetic stimulant due to inhibition of MAO(Monoamide Oxidase) and direct cathecholamine release: * * inhibitis reuptake of serotonin * * direct stimulation of dopamine and serotonin receptors

Answer 99

- Toxicity is due to the psychoactive compound delta-9-tetrahydrocannabinol (THC). - “Hashish” refers to the highly concentrated resin from the flowering portion of the plant.

Answer 100

11-hydroxy-delta- 9-THC

Answer 101

- CB1 --> Located in CNS | - CB2 -> Located in peripheral tissues

Answer 102

acetylcholine, glutamate, GABA, norepinephrine, dopamine, 5-HT

Answer 103

TRUE. dog urine may contain altered THC metabolites not detected via human drug-screening kits, making their use controversial

Answer 104

- doses over 0.1g/kg --> massive release of insulin and hypoglycemia for 12-48h - doses >0.5g/kg --> hepatic necrosis and fulminant liver failure in 9 to 72h post-ingestion

Answer 105

- caffeine | - theobromine

Answer 106

Pancreatitis

Answer 107

onions, leeks, chives and garlic (cebollas, puerros, cebollines y ajo)

Answer 108

- Hemolysis - Anemia - Heinz bodies - Methemoglobinemia

Answer 109

- abdominal distention - GI obstruction - respiratory and vascular decompensation - Ethanol production due to yeast fermentation --> signs of alcohol toxicity (CNS depression, ataxia, severe cases can require mechanical ventilation

Answer 110

Metaldehydes - signs: muscle tremors, hyperestesia, tachycardia, hyperthermia, severe neuro signs (seizures), respiratory failure - Full recovery can take up to 3 days in severely affected animals, most of them recover within 24h

Answer 111

- local coagulative tissue necrosis - mouth --> pain, dysphagia, vomiting, ulcers - eyes: corneal ulceration/melting

Answer 112

Acids are some of the few toxins where decontamination is not advocated due to the risk of worsening corro- sive injury. Initially, administering water or milk to the patient may dilute the product and limit the effects of exposure. Following this, treatment is mostly sympto- matic and geared towards pain management. For dermal or ocular exposures, flushing with copious amounts of water for over 15 minutes is recommended.

Answer 113

These agents will cause severe corrosive injury without associated pain, which is why clinical signs may not immediately be apparent. Clinical signs that do develop are often related to the underly- ing mucosal damage caused to the gastrointestinal tract, which can be severe enough to cause perforation.

Answer 114

- Zinc - Copper - Zinc - IV hemolysis

Answer 115

- Water administration to delay the chance or internal corrosive damage (most of batterias contain components alkaline in nature) - Feeding a bulky diet may help the bateri to pass - Sx or endoscopy for removal

Answer 116

- They can attract to each other from different segment of bowel and cause pressure necrosis and subsequent septic peritonitis

Answer 117

L- type voltage sensitive calcium channels

Answer 118

- N-type -->neuronal - T-Type --> transient - L-type --> long-lasting --> they have a prolonged opening time and are high conductance (large amounts of Ca can pass rapidlythrough them and cause sudden changes in intracellular Ca)

Answer 119

Atria, vascular smooth muscle, skeletal muscle ** in cardiac and skeletal muscle the density of L- channels is higher in the t-tubules than in the surface sarcolema….??

Answer 120

- phenylalkylamines (e.g., verapamil) - benzothiazepines (e.g., diltiazem) - dihydropyridines (e.g., amlodipine). * * The structural differences between the classes allow them to associate with distinct binding sites on the calcium channel, resulting in varying potency and tissue affinities * * All three types of calcium channel blockers exert the majority of their effects on cardiac myocytes, pacemaker cells, and vascular smooth muscle

Answer 121

Phase 2 of the action potential

Answer 122

- In cardiac smooth muscle = within Purkinje cells and myocytes, opening of the L-type calcium channels in response to membrane depolarization increases calcium conduc- tance (phase 2 of the action potential). This inward flow of calcium triggers the release of additional calcium into the cytoplasm from the sarcoplasmic reticulum. Intracellular calcium binds to troponin, changing its conformation and enabling cross bridging of actin and myosin and subsequent contraction of the muscle to occur - In vascular smooth muscle = opening of calcium channels increases the cytosolic calcium concentration. This calcium interacts with calmodulin, leading to phosphorylation of the myosin light chain and subsequent actin-myosin binding. This results in smooth muscle contraction and vasoconstriction

Answer 123

Calcium channel blockers prevent the rise in intracellular calcium needed for formation of the calcium-calmodulin complex and thus cause dilatation of systemic and coronary arteries and arterioles. Veins have less smooth muscle in their wall, thus, at therapeutic concentrations, calcium channel blockers have minimal effects on the venous system.

Answer 124

The beta cells (B2) of the pancreatic islets, which produce insulin, also contain L-type calcium channels. Calcium influx into pancreatic islet cells via L-type channels is required for insulin release. High doses of calcium channel blockers may induce insulin resistance, which causes serum glucose levels to rise, while intracellular glucose stores fall.

Answer 125

Kidneys and adipose tissue.

Answer 126

- sinus and av nodes | - myocardium

Answer 127

Smooth muscle of: - bronchial wall - vascular walls (coronary, hepatic, skeletal arteries) - Pancreas - GI tract - Reproductive tract

Answer 128

B1-B2: - Propanolol - Sotalol Specific /B1: - Esmolol - Atenolol

Answer 129

β-receptor in the cardiac nodal cell membrane or in the cardiomyocyte cell membrane stimu- lates the membrane-bound enzyme, adenyl cyclase, which raises the intracellular concentration of cyclic AMP. Cyclic AMP activates protein kinases that phosphorylate the L-type calcium channel, increasing myocellular calcium entry, which then triggers the release of more calcium from the sarcoplasmic reticulum. This calcium interacts with the myocardial contractile machinery and produces systole.

Answer 130

Protein kinases phosphorylate a protein, phospholamban, which causes the sarcoplasmic reticulum to take up calcium more rapidly, allowing relaxation (diastole).

Answer 131

- renin - renin - aldosterone

Answer 132

- hepatic - hepatic - Propanolol

Answer 133

- kidney | - Renal

Answer 134

Esmolol is water soluble but does not accumulate in animals with renal disease because it is metabolized by erythrocyte esterases.

Answer 135

FALSE. Is the opposite.

Answer 136

In patients with heart failure, chronic increases in circulating catecholamine concentrations and increased sympathetic nervous system activity cause down-regulation of β-adrenergic receptors. Fewer receptors are present to which a β-blocker may bind. Despite decreased numbers of receptors, many patients with com- promised myocardial function rely on stimulation of remaining β-receptors to maintain myocardial contractility. In these circum- stances, acute administration of medium to high doses of a β-blocker can result in lethal decreases in contractility and heart rate.

Answer 137

- Lower aldosterone due to decreased catecholamine-induced release of renin in B cells of the kidneys - Decreased uptake of K by the cells --> Normally, agonist binding to the β2-adrenergic receptor stimulates the formation of cyclic AMP, which acts through protein kinase A to phosphorylate and activate the Na+/K+-ATPase pump, leading to the influx of potassium into cells. Competitive inhibition of the β2 -receptor by β-blockers decreases Na+ /-K+ -ATPase function and thus reduces potassium uptake by cells resulting in hyperkalemia.

Answer 138

Studies have shown that calcium blockage inhibits alveolar fluid clearance by interfering with transepi- thelial sodium and potassium transport. Combined with excessive fluid therapy during resuscitation, selective precapillary vasodilation may result in pulmonary transudation.

Answer 139

Yes, can be administered every 4 to 6 hours for two to four repeated doses if a sustained-release product was ingested.

Answer 140

Elimination of calcium channel blockers and lipid-soluble β-blockers (e.g., propranolol) via extracorporeal removal procedures (e.g., hemodialysis, hemoperfusion) is ineffective because these compounds are highly protein bound and have large volumes of distribu- tion. It may be possible to remove water-soluble β-blockers (e.g., atenolol and esmolol) using hemodialysis.

Answer 141

TRUE - In animals with moderate to severe β-blocker intoxication, β-agonist drugs may not be effective because most adrenergic receptors are blocked.

Answer 142

(1) Ca2+ enters the cell through voltage gated L-type Ca2+ channels. It is then pumped into the sarcoplasmic reticulum via the sarcoplasmic endoplasmic reticulum Ca2+ -ATPase (SERCA). In the sarcoplasmic reticulum the Ca2+ becomes bound to the high-capacity Ca2+ binding protein calsequestrin (CalS). The stored Ca2+ is released from the sarcoplasmic reticulum when the Ca2+ activated Ca2+ channel is opened. The released Ca2+ pairs with troponin to cause muscle contraction via actin and myosin fibers. (2) EPI (epinephrine) binds and stimulates β-receptors that are not occupied or blocked by a β-blocker (BB). This in turn activates the attached Gs protein that activates adenylate cyclase (AC). AC catalyzes the conversion of adenosine triphosphate (ATP) to cyclic adenosine monophosphate (cAMP). This then activates protein kinase A (PKA), which stimulates the opening of dormant Ca2+ channels thus enhancing the release of Ca2+ from the sar- coplasmic reticulum. (3) Glucagon bypasses the β-receptor and acts directly on the Gs protein, stimulating conversion of ATP to cAMP. Thus glucagon can enhance myocardial contractility, heart rate, and atrio- ventricular conduction. 4) Insulin improves the outcomes of β-blocker and calcium channel blocker toxicity via its positive inotropic effects and its positive effects on myocardial carbohydrate metabolism"

Answer 143

The sarcoplasmic endoplasmic reticulum Ca2+ -ATPase (SERCA). Pumps Ca into the sarcoplasmic reticulum.

Answer 144

In high concentrations, calcium channel blockers inhibit mitochondrial calcium entry at the sarcolemma and mitochondrial membrane, which in turn can decrease pyruvate dehydrogenase activity. Pyruvate cannot enter the Krebs cycle and lactate accumulates, producing a metabolic acidosis.

Answer 145

MOAIs (Monoaminde oxydase inhibitors) inhibit breakdown of serotonin by inhibiting this enzyme.

Answer 146

Amphetamines

Answer 147

selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs)

Answer 148

Enterochromafin cells and myenteric plexus of the GI tract

Answer 149

Dense granules, platelet agreggation

Answer 150

Vasoconstriction, uterine contraction, intestinal peristalsis, bronchoconstriction.

Answer 151

midline raphe nuclei of the lower pons and medulla

Answer 152

hydroxylation and decarboxilation of the essential aa tryptophan by tryptophan hydroxylase

Answer 153

After release into synaptic cleft there is an active reuptake mechanism and serotonin get inactivated by the monoamide oxidase to form 5-hydroxyindoleacetic acid. This substance is then eliminated in the urine.

Answer 154

Hyperexcitability and vomiting… followed by ataxia, lethargy and tremors.

Answer 155

Disruption of Na-K pump.

Answer 156

- neurologic (mydriasis, restlessness, ataxia, somnolence, tremors, transient blindness, hyperstesia, seizures, paresis, coma) - GI (vomit, diarrhea, abdominal pain, ptyalism, flatulence, bloat) - Cardiac (tachycardia, arrhythmias) - Hyperthermia

Answer 157

~15mg/kg (therapeutic doses fallin in the range of 2-4mg/kg)

Answer 158

- Toxic doses dogs: (0.3-50mg/kg) * *Mild: 1-3mg/kg --> lethargy, salivation * * Moderate: 8-10mg/kg --> tremors, lethargy * * Severe: >25mg/kg --> seizures - 100mg/kg dogs; 50mg/kg cats

Answer 159

yes --> charcoal q6h indicated

Answer 160

Excessive concentration of epinephrine and norepi. / Tx with short acting B-blocker (esmolol 200-500mcg/kg IV) or Nitroprusside (0.5 - 3 mcg/kg/min)

Answer 161

Cyproheptadine 5HT1A and 5HT2 receptor antagonist 1.1mg/kg dogs, 2-4mg/kg cats q4-6h if oral route not possible or patient received AC ---> tablets can be crushed and given rectally Chlorpromazine 5HT2 receptor antagonism 0.2-0.5mg/kg IV, IM, SQ q6h can cause sedation and hypotension

Answer 162

TRUE, not enough evidence to support regular use.

Answer 163

2, 7, 9, 10

Answer 164

Activation of coagulation factors II, VII, IX, and X (the vitamin K– dependent factors) requires reduced vitamin K (hydroquinone) for posttranslational γ-carboxylation. Activation of these factors leads to oxidation of reduced vitamin K to inactive epoxide. The enzyme vitamin K reductase catalyzes the conversion of inactive epoxide back to active hydroquinone. Anticoagulant rodenticides antagonize the action of vitamin K epoxide reductase, so levels of hydroquinone decrease.

Answer 165

As the vitamin K–dependent factors become depleted.

Answer 166

warfarin-based rodenticides (first generation) now are used rarely; they have been replaced by the second-generation anticoagulants. Second-generation anticoagulants include the coumarin-based generics: brodifacoum, difenacoum, and bromadiolone and the indandiones: diphacinone (also called diphenadione) and chlorophacinone. The second- generation anticoagulants retain the same basic nucleus, but the chemical structures were selected for increased potency (single lethal feeding potential), longer duration of activity, and efficacy against resistant rodents.

Answer 167

48 hours --> Factor VII levels will be depleted after 48 hours, resulting in a prolongation of the PT; however, this is not enough time for depletion of the other factors that would result in clinical bleeding

Answer 168

Only 8.3% of dogs required vitamin K1 therapy, and none of them had adverse events develop during the time period between ingestion and starting vitamin K1 therapy.

Answer 169

Proteins Induced by Vitamin K Antagonism thought previously to be a more specific test for diagnosing However, it can be elevated with other disease processes, particularly severe liver disease and/or malabsorption and maldigestion syndromes. One study found that performing a PT and a PIVKA simultaneously added no additional diagnostic information.

Answer 170

anticoagulation rodenticide screens using spectrophotometry (available at veterinary laboratories), which can demonstrate quantitatively the presence of the toxin in whole blood

Answer 171

FALSE - There is better bioavailability of vitamin K1 when ingested, so therapy should be switched from subcutaneous to the oral route as soon as possible

Answer 172

- cholecalciferol - 25-hydroxycholecalciferol - 1,25-dihydroxycholecalciferol

Answer 173

Acute kidney injury * * Hypercalcemia --> how? * * soft tissue mineralization * * Dehydration/hypoperfusion Cardiac arrhythmias: * * mineralization of the heart * *changes in the ratio of intracellular-to-extracellular ion concentrations * * increase in the depolarization threshold.

Answer 174

Inhibition of ADH

Answer 175

- Neoplasia/hypercalcemia of malignancy - Hypoadrenocorticism/Addison's - CKD - Primary hyperparathyroidism - Osteolitic bone disease - Ingestion of Vitamin D ointments or supplements (ex. psoriasis cream) - Idiopathic in cats

Answer 176

The high sodium concentration of 0.9% NaCl (154 mEq/L) induces a calciuresis. Additional Na competes in renal tubule for Ca reabsorption + is a calcium free solution (dilutional effect)

Answer 177

Furosemide - - Mechanism: enhances renal calcium loss - - Considerations: should be administered only after fluid deficit correction Glucocorticoids - - Mechanism: causes reduced bone absorbtion, decreased intestinal absorbtion and increased renal excretion - - Considerations: glucocorticoids given only after other diagnoses of hypercalcemia have been excluded Salmon calcitonin - - Mechanism: In addition to inducing a calciuresis, salmon calcitonin inhibits osteoclast activity and thus reduces the resorption of calcium from bones - - Considerations: there is a risk of anaphylaxis with salmon calcitonin therapy and therefore bisphosphonate therapy typically is preferred over calcitonin. Biphosphonate therapy (pamidronate) - - Mechanism: inhibits osteoclastic bone resorption and reduces calcium concentrations within 48 hours of administration - - Considerations:

Answer 178

- No to mild azotemia: fair to good | - Hypercalcemia and AKI: poor

Answer 179

Uncoupoling of oxidative phosphorilation and decreased production of ATP --> decreased cellular energy --> inhability of ATP dependent transport pump to function --> malfunction of Na/K/ATPase pump --> build up of IC Na --> cerebral edema --> increased ATP.

Answer 180

- Dogs: 2.4 - 4.7mg/kg | - Cats: 0.3 - 1.8 mg/kg

Answer 181

Clinical signs with lower doses may manifest between 1 and 3 days; signs include hind limb ataxia, paresis or paralysis, and CNS depression

Answer 182

TRUE - Repeated doses of activated charcoal should be administered (3 to 5 g/kg q6-8h) for 48 hours

Answer 183

- administration of mannitol to reduce cerebral edema - elevation of the head at a 15- to 30-degree incline - prevention of jugular compression - maintenance of normocapnia

Answer 184

No reports exist of dogs ingesting more than 5 mg/kg bromethalin, developing neurologic signs, and surviving. However, there is a report of a dog that survived after ingesting a lower dose of bromethalin (less than 2.5 mg/kg), which led to tremors, ataxia, and muscle weakness.

Answer 185

Zinc phosphide - MOA: after contact with gastric acid zinc phosphide is hydrolyzed to phosphine gas and free radicals --> the lower the gastric pH the more phosphine gas generated --> phosphine gas (active form) inhibits cytochrome C oxidase and causes disruption of mitocondrial respiration and production of ROS (it's corrosive, directly toxic to heart, adrenal glands, kidneys)--> Clinical signs start 15min to 4h after ingestion --> GI signs more common, but also possible: neurologic, respiratory, cardiovascular Strychnine - MOA: Strychnine prevents the uptake of glycine at inhibitory synapses of Renshaw cells in the CNS. This inhibition of an inhibitory pathway is termed disinhibition and results in a net excit- atory effect from an excessive afferent input and efferent response. Onset of stimulant activity, including apprehension and muscle con- tractions, occurs within minutes to hours of ingestion. Signs progress to convulsions, extensor rigidity, and death --> Animals often die from respiratory muscle paralysis and hypoventilation; mechanical ventilation of the paralyzed patient therefore may prove.

Answer 186

- Caution is recommended strongly because veterinary hospital staff treating animals can be poisoned from phosphine gas. The unpleasant odor of phosphine (smells like acetylene, garlic, or rotting fish) may be detectable on the breath, vomitus, or carcass. - moving the animal outside, inducing vomiting, and standing upwind of and above animal level to reduce exposure to phosphine gas. The animal then should be removed from the vicinity and the area flushed with copious amounts of water (while remaining upwind). If the animal vomits in an enclosed area, the area should be vacated and the fire department contacted. If practical, windows and doors should be opened, and if personnel are exposed to the phosphine gas, they should seek medical attention immediately if they are experiencing symptoms.

Answer 187

Paint ball toxicity

Answer 188

1st generation: - Chlorphacinone - Diphacinone - Warfarin - Dicoumarol 2nd generation: - Brodifacoum - Bromadiolone - Difenacoum - Difethialone

Answer 189

- Toxic: as low as 0.5mg/kg | - Lethal: 2mg/kg

Answer 190

- AKI | - GI mineralization

Answer 191

- High iCa - High phosphorus - Low PTH

Answer 192

Guarded to grave if clinical signs present - can cause hepatic and kidney injury within 48 to 72h - death may results as a consequence of: * * combination of cardiogenic and non-cardiogenic PE * * neurological signs * * acid-base disturbances * * renal failure

Answer 193

- reversible inhibitor of acetylcholinesterase - Atropin might help clinical signs by blocking muscarinic receptors but patient will need ventilation and intensive supportive care to prevent respiratory arrest since there is no antidote to prevent stimulation of nicotinic receptors.

Answer 194

- primarily antifreeze (concentration of EG greater than 95% in some products) - also in paint, adhesives, wood stain, windshield deicers

Answer 195

- Dogs: 6.6ml/kg | - Cats: 1.5ml/kg

Answer 196

AKI: - Direct injury of renal tubular epithelium by glycolic acid - deposition of Ca oxalate crystals in tubular lumen metabolic acidosis - gain of acid --> high AGAP metabolic acidosis

Answer 197

Glycoaldehyde

Answer 198

Utilization due to crystal formation --> Ca binds to oxalic acid and forms Ca oxalate crystals

Answer 199

- dogs: 59-70% | - cats: 96-100%

Answer 200

1. within several hours --> vomiting, lethargy, PU/PD, ataxia, muscle fasciculations, seizures coma --> in dogs neuro signs can resolve within 12h (false recovery) 2. 12-24h after ingestion --> cardiopulmonary signs develop (tachyarrhytmias, tachypnea, hypocalcemia 3. 24-72 hours after ingestion --> Oliguric/anuric AKI

Answer 201

- 1 hour - 6 hours - 18 hours

Answer 202

- freezing point osmometry or vapor pressure osmometry (uncommonly available) - (2Na+K)+(glu/18)+(BUN/2.8) - Normal osmolal gap <10mOsm/L

Answer 203

- 3 hours - 6 hours - 48 hours

Answer 204

An erroneous hyperlactatemia may be reported by enzymatic point-of-care (POC) machines and can be attributed to the measurement of glycolate, a chemically similar metabolite of EG [8]. As lactic aci- dosis also results in a high anion gap metabolic acidosis, this could result in a missed diagnosis of EG intoxication.

Answer 205

3-6 hours after ingestion

Answer 206

Calcium oxalate monohydrate crystals are the most common type observed and have a distinct appearance, looking like long, clear, six-sided or “picket fence” shaped structures, versus the square envelope shape of the dihydrate crystals.

Answer 207

Wood’s lamp to look for fluorescence can be performed as many antifreeze solutions are made with sodium flu- orescein dye in order to detect radiator leaks. Since this is not found in all solutions, and is only excreted in the urine for 6 hours following ingestion of antifreeze [9], a negative test does not exclude the diagnosis of EG intoxication.

Answer 208

Gas chromatography (not readily available) and EG levels are usually not detectable in serum or urine 48 to 72h after ingestion.

Answer 209

- Propylene glycol (carrier inseveral meds--> diazepam, AC) - glycerol - ethanol

Answer 210

Preventing metabolism of EG is accomplished by competitively inhibiting the function of alcohol dehydrogenase (ADH) with ethanol or fomepizole (4-methyl-1H-pyrazole, or 4-MP). These two antidotes have a higher affinity for the enzyme than EG, which allows excretion of the toxin unchanged into the urine.

Answer 211

- CNS depressant - increases serum osmolality - induces diuresis

Answer 212

Fomepizole: - Dogs: 20 mg/ kg 5% IV initially, followed by 15 mg/kg IV at 12 and 24 hours and 5 mg/kg IV at 36 hours. - In cats, a higher dose is required at 125 mg/kg IV initially, then 31.25 mg/kg IV at 12, 24, and 36 hours. Ethanol: - Because of ethanol’s short half-life, ideally it should be administered as a CRI with a 1.3 mL/kg IV bolus of 30% ethanol followed by a CRI of 0.42 mL/kg/h for 48 hours

Answer 213

- Appears to exert its analgesic effects via central cyclo-oxygenase (COX) inhibition. APAP crosses the blood–brain barrier and inhibits the central COX enzyme pathway, with only weak peripheral COX inhibition - Seems to act in the previously called COX3 (now recognized as central COX1 variant) localized in the dog's brain - Other theories of APAP’s mechanism of action include blockade of substance P’s nocic- eptive actions via N-methyl-D-aspartate inhibition and activation of serotonergic nociception pathways centrally - Has analgesic and antipyretic effects but not antiinflammatory - Appears to inhibit the peroxydase portion of prostaglandin H2 synthase - Can act as a selective COX 2 inhibitor in some tissues

Answer 214

- Glucuronidation is the main metabolic pathway in dogs, followed by sulfuric acid conjugation. In contrast, cats primarily use the sulfation pathway. - If the glucuronidation and sulfation pathways are saturated, residual APAP is metabolized by CYP2E1 and CYP1A2 (cytochrome p450) oxidation to the toxic compound N-acetyl-p- benzoquinone imine (NAPQI), which is converted into non-toxic metabolites by glutathione - If glutathione stores are depleted to less than 70% of normal, NAPQI remains in its toxic form and binds to hepatic cell membranes, causing necrosis and hepatotoxicity. - Glutathione depletion also leads to oxidative damage to the heme in red blood cells, causing methemoglobinemia in dogs and cats and Heinz body anemia in cats.

Answer 215

Renal glutathione depletion and damage of renal proteins and cell death secondary to NAPQ1

Answer 216

They lack a specific form of glucuronyl transferase, hepatic acetaminophen-directed uridine 5′-diphosphate, which is needed to conjugate APAP to glucuronic acid. - Cat erythrocytes are also more susceptible to oxidative damage by NAPQI due to the increased number of sulfhydryl groups on feline heme compared to other species.

Answer 217

- 50 - 100mg/kg | - 10 mg/kg

Answer 218

Ascorbic acid reduces methemoglobin to hemoglobin, but its effectiveness in patients with acetaminophen tox- icity is questionable. Recommended doses include 10 mg/kg PO or IV every 6–12 hours [7] or 30 mg/kg IV every 6 hours.

Answer 219

Methylene blue reduces methemoglobin to hemoglobin but it should be used cautiously in cats as a treatment for APAP toxicosis [27]. At high doses, it has the poten- tial to induce methemoglobinemia by oxidizing heme [27]. Methylene blue is generally not recommended as a treatment for methemoglobinemia in cats.

Answer 220

- Glutatione - Cysteine - mercapturic acid - APAP-glucuronide - APAP-sulfate

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