Corticosteroids, AED, GI (+ very few Abx) Flashcards
What class of drug is caffeine
Methylxanthine
What kind of effect does caffeine have on dogs
Mild CNS stimulation, moderate bronchodilation
What class of drug is theophylline?
Methylxanthine
What effect does theophylline have
Bronchodilator
What is a side effect of methylxanthines (give examples)
CNS overstimulation (caffeine, theophylline)
What are cortocosteroids
Group of natural and synthetic substances mimicing the actions of cortisol
What actions are therapeutic used of cortocosteroids base on
Glucocorticoids (rather than mineralocorticoids)
What group of drugs causes anti-inflammation, imuunosuppression, metabolic changes, electrolyte balance and cardiovascular homeostasis?
cortocosteroids
Name the physio effects of cortocosteroids
anti-inflammation, imuunosuppression, metabolic changes, electrolyte balance and cardiovascular homeostasis
What are the effects of low, medium and high doses of cortocosteroids
Low - replacement Rx for adrenal insufficiency Medium- antiinflammatory High- immunosuppression
What is the most widely used class of drugs in veterinary medicine
cortocosteroids (and over used!)
What causes a delayed response in corticosteroids
Takes hours due to requirement of protein synthesis
What drug class will treat addisions disease
cortocosteroids
Describe the HPA
CNS stimulation signals they hypothalamus which releases CRH to the pituitary gland, which releases ACTH to adrenal gland, which produces cortisol. Cortisol has negative feedback onpititary and hypothalamus production of hormones
What can treat hyperactivation of the HPA axis
Trilostant (vetoryl) inhibits enzyme in the adrenal cortex to decrease cortisol synthesis
What are the paths of glucocorticoid actions
- genomic response to alter protein synthesis (slow- medium) 2/3 - non-genomic response to receptors in cytosol and on membrane
Describe the effects of glucocorticoids on carbohydrate metabolism
Increased glyconeogenesis and decreased cellular glucose use leading to hyperglycemia
Describe the effects of glucocorticoids on protein
Catabolism - amino acids sent to gluconeogenesis- protein loss from bone can cause osteoporosis, thnning of skin, delayed healing, muscle wasting
Describe the effects of glucocorticoids on fatty acid
Mobilizatioon from adipose
How do corticosteroids affect the inflammatory cascade
At high doses, decrease of enzyme activity, leukocyte infiltration and vasoactive/chemotactic factors leading to block of cascade
Describe the effects of glucocorticoids on electrolytes
Na retention, loss of K and Ca, decreased ADH leads to PUPD
Why should glucocorticoids be withdrawn slowly
HPAA suppression due to exogenous
What are the side effects of glucocorticoids (name 7)
Protein catabolism HPAA suppression Immunosuppression GI ulceration due to loss of GI protectant Diabetes Hypothryoidism Electrolyte imblance
Name the chemistry changes that are from glucocorticoids (4)
Glucosuria, increased cholesterol, decreased potassium, decreased thyroid
Do glucocorticoids treat cushings or addisons
Treat Addisons (hypo)- can push into iatrogenic Cushings (hyper)
What are the contraindications for glucocorticoids
Pre-existing bacterial/fungal/viral infections, pregnancy, diabetes (causes insulin resistance), renal disease/heart failure (due to fluid overload), young animals and GI ulcers
What are the four classes of glucocorticoids
A- short acting B- intermediate C- long acting D- not defined
What class of glucocorticoids does prednisone fall into?
A- short acting
What class of glucocorticoids does dexamethasone fall into?
C- long acting
What are the routes of glucocorticoid use
Topica, inhaled, oral, systemic
What is the elimination route of glucocorticoids
Hepatic
What effect does the moiety of corticosteroids have?
Side chains/esters delay metabolism and enhance duration of metabolism
Describe the pharmacodynamics of corticosteroids. What can affect this
PD does not match PKinetics - bio actions are longer lasting than their levels in plasma (different plasma and biologic half time). Different ester or free alcohol additions can change the biological half life
What determines the effect duration of corticosteroids
Ester form used
Describe effects of ester solubility on corticosteroids
highly soluble esters allow fast absorption (minutes to hours) moderately insoluble esters absorb over days to weeks poorly soluble esters absorb over weeks to months
What is the most widely used corticosteroid agent across species
Dexamethasone
What is the duration of dexamethason
Long acting
What is the main activity of dexamethasone
Glucocorticoid (little mineralo)
What is the benefit of corticosteroids that display primarily glucocorticoid actions
Less effect on fluid balance
What are the additional side effects of dexamethasone
Colonic perforation and laminitis in horses
What are the routes of administration of dexamethasone
PO, IM, IV, topical/ophtho
What is a synthetic drug which has more mineralocorticoid activity than other sythetic agents of the same type
Prednisone/solone
Describe the difference between pred/prednisolone
Prednisone is converted to prednisolone in the liver
Why would one Rx -P’solone over pred?
P’solone is easier on the liver (cats and horses especially)
Which animals are recommended to use P’‘solone over pred?
Horses and cats
Fat cats vs skinny cats- prednisone vs ‘solone
Fat cats ok to give prednosone
What corticosteroid can be given to a cat with liver and heart failure and why
methyl-prednisolone- devoid of mineralocorticoid activity and -solone easier on liver
What are the UFVH formulary warnings for prednisone
Do not use in animals with severe bacterial or fungal infections
What are the UFVH formulary warnings for dexamethasone
May cause laminitis in horses, GI bleeding or colonic perforation
What are the UFVH formulary warnings for prednisolone
Do not use in animals with corneal ulceration
What change in dose is necessary in corticosteroids in stressed animals
Dose may need to be increased as body would normally increase
What is the dose for prednisone anti-inflammatory
1 mg/kg/day
What is the dose for dexamethasone
1/7th prednisone - (1 mg/kg/day)/7
After what duration of time should corticosteroids be slowly withdrawn
After more than 1-2 weeks of use
What methods can be used to prevent gastric ulceration
Buffer stomach acid, inhibit receptors or inhibit H/K ATPase
What are the advantages and drawbacks of antacids
Inexpensive but frequent administration needed, can cause diarrhea (magnesium/maalox) or alkylosis (sodium bicarbonate)
Name a drug interaction for antacids
Enrofloxacin
What kind of Rx is famotidine
H2 inhibitor - prevent gastric ulceration
What kind of Rx is ranitidine
H2 inhibitor - prevent gastric ulceration, + prokinetic *think ran through the gut (zantac)
What kind of Rx is omeprazole
PPI- H/K ATPase (proton pump) inhibitors - prevent gastric ulceration
What common cautions are there with H2 inhibitors preventing gastric ulceration
Liver, +/- competition for p450 enzymes
How frequently should ranitidine be given
BID
How frequently should famotidine be given
BID
What side effects does ranitidine have?
Slight interference with p450 in the liver
What side effects does famotidine have
Liver complications but no interference with p450
*What replacement drug could be given in place of famotidine or ranitidine in liver failure patients
Nizatidine - no interference with p450
What kind of drugs are omeprazole, pantoprazole, lansoprazole
PPI (H/K ATPase) - to prevent gastric ulceration
What is the mechanism of PPI drugs
Reacts with active ATPase to inhibit H/K Pump
How should PPI drugs be given
Give 30 minute before meal, give in intact capsule or tablet with bicarbonate because they interact with gastric acid
What kind of drug is omeprazole
PPI- to prevent gastric ulceration
Which PPI can be given IV
pantoprazole
Which H2 inhibitor can be given IV
Famotidine
Which PPI is ok to split tablets?
Omeprazole
What is an advantage of Lansoprazole
Formulated with HCO3 as an oral liquid for dogs
What is an advantage of pantoprazole?
Can be given IV in anorexic patients
What kind of drug is mistoprostol
PGE1 (prostaglandin) analog - to prevent gastric ulceration
What drug is best in response to NSAID toxicity
Mistoprostol (wont help with hemorrhage from prednisone)
What are the effects of mistoprostol
Mimics prostaglandins Low dose- stimulates blood flow High dose- antacid
What is a side effect of mistoprostol
Can induce labor or abortion (PGE1 analog gastric ulcer preventative)
What kind of drug is sucralfate
Mucosal coating chelating and complexing agent to prevent gastric ulcer
Describe the mechanism of action of sucralfate
Prodrug which is converted by acid into a sugar polymer that coats stomach lesions and works as an antacid
What interactions are reported with sucralfate
Aluminum inhibits enrofloxacin so it should be given 1-2 hours before or more than 6 hours after sucralfate is given
*What are good sources of omega three fatty acids
Fish oil (EPA and DHA), linseed oil (a-linoleic acid)
What kind of drugs are cisapride and mosapride
Prokinetics
What is a precaution to note in cisapride
This prokinetic enhances reduced motility in stressed patients or those on steroids (due to slow gastric emptying)
What is the function and mechanism of H2 inhibitors
H2 receptors are found on parietal cells which secrete acid
What enzyme do prokinetics work on?
acetyl cholinesterase
What precautions must be taken with PPIs
Gastrin build up can occur, so must wean off
What are the two models for vomiting
Vomiting center in reticular formation CRTZ (chemoreceptor trigger zone) on floor of ventricle in dorsal medulla
What types of drugs induce emesis
Dopamine agonist Adrenergic alpha agonists Gastric irritants
What kind of drug is apomorphine
Dopamine agonist emesis inducer
What is the mechanism of apomorphiine
Dopamine agonist which acts through the CRTZ
Why might apomorphine not work in cats
They may not have dopamine receptors in CRTZ
What type of drug is xylazine
Emesis inductor via alpha adrenergic agonism
What type of drugs are ipecac and H2O2
Gastric irritant inducers of emesis
What receptors are targeted in anti-emetics
- Antimuscarinics (weak antiemetic) - Alpha 2 antagonists - NK1 receptor antagonists - Dopamine antagonists - 5HT3 antagonists
What kind of drug is Centrine
antiemetic non-specific antimuscarinic
What is the mechanism of Centrine
Antimuscarinic which reduces small intestinal motility and gastric emptying
What is a drug interaction of Centrine
Blocks prokinetics
What kind of drugs are chlorpromazine, prochlorperazine, acepromazine?
Antiemetics : Phenothiazines - alpha 2 antagonists
What kind of drug is cerenia
Antiemetic- NK1 (neurokinin) receptor antagonist in vomiting center
What is the drug name for cerenia
Maropitant
What drug type is safe to combine with maropitant
5HT3 antagonists (maropitant is cerenia)
What drug interactions are noted in maropitant
Ca channel blockers, cisapride (prokinetic), cyclosporine
What type of drug is metoclopramide and what does it target
Antiemetic- dopamine agonist in CTZ Prokinetic- 5HT4 agonist
What cautions should be noted in metoclopramide
Crosses BBB and can cause tremor
*What Dopamine antagonist would be a good alternative to metoclopramide in neuro patients?
Domperidone - because it does not cross the BBB
What is the effect and mechanism of 5HT3 antagonists
Anti-emetic - CTZ and vagal afferents from stomach
What kind of drug is ondansetron
5HT3 anti-emetic
What are the receptors involved in motion sickness anti-emetic drugs
-Inhibition of: + M1 (acetyl choline) in vestibular and CRTZ + H1 in vestibular apparatus
What does inhibiting M1 and H1 receptors do
Control motion sickness
What drugs should be used for chemotherapy associated emesis
Ondansetron and other 5HT3 antagonists
*What is a less expensive option of 5HT3
Mirtazipine (instead of ondansetron)
What effect does blocking cholinergics by centrine have?
Prokinetics
What is the mechanism and effects of metaclopramide
Increases tone in esophageal sphincter, relaxes pylorus, and romotes gastric emptying (cholinergic 5HT4 agonist) Antiemetic (dopamine antagonists)
What kind of drug is cisapride
mixed 5HT3 antagonist/5HT4 agonist, prokinetic
What is the mechanism of action of cisapride
Prokinetic via release of acetyl choline to smooth muscle of intestine
What are cautions in cisapride
Prolongs QT interval to cause fatal dysrhythmias in humans and boxers Obstipation in cats
What drug should be used to reduce reflux during anesthesia in dogs?
Cisapride
*What kind of drug is bethanacol
Muscarinic agonist prokinetic
What is a side effect of bethanacol
Ineffective unless at high doses when SLUD occurs
What are the two types of motility rhythms
*** and house keeper contractions
What secondary effect does a 1/10th dose of erythromycin produce and why
Prokinetic via motilin agonist action on housekeeper contraction
What secondary effect do ranitidine and nizatidine have
Prokinetic
What drug should be used as a thoracic epidural analgesic for post operative ileus?
Lidocaine
*What can be used to help with ileus in canines due to action on GI hormones?
Octreotide
What effect do morphine agonist antidiarrheals have
Promotes segmental (mixing) contractions but not propagating (propulsive) - this slows transit and aids absorption
What is the usual origin of diarrhea in dogs
Osmotic
What kind of drugs are loperamide and diphenoxalate
Weak central action morphine agonist antidiarrheals loperamider (immodium) diphenoxalate (lomotil)
What secondary effect does diphenoxalate
Diphenoxalate (lomotil) also has atropine to inhibit secretion
What is the effect of bismuth subsalicyclate
Inhibitor of SI secretion (think sub-sali-vate - less secretions)
What are Kaolin, attapulgite, dioctahedral smectite
Antidiarrheal absorbents of uncertain efficacy; minerals absorb water for firmer feces but no change in water loss
What patients should not get cisapride
Boxers! dysrhythmia (boxers have a lot of heart and a lot of pride)
Why should antibiotics be avoided for the gut
Bacterial infections are rare and Abx destabilize normal flora
What situations should antibiotics in GI issues be used
When sepsis is likely due to breakdown of mucosal barrier (parvo, chemo), sometimes in hemorrhagic diarrhea and prolonged starvation, and specific infections
What antibiotics should be used in hemorrhagic diarrhea and prolonged starvation for the upper intestine
Gram + and -, first generation cephalosporins
What antibiotics should be used in hemorrhagic diarrhea and prolonged starvation for the lower intestine
Combo gram negative and anaerobes
What should be used for salmonella and acute pancreatitis
Enrofloxacin
What should be used for boxer colitis and e. coli colonization
Enrofloxacin
What should be used for clostridial colitis
Metronidazole
In SI dysbiosis, which antibiotics should be used
Tetracycline, metronidazole, tylosin
What organism is in Fortiflora
Enterococcus faecium
What organism is in Prostora Max
Bifidobacterium animals (think FIDO and MAX as dog names)
How should probiotics be used?
Every day because population is determined by food supply, so will be immediately eliminated if not
How are oligisaccharides, beet pulp and soluble fiber used?
Pre-biotic carbohydrates not digested in SI
What is the purpose of beet pulp
Prebiotic mixing soluble and insoluble fiber
What methods can be used to control diarrhea
Contraction via morphine agonists, inhibitors of SI secretion, absorbents
GI: What is the immunosuppressive dose of prednisone/solone
1-2mg/kg bid for 2-4 weeks
What is the weaning recomendation for pred
Reduce by half every 2-3 weeks until every other day at low dose. Increase one step if signs occue
What corticosteroid anti-inflammatory should be used if acites is present
Dexamethasone
What kind of drug is budesonide?
corticosteroid
Why is pred usually just used at antiinflammatory doses?
Bc leukotriene inhibitors are more effective than PG inhibitors like pred
What is the metabolism of budesonide
First pass through liver - so less side effects than prednisone
What kind of drugs are azathioprine, cyclophosphamide, chlorambucil?
Alkylating agents for anti-inflam/immuno
What is azathioprine used for
lowering long term pred use
How should azathioprine be given
To lower long term pred use: One month to work, so give for three months SID then EOD
What precautions should be taken with azathioprine?
Monitor WBC count
What kind of drug is cyclophosphamide?
alkylating agent for antiinflamm/immunosuppressive
What are the benefits of cyclophosphamide
Rapid onset compared to azathioprine
What are the possible side effects of cyclophosphamide
Hemorrhagic cystitis, neutropenia
What type of drug is chlorambucil
Alkylating agent for antiinflammation and immunosuppression
What drug should be used for small cell lymphoma and IBD
Chlorambucil
What kind of drug is cyclosporine and what is its action
Anti-inflammation/immune suppressive- modifies cell mediated immunity
What drug should be used for anal fistulas
Cyclosporine
How can dose of cyclosporine be lowered
Give with ketoconazole
What is the effect and mechanism of leflunomide
Suppression of T cell function by inhibiting pyrimadine synthesis
What is the effect of mycophenolate mofetil
Suppression of T cells function by inhibiting purine synthesis
What are the osmotic agents that can be used as laxatives
Magnesium sulfate (epsom salts) and Colyte
What drug should be used before a colonoscopy
Colyte
What are the bulk forming osmotic agents that can act as laxatives
Insoluble fiber; Soluble fibers: methylcellulose, psyllium, and pumpkin; Indigestible sugars: lactulose
What kind of drug is magnesium sulfate?
Epsom salts: osmotic agent laxative
What laxative should be used in cats
Pumpkin
What lubricants can be used as laxatives
mineral oil, petrolatum
What kind of drug is petrolatum
Lubricant laxative- Laxitone!
Name the drugs that can be used to treat whip worms
Fenbendazole (panacur), febantel (drontal), moxidectin (adv. multi), milbemycin (trifexis)
What caution should be taken with mineral oil
risk of inhalation pneumonia
Why should phsphate fleet enemas be avoided?
Can cause toxicity hypophosphatemia
What is a possible side effect of bismuth subsalicylate
Peptobismol- can cause black feces from the bismuth
What are the risks of sulfasalazine?
Risk of dry eye autoimmune disease
What is a good alternative to sulfasalazine?
Olsalazine - lower side effects but very expensive
What kind of drug is sulfasalazine?
Aminosalicylate anti-inflammatory to treat colitis
When should prophylactic antibiotics be used
20-30 minutes before surgery, q 90 minutes after
Which antibiotic is best for pre-sx
Cefazolin
What is Cmax
Maximum serum concentration of a drug
What is MIC
Minimum inhibitory concentration
Cmax/MIC ratio- what should be high/low
Cmax high, MIC low
What is AUC
Area under the curve for plasma concentration
*****What is AUC24/MIC
Ratio of area under the plasma concentration time curve for a 24 hour interval to the MIC
What is T>MIC
The percentage of time during a dosing interval that a drug exceeds MIC
What is Tmax
Time to maximum plasma concentration
What is Cl total
Plasma clearance of a drug in a period of time- how fast it can be removed from the patient
****What is AUC
The extent of drug absorption
What effect does doubling a dose have on Cmax and T1/2
Doubles the Cmax and adds a half life, but doesnt change the length of the half life
What does it mean to be concentration dependent
As concentration increases, efficacy also increases
What Pk/Pd parameter relates to concentration dependent drugs
Cmax/MIC and AUC24/MIC
Cmax/MIC and AUC24/MIC are parameters related to what Pk/Pd profile
Concentration dependent
What does it mean to be time dependent?
Increases in dose will not change efficacy
What Pk/Pd parameters relate to time dependent drugs with no persistent effects?
T>MIC
T> MIC is a Pk/Pd parameter related to what profile?
Time dependent with no persistent effects
What is the goal of therapy with concentration dependent drugs
Maximize concentration
What is the goal of therapy with time dependent, no persistent effects drugs
Maximize duration of exposure
What is the goal of therapy with time dependent, with persistent effects drugs
Maximize the amount of the drug
What Pk/Pd parameter is related to time dependent, with persistent effects drugs
AUC24/MIC
AUC24/MIC is a Pk/Pd parameter for which profile
time dependent, with persistent effects drugs
For concentration dependent drugs, Cmax should be
8-10 times MIC
How long should the inter-dosing interval exceed MIC in drugs like penicillin
30-50%