Pharmacology II Set II

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What three things regulate the gastrointestinal system?

Intrinsic nerves
Extrinsic autonomic nervous system
Circulating and locally acting hormones

What neurotransmitter stimulates appetite?

GABA

What neurotransmitter inhibits appetite?

Serotonin (5-HT)

What benzodiazepine compounds are used to stimulate appetite in cats?

Diazepam
Oxazepam

What antihistaminic agent with anti-serotonin properties is an appetite stimulant dug for cats?

Cyproheptadine

What are some appetite stimulants used in animals?

Glucocorticoids
B vitamins
Anabolic steroids
Megestrol acetate
Oxazepam and Diazepam
Cyproheptadine

What anorectic agent increases serotonin levels, increases heart valve disease, and was withdrawn from the market?

Fenfluramine

What anorectic agent contains dirlotapide, inhibits fat absorption from small intestines, and is a preferred anti-obesity drug for dogs?

Slentrol

Which animals are capable of emesis?

Carnivores
Primates
Swine
Certain birds
Reptiles

What is the primary neurotransmitter mediating emesis from peripheral receptors?

Acetylcholine

What are some peripherally acting reflex emetics?

Warm, saturated solution of table salt
3% hydrogen peroxide
Ipecac

Should Ipecac be used in cats?

No never

What centrally acting emetic is a synthetic derivative of morphine, stimulates dopaminergic receptors in CTZ, and is used in dogs?

Apomorphine hydrochloride

What can excessive doses of apomorphine cause?

CNS depression

What centrally acting emetic in cats is a alpha2 adrenergic receptor agonist, most commonly used for it's analgesic and sedative action, and has the side effect of bradycardia?

Xylazine

What centrally acting anti-emetics can control emesis due to motion sickness in dogs and cats for about 8-12 hours?

Cyclizine hydrochloride
Meclizine hydrochloride
Diphenhydramine
(Anti-histaminergics)

What centrally acting anti-emetics can penetrate the blood brain barrier, used to control motion sickness in dogs, and contraindicated in cats?

Belladonna alkaloid
Hyoscine (Scopolamine)
Dicyclomine hydrochloride
Isopropamide iodide
(Antimuscarinics)

What alpha2 adrenergic receptor antagonists are able to block the vomiting reflex at both the CTZ and the emetic center, well absorbed after oral administration, and undergo first-pass hepatic metabolism?

Phenothiazines

What are the side effects of phenothiazines and what animals are they contraindicated in?

Side effects - sedation and hypotension
Contraindicated in animals with seizures

What drugs active at the CTZ antagonize dopamine receptors, are major tranquilizers with a potent antiemetic activity, and has side effects of sedation and hypotenstion?

Haloperidol
Droperidol
(butyrophenone derivatives)

Which antiemetic is mediated by blockade of neurotransmission in CTZ, has prokinetic effects, and antagonizes apomorphine-induced emesis?

Metoclopramide
Side effects - hyperactivity, restlessness, tremors and constipation

What peripheral 5HT3 serotonin antagoinists block neurotransmission in the CTZ, and interfere with the action of serotonin on peripheral receptors in the GI tract?

Cyproheptadine - small animals
Ondansteron - dogs, cats, and ferrets

What anticholinergics exert it's antiemetic activity by: inhibiting vagal afferent impulses, relaxing GI smooth muscle spasms, and inhibiting gastroenteric secretions?

Glycopyrrolate
Propantheline
Methscopolamine
Isopropamide

What gastric antisecretory drugs acts on M1, M2, and M3 receptors and decreases gastric motility and secretion, ?

Atropine
Propantheline
(anticholinergics)

What anticholinergic has selective action on gastric M1 receptors and inhibits food-induced gastric acid secretion by 50-60%?

Pirenzepine

What gastric antisecretory drugs reduce gastric secretion of both hydrochloric acid and pepsin by reversibly inhibiting the interaction of histamine with parietal cell H2 receptors?

Cimetidine
Ranitidine
Famotidine
Nizatidine

What H2 receptor antagonist has the longest duration of action?

Famotidine

What H2 receptor is rapidly absorbed from GIT with excellent bioavailability (97%), is eliminated by renal excretion unchanged, and is the preferred H2 receptor antagonist in hepatic disease condition?

Nizatidine

What drug increases renal clearance of ranitidine by 50%?

Probenecid

What H2 receptor antagonist reduces hepatic blood flow by 20%?

Cimetidine

What are some side effects of H2 receptor antagonists?

Thrombocytopenia (ceimetidine)
Rebound acid hypersecretion
Relapse of gastroduodenal ulcers

What drug is a substituted benzimidazole that irreversibly inhibits the H, K-ATPase proton pump, is formulated as encapsulated enteric-coated granules, and is used to control acid secretion in patients refractory to H2 receptor antagonists?

Omeprazole

What are some adverse reactions to omeprazole?

Suppression of the acid barrier to bacterial entry
Parietal cell hyperplasia and hypertrophy of gastric mucosa
Inhibits cytochrome P450 enzyme

What prostaglandin is an analog of PGE1, does not alter the serum gastrin levels; hence it prevents rebound acid hypersecretion?

Misoprostol

What are the side effects of misoprostol?

Stimulates intestinal motility and secretion leading to diarrhea
Increases uterine contraction (contra-indicated in pregnant animals)

What cryoprotective drugs are weak bases that react with gastric hydrochloric acid to form an insoluble colloid and water?

Antacids

What are some antacids?

Aluminum hydroxide
Magnesium hydroxide
Calcium carbonate

Which type of antacids include salts of aluminum, magnesium, and calcium, inactivates pepsin, binds bile salts and induces local prostaglandin synthesis, and is used clinically to control serum phosphate in patients with renal disease?

Non-systemic antacids

What is a systemic antacid?

Sodium bicarbonate

What is the preferred cytoprotective drug for treatment of ulcers?

Sucralfate

What are the cytoprotective effects of sucralfate?

Binds to and inactivates bile acid and pepsin
Stimulates secretion of mucous and bicarbonate
Stimulates synthesis of PGs and sulfhydryl ions
Directs epidermal growth factor to ulcer lesion
Increases mucosal blood flow

Should sucralfate be administered with cimetidine?

No it binds cimetidine

What cytoprotective agent absorbs toxins, has mild antibacterial action against Helicobacter and intestinal pathogens, and decreases intestinal secretions in many diarrheal conditions?

Bismuth subsalicylate

What drug is a synthetic choline ester, enhances the amplitude of contractions throughout GIT, and has adverse side effects of abdominal cramps, diarrhea, salivation, and bradycardia?

Bethanechol

When should Bethanechol not be administered?

Mechanical obstruction of intestine or urinary tract
Animals with peritonitis
Intestinal wall is less viable

What prokinetic drug is a lipid soluble derivative of para-aminobenzoic acid, enhances the release of acetylcholine from cholinergic neurons of myenteric plexus, and does not increase gastric or pancreatic secretion?

Metoclopramide

What are the actions of metoclopramide?

Physiologically antagonizes emesis by:
Increasing tone of esophageal sphincter
Increase force and frequency of gastric antral contractions
Relaxes pyloric sphincter facilitating rapid gastric emptying

How is metoclopramide excreted?

Through kidney and liver after first-pass metabolism

Which prokinetic drug has the broadest spectrum of action, causes dose-dependent increased activity at all sites of GIT, and enhances the release of acetylcholine and cholinergic neurotransmission in myenteric plexus?

Cisapride

What prokinetic drug is a dopamine antagonist and acts peripherally?

Domperidone

What are some anticholinergic agents that decrease intestinal motility and secretions?

Atropine
Hyoscine
Aminopentamide
Dicyclomine
Glycopyrrolate
Camylofine

What anticholinergic drug is used to control diarrhea in calves and for the management of mild colic in horses?

Hyoscine butylbromide - metamizole combination

When are opioid use for decreased intestinal motility and secretions contra-indicated?

When diarrhea is due to invasive bacterial infection

What opioids are are congeners of meperidine, clinically used as anti-diarrheal drugs, and involve the presynaptic inhibition of acetylcholine release from cholinergic neurons of the enteric nervous system's myenteric plexus?

Dipehoxylate
Loperamide

What opioid is an active metabolite of diphenoxylate and contain a low dose of atropine sulphate in order to reduce the opioid drug abuse in humans?

Difenoxin

What opioid should be used with extreme care in cats because overdosage causes marked excitability with other clinical signs such as mydriasis, goose-stepping gait and loss of balance?

Diphenoxylate

What opioid reduces excessive intestinal secretion as well as prolongs intestinal transit time?

Loperamide

What opioid is a camphorated tincture of opium and used as an antidiarrheal preparation in foals?

Paregoric

What are some antidiarrheal drugs used in cats?

Propantheline
Bismuth subsalicylate suspension
Loperamide hydrochloride

What GI protectant and absorbent is absorbed into the systemic circulation, can also absorb E. coli enterotoxins, and should be used cautiously in cats?

Bismuth subsalicylate

What drug is used primarily as an absorbent, has a large surface area and is the best choice for emergency treatment of poisoning?

Activated charcoal

What GI protectant and absorbent is a basic anion exchange resin, binds to bile acid, is insoluble in water, and not absorbed?

Cholestyramine

What are some adverse effects of cholestyramine?

Nausea
Constipation
Steatorrhea
Decreased absorption of fat-soluble vitamins

What drugs facilitate elimination of soft-formed stool?

Laxatives

What drugs produce more of a fluid evacuation?

Cathartics

What is the most commonly used emollient laxative and chronic use may impair absorption of fat-soluble vitamins like (A,D,E and K)

Mineral oil

What are some adverse effects of using mineral oil as a laxative?

Development of granulomatous lesions after long term use
Accidental administration of oil to trachea (lipid pneumonitis)
Mineral oil may leak through the anal sphincter and interfere with the healing of wounds in the anorectal region

What emollient laxative is an anionic surface-active agent, has maximal fecal softening may occur after 3 days of treatment, used to facilitate earwax removal, and is used for treating simple impactions of the colon in horses?

Docusate sodium

What bulk-forming laxatives are used in dogs and cats?

Bran
Unprocessed wheat bran
Psyllium granules

What bulk-forming laxative is used as a mild laxative for horses?

Bran mash
Psyllium

What bulk-forming laxative is commonly used in equine practice to treat impactions caused by ingestion of sand?

Psyllium

What saline purgative enhances the release of cholecystokinin (CCK) and is commonly used in cattle?

Magnesium sulphate (Epsom salt)

What saline purgative is preferred for use in horses?

Sodium sulphate (Glauber's salt)

What saline purgative is used in dogs, cats, and foals, and the amount absorbed could produce toxicity in animals with impaired renal function?

Magnesium hydroxide (milk of magnesia)

What osmotic purgative is a synthetic disaccharide, passes undigested to the large intestine, and lowers the pH of colonic contents?

Lactulose

What is lactulose indicated for?

Treat constipation in dogs and cats
Treat hepatic encephalopathy in horses, dogs and cats
Enema in dogs

What irritant cathartic is produced from the bean of Ricinus communis, hydrolyzed by pancreatic lipase enzymes to glycerol and ricinoleic acid, and stimulates intestinal peristalisis?

Castor oil

What irritant cathartic is produced from the bark of buckthorn (Rhamnus purshiana) and senna, obtained from the dried leaves or pods or Cassia actuifolia, and releases active aglycones (emodins) in large intestine?

Anthraquinone purgatives (Danthron)

What can repeated administration of Anthraquinone purgatives cause?

Superpugation in horses

Should you use neuromuscular purgatives for a mechanical obstruction of the intestine?

NO

What drug can be administered as an enema but may cause irritation of mucosal lining of the intestinal tract in neonatal foals?

Docusate sodium (mineral oil safer)

What type of enemas are administered through cuffed urinary catheter to relieve refractory impactions?

Retention enemas using 4% solution of acetylcysteine

What are substances that cause contraction of the gall bladder?

Cholagogues (dietary fat and concentrated magnesium sulfate)

What are substances that increase the secretion of bile by the hepatocytes?

Choleretics

What are some naturally occurring bile acid conjugates that enhance bile flow?

Glycocholate
Taurocholate

What drug is a secondary bile acid and is used to dissolve (cholesterol) gallstones non-surgically in patients?

Ursodeoxycholic acid (UDCA)

What drugs are used to treat frothy bloat in cattle?

Dimethicone
Poloxalene (and prevent)
Docusate sodium
Vegetable oil

Can fish oils be used to treat frothy bloat?

No, they stabilize the foam

What cardiac glycosides are produced from Digitalis purpurea and Digitalis lanata?

Digoxin
Digitoxin
Ouabain
(collectively called Digitalis)

What are the cardiovascular effects of Digitalis?

Improved myocardial contractility
Increased cardiac output
Diuresis
Diminuation of edema
Controls cardiac arrhythmias
Reduction in blood volume, venous pressures, heart size, and heart rate

What is the mechanism of action of Digitalis?

Increases calcium availability in myocardial fibers
Positive inotropic action on heart due to inhibition of Na/K ATPase enzyme

In Digitalis therapy, is diuresis possible if edema does not accompany with CHF?

No

What are some extracirculatory effects of Digitalis therapy?

Production of aqueous humor and CSF may be partially inhibited
Vomiting in dogs followed by protracted diarrhea

What are the therapeutic indications of digitalis?

Congestive heart failure
Atrial arrhythmias (mostly atrial fibrillation/flutter)

What is the main aid of digitalis therapy?

Determine the smallest amount of glycoside that is affective in patient without producing toxicity

Should hepatic function and renal function be considered when administering digitalis therapy>

Yes, should be reduced if they are impaired

What routes of administratoin of digitalis are preferred?

IV and oral route

What are some clinically signs of digitalis toxicity?

Protracted diarrhea
Chronic weight loss
Arrhythmias
Complete heart block
Dropped beats
ST segment changes

A low concentration of what mineral potentiates digitalis arrhythmogenicity?

Hypokalemia

A high concentration of what mineral antagonizes arrhythmogenic potential?

Hyperkalemia

What can be used to treat digitalis toxicity?

Withdraw glycoside therapy
Oral potassium supplementation
Cholestyramine resin given to bind glycoside in GIT
Anti-arrhythmic agents such as lidocaine, propanolol, and phenytoin

If there is an AV block due to digitalis toxicity what two treatments should be avoided?

Antiarrhythmic agents and K therapy should be avoided

What is the preferred loop-acting diuretic, has the action at the luminal membrane of the thick ascending limb of the loop of Henle, and inhibits Na/K/2Cl co-transport mechanism?

Furosemide

Animals in what conditions show a decreased response to furosemide?

Animals with low cardiac output and poor renal perfusion

What diuretic inhibits Na/Cl symporter in distal convoluted tubule, produces a higher K excretion in urine, and increases Ca reabsorption?

Thiazide diuretics

What diuretics decrease K excretion in urine by competitively antagonizing aldosterone secretion or directly inhibiting the resorption of sodium ion?

Postassium sparing diuretics (Triamterene, amiloride)

What combination of drugs produces diuretics without either delayed onset of action or excessive urinary excretion of potassium?

Hydroflumethiazide
Spironolactone

After a steady state of plasma digoxin concentration has been achieved, what drug can be administered to abolish atrial dysarrhythmias?

Quinidine

What drugs are considered nonglycoside, noncatecholamine inotropic drugs?

Phosphodiesterase inhibitors (Amrinone and milrinone)

What phosphodiesterase inhibitor exerts a positive inotropic action on the failing heart, increases myocardial oxygen consumption, and decreases ventricular filling pressure (preload) and vascular resistance (afterload)?

Amrinone

What is the major clinical indication of amrinone?

Treatment of acute myocardial failure in cats and dogs

What drug is a selective inhibitor of phosphodiesterase III and increases binding efficiency of cardiac myofibril to the calcium ions without increasing oxygen demand?

Pimobendam

What are some side effects of pimobendan?

Tachyarrhythmias in humans

What drug is a direct B1 agonist, increases myocardial output and decreases ventricular filling pressure, and can produce tachycardia (weak positive chronotropic action)?

Dobutamine

What are some drawbacks of administering Dobutamine?

Arrhythmias
Tachyphylaxis

What are some clinical indications of Dobutamine?

Acute treatment of dilated cardiomyopathy associated with CHF
Alternative to dopamine in cardiogenic shock conditions
Management of hypotension during anaesthesia in horses

What drug is a theophylline-ethylenediamine complex, inhibits phosphodiesterase enzyme, contains 86% anhydrous theophylline, and has a principal effect of bronchodilation?

Aminophylline

What is aminophylline used to treat?

Acute pulmonary edema

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