Pharmacology Flashcards
Describe Emetics with examples
The main reason for induction of emesis is in management of poisoning (non corrosive). For example Xylazine - is an alpha 2 agonist used as a sedative, indces vomiting especially in cats and dogs after i/m administration. Ipecacuanha - acts as a local irritant, available as a paediatric formulation. Opiates - apomorphine - has an emetic action predominant over its other opioid effects. Can be given any route, subsequent administrations may see reduced efficacy - depression of the emetic centre. It causes respiratory depression with overdose.
Describe the process of emesis?
A complex process, with a wide number of triggers and pathways being able to induce the vomiting reflex. The main neurotransmitter is acetylcholine but serotonin, dopamine, substance P and histamine are also important. In cats and dogs, stimulation of alpha2 adrenoceptors also induces emesis. The emetic centre is protected by the blood brain barrier. The chemoreceptor trigger zone is not so well protected by the BBB which is incomplete in this region.
Describe maroopitant?
It is a licensed anti emetic for dogs. Its mechanism of action is Via neurokini -1 receptor antagonist. It blocks the effect of substance P (neurotramsmitter at these receptors). It acts in final common pathway in the emetic centre > broad spectrum anti emetic. Works for motion sickness, GI irritation, pancreatitis, chemotherapy induced. It is orally bioavailable, low oral bioavailability due to first pass hepatic metabolism. It has non linear kinetics, hepatic metabolism - 2 isoenzymes one low capacity one high capacity. It is widely distributed and highly bound to plasma protein. Wide dose range depending on cause of vomiting i.e higher dose for motion sickness. Once daily dosing schedule. It can be given orally or parenterally.
What is metoclopramide?
An anti emetic now licensed in dogs and cats. Its mechanism of action is both centrally and peripherally acting complex. It centrally inhibits D2 and 5HT3 receptors in CRTZ. Peripherally inhibits D2 receptor and induces the release of local ACh. Results in oesophageal sphincter tone increase, increased gastric contractions, dereased pyloric sphincter tone, increased peristalsis of upper intestine (prokinetic effect). It may have behavioural alterations, constipation, CI in gGI obstruction and CI in epilepsy.
Describe antihistamines as anti emetics?
They work against motion sickness at the vestibular apparatus, histamine via H1 receptors is a key neurotransmitter. Antihistamines such as cyclizine HCL, meclizine HCL and diphenhydramine HCL, drowsiness and xerostomia are side effects. Oral bioavailability good, hepatic metabolism and renal elimination.
Describe the phenothiazines as anti emetics?
They are broad spectrum anti emetics. Low doses block dopamine and histamine receptors. Higher doses have antimuscarinic effects also. Acepromazine, chlorpromazine and prochlorperazine. Sedation and hypotension are side effects. Decrease desirability in older/sick animals.
Describe the butyrophenone derivatives as anti emetics
E.g Haloperidol, anti dopaminergic effects, potent tranquilisers.
What are the serotonin antagonists?
They block the effect of serotonin on 5HT3 receptors. Examples include cyproheptadine and ondansetron. Ondansetron used especially for human patients to control vomiting associated with chemotherapy. Ondansetron also used in small animals, can be given orally or parenterally, has a short half life and undergoes hepatc metabolism.
What are the peripherally acting anti emetics?
Protectants - decrease irritatio, anticholinergics - decrease pns effects, prokinetics - decreased likelihood of vomiting due to increased GI Contraction.
Describe the anti ulcer drug cimetidine?
H2 receptor antagonist - orally bioavailable, food decreases bioavailability, hepatic metabolism and renal elimination of conjugated and active drug, t 1/2 hour, decreases gastric acid and pepsin production. It is an inhibitor of microsomal enzymes and will decrese hepatic blood flow by about 20%. Decrease metabolism of flow dependent drugs e.g lidocaine and proanolol. May get rebound hypersecretioin on cessation. Least powerful - Famotdine > raniitidine> cimetidine.
Describe the anti ulcer drug famotidine?
Does not inhibit liver enzymes, can be given i/v, has a longer half life vs cimetidine, SIB/BID dosing, dose reduction in renal failure (human data).
Describe the anti ulcer drug ranitidine?
Does not inhibit liver enzymes, can be given i/v, longer half life vs cimetidine, has prokinetic activity,also dose reduction in renal failure.
Describe omeprazole the anti ulcer drug?
It is a substituted benzimidazole & a proton pump inhibitor - more potent than the H2 blockers. Irreversibly inhibits the potassium ATPase pump in the luminal surface of the parietal cell. It is a basic drug that requires enteric coated formulation. Dissolution and absorption occurs in the small inteestine. On absorption the drug is ion trapped in the parietal cells. (pH is much lower compared to other cells). Absorption improves over first 4-5 days as pH in the GI tract increases. Enzyme is permanently inhibited so HCl production only resumes when new enzyme molecules have been found. High plasma protein binding, hepatic metabolism and short half life about 1 hour.
What is misoprostol?
An anti ulcer drug - a prostaglandin analogue. It is a synthetic analogue of PGE1. IT acts locally - absorbed drug is rapidly metabolised. Decreases cAMP in the parietal cell, increases bicarbonate and mucous production and enhances mucosal blood flow and mucosal epithelialisation. Anti ulcer and cytoprotective agent. Reduces secretion of histamine from mast cells. Unabsorbed drug in the SI can cause diarrhoea - generally resolves after a few days. Used primarily to prevent and treat gastric ulceration caused by NSAIDS.
Name some other anti ulcer drugs?
Any other agent that neutralises gastric acid. Examples include sodium bicarbonate and aluminium hydroxide. Not especially efficacious. Need to be administered very frequently e.g 6 X daily or with every meal. Can get hypersecretion of HCl as AlOH also binds phosphates and is used in renal failure to help reduce blood phosphate levels.
Describe Cytoprotectants?
Misoprostol, antacids and sucralfate - antacids e.g aluminium hydroxide - inactivate HCl, binds pepsin and bile salts also, binds intestinal phosphate (renal disease), can cause constipation, alkalinize urine (ion trapping and increase elimination of acidic drugs).
What is Sucralfate?
A dissacharide aluminium hydroxide product. In acidic environment acquires negative charge and binds to positively charged elements of exposed epithelial cels at sites of ulceration. It seals the ulcer, prevents leakage of protein and electrolytes abd binds epidermal growth factor. It requires an acid environment to work and binds to bile acids and pepsin. It increases local blood flow perhaps by increasing prostaglandin or NO locally. It acts locally - is not absorbed, it binds and inactivates cimetidine and other orally administered drugs.
Describe emollient laxatives?
Act locally - unchanged. They lubricate and soften the faecal mass. They include mineral oils and yellow and white soft parafiins. Prolonged use may reduce absorption of fat soluble vitamins. Local absorption may cause granulomatous lesions. May reduce bowel irritability leading to constipation.
Describe bulk laxatives
These are not absorbed but act locally. They are hydrophilic and absorb water increasing faecal bulk and water content and stimulating peristaltic movement. Examples include sterculia, Isphaghula and bran. Adequate water intake is crucial.
Describe osmotic laxatives
Examples iclude magnesum sulfate (Epsom salts), sodium sulfate (Glauber’s salt) and lactulose. These hypertonic solutions draw water into the intestine causng bowel distension and peristalsis. Water availability is crucial in the case of lactulose, intestinal PH is reduced, ammonia producing gut flora are reduced. Phosphates and sodium citrate are also used as osmotic laxatives. Administered as enema preparations. Phosphate enemas should not be given to small dogs and cats as this can induce hyperphosphataemia.
Describe stimulant laxatives?
Should neer be used if obstruction is suspected. Examples include bisacodyl and phenopthalein. These are diphenylmethane stimulants. Their precise mechanism of activity is not clear but they appear to stimulate colonic smooth muscle and the myenteric plexus. Phenopthalein undergoes some degree of enterohepatic recycling.
Describe Prokinetics
- Metoclopramide - used as an anti emetic, also used to prevent post op ileus in horses. 2. PArasympathomimetics such as carbachol - QAC and can cause intestinal rupture. 3. aantimicrobial erythromycin - has prokinetic effects probably through stimulaton of ACh release. 4. Ranitidine 5. Cisapride - acts primarily as an agonist at 5HT4 receptors in the GI tract. Increases lower oesophageal sphincter pressure, gastric emptyng, SI and colonic motility. More otent than metoclopramide. Administered orally. Withdrawn from market in UK and US human market.
Describe spasmolytics/drugs to treat diarrhoea
Antimuscarinics - eg atropine sulphate, propantheline and hyoscine. Propantheline is less lipid soluble than atropine so has reduced CNS effects. Opioids - diphenoxylate Hcl, codeine and lopearmide, increase segmental contractions and decrease peristalsis. Diphenoxylate and loperamide are both metabolised in the liver. Diphenoxylate s more completely absorbed following oral administration. Care should be taken when using in cats. Loperamide may be used in horses. Diphenoxylate combined with atropine available.
What are adsorbents?
Thought to adsorb toxins from the GI tract. They may also prevent the adsorption of other drugs. Examples include kaolin, pectin, bismuth salts, activated charcoal, calcium carbonate. Often used in combination in commercial products.
Describe Bismuth the Adsorbent?
Bismuth can come in a variety of forms. Bismuth subnitrate, subarinbate and subsalicylate. The subsalicyclate form is cleaved into bismuth and salicylate. The latter is systemically available and has anti prostaglandin effects - take care in cats. Has been shown to have antimicrobial and anti secretory effects in some species.
What is activated charcoal?
A very effective adsorbent. Used in the treatment of ingested toxins. Pore size is important. Powder more efficacious than tablets. Forms a stable complex with the substance which is then evacuated from the body.
Describe Cholestyramine
A drug used in human medicine to lower cholesterol. It stay sin the GI tract and binds bile acids, preventing their reabsorption. In rabbits it can be used in antibiotic induced diarrhoea as it binds and absorbs clostridia toxin.
How do appetite stimulants work?
Appetite mainly controlled by the ventral and lateral nuclei of the hypothalamas. Neurotransmitters involved - noradrenaline, dopamine and GABA stimulatory, serotonin inhibitory. Neuropeptides CCK, CRF and calcitonin inhibit appetite, while pancreatic polypeptides and opiates stimulate appetite.
What are the benzodiazepines used for?
Used as an appetite stimulant. Diazepam most effective. Used mainly in cats. Inhibits satiety centre and GABAminergic effects. Administered I/v.
What is cyproheptadine used for?
As an appetite stimulant - it has anti serotonin effects, good oral bioavailability with a half life of about 13 hours. It is given orally once or twice daily in cats.
What is ursodeoxycholic acid UDCA)?
It is a naturally occuring bile acid. It has less cellular toxicity than many other bile acids i.e hydrophobic membranocytolytic BAs. It is preferentially absorbed from the GI tract. It is also a choloretic agent increasing the elimination of toxic bile acids from the liver. It thereby helps protect the diseased liver from toxic bile acids. It is given orally once daily and should be avoided in biliary obstruction.
What is SAMe (S-adenosyl-L-methionine)?
It acts as a methyl donor. It has been shown to improve hepatic parameters in a number of disease conditions. It is important for a large number of processes within the liver including the formation of glutathione. Glutathione is important as an antioxidant and for the scavenging of ROS - glutathione often deficient in liver disease.
What is Silibinin (milk thistle)
It is thought to have antioxidant, anti inflammatory anti fiibrotic effects. It is thought to promote regneration. Experimentally protects dogs from amanita mushroom poisoning. Dosing is empirical - clinical efficiency not well established.
What are penicillamine and trientine used for?
Used in copper hepatotoxicoses. Penicillamine is an anti arthritis drug and also a chelating agent. It binds copper, should be given on an empty stomach., it has a variable oral bioavailability, mainly renal elimination but also hepatic, elimination is slow. Trientine - is an alternative to penicillamine, has been associated with acute renal failure in dogs.
