9. GI drugs Flashcards
Alpha glucosidase inhibitors
slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity.
Biguanides
Reduce hepatic glucose output and increase peripheral cellular glucose uptake.
The meglitinides
Short-acting secretogogues acting on a different site of the KATP receptors.
The sulphonylureas
Insulin secretogogues, stimulating insulin secretion from beta cells of pancreatic tissue. These inhibit the KATP channels.
The thiazolidinediones
Influence insulin-sensitive genes,
enhance production of mRNAs of insulin-dependent enzymes. The final result is better use of glucose by the cell
Omperazole What How works & reacts w/ Enzyme inhib? T1/2 Intractions
Omeprazole is a proton pump inhibitor (PPI) that is inactive at neutral pH.
In an acid environment it rearranges into two types of reactive molecule that react with sulphydryl groups in the hydrogen ion/potassium ion ATPase (not hydroxyl groups).
The enzyme is irreversibly inhibited and thus acid secretion resumes only after new enzyme is synthesised.
Omeprazole has an elimination half life of 40 minutes.
Proton pump inhibitors are associated with many drug interactions that include enhancing the effect of phenytoin and warfarin, and the possible inhibition of diazepam metabolism.
Most common causes of drug-induced dystonic reactions are: x3
neuroleptics (antipsychotics)
antiemetics (especially prochlorperazine, and metoclopramide)
antidepressants
Prochlorperazine - problems
Rx
3 lines
ological sequelae following the administration of the neuroleptic agent, prochlorperazine, is 16% restlessness (akathisia) and 4% dystonia.
Specific treatment of dystonia include:
Benztropine (first line treatment):
Adult - 1-2 mg by intravenous injection
Child - 0.02 mg/kg to maximum of 1 mg
Benzodiazepines (second line treatment).
Midazolam:
1-2mg intravenously, or
diazepam dose 5-10mg IV/PO
Antihistamines (H1receptor antagonists) with anticholinergic activity:
used especially if benztropine is not available
promethazine 25-50 mg IV/IM, or
diphenhydramine 50 mg IV/IM (1 mg/kg in children).
NAC
How to know when use
Empiric used?
When to stop
Microcirc
Anaphylaxis
Check @ 4 hours
Plot on nomogram - rx line
8 + hours
Level not avail <8h
Uncert timing
Unconcious patient
INR <2
microcirculation has been shown to improve.
Non-toxic sulphation of paracetamol is increased by NAC and it has additional antioxidant properties.
Anaphylactoid reactions can occur in as many as 15% of patients
HT3 act
Tropisetron
granisetron
specific 5-HT3 receptor antagonists and block receptors in the gastrointestinal tract and central nervous system
Metoclopramide is predominantly a dopamine antagonist that acts centrally at the chemoreceptor trigger zone, but at high doses it competitively antagonises 5-HT3 receptors.
Ranitidine
lansoprazole
actions
is an H2 receptor antagonist and
lansoprazole blocks the hydrogen-potassium adenosine triphosphate enzyme system (proton pump inhibitor).
Metoclopramide acts
Metoclopramide is predominantly a dopamine antagonist that acts centrally at the chemoreceptor trigger zone, but at high doses it competitively antagonises 5-HT3 receptors.
Hypokalaemia
Thiazides inhibit sodium reabsorption at the distal convoluted tubule. Hypokalaemia is a common side-effect.
Insulin
*avoid dig - higher toxicity
Hyperkalaemia
Aldosterone antagonists (for example, spironolactone) are used as potassium sparing diuretics and may cause hyperkalaemia.
ACE inhibitors may cause hyperkalaemia. Inhibition of angiotensin II results in a reduction in aldosterone levels. Aldosterone is a steroid hormone with mineralocorticoid activity, is mainly recognized for its action on sodium reabsorption in the distal nephron of the kidney, which is mediated by the epithelial sodium channel (ENaC). Associated with sodium absorption is potassium excretion. Inhibition is likely to cause significant hyperkalaemia.
Causes of DI
Causes of diabetes insipidus (DI) include:
Lithium
Gentamicin
Amphotericin B and
Demeclocycline (not tetracycline, amoxicillin, and salbutamol).
Alcohol interacts w/
Griseofulvin
Triazolam and chlorpropamide (effects are potentiated)
Metronidazole causes an “Antabuse” reaction.
Carbimazole
What class
Used for
How
Safe preg?
Dose?
Prob baby
Breast feeding?
S/E
Thionamide - thyrotoxicosis
blocking the iodination of thyroid hormone.
Safe - low dose
may cause fetal hypothyroidism.
appear in milk - ok if development mon it
Side effects include
rash,
hair loss and
rarely agranulocytosi
Bilirubin
where conjugated by what
incr by & inhib by
Conjugation occurs in the hepatocytes and is catalysed by the enzyme glucuronyl transferase.
Increased by rifampicin, which is an enzyme inducer, and inhibited by valproate.
lbert’s syndrome the bilirubin cannot enter the hepatocyte causing unconjugated bilirubinaemia.
With Crigler-Najjar syndrome the bilirubin cannot conjugate causing unconjugated bilirubinaemia.
In Dubin-Johnson syndrome the conjugation is unimpaired but the bilirubin cannot leave the hepatocyte causing conjugated bilirubinaemia.
Paracetamol metabolism
Glutathione is rapidly exhausted
ph1 = NAPQI
bind sulphylhydryl group & = centrilob necro
Depletion of glutathione results in high levels of NAPQI with the potential for hepatocellular damage
Gastric emptying
Delay
Alcohol Dopamine Anticholinergics Mid-late 3rd trimester Fear Anxiety Pain
Prokinetic drugs such as metoclopramide, erythromycin and cisapride promote gastric emptying.
GI Luminal pressure
Neostigmine
(other se
Sux
Morphine
Isoflurane
adrenaline
Neostigmine is an acetylcholinesterase inhibitor used to increase the concentration of acetylcholine at the neuromuscular junction and promotes muscarinic effects:
Bradycardia Increased gastrointestinal motility and intraluminal pressure Increased bladder contractility Sweating Miosis Bronchospasm.
Suxamethonium is a depolarising muscle relaxant that is structurally composed of two acetylcholine molecules joined together and produces muscarinic effects resulting in increased gastrointestinal motility and increased intraluminal pressure.
Morphine increases tone and decreases motility in many parts of the gastrointestinal tract.
Isoflurane like all the volatile anaesthetic agents relaxes smooth muscle and potentiates the effect of non-depolarising muscle relaxants, but has no effect on the gastrointestinal tract.
Epinephrine does not increase intraluminal pressure.
Omeprazole
use
- Gastric ulcer disease,
- Reflux oesophagitis
- Zollinger-Ellison
Omeprazole irreversibly blocks the proton pump by forming a stable co-valent bond with K+/H+-ATPase found in the parietal cells of the stomach. K+/H+-ATPase is the final common pathway for gastric acid secretion. As the half-life of renewal of the pumps is about 18 to 24 hours, a single intake allows an inhibition of almost 24 hours.
Omeprazole will decrease both the volume and the acidity of the gastric secretions.
Side effects include an inhibition of hepatic cytochrome P450, rashes and gastrointestinal disturbance.
Omeprazole is a prodrug as it is degraded by gastric acid. It is prepared as an enterically coated capsule and is absorbed from the small intestine.
Omeprazole undergoes hepatic metabolism to inactive metabolites which are excreted in the urine (80%) and the bile (20%
Pred 5mg equivalent to
Hydrocort
Cortisone
Dexamethasone
Methylpred
Prednisolone 5 mg is equivalent to hydrocortisone 20 mg.
Prednisolone 40 mg is equivalent to 8 × 20 mg = 160 mg.
Prednisolone 5 mg is equivalent to :
Cortisone acetate 25 mg
Dexamethasone 750 mcg
Hydrocortisone 20 mg
Methylprednisolone 4 mg.
Metoclopramide
antag @
Side effects
Rx w/
Fx on LES & Barrier
Although it primarily has an antagonistic action at dopamine receptors, metoclopramide is a 5-hydroxytryptamine (5-HT) antagonist at higher doses. Its extrapyramidal side effects can be treated with procyclidine which has antimuscarinic properties.
Metoclopramide is relatively free of side effects, apart from oculogyric crises (an extrapyramidal effect) and drowsiness.
The peripheral effects of metoclopramide inhibiting the action of dopamine are illustrated by its enhancement of antral and fundal contractility and relaxation of the pylorus. The net effect is to increase the rate of gastric emptying.
The lower oesophageal sphincter pressure is, however, increased and this leads to an increase in barrier pressure.
Increases barrier pressure.
Decreased LES
Vasopression
effect
Synthesized in released
Anabolic effect
Vasopressin has a very strong pressor effect, and is synthesised in the hypothalamus, but is released from the posterior pituitary.
Peripheral resistance to insulin is often seen in non-insulin dependent diabetes mellitus (type II) and plasma levels may be normal.
Insulin does have anabolic effects.
Corticosteroids are used in the management of Addison’s disease and have many side effects including osteoporosis and hyperglycaemia.
What diabetic drug needs to be ommited before surgery
safe to continue
The sodium-glucose co-transporter-2 (SGLT-2) inhibitors (gliflozins) lower blood sugar by preventing glucose reabsorption by the renal proximal convoluted tubule.
They have been linked with the development of post-operative euglycaemic ketoacidosis. SGLT-2 is expressed in pancreatic alpha-cells, and SGLT-2 inhibitors promote glucagon secretion.
A decrease in the renal clearance of ketone bodies may contribute to metabolic disturbance. This is more likely with prolonged starvation, metabolic surgical stress and inter-current illness.
Drugs that require omission on the day of surgery when fasting due to the risk of hypoglycaemia include the
Meglitinides (e.g. repaglinide, nateglinide) and the Sulphonylureas (e.g. glibenclamide, gliclazide and glipizide).
Drugs that when fasting that can be continued include:
Acarbose
Dipeptidyl peptidase-IV (DDP-IV) inhibitors (e.g. sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin)
Glucagon-like peptide-1 (GLP-1) analogues (e.g. exenatide, liraglutide, lixisenatide)
Metformin
Pioglitazone
Prokinetics y / n
Metoclopramide
Cisapride
Erythryomycin
Dopexamine
Vanc
Pro-kinetic drugs increase the rate of gastric emptying and intestinal motility.
Metoclopramide, cisapride and erythromycin have all been successfully used in this role.
Loperamide is an opioid agonist which reduces intestinal motility.
Dopexamine increases splanchnic perfusion but does not have pro-kinetic properties.
Vancomycin similarly has no therapeutic effect on intestinal motility.
