CICM First Part Exam Practice SAQs 05072019

Here are the practice questions from last week’s written exam practice session at The Alfred ICU, with recommended quick reference resources (but don’t forget to study the recommended texts!):

Q1.

Compare and contrast the pharmacology of metoclopramide and erythromycin when used as prokinetic agents.

Metoclopramide

A benzamide (chlorinated
procainamide derivative) 
Erythromycin

A macrolide
Dosage, route, and pharmaceutics
10mg Q8H IVclear, colourless solution for injection containing 5 mg/ml of metoclopramide hydrochloride
Tablets and syrup not typically used as prokinetics

 100mg Q6H or 250mg Q12H
Tablets and syrup not typically used as prokinetics (or topical!)
Mechanism of Action
Prokinetic effect due to:
1. antagonism of peripheral dopaminergic (D2) receptors
2. augmentation of peripheral cholinergic responses, and
3. direct action on smooth muscle to increase tone.
Effects:
Increased uterine peristalsis
Increase LOS tone
Accelerates gastric emptyingIncreases gastric contraction amplitudeDecreases SI transit time
Other:
anti-emetic effect (central D2, 5HT3 blocker, visceral nerve sensitivity effects)No effect on gastric secretion
 Prokinetic action due to agonism at motilin receptors
chronotropic effect on neuronal receptors
enhances motilin release from enterochromaffin cells in duodenum (stimulates MMC)
enhanced contractile effects on LOS tone, gastric antrum and duodenum
Other:
Macrolides are antibiotics that bind bacterial ribosomal proteins (50s subunit) and inhibit peptide translocase

Pharmacokinetics
A: IV (PO has rapid absorption but 32-97% bioavailability due to first pass metabollsim)
D: 13–22% protein-bound in the plasma; VD is 2.2–3.4 l/kg.M:  liver sulfation
E: Renal elimination of 20% unchanged, and as sulfated metabolite or conjugates with sulfate or glucuronide,  t ½ = 2.6-5h
Not removed by dialysis
A: IV (PO has (10–60% with first pass metabolism)
D: VD = 0.34–1.22 l/kg 
M: hepatic demethylation
E: CL 5–13.2 ml/min/kg; the half-life is 1.6 hours, with 2–15% of the drug being excreted unchanged in the urine Not removed by haemo ltration or dialysis
Adverse effects & interactions
prolonged QT
EPS – dystonic reaction esp in young females, akathisia, NMS
metHb in overdose
Drowsiness, neuroleptic effect
GI disturbance
Dizziness, Hypotension, arrhythmia, hypertension (phaeo)
Stimulates prolactin, aldosterone release
Allergy
CI: parkinson’s, gastric outlet obstruction

prolonged QT
hepatic dysfunction
overgrowth of non-susceptible organisms and clostridium difficile, possibly antibiotic resistance
drug interactions due to CYP450 3A4 inhibition: methylprednisolone, warfarin, phenytoin, ciclosporin, theophylline, sodium valproate, tacrolimus, midazolam, digoxin (all increased levels)
Porphyria
nausea, vomiting, and diarrhoea
Allergy
Possible ototoxicity
Other
Less effective single agent
Synergistic effect when used with erythromycin
Tachyphyllaxis after 72h


Most effective single agent
Synergistic effect when used with metoclopramide
Tachyphyllaxis after 72h

Q2.

Describe the gastrointestinal secretions from the salivary glands, stomach, and pancreas that have a role in digestion, including their regulation.

Learn more here:

http://www.partone.litfl.com/gastric_secretions.html

Q3.

Compare and contrast the digestion and absorption of fat, protein, carbohydrates

Note that storage and distribution is also included in the table below.

FatProteinCarbohydrates
Types
Triglycerides (TAGs) are main constituent of body fat & dietary fat
3 FAs + glycerol
Polypetides (chains of amino acids)mono-/ di-/ oligo-/ polysaccharides
Water solubility
Insoluble (LCFAs)
Clump together in chyme and are hard to digest due to the low surface area:volume ratio. 
SCFAs + MCFAs are soluble
SolubleSoluble
Speed of digestion
Slow
MediumRapid
Mouth
Mastication
Salivary lipase
Emulsified with phospholipid
MasticationMastication
Salivary amylase (amylose and amylopectin -> dextrins and maltose)
Stomach
Minimal (mechanical)
Denaturation (acid)
Pepsin
Mechanical
Minimal (mechanical)
Small intestine
Emulsification by:
bile salts – amphipolar molecules that form a mixed micelle with FAs which can be further digested by enzymes or directly absorbed;
Partially digested fat;
Mechanical action of the stomach

Once emulsified, triglycerides can be hydrolysed by pancreatic lipase into fatty acids and monoacylglycerol.
Pancreatic zymogens e.g. tryptase -> oligo-peptides and amino acids
Intestinal amino-peptidases -> di/tri-peptides and amino acids

pancreatic amylase (shorter chains)
Intesitinal disacharidases (sucrase, maltase, lactase)
Absorption in small intestine
Mixed micelles, free fatty acids, monoacylgylcerol, and cholesterols are absorbed via facilitated diffusion into the enterocyte (SI)
Transporters for amino-acids and di/tri-peptides in brush border of duodenum or proximal jejunum:
Facilitated diffusion
Active transport
Monosaccharide transporters in brush border:
Facilitated diffusion (fructose)
Active transport (glucose, galactose)
Distribution and storage

From the enterocyte:SCFAs (< 12 C atoms) enter the portal vein and travel directly to the liver
LCFAs are re-esterified and packaged with a layer of protein and cholesterol to form a chylomicron (CM)
Re-esterification maintains the concentration gradient for diffusion of fatty acids, allowing further uptake to occur.
CMs ejected into the lymphatics and travel to the systemic circulationCMs removed from circulation by lipoprotein lipase
Lipoprotein lipase is found on capillary endothelium and bound to albumin.
Lipoprotein lipase breaks down TAG in CM and VLDL to FFAs and glycerol (heparin cofactor)
FFAs and glycerol are then free to enter adipose tissue
Enter entero-hepatic circulation
50-65% remain in liver and are used to synthesize protein, nitrogen containing compounds and form purine/pyrimidine bases
Others enter circulation and taken up by all cells of the body
Glucose load stimulates biphasic insulin secretion from beta cells when BGL >5.6 mmol/L via GLUT2-mediated sensing.
Liver: 5% of ingested glucose is promptly converted to glycogen in the liver via GLUT2 transport; Activates glucokinase and glycogen synthase (while inhibiting liver phosphorylase); Excess glucose also converted to TAG in liver, then transported as VLDL to adipose tissue where they are converted to FFAs for uptake (promoted by insulin activation of lipoprotein lipase)
Adipose tissue: 30-40% ingested glucose is converted to fat; Uptake via insulin-induced GLUT4; Converted via glycolysis to glycerol and acetylCoA, leads to fatty acid formation
Skeletal muscle (and cardiac muscle): preferentially uses glucose due to insulin effect increasing GLUT4 transporters; replenishes glycogen stores 
Neurons: Glucose enters neurons without insulin effect via GLUT3
Other
Some SCFAs absorbed via colon from bacterial action on indigestible carbohydrates


CICM First Part Exam Syllabus

  • X1: Gastrointestinal Physiology
  • X2: Gastrointestinal Pharmacology

You can access all the previous practice questions since 2015 here:
https://docs.google.com/document/d/1r8JTbV6lEzMg7I0R5fCwPMaIY3elNobgcQy-bCt7F4M/edit?usp=sharing
See this link on INTENSIVE for exam resources:
https://intensiveblog.com/resources/#3

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