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MP322 > L8 - L13 > Flashcards

L8 - L13 Flashcards

1
Q

Dry Granulation

A
  1. pressure is applied
  2. intermediate product is broken
  3. it is milled and sieved

good because there is less steps so more economical
cheap
copes with range of materials

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2
Q

Diarrhoea
- acute </= 14days
- persistent > 14days
- Chronic > 30 days

A

Inflammatory - bacterial, viral, or parasitic infection

  • bloody stool, fever, abdominal cramping
  • small frequent bowel movements

Non-Inflammatory - watery, no fever

Osmotic - unabsorbed solutes, improves with fasting, small stool volume and due to malabsorption

Secretory - large volume.
altered ion transport across mucosa
- doesn’t improve with fasting

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3
Q

Causes of Diarrhoea
- Infectious + Non-Infectious

A

Infectious
bacteria - E. Coli, salmonella, C. dificille
viruses - rotavirus, norovirus, adenovirus
parasites - entamoeba histoltica, giarda lamblia

Non-Infectious (usually from medicines)
- CV Drugs - digoxin, propranolol, ACE inhibitors
- GI Drugs - antacids, laxatives, H2 antagonists
- Endocrine - oral hypoglycaemics, thyroxine
- Antibacterial - amoxicillin, erythromycin

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4
Q

Mechanisms Causing Diarrhoea
- Cl- Transport in Intestine

A
  1. when K+ is low inside cell the K+/Na+/Cl- cotransporter is activated bringing all 3 solutes from blood through basal membrane of epithelial cells
  2. Cl- is secreted out of Cl- channels into lumen through apical membrane
  3. Na+ and water follow paracellularly (transcellular for water too)
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5
Q

Mechanisms Causing Diarrhoea
- Cholera Infection

A
  1. cholera toxins from Vibrio Cholerea enters cell activating G-protein which activates adenylyl cyclase
  2. which increases cAMP & PKA to open chlorine channels
  3. increased efflux of chlorine (and water) leading to diarrhoea
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6
Q

Mechanisms Causing Diarrhoea
- Increasing Motility

A

increasing intestinal motility will cause inadequate absorption

  • drugs with cholinergic activity - pilocarpine
  • Donepezil - prevents breakdown of ACh causing increased motility
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7
Q

Drug Treatment of Diarrhoea
- Anti Motility Drugs

Diphenoxylate + Codeine Phosphate

A

Diphenoxylate - usually given as mixture with atropine

  1. activates u opioid receptors decreasing ACh release
  2. causes decreased peristaltic activity & increasing segmental contraction

Codeine Phosphate - symptomatic relief of diarrhoea
- similar mechanism to diphenoxylate
- POM aswell

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8
Q

Consequences of Opiates Treating Diarrhoea

A
  • rebound constipation if it slows transit too much
  • higher doses can have CNS effects
  • can lead to opioid dependence
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9
Q

Drugs Treating Diarrhoea
- Racecadotril

A
  1. Racecadotril is a pro-drug which is metabolised to thiorphan
  2. Thiorphan inhibits enkephalinase to stop the breakdown of enkephalins
  3. enkephalins activates S opioid receptor decreasing cellular cAMP levels which decreases secretion of Cl-
  4. less water will be secreted. diarrhoea will be cured
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10
Q

Constipation Causes
- Primary + Secondary

A

Primary constipation:
Normal-transit constipation
– difficult to empty bowel, possible IBD with constipation
Slow-transit constipation (colonic inertia)
– colon doesn’t transport substances along quick enough
Pelvic floor dysfunction
- Irritable bowel syndrome with constipation

Secondary:
- medications, metabolic disorders, endocrine disorders

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11
Q

Drugs inducing Constipation

A
  • Drugs with motility-slowing activity:
    antidepressants, antihistamines, antimuscarinics
  • opioids
  • drugs affecting electrolytes
  • laxative misuse
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12
Q

Constipation Treatment
- Laxatives

A

osmotic - ispaglahusk, macrogol (laxido)
bulk-forming - Fybogel
stimulant - Bisacodyl (not for pregnant women)
faecal softeners - arachis oil

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13
Q

Constipation Treatment
- Linaclotide (osmotic)
- GC-c

A
  1. activates guanylate cyclase C (GC-C) which increases cellular cGMP & activates PKG
  2. this causes phosphorylation of CL- channel, opening it, allowing efflux of Cl-
  3. water follows chlorine secretion into lumen
  • can’t be taken orally as doesn’t pass Lipinski 5 rule
    side effects - diarrhoea, vomiting, nausea, abdominal pain
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14
Q

Constipation Treatment

  • Lubipristone
  • activates CLC-2 channel
A
  • derived from functional fatty acids
  • can be taken orally, logP around 5
  1. Lubipristone directly activates a Cl- channel on apical membrane, CLC-2
  2. increases efflux of Cl- and water

side effects - diarrhoea, vomiting, nausea, abdominal pain

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15
Q

What Are Steroids
- derived from lanosterol in animals
- produced by adrenal glands in humans

A
  • hormone molecules that control biological events
  • Sex hormones, inflammation, immunomodulation, stress (cortisol)
  • glucocorticosteroids important in controlling inflammation
  • ALL share same 4-ring backbone
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16
Q

Steroid Backbone

A

A, B, C are 6-membered rings
D is 5-membered ring

17
Q

Lipinsky Rule of 5
- for orally absorbed drugs

A
  • molecular weight under 500Da
  • no more than 5 H bond donor groups
  • no more than 10 H bond acceptor groups
  • LogP less than 5
  • doesn’t apply to antibiotics because they are partially derived from nature
18
Q

Administration and Formulation of Steroids

A

oral or rectal
- GR or MR or enaemae/foams

LogP values between 0.5 - 1.2 so absorption in stomach or colon

19
Q

Antimotility Drugs

  • codeine phosphate, diphenoxylate & morphine
  • loperamide too but has evidence of Ca+ channel blocking
  • have similar mechanisms of action
A
  • agonist to u opioid receptors on neuronal varicosities which decreases ACh release which decreases peristaltic activity

codeine relatively lipophilic due to aliphatic tertiary amine
- mixed with acid to make salt form, codeine phosphate
- increases solubility helping with absorption.

20
Q

Diarrhoea Treatment
Atropine
- Muscarinic ACH antagonist

A
  • decreases ACh release and decrease peristaltic activity
  • anti motility drug
21
Q

Antimotility Drugs and Ionisation

A

ionised by forming salt
- antimotility drugs (except racecodatril) have aliphatic tertiary amine making it extremely lipophilic and LogP above 5

  • reacted with acid in stomach to form salt to make it more readily dissolved so it can be absorbed
  • it creates equilibrium with parent drug (unionised form) to absorb through membranes into blood
22
Q

Antimotility Drugs
- Racecodatril

A
  1. Racecodatril is pro-drug. metabolised into thiorphan
  2. thiorphan inhibits enkephalinase which lets enkephalins live longer
  3. enkephalins active S opioid receptors to decrease cellular cAMP levels which reduce electrolyte secretion
  • not formulated as a salt because there is no tertiary amine or groups to dissociate as a salt
23
Q

Reasons for MCR
- medicine care & review service

A

Prescribing - error rate 7.5%
Dispensing - error rate 3.3% of all prescriptions
Patient Compliance - non-compliance 30-50%
Workload

24
Q

Patient Factors to go on MCR

A
  • must be permanently registered with GP in scotland
  • have one or more LTC that requires medication
  • high risk medications
  • smoking cessation and gluten-free foods
  • new medicines
25
Q

Patients Unsuitable for Serial Script
- LT medicines with 24, 48, 52 week terms
- medicines cannot be altered must be cancelled

A
  • drugs needing dose titrations
  • patients whose medications frequently change
  • patients who are admitted to hospital regularly
  • controlled drugs and cytotoxins
  • drugs needing close monitoring
26
Q

Mucosal Malabsorption Diseases

A

Crohn’s or Coeliac
- abnormal epithelium so absorption is deficient

Surgical or Congenital Abnormality
- short bowel, less area for absorption

27
Q

Pre-Mucosal Digestion Diseases

A

Cystic Fibrosis or Pancreatitis
- insufficient digestive agents, macronutrients not broken down

Small Intestine Bacterial Overgrowth
(mucosal and pre-mucosal)
- damage to mucosa

28
Q

Crohn’s Disease (mucosal)
- Malabsorption linked to inflammation

A

common deficiencies
- Iron deficiency anaemia
- B12/folate deficiency
- Vit D + Calcium (osteoporosis and osteomalacia)

29
Q

Coeliac (mucosal)
- glutenintolerance
- Autoimmune condition

A
  1. gluten activates abnormal mucosal response
  2. chronic inflammation and damage to small intestine mucosa
  3. fatigue, weight loss, diagnosed by serological testing

common complications: - anaemia
- osteoporosis (Vit D and Calcium malabsorption)

Treatment : remove gluten from diet

30
Q

Short Bowel Syndrome
- usually from surgery
- can be congenital

A
  • may require parenteral nutrition
  • if on other medications, higher dose required (contraceptives, thyroid, folic acid)
  • osteoporosis and vitamin deficiencies
  • requires supplementation of calcium, vit D & minerals
31
Q

Chronic Pancreatitis (pre-mucosal/digestive)
- strong association with excess alcohol

A

Inflammation of pancreas leading to decreased function
- less pancreatic enzymes
- can’t break down macro nutrients

Tests: faecal elastase + fat soluble vit deficiencies

32
Q

Cystic Fibrosis (pre-mucosal/digestive)
- Inherited

A
  • Decreased Cl- secretion, increased Na+ absorption
    = thick mucus – inhibits absorption

Steatorrhea - fat in stools
osteoporosis , Malnutrition , weight loss

Treatment: pancreatic enzyme supplements, Fat-soluble vitamin supplements, calorie replacement

33
Q

Fat + Vitamin Malabsorption

A

problem with absorption or digestion (insufficient enzymes or bile)
- causes steatorrhea ( fat in stools)

Fat Malabsorption impacts absorption of fat soluble vitamins A, D, E & K

Vit D deficiency- osteoporosis, osteomalacia (rickets)
Vit K deficiency - clotting problems

34
Q

Nutrient vs Malabsorption Symptom

A

Fat - steatorrhea
Protein - weight loss, malnutrition
Carb - bloating, diarrhoea, flatulence
Vit D/Calcium - osteoporosis and bone problems
Vit E - neurological problems
Vit K - coagulation problems
Vit A - night blindness

MP322 (4 decks)

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