L8 - L13 Flashcards
Dry Granulation
- pressure is applied
- intermediate product is broken
- it is milled and sieved
good because there is less steps so more economical
cheap
copes with range of materials
Diarrhoea
- acute </= 14days
- persistent > 14days
- Chronic > 30 days
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
Causes of Diarrhoea
- Infectious + Non-Infectious
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
Mechanisms Causing Diarrhoea
- Cl- Transport in Intestine
- 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
- Cl- is secreted out of Cl- channels into lumen through apical membrane
- Na+ and water follow paracellularly (transcellular for water too)
Mechanisms Causing Diarrhoea
- Cholera Infection
- cholera toxins from Vibrio Cholerea enters cell activating G-protein which activates adenylyl cyclase
- which increases cAMP & PKA to open chlorine channels
- increased efflux of chlorine (and water) leading to diarrhoea
Mechanisms Causing Diarrhoea
- Increasing Motility
increasing intestinal motility will cause inadequate absorption
- drugs with cholinergic activity - pilocarpine
- Donepezil - prevents breakdown of ACh causing increased motility
Drug Treatment of Diarrhoea
- Anti Motility Drugs
Diphenoxylate + Codeine Phosphate
Diphenoxylate - usually given as mixture with atropine
- activates u opioid receptors decreasing ACh release
- causes decreased peristaltic activity & increasing segmental contraction
Codeine Phosphate - symptomatic relief of diarrhoea
- similar mechanism to diphenoxylate
- POM aswell
Consequences of Opiates Treating Diarrhoea
- rebound constipation if it slows transit too much
- higher doses can have CNS effects
- can lead to opioid dependence
Drugs Treating Diarrhoea
- Racecadotril
- Racecadotril is a pro-drug which is metabolised to thiorphan
- Thiorphan inhibits enkephalinase to stop the breakdown of enkephalins
- enkephalins activates S opioid receptor decreasing cellular cAMP levels which decreases secretion of Cl-
- less water will be secreted. diarrhoea will be cured
Constipation Causes
- Primary + Secondary
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
Drugs inducing Constipation
- Drugs with motility-slowing activity:
antidepressants, antihistamines, antimuscarinics - opioids
- drugs affecting electrolytes
- laxative misuse
Constipation Treatment
- Laxatives
osmotic - ispaglahusk, macrogol (laxido)
bulk-forming - Fybogel
stimulant - Bisacodyl (not for pregnant women)
faecal softeners - arachis oil
Constipation Treatment
- Linaclotide (osmotic)
- GC-c
- activates guanylate cyclase C (GC-C) which increases cellular cGMP & activates PKG
- this causes phosphorylation of CL- channel, opening it, allowing efflux of Cl-
- 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
Constipation Treatment
- Lubipristone
- activates CLC-2 channel
- derived from functional fatty acids
- can be taken orally, logP around 5
- Lubipristone directly activates a Cl- channel on apical membrane, CLC-2
- increases efflux of Cl- and water
side effects - diarrhoea, vomiting, nausea, abdominal pain
What Are Steroids
- derived from lanosterol in animals
- produced by adrenal glands in humans
- hormone molecules that control biological events
- Sex hormones, inflammation, immunomodulation, stress (cortisol)
- glucocorticosteroids important in controlling inflammation
- ALL share same 4-ring backbone
Steroid Backbone
A, B, C are 6-membered rings
D is 5-membered ring
Lipinsky Rule of 5
- for orally absorbed drugs
- 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
Administration and Formulation of Steroids
oral or rectal
- GR or MR or enaemae/foams
LogP values between 0.5 - 1.2 so absorption in stomach or colon
Antimotility Drugs
- codeine phosphate, diphenoxylate & morphine
- loperamide too but has evidence of Ca+ channel blocking
- have similar mechanisms of action
- 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.
Diarrhoea Treatment
Atropine
- Muscarinic ACH antagonist
- decreases ACh release and decrease peristaltic activity
- anti motility drug
Antimotility Drugs and Ionisation
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
Antimotility Drugs
- Racecodatril
- Racecodatril is pro-drug. metabolised into thiorphan
- thiorphan inhibits enkephalinase which lets enkephalins live longer
- 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
Reasons for MCR
- medicine care & review service
Prescribing - error rate 7.5%
Dispensing - error rate 3.3% of all prescriptions
Patient Compliance - non-compliance 30-50%
Workload
Patient Factors to go on MCR
- 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
Patients Unsuitable for Serial Script
- LT medicines with 24, 48, 52 week terms
- medicines cannot be altered must be cancelled
- drugs needing dose titrations
- patients whose medications frequently change
- patients who are admitted to hospital regularly
- controlled drugs and cytotoxins
- drugs needing close monitoring
Mucosal Malabsorption Diseases
Crohn’s or Coeliac
- abnormal epithelium so absorption is deficient
Surgical or Congenital Abnormality
- short bowel, less area for absorption
Pre-Mucosal Digestion Diseases
Cystic Fibrosis or Pancreatitis
- insufficient digestive agents, macronutrients not broken down
Small Intestine Bacterial Overgrowth
(mucosal and pre-mucosal)
- damage to mucosa
Crohn’s Disease (mucosal)
- Malabsorption linked to inflammation
common deficiencies
- Iron deficiency anaemia
- B12/folate deficiency
- Vit D + Calcium (osteoporosis and osteomalacia)
Coeliac (mucosal)
- glutenintolerance
- Autoimmune condition
- gluten activates abnormal mucosal response
- chronic inflammation and damage to small intestine mucosa
- fatigue, weight loss, diagnosed by serological testing
common complications: - anaemia
- osteoporosis (Vit D and Calcium malabsorption)
Treatment : remove gluten from diet
Short Bowel Syndrome
- usually from surgery
- can be congenital
- 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
Chronic Pancreatitis (pre-mucosal/digestive)
- strong association with excess alcohol
Inflammation of pancreas leading to decreased function
- less pancreatic enzymes
- can’t break down macro nutrients
Tests: faecal elastase + fat soluble vit deficiencies
Cystic Fibrosis (pre-mucosal/digestive)
- Inherited
- 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
Fat + Vitamin Malabsorption
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
Nutrient vs Malabsorption Symptom
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
