Drugs Affecting Gut Motility Flashcards
Breifly describe the myogenic control of the gut.
Rhythmic contraction co-ordinated by slow waves of depolarisation throughout the smooth muscle. Current spreads passively across gap junctions.
Which cells act as the gut motility pacemakers?
Interstitial cells of cajal
Which nerves stimulation increases force of gut contractions?
Post-ganglionic cholinergic enteric part of the ANS.
Which nerves inhibit guy contraction?
Non-adrenergic inhibitory NS
What is Auerbach’s plexus?
Nerve plexus that lies between the circular and longitudinal muscle layers
What is Meissner’s plexus?
Nerve plexus that lies within the submucosa
What is Hente’s plexus?
Nerve plexus that lies in the circular muscle adjacent to submucosa
What is Cajal’s plexus?
Nerve plexus in circular muscle adjacent to longitudinal muscle.
What is the main action of the intestino-interstinal inhibitory reflex?
Distension of one part of the intestine causes inhibition of the whole.
What does gastrin promote?
Acid secretion
What does cholecytokinin promote?
Small intestine - release of bile from gall bladder and enzymes from pancreas
What can we do for nausea and vomiting?
Give an anti-emetic
What is emesis?
Vomiting!
Gastric contents is propelled through a relaxed oesophagus and cardia due to abdominal wall and diaphragm contraction.
What causes emesis?
Pregnancy Medications Toxins Pain Irradiation Smell/touch RICP Stomach stretching or inflammation Rotational movement
What central pathway is important in emesis?
Central chemosensory trigger zone (vomiting centre within it).
Which apparatus is involved in emesis?
Vestibular apparatus
Medullary centre
4th ventricle
Decribe the inputs to the medulla in the mechanism of emesis.
Ach and H1 from vestibular apparatus, and Dopamine from the 4th ventricle -> Medullary centre (ACh, H1, 5HT3)
What broad classes of drug can we use as anti-emetics?
- D2 receptor antagonists
- 5-HT3 receptor antagonists
- Antimuscarinics
- H1 receptor antagonists
- Other agents
What other agents can be used in anti-emesis?
Cannabinoids e.g. nabilone
Benzodiazapines e.g. lorazepam
What D2 antagonists can we use as anti-emetics?
Domperidone
Metoclopramide
Phenothiazines
What 5-HT3 antagonists can we use as anti-emetics?
Ondansetron
Granisetran
What antimuscarinics can we use as anti-emetics?
Hyosine
What H1 antagonists can we use as anti-emetics?
Cyclizine
Promethazine
Which antiemetic is indicated for acute N/V?
Domperidone
Which antiemetic is indicated firts line for radiation sickness, chemotherapy sickness, or post-operatively?
Ondansetron
Which antiemetic is indicated for GI N&V, migraine sickness, or post-op most commonly?
Metoclompromide - most commonly prescribed anti-emetic
Which agent is effective for motion sickness as well as an add on in chemotherapy?
Hyosine
Which anti-emetic is the second most commonly prescribed? Why?
Cyclizine - different mechanism to metoclompromide but v efficacious
Which agent is good for opioid induced N&V?
Promethazine
Where does domperidone work?
Postrema on the floor of the 4th ventricle and locally in the stomach to increase the rate of gastric emptying
How can domperidone be given?
PO or PR
Why is PO administration not ideal in this class of drug?
Coz if they’re actively vomiting, how are we going to get it down them??
Does domperidone cross the BBB?
No
What are the potential ADRs of domperidone?
Galactorrhoea (stimulates prolactin release)
Dystonia (rare)
Where does ondansetron work?
Postrema on floor of 4th ventricle
Vagal afferent nerves of GI tract
How can ondansetron be given?
IV
IM
Orally
What can we give alongside ondansetron to increase its efficacy as an anti-emetic?
Single dose of a corticosteroid (prednisolone or hydocortisone).
What are the ADRs of ondansetron?
Headaches
Constipation
Flushing if given IV
Aside from its main effect, what other MoA does metoclopramide have?
Anti-cholinergic effect and blocks vagal afferent 5-HT3 receptors
How is metoclopramide given?
PO
IV
IM
How frequently should metoclompramide be given and why?
3 times a day as the t1/2 is roughly 4 hours
What are the ADRs associated with metoclopramide?
Extrapyramidal S/Es in 1% of pts
Galactorrhoea
Who should we avoid giving metoclopramide?
Parkinson’s pts
How can we administer hyoscine?
PO
Patch (transdermal)
How long do the effects of hyoscine usually work?
For roughly 2 hours
What ADRs are associated with hyoscine?
Systemic anticholinergic effect
Bradycardia
Aside from its H1 antagonism, what other effect can cyclizine have?
Anti-muscarinic effects
How can cyclizine be given?
PO
IV
IM
Who should avoid cyclizine?
Pts with myocardial ischaemia or on medications that prolong QT interval.
How does cyclizine have a sedative effect?
It crosses the BBB
What is the major ADR associated with cyclizine?
QT prolongation
What kinds of laxative are there?
Non-pharmacologically Bulk forming Faecal softeners Osmotic laxatives Irritant/stimulant
How can we target constipation non-pharmacologically?
By looking at the causes and treat this to treat the symptom (constipation)
What can cause constipation?
DM PD Dehydration Pregnancy Mechanical obstruction Cancer Drugs
Which drugs are the worst offenders for causing constipation?
Opioids
What interventions can we use to treat constipation conservatively?
Increase fluid intake
High fibre diet
Exercise
Stop/reduce opioids
Other than opiods, what other drugs can cause constipation?
Anticholinergics Alluminium antacids TCAs SSRIs Antiepileptics Antipsychotics Antispasmodics Ca2+ supplements Diuretics via dehydration Iron supplements Verapamil
Decribe how bulk laxative work.
Insoluble and non-absorbable substances that cause gut distension and draw in water to stimulate peristalsis
What diet component is most like bulk laxatives?
Fibre from plants/cellulose, bran, linseed, etc
What are the 2 main bulk laxatives?
Fybogel
Ispaghula
How long do bulk laxatives take to work?
A few days
What is important when taking bulk laxatives?
Fluid intake must remian normal
Ideally pt should be on a high fibre diet.
What is the main ADR associated with bulk laxatives?
Flatulance
When are bulk laxatives contraindicated?
GI adhesions or ulceration
Why are bulk laxatives contraindicated in these situations?
They may cause intestinal obstruction
Enema vs suppository
Enema is liquid (or even sometimes gas), suppository is solid like a tablet. Both inserted into the rectum.
What are the 2 types of faecal softeners?
Arachis oil (enema) Glycerol (suppository)
Are faecal softeners good?
Safe, but not always effective
When are faecal softeners indicated?
Same as bulk laxative but can also be given in the presence of adhesions, anal fissure, or haemorrhoids.
What are the osmotically active laxatives?
Mg and Na salts
Lactulose
Macrogols
What are Mg and Na salt laxative also known as?
Saline purgatives, or phosphate enemas
How do saline purgatives work?
Cause water retention in bowel to increase peristalsis
How quickly do salt purgatives work?
Very, and very effectively too.
What is lactulose?
Disaccharide of galactose and fructose that cannot be hydrolysed in digestive enzymes
How does lactulose work as a laxative?
Lactulose is fermented by gut bacteria to form acetic and lactic acids. These draw in water for an osmotic effect.
How long does lactulose take to work?
~48 hours
Which laxative is good in liver failure and why?
Lactulose as it reduced production of ammonia by gut bacteria
What is the macrogol ive heard of?
Movicol i.e. polyethylene glycol
How is movicol given?
Orally as a powder with fluid
How quickly does movicol work?
Initially within a few hours, but full effect takes 2-4 days
Which laxative is given most commonly 1st line in hospitals?
Lactulose
What do we need to be aware of with osmotically active laxatives?
Caution is required to prevent intestinal obstruction
What are the irritant/stimulant laxatives?
Senna
Bisacodyl
Castor oil
Sodium picosulphate
How do irritant laxatives work?
Excite sensory nerve endings -> water and electoryle retention, and peristalsis
When are irritant/stimulant laxatives used most commonly?
Alongside an osmotic laxative
In faecal impaction
Surgical prep
How quickly do irritant laxatives work?
within 6-8 hours, so take them at night for a poop in the morning.
What is a problem associated with repeated use of irritant laxatives?
Colonic atony -> constipation
Also hypokalaemia
Tell me about castor oil.
Powerful laxative
Give PO
Works in ~ 3 hours for watery stool.
Obsolete clinically***
Which of the irritant laxative are most commonly used?
Anthraquinones (including Senna)
What can senna cause?
Abdominal cramps
What can overuse of senna etc cause?
Melanosis coli
How does senna work?
Broken down by gut bacteria to produce anthranol and 1,8 - dihydroxy-anthrone
How do we decide which laxative to use?
By whether the stool is hard or soft, and any contraindications.
How does long term laxative use lead to hypokalaemia?
Decreased water and Na uptake from gut, so increased renal retention of water and Na, in exchange for K excretion.
What is most diarrhoea like in terms of duration?
Self limiting
What do we need to keep an eye on with diarrhoea?
Dehydration, and electrolyte balance
What could diarrhoea be a symptom of, if not infective in nature?
Constipation (overflow diarrhoea)
What are the 3 type of anti-diarrhoea medication?
Antimotility
Bulk forming
Fluid absorbants
What are the anti-motility diarrhoea drugs?
Opiate analgesics, or opiate alanogues
Which opiate analgesic can we use in diarrhoea?
Codeine
Why are opiate analogues better?
Work on opiate receptors in gut much more effectively than morphine, but don’t pass into CNS well.
What are anti-motility diarhhoea drugs good for, and bad for?
Good for chronic diarrhoea
Bad for IBD (as can cause toxic megacolon)
What opiate analogues are there?
Loperamide
Imodium
Which anti-diarrhoea drugs are good for IBS or those with an ileostomy?
Bulk forming ones
Why are bulk formers good for IBS pts?
Can be used to treat constipation and diarrhoea! Magic…..
What is kaolin?
A fluid adsorbent
Is kaolin used much?
No
Are there specific drugs for specific causes of diarrhoea?
Yes
What are the specific causes of diarrhoea that we can target?
Bilt salt induced
Pancreatic malabsorption
How can we treat bile salt induced diarrhoea?
With cholestryamine, a bile acid sequestrant.
How can we treat pancreatic insufficency-induced diarrhoea?
Pancreatci enzymes
How can we treat gut hypermotility?
With smooth muscle relaxants such as peppermint oil, alverine, and mebeverine.
Tell me about mebeverine.
Reserpine derivative.
Relieves spasms of intestinal muscle
Useful alongside a bulk forming agent
No systemic antimuscarinic ADRs
