drugs acting on GIT + antiemetics + diuretics Flashcards
what drugs do you know that act on the GIT?
those that regulate acid
* ant acids
* H2 receptor antagonists
* PPI
* prostaglandins
those that regulate gastric emptying
* prokinetics
* slow gastric emptying - opioids
those that influence N&V
* emetic agents
* antiemetic agents
what are the roles of antacids? give examples
antacids work via neutralisation of stomach acid.
most commonly either Mg or alimium salts
e.g. Mg Carbonate or aliminium hydroxide.
also calcium carbonate.
these react with HCL to produce salts and CO2 and water.
relieve gastritis, protect ulceration
there is also sodium citrate often used in obsterics for emergency section.
common side effects of ant acids
magnesium = diarrrhoea
aliminum = constipation
can alter absorption of other compounds e.g. aspirin
belching due to CO2 production
which drugs act as mucosal protectors?
sucralfate
produces a physical barrier protecting mucosal layer.
no systemic effect, no change to pH or motility
however can reduce absorption of other drugs. e.g. warfarin.
what drugs act as prostaglandin analogues? side effects?
misoprostil = can be used to prevent ulcers by improving blood flow to mucosa and promoting mucus secretion
side effects include - increases uterine tone, diarrhoea, menorrhage
give examples of H2 antagonists and their mechanism
ranitidine, cimetidine , famotidine
competitive antagonism H2 receptors on parietal cells and preventing stimulation to acid release
hence reduces HCL production
what are the side effects of H2 antagonist?
cimetidine - CYP450 inhibitor, can cause bradycardia and hypotension, antiandrogenic (low sperm, gynacomastia)
ranitidine - link to gastric cancers so not used as much. can cause arrhtyhmias IV
give examples of PPIs and how they work?
omeprazole (20mg/40mg or IV 40mg), lanzoprazole (15mg/30mg), pantoprazole
work via irreversible inhibtion of H/K ATPase synthesis. leads to destruction of these proteins
increases pH
reduces gastric secreteions
describe the pharmacokinetics of PPIs..
omeprazole is a prodrug, activated within parietal cells.
hepatically metabolised and renal/bile excretion
lansoprazole, faster onset, better for severe cases
how does metaclopramide work?
normally a dopamine receptor antagonist for N&V
also
binds 5HT3 in gut on vagal afferent ending
increases stimulation of vagus nerve
release of Ach - increased motility, relaxed pylorus
which drugs affect gastric motility ?
prokinetics - erythromycin (motilin receptor), neostigmine (increased Ach), metoclopramide (5HT3 antagonist)
inhibition - opioids of u receptor in myenteric plexus. antimuscarinics (hyoscine, atropine)
how can antiemetics be classified?
by receptor mechanism
4 main NT involved in N&V= Acetylcholine, dopamine, histamine, serotonin
also substance P (neurokinin)
hence
5HT3 antagonist = ondansetron
H1 = cyclizine, promethazine
muscarinic receptor antagonist = hyoscine
dopamine antagonist = metaclopramide, domperidone , prochlorperizine
what are the uses of D2 recpetor antagonist?
mainly used as antipsychotics
but also in N&V
side effects of D2 antagonists antiemetics..
related to reduced dopamine
extrapyramidal effects = parkinsonism, occulogyric crisis, tardative dyskinesia, neuroleptic malignant syndrome
high prolactin - galactorrhoea, gynaecomastia
which D2 antagonist does not cause parkinsonism symptoms?
domperidone antiemetic that doesnt cross BBB so more favourable side effects.
what anti-emetics can be used in parkinsons
avoid D2 receptor antagonism
although can use domperidone - doesnt cross BBB
cyclizine or ondansetron can be used
describe a hollistic anti-emetic strategy…
prevention - identify those at risk, use TIVA, avoid N20 , avoid dehydration , opioid sparring
anti-emetics - ondansetron and dexamethasone pre op
technique - reduced gastric inflation , regional anaesthesia
post op - cyclizine, ondansetron as rescue , good pain management
which drugs act on the chemoreceptor trigger zone and nucleus tractus solitarus?
CTZ = D2, 5HT3
NTS = H1 and AchR
which antiemetics are used in kids
ondansetron, dexamethasone
avoid cyclizine esp under 6
what are the features of neuroleptic malignant syndrome and how is it managed?
incidious onset from too little dopamine
rigidity, hyperthermia, confusion
sweating, tachycardia
stop treatment
bromocriptine / dantrolene / procyclidine
cooling
how is occulogyric crisis treated?
procyclidine
can you classify the diuretic agents..
can be classed by location they act
PCT - carbonic anhydrase inhibitors e.g. acetazolamide
LoH -
* osmotic diuretic (mannitol),
* loop diuretics (furosemide, bumetanide) - inhibit Na/K/Cl pump
DCT
* thiazides (indapamide, bendroflumethazide) - inhibit Na/Cl cotransporter
* ENaC - block Na rebsorption - amiloride - later in DCT
collecting duct
* aldosterone inhibitors - spironolactone , epleronone. inhibit synthesis of ENaC, Na/K ATPase, H/K. hence Na reabsorption
what is mannitol?
polysaccrahide alcohol derivative that is not digested and thus acts osmotically within vasculature.
classed as an osmotic diuretic
180 daltons so freely filtered at kidneys, not reabsorbed, so draws water into tubules by osmosis.
in circulation also acts via osmosis e.g. across BBB to reduce oedema.
can also be used in bowel prep acting locally to draw water into the bowel when given enterally
due to its osmotic effects it also increases circulatory volume and so contraindicated in HF
cant be used if BBB is damaged or repeatedly as eventually crosses BBB whcih would result in worsening of oedema
dose 1g/kg
how does acetazolamide work?
inhibits carbonic anhydrase in PCT
carbonic anhydrase is responsible for conversion of H20 and CO2 to H2CO3.
this normally produces H+ and HCO3 which are implicated in Na and Cl reabsorption
hence reduces NaCl reabsorption = diuresis
but also treats metabolic alkalosis by excreting HCO3
what are the uses of acetazolamide?
diuretic
treatment of metabolic alkalosis
or respiratory altitude e.g. altitude sickness
glaucoma
anti-epileptic
how do loop diuretics work?
inhibit Na/2Cl/K ATPase on TAL
less of these reabsorbed
less negative osmotic gradient created by loop of henle - less water can be reabsorbed.
more ions excreted in filtrate
what are the indications for furosemide?
pulmonary oedema
congestive cardiac failure
promote diuresis in CKD/AKI
other forms of fluid over load e.g. cirhosis and acites.
treatment of hypercalcaemia
side effects of furosemide?
volume related - orthostatic hypotension, reduced GFR (may worsen AKI), reduced preload and CO.
electrolyte - low K, low Ca, high Na
CVS - also has mild vasodilatory effect - reduced SVR
other = ototoxic
what are the pharmokinetics of furosemide like?
IV or oral
-good BO
minimally metabolised, mostly excreted renally un changed
how do diuretics effect levels of Na and K
lowers
inhibits Na/Cl symptorter in early DCT
so less Na reabsorbed
more Na delivered to later tubules
therefore drives Na/K ATPase
hence more K excreted too
indications for thiazides?
diuretic - HF
HTN
hypercalcauria - reduces Ca excretion in urine
pharmacodynamics of thiazides
CVS - hypotension (less effective than loop), vasodilation
renal - reduced GFR
electrolyte - lowers Na, K, increases Ca ,
can precipitate gout and hyperglycaemia
impotence, rash
how do thiazides and loop diuretics effect acid base balance?
loop - acidaemia
thiazides - alkalosis
what is a thiazide like diuretic?
e.g. indapamide
acts like thiazide
but slightly different structure - no benzothiazide ring
how does spironolactone work? including pharamacodynamics
competitive aldosterone receptor inhibitor - intracellular receptor, alters gene expression
reduced ENaC, Na/K ATPase, Na/H , K channels
results in
excretion of Na + hence water + hypotension
reabsorption of K
acidosis
other - gynaecomastia
when is spironolactone used?
K+ sparing diuretic e.g. when K low and diuresis is required - liver disease
conns syndrome
advantage of epleronone over spironolactone
fewer anti-androgen effects
no gynaecomastia
what is amiloride?
ENaC channel inhibitor
on distal DCT
Na excreted because reabsorption inhibited
less K excreted so increases K
what are the unwanted effects of acetazolamide?
can cause a metabolic acidosis
what are the other effects of mannitol (other than osmotic diuresis)
free radical scavenger - may protect brain against reperfusion
release of renal prostaglandins - protects kidneys, improves blood flow
tell me about ondansetron..
commonly used anti emetic for preventive and treatment of N&V perioperatively and in medicine
5HT3 antagonist
comes as clear colourless solution - 2mg/ml
given as 4mg /8mg IV or orally and also IM TDS
or dose of 0.1mg/kg in paediatrics
pharmacodynamics
- blocks 5HT3 peripherally and at vomitting centre
- GI - constipation
- long QT , bradycardia
- neuro = flushing, headaches
kinetics
- oral, IM, IV - 60% BO . takes about 30mins to work.
- large VD
- hepatic metabolism, inactive metabolites
- renally excreted
- half life 3 hours
tell me about cyclizine
piparazine derivative
commonly used antiemetic perioperatively and in community and other fields of medicine
works via H1 antagonism
comes as clear colourless solution of 50mg / ml. diluted up to 10ml of saline
given as 50mg TDS (25mg in elderly)
or 1mg/kg in children
also as oral tablets - 50mg
dynamics
H1 receptor antagonisms
mostly in vestibular apparatus and NTS
so good for motion sickness
also has some anti-muscarinic actions
CVS - tachycardia, arrhythmias
CNS - drowsiness, feeling of high when given too quickly
GI - dry mouth
kinetics
- IV/ PO - good BO 80%
- large Vd
- liver and renal
how does aprepritant work?
neurokinin 1 receptor antagonist
blocks substance P effects
has a role in N&V
relatively new class of antiemetic
traditionally given in chemo
how does hyoscine work? side effects
hyoscine is a muscarinic antagonist (M3)
2 forms - hyoscine hydrobromide and hyoscocine butylbromide
hyoscine hydrobromide = works in CNS (NTS and vestibular centre) as antiemetic. also has sedative effects and can cause hallucinations/ confusion.
hyoscocine butylbromide = works periphrally at gut to prevent spasms = buscopan
tell me about dexamethasone
synthetic glucocorticoid
used for N&V prevention, supression of inflammatory disease, CNS pathology (tumours), croup, covid pneumonitis and septic shock
comes as clear colourless solution 3.3mg/ml.
usually 6.6mg given IV (0.1mg/kg in children)
can also be given orally
pharmacodynamics
- effects of steroids
- GI - anti-emetic
- metabolic - increases glucose (glycogenolysis, gluconeogenesis), lipolysis
- CVS - fluid retention and Na retention, HTN
- CNS - changes to mood and sleep, reduced oedema
- long term - osteoporosis, muscle breakdown.
- can cause peroneal burning if given IV
caution in diabetics
kinetics
IV / oral - good BO
large Vd
hepatic and kidneys
what is metoclopramide?
antiemetic agent
D2 antagonist (also with 5HT3 inhibition and Ach stimulation)
also works as a prokinetic
can be given orally or IV or IM
given 10mg TDS
pharmacodynamics
GI - antiemetic, increased motility, increased LOS, reduced pylorus tone
CNS - extrapyramidal
endocrine - hyperprolactin
tell me about prochlorperazine
antiemetic and antipsychotic agent
works via D2 antagonism
can be given IM or IM
side effect - extrapyramidal, hyperprolactin
also long QT
