Drugs influencing GIT motility

Local
Emetics
Central

Drugs influencing GIT

motility

Emetics &
antiemetics

Anticholinergic

Anti-diarrhoeal
agents

Antihistamine

Laxative and
cathertics

Antiemetics

D2 receptor
antagonist
5HT3 receptor
antagonist
Cannabinoids

Emetics & Antiemetics

Definition
Emetics:
Drugs which induce vomiting
Therapeutic emesis is rarely
required except in cases of
poisoning
Antiemetics:
Drugs which suppress the vomiting
If the cause of vomiting cant be
removed, it may be desirable to
attempt to prevent / suppress it by
drugs to the consequences of
vomiting

Pathophysiology N&V
Vomiting center loosely organized neuronal region & coordinates act of vomiting thru
interactions w/ CN VIII,CN X & NTS
Sources afferent input to vomiting center:
1. Chemoreceptor trigger zone (CTZ) which is outside the BBB & accessible to
emetogenic stimuli in blood / CSF. It rich in dopamine D2 receptor & opiod
receptors, serotonin 5HT3 & NK1 Receptors
2. Vestibular system motion sickness via CN VIII & rich in muscarinic M1 &
histamine H1 receptors
3. Vagal & spinal afferent nerves from GIT rich in 5 HT3 receptors. Irritation of GIT
by chemotherapy, distention, acute infectious gastroenteritis release mucosal
serotonin & activation of the receptors stimulate vagal afferent input to
vomiting center & CTZ
4. CNS: psychiatric disorders, stress

1.
2.
3.
4.
5.
6.

Types
Local
mustard & water
warm hypertonic solution of
salt
salts of heavy metals
1% Cupric sulphate
1% Zinc sulphate
Ipecac*** (alkaloid) syrup

MOA: irritate sensory nerve

endings in the pyloric half of the
stomach

Central
1. Apomorphi
ne selective
action on
CTZ
2. Ipecacuanh
a - locally
irritates the
gut &
centrally
acts on
CTZ

Emetics
Indications
1. Acute
1.
poisoning
by noncorrosive
substances
2.
2. Acute
indigestion
due to
3.
excessive
intake of
4.
food

CI
Poisoning by corrosives - cause scarring
eg, strong acids & alkalis - gastric perforation & damage
to esophagus
petroleum distillates - chemical pneumonitis due to
inhalation
Comatose, stuporous or delirious patients d/t
asphyxiation & aspiration pneumonia d/t lack of coughing
reflex
Pregnancy, hernias, advanced PU & other GI erosions d/t
intra-abdominal pressure is dangerous
Cardiac decompensated patient & hypertensive patient
d/t BP
5. Young children, debilitated patient d/t BP

Antiemetics
Drugs
1. Anticholinergics: Hyoscine

Classification
Site of action
Vomiting center &

Drugs
4. 5HT3 receptor

Site of action
CTZ & gut

MOA
Act either on Vomiting
Center(VC) / on CTZ

2. Anti-histamine:
Cinnarizine
Cyclizine
Meclizine
Diphenhydramine (Benedryl)
Dimenhydrinate (Dramamine)
Promethazine (Phenergan)
3. D2 receptor antagonists Phenothiazines:
o Chlorpromazine(Buromazine)
o Prochlorperazine (Stemetil)
o Perphenazine
Butyrophenone : Haloperidol
Metoclopramide
Domperidone (Motilium)

Hyoscine
(Scopolamine)
Cyclizine &
Meclizine

Promethazine

gut
Vomiting center
and gut

antagonists
Ondansetron
Tropisetron
Granisetron
5. Cannabinoids:
Nabilone
Pronabilol
Dronabinol

CTZ

Anti-emetic effect
1. VC anticholinergic
action, antihistaminic
action
2. CTZ - antidopaminergic /
5HT3 antagonist action

CTZ

CTZ
CTZ & gut
CTZ & gut

MOA
block central muscarinic receptor on VC & gut
(relaxation of GIT)

PK / Dosage
0.65 - 0.75 mg
IM

Inhibition of histamine receptor & cholinergic

receptor in VC

1. Cyclizine shortest
DOA, 50
mg TDS
2. Meclizine longest
DOA, 24
hrs / more,
single dose
50 mg
Dose- 25 mg
BD

chemically a phenothiazine but functionally an

antihistamine

Uses
motion sickness (given 1
hr b4 journey, lasts for 4
- 6 hrs)
Meclizine: motion
sickness & Rx vertigo d/t
labryth dysfx

morning sickness

CI / DI

Diphenhydram
ine &
dimenhydrinat
e
Phenothiazine
&
chlorpromazin
e
Prochlorperazi
ne &
perphenazine
Metochlopromi
de

Sedating properties

Dose- 50 - 100
mg TDS

central inhibition of dopamine receptor on CTZ

(w/ non sedative dose)

motion sickness &

Menieres disease

Drowsiness (common)

Phenothiazine: potent
antiemetic & sedative

Dose - 25 - 50
mg 8 hourly IM
*structurally related to procainamide (lacks LA &
antiarrhythmic action)

Actions
1. antiemetic action
2. prokinetic action lower esophageal sphincter tone
gut peristalsis & emptying ,relaxation of
pyloric antrum & duodenal cap
MOA:
1. Central: inhibits dopamine D2 r/c on CTZ
2. Peripheral All these facilitate ACh release
from enteric neurons
may be d/t 5HT4 r/c agonistic action
5HT3 r/c antagonist action
D2 r/c blocking action on cholinergic enteric
neurones

rapidly &
completely
absorbed
1st pass
metabolism
present
Bioavailabil
ity 75%
T : 4-6 hr
Dose: 10
mg 8
hourly oral,
IM, IV

w/ piperazine side chain

are more powerful
antiemetics
1. Gastro esophageal
reflux disease
(together with
antisecretory drugs)
2. patients w/ delayed
gastric emptying d/t
postgastrectomy,
diabetes
gastroparesis
3. Non ulcer dyspepsia
(symptomatic
improvement in
chronic dyspepsia)
4. small bowel
intubation
5. to empty stomach
before emergency
anaesthesia & labour
6. prevention & Rx
vomiting caused by GI
disorder, cytotoxic

drowsiness,hypotensi
on, extrapyramidal
effects
A/E
1. extrapyramidal
dystonia: >
common in
children & young
adults w/ high
dose fatigue,
motor restless,
spasmodic
torticollis
(involuntary
twisting of neck),
occulogyric crises
(involuntary
upward eye
movement)
2. gynaecomastia,
galactorrhoea (due
to prolactin
secretion),
menstrual disorder

drugs, radiation &

uraemia

3. somnolence,
drowsiness,
dizziness,
diarrhoea
CI
1. intestinal
obstruction
2. perforation
3. haemorrhage

Domperidone

MOA
1. blocks dopamine receptor in CTZ (D2)
2. activation of dopamine receptor inhibit
cholinergic smooth muscle activation
blockade of D2 receptor oeso & gastric
contraction
Actions
1. tone in lower esophageal sphincter
2. Relax pyloric sphincter
3. Not penetrate well into BBB (no CNS effects)
4. Antagonise D2 in pituitary (prolactin level)
5. block adrenoreceptor increase motility by
relaxation

Ondansetron

Nabilone

dose 8 mg
TDS

vomiting d/t stimulation of CTZ, used when other

drugs failed

for cytotoxic drug

induced & radiation
induced vomiting , postop vomiting

Motion sickness

Hyoscine
best for motion
sickness, short
lasting
Other drugs:
o Cinnarazine
o Cyclizine
o Dimemhydrinate
o Promethazine
For prophylaxis, an
antiemetic is best
taken 1 hr before
exposure to the
motion
Once motion sickness
has started, IM, SC or
rectal routes are
required
Alternatively,
hyoscine may be
administered as a
dermal patch

Management
Vomiting d/t cytotoxic drug
Vomiting after
general anaesthesia
Metoclopramide
5HT3 receptor antagonist
or
(ondansetron) effective
5HT3 receptor
For severe vomiting,
antagonist
ondansetron plus
(ondansetron)
dexamethasone w/ or w/o
or
lorazepam (all given IV)
butyrophenone
most effective combination &
(haloperidol,
well tolerated
droperidol)
Metoclopramide may be
substituted for ondansetron

Vomiting d/t pregnancy

Occurs at 10-11
weeks & usually
resolves by 13-14
weeks of gestation
By reassurance that
the problem is
transient &
discussion of diet*
Rarely, decision is
taken to take a drug
H1 receptor
antagonist or
phenothiazine (eg,
promethazine) is
preferable
Pyridoxine deficiency
may occur in
hyperemesis
gravidarum which
requires IV fluids &
multivitamin
supplement

Vertigo

Antimuscarinics
&
phenothiazines
are generally
preferable
Cyclizine /
prochlorperazine
may be used to
relieve an acute
attack
Betahistine (a
histamine
analogue) used to
improve blood
circulation to the
inner ear in
Menieres disease;
also cinnarazine