Antiemetic Drugs for diarrhea constipation pdf - د. نجلاء

Antiemetic , Drugs for

diarrhea &constipation

Drugs Used to Control Nausea and

Vomiting

Two brainstem sites have key roles in

the vomiting reflex pathway

the vomiting reflex pathway..

1. Chemoreceptor trigger zone (in area

Chemoreceptor trigger zone (in area

postrema

postrema at the caudal end of fourth

at the caudal end of fourth

ventricle) is outside the blood‐brain barrier.

2. Vomiting center (in the lateral reticular

Vomiting center (in the lateral reticular

formation of the medulla, coordinates the

motor mechanisms of vomiting).

Drugs Used to Control Nausea and

Vomiting

Two brainstem sites have key roles in

the vomiting reflex pathway

the vomiting reflex pathway..

1. Chemoreceptor trigger zone (in area

Chemoreceptor trigger zone (in area

postrema

postrema at the caudal end of fourth

at the caudal end of fourth

ventricle) is outside the blood‐brain barrier.

2. Vomiting center (in the lateral reticular

Vomiting center (in the lateral reticular

formation of the medulla, coordinates the

motor mechanisms of vomiting).

•• The vomiting center also responds to

The vomiting center also responds to

afferent input from the vestibular system,

the periphery (pharynx and

gastrointestinal tract), and higher

brainstem and cortical structures.

•• The vestibular system functions mainly in

The vestibular system functions mainly in

motion sickness.

•• The vomiting center also responds to

The vomiting center also responds to

afferent input from the vestibular system,

the periphery (pharynx and

gastrointestinal tract), and higher

brainstem and cortical structures.

•• The vestibular system functions mainly in

The vestibular system functions mainly in

motion sickness.

Causes of nausea and vomiting



Motion sickness



Pregnancy



Hepatitis



Chemotherapeutic agents

Classes of Anti Emetic



Phenothiazines

Serotonin‐receptor blockers



Benzamides



Butyrophenones



Benzodiazepines



Corticosteroids



Cannabinoids



Substance P/neurokinin‐

Substance P/neurokinin‐11‐receptor blocker

‐receptor blocker

Classes of Anti Emetic



Phenothiazines

Serotonin‐receptor blockers



Benzamides



Butyrophenones



Benzodiazepines



Corticosteroids



Cannabinoids



Substance P/neurokinin‐

Substance P/neurokinin‐11‐receptor blocker

‐receptor blocker

Phenothiazines

Prochlorperazine

Thiethylperazine



Blocking dopamine receptors



They are effective against low or

moderately

moderately emetogenic

emetogenic

chemotherapeutic agents

Side Effects

1. Hypotension

Hypotension

2. Extrapyramidal

Extrapyramidal symptoms and

symptoms and

sedation

sedation..

Phenothiazines

Prochlorperazine

Thiethylperazine



Blocking dopamine receptors



They are effective against low or

moderately

moderately emetogenic

emetogenic

chemotherapeutic agents

Side Effects

1. Hypotension

Hypotension

2. Extrapyramidal

Extrapyramidal symptoms and

symptoms and

sedation

sedation..

Serotonin‐Receptor Blockers (

Serotonin‐Receptor Blockers (55‐HT

‐HT33

Receptor Blockers)

Ondansetron

Granisetron

Palonosetron

Dolasetron

Mechanism of Action of

Mechanism of Action of 55‐HT

‐HT33

Receptor Blockers



Selectively block

Selectively block 55‐HT

‐HT33 receptors

receptors



In the periphery (visceral vagal afferent

fibers)



In the brain (chemoreceptor trigger zone).

Serotonin‐Receptor Blockers (

Serotonin‐Receptor Blockers (55‐HT

‐HT33

Receptor Blockers)

Ondansetron

Granisetron

Palonosetron

Dolasetron

Mechanism of Action of

Mechanism of Action of 55‐HT

‐HT33

Receptor Blockers



Selectively block

Selectively block 55‐HT

‐HT33 receptors

receptors



In the periphery (visceral vagal afferent

fibers)



In the brain (chemoreceptor trigger zone).

Pharmacokinetic of

Pharmacokinetic of 55‐HT

‐HT33

Receptor Blockers



These drugs can be administered as

a single dose prior to chemotherapy

(intravenously or orally)



Long duration of action.



Metabolized by the Liver to an

active metabolite ,eliminated

through the urine.

Pharmacokinetic of

Pharmacokinetic of 55‐HT

‐HT33

Receptor Blockers



These drugs can be administered as

a single dose prior to chemotherapy

(intravenously or orally)



Long duration of action.



Metabolized by the Liver to an

active metabolite ,eliminated

through the urine.

Side Effect of

Side Effect of 55‐HT

‐HT33 Receptor

Receptor

Blockers

1. Headache (common side effect).

Headache (common side effect).

2. Prolongation of QT Interval(with

Prolongation of QT Interval(with

dolasetron

dolasetron))

Side Effect of

Side Effect of 55‐HT

‐HT33 Receptor

Receptor

Blockers

1. Headache (common side effect).

Headache (common side effect).

2. Prolongation of QT Interval(with

Prolongation of QT Interval(with

dolasetron

dolasetron))

Benzamides

Metoclopramide is highly effective at high

doses against

doses against cisplatin

cisplatin,, preventing emesis

preventing emesis

in 30

30--40

40%

Side Effects

Antidopaminergic

Antidopaminergic side effects (sedation,

side effects (sedation,

diarrhea)

Benzamides

Metoclopramide is highly effective at high

doses against

doses against cisplatin

cisplatin,, preventing emesis

preventing emesis

in 30

30--40

40%

Side Effects

Antidopaminergic

Antidopaminergic side effects (sedation,

side effects (sedation,

diarrhea)

Butyrophenones

Droperidol

Domperidone

Haloperidol



Act by blocking dopamine receptors.



Moderately effective

Moderately effective antiemetics

antiemetics..



Droperidol

Droperidol had been used for sedation in

had been used for sedation in

endoscopy and surgery ( in combination with

opiates or benzodiazepines).



Haloperidol or

Haloperidol or metoclopramide

metoclopramide uesd

uesd for

for

preventing

preventing cisplatin

cisplatin‐‐induced emesis.

induced emesis.



The most important side effects is prolong the

QT interval

Butyrophenones

Droperidol

Domperidone

Haloperidol



Act by blocking dopamine receptors.



Moderately effective

Moderately effective antiemetics

antiemetics..



Droperidol

Droperidol had been used for sedation in

had been used for sedation in

endoscopy and surgery ( in combination with

opiates or benzodiazepines).



Haloperidol or

Haloperidol or metoclopramide

metoclopramide uesd

uesd for

for

preventing

preventing cisplatin

cisplatin‐‐induced emesis.

induced emesis.



The most important side effects is prolong the

QT interval

Benzodiazepines

Lorazepam

Alprazolam



Used in treating anticipatory vomiting.



Beneficial effects due to their sedative,

anxiolytic

anxiolytic properties.

properties.

Corticosteroids

Corticosteroids
Dexamethasone

Dexamethasone
Methylprednisolone

Methylprednisolone



Their antiemetic mechanism may involve

Their antiemetic mechanism may involve
blockade of prostaglandins.

blockade of prostaglandins.



Effective against mildly to moderately

Effective against mildly to moderately
emetogenic

emetogenic chemotherapy.

chemotherapy.



Used alone or in combination with other

Used alone or in combination with other
agents.

agents.

Corticosteroids

Corticosteroids
Dexamethasone

Dexamethasone
Methylprednisolone

Methylprednisolone



Their antiemetic mechanism may involve

Their antiemetic mechanism may involve
blockade of prostaglandins.

blockade of prostaglandins.



Effective against mildly to moderately

Effective against mildly to moderately
emetogenic

emetogenic chemotherapy.

chemotherapy.



Used alone or in combination with other

Used alone or in combination with other
agents.

agents.

Cannabinoids

Marijuana Derivatives

((Dronabinol

Dronabinol &

& Nabilone

Nabilone))



Effective against moderately

emetogenic

emetogenic chemotherapy.

chemotherapy.

Side Effects



hallucinations, sedation,

vertigo&disorientation

vertigo&disorientation..

Cannabinoids

Marijuana Derivatives

((Dronabinol

Dronabinol &

& Nabilone

Nabilone))



Effective against moderately

emetogenic

emetogenic chemotherapy.

chemotherapy.

Side Effects



hallucinations, sedation,

vertigo&disorientation

vertigo&disorientation..

Substance P/Neurokinin‐

Substance P/Neurokinin‐11‐Receptor Blocker

‐Receptor Blocker

Aprepitant



Antagonist

Antagonist to

to neurokinin

neurokinin receptor in the brain.

receptor in the brain.



Administered orally with

Administered orally with dexamethasone

dexamethasone and

and

palonosetron



little or no affinity for serotonin (

little or no affinity for serotonin (55--HT

HT33),),

dopamine, and corticosteroid receptors



Used for chemotherapy

Used for chemotherapy--induced nausea &

induced nausea &

vomiting and postoperative nausea and vomiting



Metabolisd

Metabolisd by CYP

by CYP33AA44..



Can also induce this enzyme

Side Effects



Constipation and fatigue (the major side effects).

Substance P/Neurokinin‐

Substance P/Neurokinin‐11‐Receptor Blocker

‐Receptor Blocker

Aprepitant



Antagonist

Antagonist to

to neurokinin

neurokinin receptor in the brain.

receptor in the brain.



Administered orally with

Administered orally with dexamethasone

dexamethasone and

and

palonosetron



little or no affinity for serotonin (

little or no affinity for serotonin (55--HT

HT33),),

dopamine, and corticosteroid receptors



Used for chemotherapy

Used for chemotherapy--induced nausea &

induced nausea &

vomiting and postoperative nausea and vomiting



Metabolisd

Metabolisd by CYP

by CYP33AA44..



Can also induce this enzyme

Side Effects



Constipation and fatigue (the major side effects).

Combination Regimens

Combination Regimens
Combination of Antiemetic Drugs

Combination of Antiemetic Drugs



Increase antiemetic activity



Decrease toxicity.



Dexamethasone + metoclopramide, a

Dexamethasone + metoclopramide, a 55‐HT

‐HT 33

antagonist,

antagonist, phenothiazine

phenothiazine,, butyrophenone

butyrophenone, a

, a

cannabinoid

cannabinoid, or a benzodiazepine

, or a benzodiazepine



Antihistamines (

Antihistamines (diphenhydramine

diphenhydramine ++

metoclopramide

metoclopramide or corticosteroids)

or corticosteroids)

Combination Regimens

Combination Regimens
Combination of Antiemetic Drugs

Combination of Antiemetic Drugs



Increase antiemetic activity



Decrease toxicity.



Dexamethasone + metoclopramide, a

Dexamethasone + metoclopramide, a 55‐HT

‐HT 33

antagonist,

antagonist, phenothiazine

phenothiazine,, butyrophenone

butyrophenone, a

, a

cannabinoid

cannabinoid, or a benzodiazepine

, or a benzodiazepine



Antihistamines (

Antihistamines (diphenhydramine

diphenhydramine ++

metoclopramide

metoclopramide or corticosteroids)

or corticosteroids)

Antidiarrheals

1. Antimotility

Antimotility agents

agents

2. Adsorbents

Adsorbents

3. Agents that modify fluid and electrolyte

Agents that modify fluid and electrolyte

transport

Antimotility

Antimotility agents

agents

Diphenoxylate

Loperamide



Have opioid‐like actions on the gut, activating

presynaptic opioid receptors in the enteric

nervous system (inhibit Ach release and

decrease peristalsis).

Side Effects



Drowsiness, abdominal cramps, and dizziness.



Toxic

Toxic megacolon

megacolon (they should not be used in

(they should not be used in

young children or in patients with severe colitis).

Antimotility

Antimotility agents

agents

Diphenoxylate

Loperamide



Have opioid‐like actions on the gut, activating

presynaptic opioid receptors in the enteric

nervous system (inhibit Ach release and

decrease peristalsis).

Side Effects



Drowsiness, abdominal cramps, and dizziness.



Toxic

Toxic megacolon

megacolon (they should not be used in

(they should not be used in

young children or in patients with severe colitis).

Mechanism of Action



Loperamide

Loperamide acts directly on circular and

acts directly on circular and

longitudinal intestinal muscles, through the

opioid

opioid receptor

receptor



Inhibits peristalsis



Reduces fecal volume



Increases viscosity



Diminishes fluid and electrolyte loss



Has

Has antisecretory

antisecretory activity

activity



Increases tone on anal sphincter

Mechanism of Action



Loperamide

Loperamide acts directly on circular and

acts directly on circular and

longitudinal intestinal muscles, through the

opioid

opioid receptor

receptor



Inhibits peristalsis



Reduces fecal volume



Increases viscosity



Diminishes fluid and electrolyte loss



Has

Has antisecretory

antisecretory activity

activity



Increases tone on anal sphincter

Adsorbent Agents

Kaolin

Pectin

Methylcellulose.

less effective than

less effective than antimotility

antimotility agents,

agents,

causing

causing constipation&interfere

constipation&interfere with

with

absorption of other drugs.

Adsorbent Agents

Kaolin

Pectin

Methylcellulose.

less effective than

less effective than antimotility

antimotility agents,

agents,

causing

causing constipation&interfere

constipation&interfere with

with

absorption of other drugs.

Agents that Modify Fluid and Electrolyte

Transport

NSAIDs (aspirin and indomethacin)



Effective in controlling diarrhea (due to inhibition of

prostaglandin synthesis).

Bismuth Subsalicylate



Salicylate component, inhibits intestinal PG &

Salicylate component, inhibits intestinal PG & Cl

secretion (decreases fluid secretion in the bowel) ,used

for traveler's diarrhea



Has antimicrobial effects and binds

Has antimicrobial effects and binds enterotoxins

enterotoxins



Has activity against H pylori

Side Effect of Bismuth Subsalicylate

1. Stool blackening

Stool blackening

2. Darkening of tongue

Darkening of tongue

3. Encephalopathy (headaches, confusion, seizures)

Encephalopathy (headaches, confusion, seizures)

Agents that Modify Fluid and Electrolyte

Transport

NSAIDs (aspirin and indomethacin)



Effective in controlling diarrhea (due to inhibition of

prostaglandin synthesis).

Bismuth Subsalicylate



Salicylate component, inhibits intestinal PG &

Salicylate component, inhibits intestinal PG & Cl

secretion (decreases fluid secretion in the bowel) ,used

for traveler's diarrhea



Has antimicrobial effects and binds

Has antimicrobial effects and binds enterotoxins

enterotoxins



Has activity against H pylori

Side Effect of Bismuth Subsalicylate

1. Stool blackening

Stool blackening

2. Darkening of tongue

Darkening of tongue

3. Encephalopathy (headaches, confusion, seizures)

Encephalopathy (headaches, confusion, seizures)

Laxatives



Accelerate the movement of food through

GIT.

Classification According to Mechanism

of Action

1. Irritants &

Irritants & stimulants of the gut

stimulants of the gut

2. Bulking agents

Bulking agents

3. Stool softeners

Stool softeners

Laxatives



Accelerate the movement of food through

GIT.

Classification According to Mechanism

of Action

1. Irritants &

Irritants & stimulants of the gut

stimulants of the gut

2. Bulking agents

Bulking agents

3. Stool softeners

Stool softeners

Irritants and Stimulants

Castor Oil



Castor oil is broken down in the small intestine to

very irritating acid to the gut



Increases peristalsis



Stimulate uterine contractions(avoided in pregnant

woman)

Cascara,

Cascara, Senna

Senna& Aloe

& Aloe



Stimulate colonic activity



Taken orally



Causes evacuation of the bowels within

Causes evacuation of the bowels within 88 to

to 10

10 hours

hours



It also causes water and electrolyte secretion into

the bowel.

Irritants and Stimulants

Castor Oil



Castor oil is broken down in the small intestine to

very irritating acid to the gut



Increases peristalsis



Stimulate uterine contractions(avoided in pregnant

woman)

Cascara,

Cascara, Senna

Senna& Aloe

& Aloe



Stimulate colonic activity



Taken orally



Causes evacuation of the bowels within

Causes evacuation of the bowels within 88 to

to 10

10 hours

hours



It also causes water and electrolyte secretion into

the bowel.

Bisacodyl



Potent stimulant of the colon. It

acts directly on nerve fibers in the

mucosa of the colon



Available as suppositories and

enteric

enteric--coated tablets

coated tablets



Cause

Cause abdominal cramps and

abdominal cramps and

potential for atonic colon with

prolonged use.

Bisacodyl



Potent stimulant of the colon. It

acts directly on nerve fibers in the

mucosa of the colon



Available as suppositories and

enteric

enteric--coated tablets

coated tablets



Cause

Cause abdominal cramps and

abdominal cramps and

potential for atonic colon with

prolonged use.

Bulk Laxatives

Hydrophilic Colloids



From indigestible parts of fruits and vegetables



Form gels in the large intestine



Causing water retention and intestinal

distension& increasing peristaltic activity.

Methylcellulose

Psyllium

Psyllium Seeds

Seeds

Bran



Have similar actions



May cause intestinal obstruction.

Bulk Laxatives

Hydrophilic Colloids



From indigestible parts of fruits and vegetables



Form gels in the large intestine



Causing water retention and intestinal

distension& increasing peristaltic activity.

Methylcellulose

Psyllium

Psyllium Seeds

Seeds

Bran



Have similar actions



May cause intestinal obstruction.

Saline and osmotic laxatives

Saline cathartics (magnesium citrate,

magnesium sulfate, sodium phosphate,

and magnesium hydroxide)



Nonabsorbable

Nonabsorbable salts ,hold water in the

salts ,hold water in the

intestine by osmosis and distend the bowel,

increasing intestinal activity and producing

defecation in a few hours.

Saline and osmotic laxatives

Saline cathartics (magnesium citrate,

magnesium sulfate, sodium phosphate,

and magnesium hydroxide)



Nonabsorbable

Nonabsorbable salts ,hold water in the

salts ,hold water in the

intestine by osmosis and distend the bowel,

increasing intestinal activity and producing

defecation in a few hours.

Lactulose



Semisynthetic disaccharide sugar ,acts as an

osmotic

osmotic laxative (

laxative (not hydrolyzed by intestinal

not hydrolyzed by intestinal

enzymes). Oral doses are degraded in the

colon by colonic bacteria into lactic, formic,

and acetic acids. This increases osmotic

pressure, thereby accumulating fluid,

distending the colon, creating a soft stool,

and causing defecation.

Lactulose



Semisynthetic disaccharide sugar ,acts as an

osmotic

osmotic laxative (

laxative (not hydrolyzed by intestinal

not hydrolyzed by intestinal

enzymes). Oral doses are degraded in the

colon by colonic bacteria into lactic, formic,

and acetic acids. This increases osmotic

pressure, thereby accumulating fluid,

distending the colon, creating a soft stool,

and causing defecation.

Stool softeners (emollient laxatives or

Stool softeners (emollient laxatives or
surfactants)

surfactants)
Docusate

Docusate sodium

sodium

Docusate calcium

Docusate calcium
Docusate

Docusate potassium

potassium



Surface

Surface--active agents (become emulsified with

active agents (become emulsified with

the stool produce softer feces



Take days to become effective.

Stool softeners (emollient laxatives or

Stool softeners (emollient laxatives or
surfactants)

surfactants)
Docusate

Docusate sodium

sodium

Docusate calcium

Docusate calcium
Docusate

Docusate potassium

potassium



Surface

Surface--active agents (become emulsified with

active agents (become emulsified with

the stool produce softer feces



Take days to become effective.

Lubricant laxatives



Mineral oil and glycerin suppositories are

considered to be lubricants(facilitate the

passage of hard stools)



Mineral oil should be taken orally in an

upright position (to avoid its aspiration &

lipid or lipoid pneumonia).

Lubricant laxatives



Mineral oil and glycerin suppositories are

considered to be lubricants(facilitate the

passage of hard stools)



Mineral oil should be taken orally in an

upright position (to avoid its aspiration &

lipid or lipoid pneumonia).