Treatment of patients with vomiting

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antiemetic drug classes mechanism of action vomiting treatment diagram

A pathophysiology diagram and pharmacological algorithm illustrating the mechanisms of chemotherapy-induced nausea and vomiting (CINV) and the corresponding sites of action for anti-emetic agents. The central anatomical figure is a sagittal section of the human brain, highlighting the Higher Centers (processing sensory/emotional stimuli), the Vomiting Center (VC) in the medulla, and the Chemoreceptor Trigger Zone (CTZ). Neural pathways connect these central regions to peripheral effectors including the GI tract and the diaphragm. The diagram maps specific drug classes to their molecular targets: 5-HT3 Receptor Antagonists (5-HT3 RA), NK1 Receptor Antagonists (NK1RA), Dexamethasone, and Olanzapine. These agents are shown inhibiting various receptors including 5-HT3, D2 (dopamine), NK1 (neurokinin-1), and H1 (histamine) receptors within the CTZ and peripheral pathways. Dexamethasone is specifically noted for its role in inhibiting prostanoid influx. Solid red lines represent predominant mechanisms of action, while dashed lines indicate minor pathways. This educational visual summarizes multi-receptor antagonism strategies used in clinical oncology to manage nausea and vomiting reflexes.

A pathophysiology diagram illustrating the mechanism of action for Antibody-Drug Conjugates (ADCs) in prostate cancer treatment. The visual depicts a three-stage sequence: antigen recognition, targeting, and apoptosis. At the top, ADCs are shown as blue Y-shaped monoclonal antibodies carrying cytotoxic 'drug' payloads (represented by pink, green, and orange ovals). These conjugates approach pink, irregularly shaped prostatic tumor cells that express specific surface antigens. A legend identifies seven key prostate cancer-associated antigens: STEAP-1 (blue crescent), B7-H3 (green curve), TROP2 (pink star), HER2 (red curve), PSMA (orange curve), TF (blue triangle), and CD46 (purple curve). The middle section shows the ADCs binding to these specific surface markers. A red downward arrow indicates the subsequent progression to 'Cell death,' where the tumor cells are rendered as shrunken, darkened gray structures. This diagram serves as an educational resource for oncology and pharmacology, highlighting selective targeting through antigen-specific recognition to deliver cytotoxic agents directly to malignant cells while sparing healthy tissue.

This pathophysiology diagram illustrates the mechanism of action for antibody-drug conjugates (ADCs) in the treatment of prostate cancer. The visual is divided into a three-step progression. First, an ADC is depicted consisting of a blue Y-shaped monoclonal antibody connected via a green 'Linker' to a yellow hexagonal 'Drug' (cytotoxic payload). Second, a central prostate cancer cell is shown expressing several key targetable surface antigens: PSMA (red triangle), TROP2 (green star), STEAP-1 (blue rectangles), CD46 (purple rectangle), and B7-H3 (orange trapezoid). An arrow indicates the first clinical phase where the ADC binds to these specific antigens. Third, the diagram depicts the outcomes of internalization, leading to the release of the cytotoxic agent and culminating in the final stage: 'Cell death', represented by a shrunken, irregular apoptotic cell. This educational graphic focuses on oncology pharmacotherapy and molecular targeting for metastatic castration-resistant prostate cancer (mCRPC).

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Treatment of Patients with Vomiting

The approach to treating vomiting depends on identifying the underlying cause. Treatment combines general/supportive measures and specific pharmacological therapy targeted at the pathophysiological mechanism.

1. General and Supportive Measures

Correct fluid and electrolyte imbalances (IV or oral rehydration as appropriate).
Identify and treat the underlying cause (e.g., bowel obstruction, diabetic ketoacidosis, raised intracranial pressure, medications, infections).
Withhold oral intake temporarily if vomiting is severe; gradually reintroduce clear fluids.
Consider nasogastric tube decompression if obstruction is suspected.
Non-pharmacological options: acupressure at the P6 (Nei Guan) point has shown benefit in some settings, particularly postoperative nausea and vomiting (PONV). Ginger (6-gingerol, 6-shogaol components act on 5-HT3, D2, NK1, and histamine receptors) has antiemetic properties in multiple clinical settings.

2. Pharmacological Treatment by Drug Class

The choice of agent depends on the cause of vomiting. The major drug classes are summarized below.

Antiemetic drug classes - mechanisms and sites of action (CTZ, vomiting center, GI tract)

A. Anticholinergic / Antihistamine Agents

Best for: Motion sickness, labyrinthine disorders (vertigo, labyrinthitis), uremia, PONV

Drug	Dose	Route
Scopolamine patch	1.5 mg / 72 hr	Transdermal
Meclizine	25-50 mg every 24 hr	PO
Dimenhydrinate (dimethindrine)	50-100 mg every 4-6 hr	PO, IM, IV
Cyclizine	50 mg every 8 hr	PO, IM
Diphenhydramine	25-50 mg every 6 hr	PO, IV, IM
Promethazine	25 mg every 6-12 hr	PO, PR, IV, IM

Side effects: Sedation, dry mouth, blurred vision, urinary retention, delirium (use with caution in the elderly). Avoid with alcohol or other CNS depressants.

B. Dopamine Receptor Antagonists (D2 blockers)

Best for: Gastroenteritis, toxin-induced vomiting, PONV, mildly emetogenic chemotherapy

Drug	Dose	Route
Prochlorperazine	5-10 mg every 6-8 hr (or 25 mg PR every 12 hr)	PO, IV, IM, PR
Metoclopramide	10-20 mg every 6-8 hr	PO, IV, IM
Trimethobenzamide	200-300 mg every 6-8 hr	IM, PO
Domperidone	Peripheral D2 antagonist; not available in the US	PO

Side effects: Extrapyramidal symptoms (dystonia, tardive dyskinesia - especially with long-term metoclopramide use), restlessness, galactorrhea, cardiac arrhythmias (domperidone). The FDA has issued a black box warning for metoclopramide regarding irreversible tardive dyskinesia with long-term use.

Metoclopramide as a prokinetic: It also stimulates gastric emptying via 5-HT4 receptor facilitation and D2 antagonism - useful in gastroparesis.

C. Serotonin (5-HT3) Receptor Antagonists

Best for: Chemotherapy-induced nausea and vomiting (CINV), radiotherapy-induced vomiting, PONV

Drug	Dose	Route
Ondansetron	4-8 mg every 8 hr	PO, IV
Granisetron	1 mg twice daily; or 3.1 mg/24 hr transdermal patch	PO, transdermal
Dolasetron	50-100 mg once	PO
Palonosetron	0.25 mg once (long-acting, half-life ~40 hr)	IV

Side effects: Constipation, headache, fatigue, QT prolongation/cardiac arrhythmias (particularly dolasetron). These are generally the safest and most widely used antiemetics.

D. Neurokinin-1 (NK1) Receptor Antagonists

Best for: Highly emetogenic chemotherapy (added to a 5-HT3 antagonist + dexamethasone regimen); PONV prophylaxis

Drug	Dose	Route
Aprepitant	125 mg day 1, then 80 mg on days 2-3	PO
Fosaprepitant	150 mg on day 1	IV

Side effects: Anorexia, fatigue, hiccups, constipation. Moderate CYP3A4 inhibitor - check drug interactions.

E. Corticosteroids

Best for: CINV prophylaxis and treatment (often combined with 5-HT3 and NK1 antagonists); PONV

Drug	Dose	Route
Dexamethasone	4-20 mg before chemotherapy or surgery	IV, PO

Mechanism in antiemesis is uncertain but likely involves prostaglandin inhibition. Highly effective when used in combination regimens.

F. Atypical Antipsychotics

Best for: Highly emetogenic chemotherapy (as a substitute or add-on); refractory CINV

Drug	Dose	Notes
Olanzapine	5-10 mg once daily	Multi-receptor antagonist (D2, 5-HT2, H1, M1)

Olanzapine-containing regimens are now considered a standard option for highly emetogenic chemotherapy alongside NK1 antagonists.

G. Cannabinoids

Best for: CINV refractory to conventional antiemetics

Drug	Dose	Route
Dronabinol (THC)	2.5 mg twice daily	PO
Nabilone	1-2 mg twice daily	PO

Side effects: Dysphoria, sedation, hallucinations, anxiety.

H. Benzodiazepines

Best for: Anticipatory emesis (anxiety-related nausea before chemotherapy)

Drug	Dose	Route
Lorazepam	0.5-2 mg before chemotherapy	IV, PO

I. Prokinetic Agents (Macrolide Antibiotics)

Best for: Gastroparesis, delayed gastric emptying

Erythromycin (motilin receptor agonist): stimulates antroduodenal contractions. Narrow dose range of efficacy; associated with tachyphylaxis and risk of sudden cardiac death (especially with CYP3A inhibitors).
Azithromycin, clarithromycin: similar motilin receptor action, used off-label in gastroparesis.

3. Treatment by Clinical Scenario

Cause of Vomiting	Preferred Agents
Motion sickness	Scopolamine patch, meclizine, dimenhydrinate
Viral gastroenteritis	Ondansetron, prochlorperazine, metoclopramide
PONV (prophylaxis/treatment)	Ondansetron, dexamethasone, scopolamine, aprepitant, droperidol
Mildly emetogenic chemotherapy	5-HT3 antagonist + dexamethasone
Highly emetogenic chemotherapy	5-HT3 antagonist + NK1 antagonist + dexamethasone ± olanzapine
Anticipatory emesis (pre-chemo)	Lorazepam
Gastroparesis	Metoclopramide, domperidone, erythromycin
Pregnancy (NVP / hyperemesis)	Pyridoxine (B6) ± doxylamine (first-line); phenothiazines; ondansetron
Refractory nausea/vomiting	Olanzapine, cannabinoids (dronabinol)

4. Refractory and Structural Options

For vomiting refractory to medical therapy in gastroparesis, more invasive options may be considered:

Gastric electrical stimulation (neurostimulator implant)
Peroral endoscopic pyloromyotomy (POP) - endoscopic procedure to divide the pyloric muscle

5. Special Populations

Pregnancy: First-line is pyridoxine (Vitamin B6) ± doxylamine (FDA-approved combination). Phenothiazines and ondansetron are used in more severe cases; however, some data suggest a possible link between ondansetron and cardiac septum defects (inconsistent evidence - consult current guidelines).
Children (PONV): Ondansetron is the preferred agent; aprepitant and dexamethasone are also used. Promethazine is avoided in children under 2 years.
Elderly: Anticholinergic agents should be used cautiously due to delirium risk. Extrapyramidal reactions with dopamine antagonists are more common.

Recent Evidence

A 2025 systematic review and Bayesian network meta-analysis in Annals of Emergency Medicine (PMID 40772912) evaluated pharmacological therapies for nausea and emesis in the emergency department - an important update for ED practice. A 2025 systematic review (PMID 40318314) examined risk prediction models for CINV, supporting tailored antiemetic prophylaxis based on patient-specific risk factors.

Sources: Goldman-Cecil Medicine (Table 118-5) | Yamada's Textbook of Gastroenterology (Table 33.2) | Rosen's Emergency Medicine, 10e

Medicine to stop mense

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Medicine to delay menstruation

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medicine to delay menstruation norethisterone medroxyprogesterone clinical use dose

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Medicines to Delay Menstruation

The principal approach is using progestogens - synthetic hormones that mimic progesterone. As long as progestogen levels remain elevated, the uterine lining is not shed, and menstruation is postponed. When the drug is stopped, the hormone level drops and withdrawal bleeding occurs within 2-3 days.

1. Norethisterone (NET) - First-line, Licensed Option

Norethisterone 5 mg (brand names: Primolut N, Utovlan) is the only progestogen specifically licensed for period delay in the UK and many other countries.

How it works

Norethisterone is a synthetic progestin that maintains the secretory endometrium, preventing the progesterone withdrawal that triggers menstruation. It is also partially metabolized to ethinyl estradiol (1 mg norethisterone converts to approximately 4-6 mcg ethinyl estradiol), which contributes to its effectiveness in postponing bleeding.

Dosing Protocol

Parameter	Detail
Dose	5 mg three times daily (TDS)
When to start	At least 3 days before the expected period onset
Maximum duration	Up to 3-4 weeks
Return of period	Within 2-3 days of stopping

Important Notes

Not a contraceptive at this dose - additional contraception is needed to avoid pregnancy.
Because it is partly converted to ethinyl estradiol, it carries a VTE (venous thromboembolism) risk similar to combined oral contraceptives. Women with a history of VTE, thrombophilia, or other VTE risk factors should not use norethisterone for this purpose.

2. Medroxyprogesterone Acetate (MPA) - Alternative (Off-label)

Medroxyprogesterone acetate 10 mg (brand: Provera) is used off-label as an alternative, particularly when norethisterone is contraindicated (e.g., high VTE risk, migraine with aura).

Parameter	Detail
Dose	10 mg two to three times daily (BD or TDS)
Advantage	Does not convert to ethinyl estradiol - lower VTE risk
Return of period	Within 3 days of stopping
Breakthrough bleeding	Can occur

3. Depot Medroxyprogesterone Acetate (DMPA) - Injection

DMPA 150 mg IM (Depo-Provera) is a long-acting injectable progestogen used primarily as contraception, but it also results in menstrual suppression over time:

No periods in ~30% of users within the first 3 months
Increases to ~55% amenorrhea after 1 year
Not suitable for short-term, one-off period delay (due to its prolonged, irreversible effect over 12 weeks)
Fertility may take up to 12 months to return after stopping

4. Combined Oral Contraceptive Pill (COCP) - For Pill Users

Women already taking a combined oral contraceptive pill can delay their period by:

Skipping the pill-free interval (or the placebo/inactive pills) and starting the next active pack immediately.
This can be done for one or more cycles.
This is the simplest option for those already on the COCP.

Contraindications / Cautions for Progestogen-Based Delay

Condition	Action
History of VTE / thrombophilia	Avoid norethisterone; use MPA instead
Migraine with aura	Prefer progestogen-only options (MPA)
Liver disease	Use with caution; avoid if severe
Pregnancy	Contraindicated
Breast cancer (current or past)	Avoid
Drug interactions	Rifampicin, anticonvulsants (carbamazepine, phenytoin), ritonavir - reduce efficacy via CYP induction

Common Side Effects

Breakthrough / irregular spotting
Headache, nausea
Breast tenderness
Mood changes, bloating
Acne

Summary Table

Drug	Dose	Licensed?	VTE Risk	Duration of Use
Norethisterone	5 mg TDS	Yes (UK)	Yes (converts to EE)	Up to 3-4 weeks
Medroxyprogesterone tablets	10 mg BD-TDS	Off-label	Lower	Short-term
DMPA injection	150 mg IM	Off-label for delay	Lower	Long-acting (12 weeks+)
COCP (skip pill-free week)	As per pill	Yes (for COCP users)	Yes	Flexible

Clinical note: Period delay medications require a medical consultation. The choice of agent depends on the patient's medical history, VTE risk factors, and any concurrent medications. Norethisterone is the standard first-line option for healthy women with no VTE risk factors.

Sources: NHS SPS - Choosing a medicine to delay periods | GPNotebook - Delaying menstruation | PMC review on norethisterone dose and duration (PMID 11235183)

Drugs to delay menstruation

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Drugs to Delay Menstruation

The mechanism behind all options is the same: maintaining elevated progestogen levels prevents the progesterone withdrawal that triggers endometrial shedding. When the drug is stopped, menstruation returns within 2-3 days.

1. Norethisterone (NET) - First-line, Licensed

Dose: 5 mg three times daily (TDS)
Start: At least 3 days before expected period
Duration: Up to 3-4 weeks
Brand names: Primolut N, Utovlan
Return of period: 2-3 days after stopping
Note: Partially converts to ethinyl estradiol - carries VTE risk. Not a contraceptive at this dose.

2. Medroxyprogesterone Acetate Tablets (MPA) - Off-label

Dose: 10 mg two to three times daily
Brand: Provera
Use when: Norethisterone is contraindicated (e.g., VTE risk, migraine with aura)
Advantage: Does not convert to ethinyl estradiol - lower VTE risk
Return of period: ~3 days after stopping

3. Combined Oral Contraceptive Pill (COCP) - For Women Already on the Pill

Simply skip the pill-free interval (or placebo pills) and start the next active pack immediately
Most convenient option for existing COCP users
Can be done for one or more consecutive cycles

4. Depot Medroxyprogesterone Acetate (DMPA) Injection - Long-term Only

Dose: 150 mg IM every 12 weeks
Causes amenorrhea in ~30% at 3 months, ~55% at 1 year
Not suitable for a short one-off delay - effect lasts 12 weeks and fertility return can take up to 12 months
Used when long-term menstrual suppression is desired

Quick Reference Table

Drug	Dose	Licensed for Delay?	VTE Risk	Best For
Norethisterone	5 mg TDS	Yes	Higher	Short-term delay, most women
MPA tablets	10 mg BD/TDS	Off-label	Lower	Women with VTE risk / migraine
COCP (skip break)	As per pill	Yes (pill users)	Moderate	Women already on COCP
DMPA injection	150 mg IM	Off-label	Lower	Long-term suppression

Key Contraindications

Avoid norethisterone in: history of VTE, thrombophilia, migraine with aura
All progestogens: contraindicated in pregnancy, active liver disease, hormone-sensitive cancers
Drug interactions: Rifampicin, phenytoin, carbamazepine, ritonavir reduce efficacy (enzyme inducers)

Always consult a clinician before using any of these agents - the appropriate choice depends on individual medical history and VTE risk profile.

Drugs for diarrhea

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Drugs for Diarrhea

Antidiarrheal drugs are categorized by their mechanism of action. The choice of agent depends on whether diarrhea is acute or chronic, and the underlying cause.

1. First-line: Oral Rehydration

Before any drug, the cornerstone of diarrhea management is fluid and electrolyte replacement:

Oral Rehydration Salts (ORS) - WHO formula (sodium, potassium, glucose, water)
In severe dehydration: IV fluids (Normal Saline or Ringer's Lactate)
Zinc supplementation (in children) reduces duration and severity

2. Opiate / Opioid-Based Antidiarrheals (Motility Reducers)

Mechanism: Act on mu-opioid receptors in the gut wall - increase segmenting colonic contractions, slow intestinal transit, increase anal sphincter tone, reduce intestinal secretion.

Drug	Dose	Notes
Loperamide	4 mg initial, then 2 mg after each loose stool; max 16 mg/day	Drug of choice - not absorbed systemically, minimal CNS effects, non-addictive at therapeutic doses
Diphenoxylate + Atropine	2.5-5 mg four times daily	Combined with atropine to deter abuse; mild CNS effects possible
Codeine	15-60 mg four times daily	More CNS/addictive potential; used when other agents fail
Tincture of opium	2-20 drops four times daily	Reserved for severe/refractory cases
Morphine	2-20 mg four times daily	For palliative/chronic severe diarrhea

Caution: Avoid loperamide and diphenoxylate when fever >38.5°C or blood is in the stool (risk of prolonging infection / toxic megacolon in C. difficile).

3. Enkephalinase Inhibitor

Drug	Dose	Notes
Racecadotril (acetorphan)	1.5 mg/kg three times daily	Inhibits enkephalinase → increases endogenous opioid effects on gut; antisecretory, not antimotility; safe in children; not approved in the USA

4. Intraluminal / Adsorbent Agents

Drug	Dose	Notes
Bismuth subsalicylate (Pepto-Bismol)	525 mg every 30 min for 8 doses	Reduces stool frequency by ~50%; also has antimicrobial properties; useful for traveler's diarrhea prophylaxis. Avoid with aspirin/warfarin, renal impairment, pregnancy
Kaolin-pectin	As directed	Older adsorbent; reduces stool fluidity

5. Antisecretory Agents

Drug	Dose	Notes
Octreotide (somatostatin analog)	50-250 mcg SC three times daily	For secretory diarrhea (VIPoma, carcinoid syndrome, chemotherapy-induced, short bowel syndrome)
Clonidine (α2-adrenergic agonist)	0.1-0.3 mg three times daily	Promotes gut fluid absorption; useful in diabetic diarrhea and opioid withdrawal diarrhea

6. Bile Acid-Binding Resins

Used when excess bile acids spill into the colon (bile acid malabsorption/diarrhea - up to 30% of IBS-D patients).

Drug	Dose
Cholestyramine	4 g one to four times daily
Colesevelam	1.875 g twice daily
Colestipol	4 g one to four times daily

7. Antibiotics (for Infectious Diarrhea)

Used when a bacterial cause is identified or strongly suspected.

Indication	Drug	Dose
Traveler's diarrhea (non-invasive)	Rifaximin	200 mg TDS x 3 days
Traveler's diarrhea (invasive / Campylobacter)	Azithromycin	500-1000 mg PO once, or 500 mg x 3 days
Traveler's diarrhea	Ciprofloxacin	750 mg once or 500 mg BD
C. difficile	Vancomycin (oral) or Fidaxomicin	Vancomycin 125 mg QDS x 10 days
C. difficile (recurrent)	Bezlotoxumab (monoclonal antibody)	Single IV infusion
Protozoal (Giardia, Entamoeba)	Metronidazole or Nitazoxanide	Metronidazole 400 mg TDS x 5-7 days

Note: Avoid antibiotics empirically in suspected Salmonella (risk of prolonging carriage) and STEC E. coli O157 (risk of HUS).

8. Drugs Specific to IBS with Diarrhea (IBS-D)

Drug	Mechanism	Notes
Eluxadoline	Mixed μ/κ-opioid agonist + δ-opioid antagonist	FDA-approved for IBS-D; avoid in prior cholecystectomy, pancreatitis, heavy alcohol use
Alosetron	5-HT3 antagonist	For severe IBS-D in women; restricted prescribing due to risk of ischemic colitis
Rifaximin	Non-absorbable antibiotic	Targets gut microbiota; 2-week course for IBS-D

9. Fiber Supplements (Stool Normalizers)

Paradoxically useful in diarrhea-predominant conditions - absorb excess water and add bulk:

Psyllium (10-20 g/day)
Calcium polycarbophil (5-10 g/day)

Summary by Diarrhea Type

Type of Diarrhea	Preferred Agents
Acute watery (e.g. gastroenteritis)	ORS + loperamide or bismuth subsalicylate
Traveler's diarrhea	Loperamide + rifaximin or azithromycin
Secretory (e.g. VIPoma, carcinoid)	Octreotide
Bile acid malabsorption	Cholestyramine, colesevelam
C. difficile	Oral vancomycin or fidaxomicin
IBS-D	Loperamide, eluxadoline, alosetron, rifaximin
Diabetic / autonomic diarrhea	Clonidine, loperamide
Pediatric acute diarrhea	ORS + zinc + racecadotril

Sources: Sleisenger & Fordtran's Gastrointestinal and Liver Disease (Tables 16.5, 110.9) | Harrison's Principles of Internal Medicine 22e | Goodman & Gilman's Pharmacological Basis of Therapeutics

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