PHARMACOLOGY – III PREPAIRED BY: MR.
RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – B, CHAPTER – 3] WEBSITE LINK: [Link]
[CHAPTER – 3]
Appetite stimulants and suppressants
1. Definitions:
• Appetite Stimulants: Medications that enhance hunger and increase food intake.
• Appetite Suppressants: Medications that reduce hunger perception and decrease food
consumption.
2. Classification and Dosage:
• Appetite Stimulants:
o Corticosteroids:
▪ Example: Megestrol acetate
▪ Dosage: Typically administered at 400–800 mg/day.
o Cannabinoids:
▪ Example: Dronabinol
▪ Dosage: Starting dose is 2.5 mg twice daily before meals.
o Anabolic Agents:
▪ Example: Oxandrolone
▪ Dosage: Ranges from 2.5 to 20 mg/day.
• Appetite Suppressants:
o Sympathomimetic Amines:
▪ Example: Phentermine
▪ Dosage: Typically 15–37.5 mg once daily before breakfast or 1–2 hours after breakfast.
o Serotonin Receptor Agonists:
▪ Example: Lorcaserin
▪ Dosage: 10 mg twice daily.
o Combination Therapies:
▪ Example: Phentermine and Topiramate
▪ Dosage: Starting at 3.75 mg/23 mg once daily, titrated up to 15 mg/92 mg once daily.
3. Mechanisms of Action and Relevance in Infectious Diseases:
A. Corticosteroids (e.g., Megestrol Acetate, Dexamethasone, Prednisolone): They are
orexigenic agents (increase food intake) by enhancing hunger signals or reducing satiety signals
(Gut fullness).
They act through different mechanisms involving the hypothalamus, neurotransmitters, and
hormone modulation.
Mechanism of Action:
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PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – B, CHAPTER – 3] WEBSITE LINK: [Link]
• Hypothalamic Modulation: These drugs inhibits pro-opiomelanocortin (POMC) neurons,
which are involved in satiety signaling (Gut fullness) and interacts with glucocorticoid receptors
in the hypothalamus that leads to an increased secretion of neuropeptide Y (NPY), a potent
appetite stimulant which leads to an increase in appetite.
• Leptin Suppression: Corticosteroids suppress leptin, a hormone that normally reduces
appetite.
• Neuropeptide Y (NPY) Activation: They stimulate NPY, a potent orexigenic peptide in the
hypothalamus.
• Anti-Inflammatory Effect: They act by binding to glucocorticoid receptors (GRs) in immune
cells which leads to downregulation of a nuclear factor kappa B (NF-κB), a transcription factor
involved in cytokine production and causes Cytokine-induced anorexia, which cause decrease
in levels of TNF-α, IL-1, and IL-6, that leads to reduced inflammation and restoration of appetite.
B. Cannabinoid Receptor Agonists (e.g., Dronabinol, Nabilone)
Mechanism of Action:
• Endocannabinoid System Activation: These agents act as CB1 receptor agonists, enhancing
dopaminergic transmission in the hypothalamus, which is associated with increased appetite.
• Ghrelin Modulation: Cannabinoids stimulate ghrelin release, a gastrointestinal hormone that
promotes hunger.
• Anti-Emetic Effects: They exert an anti-nausea effect by modulating serotonergic and
dopaminergic pathways in the brainstem which reduces nausea and vomiting, promotes food
intake.
C. Anabolic Androgenic Steroids (e.g., Oxandrolone, Nandrolone, Testosterone Derivatives)
Mechanism of Action:
• Androgen Receptor Activation: This drug stimulates androgen receptors (ARs) in muscle and
other tissues and enhances protein synthesis and nitrogen retention, which causes an
increased muscle mass, strength, and reduces muscle catabolism and also inhibits
glucocorticoid-induced protein degradation; these promotes muscle growth and recovery.
• Catabolism Inhibition: In this, the suppression of glucocorticoid-induced muscle
degradation occurs which preserves a lean body mass.
Appetite Suppressants (Anorexigenic Agents): Appetite suppressants function by reducing
hunger perception, prolonging satiety, and increasing metabolic rate.
These agents are commonly prescribed for obesity management and have limited applications in
infectious diseases.
A. Sympathomimetic Amines (e.g., Phentermine, Diethylpropion, Benzphetamine)
Mechanism of Action:
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PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – B, CHAPTER – 3] WEBSITE LINK: [Link]
• Hypothalamic Stimulation: Appetite suppressants increase norepinephrine and dopamine in
the lateral hypothalamus, reducing hunger by inhibiting orexigenic peptides and enhancing
satiety signals. Drugs like phentermine and bupropion-naltrexone aid in weight loss and
obesity management by curbing food intake.
• Adrenergic Activation: It stimulates β-adrenergic receptors, enhancing lipolysis and
thermogenesis by increasing fat breakdown and energy expenditure. This occurs through
cAMP activation, promoting fat oxidation and heat production via HSL and UCP1. These
effects make β-agonists like phentermine and ephedrine effective for weight loss and
metabolic regulation.
B. Serotonin Receptor Agonists (e.g., Lorcaserin, Fenfluramine, Dexfenfluramine)
Mechanism of Action:
• 5-HT₂C Receptor Activation: 5-HT₂C receptor activation enhances serotonin-mediated
satiety, reducing hunger and food intake. Drugs like lorcaserin stimulate POMC neurons,
triggering α-MSH release, which activates MC4R to promote satiety. This pathway aids in
obesity management by curbing appetite.
• Dopaminergic Modulation: Dopaminergic modulation reduces food cravings by regulating
the mesolimbic reward pathway. Drugs like bupropion increase dopamine levels in the
nucleus accumbens, decreasing hedonic eating and compulsive food intake. By altering
reward-driven behaviors, these drugs help in obesity management by curbing cravings and
promoting sustained weight loss.
C. Combination Therapy (e.g., Phentermine + Topiramate, Bupropion + Naltrexone)
Mechanism of Action:
• Phentermine: Phentermine suppresses appetite by enhancing norepinephrine activity in the
hypothalamus. It increases NE release and inhibits its reuptake, activating α1-adrenergic
receptors to reduce hunger. Additionally, it suppresses orexigenic peptides like neuropeptide
Y (NPY) and AgRP, which stimulate food intake. Used for short-term obesity management,
phentermine aids in caloric restriction and weight loss when combined with diet and exercise.
• Topiramate: Topiramate suppresses appetite by inhibiting glutamatergic
neurotransmission, enhancing GABAergic activity, and modulating hypothalamic pathways
to increase satiety. It blocks AMPA and kainate receptors, reducing excitatory signals linked to
food cravings, while enhancing GABAergic inhibition, promoting fullness. Often combined with
phentermine (Qsymia), it helps in weight management by decreasing binge eating and
compulsive food intake.
3. Comparison of Mechanisms and Infectious Disease Relevance
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PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – B, CHAPTER – 3] WEBSITE LINK: [Link]
Infectious Disease
Drug Class Mechanism of Action
Relevance
Corticosteroids (Megestrol, Inhibits POMC neurons, Used in cachexia from
Dexamethasone) suppresses leptin, increases NPY HIV/AIDS, TB, cancer
Cannabinoids (Dronabinol, Activates CB1 receptors, increases Used in HIV/AIDS-related
Nabilone) ghrelin and dopamine anorexia
Anabolic Steroids (Oxandrolone, Stimulates androgen receptors, Used in muscle wasting
Nandrolone) increases protein synthesis (HIV, TB, cancer)
Sympathomimetics Increases NE and dopamine, Limited use in infections,
(Phentermine) promotes thermogenesis mainly for obesity
Activates 5-HT₂C receptors,
Serotonin Agonists (Lorcaserin) Not used in infections
reduces cravings
Combination Therapy NE release + GABAergic effects Used for obesity-related
(Phentermine + Topiramate) reduce hunger metabolic diseases
4. Therapeutic Effects and Clinical Uses:
• Appetite Stimulants:
o Megestrol Acetate: Used to treat anorexia, cachexia, or significant weight loss in patients
with AIDS or cancer.
o Dronabinol: Indicated for anorexia associated with weight loss in AIDS patients and for
nausea and vomiting associated with chemotherapy.
o Oxandrolone: Employed to promote weight gain after weight loss following extensive surgery,
chronic infections, or severe trauma.
• Appetite Suppressants:
o Phentermine: Short-term adjunct in a regimen of weight reduction based on exercise,
behavioral modification, and caloric restriction in the management of exogenous obesity.
o Lorcaserin: Used as an adjunct to a reduced-calorie diet and increased physical activity for
chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m² or
greater (obese) or 27 kg/m² or greater (overweight) in the presence of at least one weight-
related comorbid condition.
o Phentermine and Topiramate Combination: Indicated for chronic weight management in
adults with obesity or overweight with at least one weight-related comorbidity.
5. Side Effects:
• Appetite Stimulants:
o Megestrol Acetate: Potential side effects include thromboembolic events, hypertension,
hyperglycemia, and adrenal suppression.
o Dronabinol: May cause dizziness, euphoria, paranoia, somnolence, and abdominal pain.
o Oxandrolone: Possible adverse effects include liver toxicity, lipid abnormalities, and
virilization in females.
• Appetite Suppressants:
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PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – B, CHAPTER – 3] WEBSITE LINK: [Link]
o Phentermine: Common side effects are increased heart rate, elevated blood pressure,
insomnia, and nervousness.
o Lorcaserin: May cause headache, dizziness, fatigue, nausea, dry mouth, and constipation.
o Phentermine and Topiramate Combination: Potential side effects include paresthesia,
dizziness, dysgeusia, insomnia, constipation, and dry mouth.
6. Contraindications:
• Appetite Stimulants:
o Megestrol Acetate: Contraindicated in patients with a history of thromboembolic disorders,
pregnancy, or those with severe hepatic dysfunction.
o Dronabinol: Should not be used in patients with a history of hypersensitivity to
cannabinoids, schizophrenia, or severe cardiovascular disease.
o Oxandrolone: Contraindicated in patients with prostate cancer, breast cancer in males,
nephrotic syndrome, or severe hepatic impairment.
• Appetite Suppressants:
o Phentermine: Should not be used in individuals with a history of cardiovascular disease
(e.g., uncontrolled hypertension, arrhythmias), hyperthyroidism, glaucoma, or during
pregnancy.
o Lorcaserin: Contraindicated in pregnancy and individuals taking serotonergic drugs due to
the risk of serotonin syndrome.
o Phentermine and Topiramate Combination: Should be avoided in pregnant women (due to
risk of fetal harm), individuals with hyperthyroidism, glaucoma, and those using MAO
inhibitors.
7. Pharmacological Actions of Appetite Stimulants and Suppressants
Nervous System: Stimulants like corticosteroids and cannabinoids enhance hunger by increasing
dopamine and neuropeptide Y, while suppressants such as sympathomimetics and serotonergic
drugs promote satiety by modulating hypothalamic pathways.
Endocrine System: Stimulants boost metabolism and appetite through IGF-1 and growth
hormone, whereas suppressants like GLP-1 agonists slow gastric emptying and improve insulin
sensitivity, aiding in weight control.
Cardiovascular System: Stimulants may cause hypertension and high cholesterol, while
suppressants like GLP-1 agonists reduce cardiovascular risks. Sympathomimetics, however, can
elevate heart rate and blood pressure.
Digestive System: Stimulants promote gastric motility and absorption, while suppressants like
orlistat block fat digestion, leading to weight loss but potential digestive issues like diarrhea and
bloating.
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PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – B, CHAPTER – 3] WEBSITE LINK: [Link]
Musculoskeletal System: Anabolic steroids enhance muscle growth, whereas prolonged use of
corticosteroids can lead to muscle wasting. Suppressants, if misused, may cause muscle loss and
osteoporosis.
Renal System: Stimulants like corticosteroids cause fluid retention, while suppressants may
impact kidney function by reducing perfusion or increasing the risk of kidney stones.
Immune System: Stimulants like corticosteroids weaken immunity, making infections more
likely, whereas suppressants such as GLP-1 agonists may have anti-inflammatory benefits.
7. Principles of Toxicology and Treatment of Various Poisonings:
• Toxicology of Appetite Stimulants and Suppressants:
o Megestrol Acetate: High doses can cause adrenal insufficiency, thromboembolism, and
severe hyperglycemia.
o Dronabinol: Overdose can result in confusion, hallucinations, increased heart rate, and
hypotension.
o Oxandrolone: Toxic doses may cause hepatic toxicity, peliosis hepatis (blood-filled liver
cysts), and cardiovascular complications.
o Phentermine: Acute toxicity manifests as restlessness, tremors, tachycardia, palpitations,
and seizures.
o Lorcaserin: Overdose may lead to serotonin syndrome, hallucinations, or bradycardia.
o Phentermine and Topiramate: Toxicity includes metabolic acidosis, cognitive dysfunction,
and cardiac arrhythmias.
• Treatment of Poisoning:
o Megestrol Acetate: Supportive care with glucose regulation and thromboembolic
monitoring.
o Dronabinol: Symptomatic management with IV fluids and benzodiazepines for severe
agitation.
o Oxandrolone: Discontinue drug, provide liver protective therapy, and monitor lipid profile.
o Phentermine and other appetite suppressants: Activated charcoal if within 1 hour of
ingestion, IV benzodiazepines for agitation, beta-blockers for tachycardia, and symptomatic
support.
8. Bioassay of Appetite-Modulating Drugs:
• Objective: To determine the potency and efficacy of appetite stimulants and suppressants using
biological models.
• Methods:
o For Appetite Stimulants:
▪ Rodent feeding models (e.g., monitoring food intake in rats after drug administration).
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PHARMACOLOGY – III PREPAIRED BY: MR. RAHUL SINGH SHAKTAWAT
[UNIT – I, PART – B, CHAPTER – 3] WEBSITE LINK: [Link]
▪ Gastrointestinal motility studies to assess drug-induced changes in peristalsis.
o For Appetite Suppressants:
▪ Rat obesity models to evaluate weight loss efficacy.
▪ Hypothalamic assays to measure neurotransmitter alterations (e.g., norepinephrine,
serotonin).
9. Correlation of Pharmacology with Related Medical Sciences:
• Endocrinology: Appetite regulation is closely linked with hormones such as leptin, ghrelin, and
insulin.
• Neurology: Appetite suppressants impact neurotransmitters like serotonin, dopamine, and
norepinephrine.
• Gastroenterology: Drugs affecting appetite alter gastric emptying and motility.
• Cardiology: Sympathomimetic appetite suppressants can affect heart rate and blood pressure,
necessitating cardiovascular monitoring.
End