VANGUARD PUPPY 5L (VANGUARD PLUS 5L)

Indications

• Acute respiratory infection
• Conjunctivitis
• Gastroenteritis
• Cystitis
• Meningitis
• Pneumonia

Dosage

Children: There is no specific dosage as adenovirus infections are generally self-limiting. Symptomatic treatment is advised.

Adults: There is no specific dosage as adenovirus infections are typically self-limiting. Supportive care is recommended.

Mechanism of action

Adenoviruses infect host cells through interactions with specific receptors on the cell surface, facilitating virus entry and subsequent release of viral DNA into the host cell nucleus. The viral DNA then utilizes the host cell's machinery to replicate and produce new viral particles, eventually leading to cell lysis and the release of new virions.

Pharmacodynamics

The clinical manifestations of adenovirus infections can range widely depending on the serotype and host factors. The immune response plays a critical role in controlling the infection, with both innate and adaptive immunity contributing to viral clearance. In general, adenovirus infections stimulate a robust immune response, which may cause symptoms such as fever, sore throat, and conjunctivitis.

Pharmacokinetics

Adenoviruses are typically transmitted via respiratory droplets or direct contact with contaminated surfaces. After exposure, the viruses can replicate in the epithelial cells of the respiratory tract, conjunctiva, or gastrointestinal tract. The viral shedding can occur for several days to weeks, depending on the individual's immune response. Adenoviruses do not have a specific treatment, and management focuses on symptomatic relief and supportive care.

Adverse effects

• Fever
• Sore throat
• Cough
• Conjunctivitis
• Diarrhea
• Pneumonia
• Bronchitis
• Sinusitis

Precautions

• In immunocompromised patients, adenovirus can cause severe disease.
• Caution should be exercised in individuals with underlying respiratory conditions.

Pregnancy

Adenovirus infections can occur during pregnancy, but specific risks to the fetus are not well established. Consultation with healthcare providers is advised.

Breast-feeding

Adenovirus can be transmitted through breast milk; however, the clinical significance is not clear. Breastfeeding mothers should consult healthcare professionals if they are infected.

Storage

Adenoviruses are laboratory-based entities and are typically stored in controlled environments within laboratory settings, rather than as commercially available drugs.

Indications

• Prevention of bacterial infections
• Immunization against specific bacterial pathogens
• Use in veterinary settings for livestock and pets

Dosage

Children: Refer to specific bacterin product guidelines for dosing information, as it can vary widely based on the type of bacterin and the disease being targeted.

Adults: Refer to specific bacterin product guidelines for dosing information, as it can vary widely based on the type of bacterin and the disease being targeted.

Mechanism of action

Bacterins work by introducing inactivated bacteria or their components into the body, which prompts the immune system to recognize these antigens as foreign. This leads to the activation of B cells and T cells, resulting in the production of antibodies. The immune system then retains a memory of these antigens, allowing for a quicker and more effective response upon future exposure to the live bacteria.

Pharmacodynamics

The pharmacodynamics of bacterins involve the induction of an adaptive immune response. Upon administration, the immune system generates specific antibodies against the bacterial antigens present in the bacterin. This response can involve both humoral and cell-mediated immunity, depending on the nature of the bacterin and the type of immune cells activated.

Pharmacokinetics

Bacterins are typically administered via injection, leading to local uptake by antigen-presenting cells. These cells process the inactivated bacteria and present the derived antigens to T cells in the lymph nodes, where immune activation occurs. The duration of the immune response can vary based on the specific bacterin and the individual’s immune status.

Adverse effects

• Injection site reactions
• Allergic reactions
• Fever
• Malaise

Precautions

• Use with caution in individuals with a history of allergic reactions to vaccines or bacterins
• Monitor for hypersensitivity reactions after administration

Pregnancy

Safety during pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Consult with healthcare provider before use, as safety in breastfeeding has not been established.

Storage

Store at recommended temperatures, usually between 2-8 degrees Celsius. Do not freeze.

Formulations

• Injectable solutions
• Suspensions

Indications

• Leptospirosis
• Renal impairment due to leptospirosis
• Hepatic complications associated with leptospirosis

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidance, as no specific dosing is provided.

Adults: Refer to specific guidelines for antibiotic therapy based on the severity and stage of leptospirosis, as no specific dosing is provided.

Mechanism of action

Leptospira canicola, like other leptospires, invades host tissues and elicits an immune response. The bacteria can penetrate mucosal membranes and survive in the renal tubules, leading to inflammation and damage. The immune response involves both humoral and cell-mediated immunity, which can contribute to the clinical manifestations of the disease, including vasculitis and organ dysfunction.

Pharmacodynamics

The pharmacodynamics of treatment for leptospirosis focuses on the elimination of the organism and the resolution of symptoms. Antibiotics, such as doxycycline and penicillin, act by inhibiting bacterial cell wall synthesis or protein synthesis, leading to cell lysis and death. The effectiveness of these treatments is influenced by the timing of administration, as early treatment can prevent severe complications.

Pharmacokinetics

The pharmacokinetics of antibiotics used to treat leptospirosis, such as doxycycline, include rapid absorption from the gastrointestinal tract, high bioavailability, and extensive tissue distribution. Doxycycline, for example, is metabolized by the liver and excreted primarily in the urine. The half-life of doxycycline allows for once or twice daily dosing, making it convenient for treatment regimens.

Pregnancy

Safety during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether canicola is excreted in human milk. Caution should be exercised when administered to a nursing woman.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Indications

• Pain management
• Inflammation
• Infections
• Chronic diseases
• Allergic reactions

Dosage

Children: Dosage for paediatric canines (puppies) also varies widely depending on the specific medication, age, and weight of the puppy. Veterinary guidance is crucial for determining appropriate doses.

Adults: Dosage for adult canines varies based on the specific medication and condition being treated. It is essential to consult veterinary guidelines or a veterinarian for appropriate dosing.

Mechanism of action

The mechanism of action of canine medications varies widely depending on the specific drug class. For example, non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase enzymes (COX-1 and COX-2), reducing the production of prostaglandins that mediate inflammation and pain. Antibiotics may work by inhibiting bacterial cell wall synthesis or protein synthesis, while corticosteroids reduce inflammation by inhibiting immune response.

Pharmacodynamics

Pharmacodynamics in canines involves understanding how drugs affect the body, including their therapeutic effects and potential side effects. For example, NSAIDs provide analgesic and anti-inflammatory effects, while antibiotics target specific pathogens to eliminate infections. The response to drugs can vary based on factors such as breed, age, and overall health status.

Pharmacokinetics

Pharmacokinetics in canine patients encompasses the absorption, distribution, metabolism, and excretion of drugs. Canine physiology can influence these processes; for example, drugs may be absorbed more quickly in dogs due to differences in gastrointestinal pH and transit time. Metabolism often occurs in the liver, with variations based on breed and age affecting drug clearance. Excretion primarily takes place through the kidneys.

Pregnancy

Safety during pregnancy has not been established. Consult a veterinarian for guidance.

Breast-feeding

Safety during lactation has not been established. Consult a veterinarian for guidance.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Indications

• Prevention of canine distemper through vaccination
• Supportive treatment for infected dogs

Dosage

Children: No specific dosage available, refer to guidelines for vaccination schedules.

Adults: No specific dosage available, refer to guidelines for vaccination schedules.

Mechanism of action

Canine distemper virus primarily infects and replicates in lymphoid tissue, leading to immune suppression, and subsequently affects epithelial tissues in the respiratory, gastrointestinal, and nervous systems. The virus enters host cells via the signaling lymphocytic activation molecule (SLAM) receptor, which is expressed on immune cells, facilitating its spread throughout the body.

Pharmacodynamics

The immune response to CDV involves both humoral and cellular immunity. Vaccination induces an immune response that generates neutralizing antibodies, which prevent viral entry into host cells. Infected animals may develop severe immunosuppression, making them susceptible to secondary infections. The clinical manifestations depend on the severity of the infection and the host's immune response.

Pharmacokinetics

The pharmacokinetics of canine distemper virus are not typically described in terms of absorption, distribution, metabolism, and excretion like conventional drugs. Instead, the focus is on viral replication and the host immune response. The incubation period for distemper can vary but generally ranges from 1 to 2 weeks. The duration of the immune response post-vaccination can last for several years, depending on the type of vaccine used.

Pregnancy

No specific data available on the effects of distemper treatment in pregnant individuals, consult relevant guidelines.

Breast-feeding

No specific data available on the effects of distemper treatment during breastfeeding, consult relevant guidelines.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Schizophrenia
• Psychotic disorders
• Severe anxiety and agitation
• Nausea and vomiting
• Intractable hiccups

Dosage

Adults: The usual starting dose for adults is 25 mg to 50 mg taken orally, which can be increased gradually to achieve the

Mechanism of action

Chlorpromazine acts as an antagonist on multiple postsynaptic receptors, including dopaminergic receptors (D1, D2, D3, D4), serotonergic receptors (5-HT1, 5-HT2), histaminergic receptors (H1), alpha-adrenergic receptors (alpha1, alpha2), and muscarinic receptors (M1, M2). This blockade leads to reduced dopaminergic activity, which alleviates psychotic symptoms, while the interaction with serotonergic and histaminergic receptors contributes to its anxiolytic, sedative, and antiemetic effects. Additionally, it has a weak presynaptic inhibitory effect on dopamine reuptake, providing mild antidepressive and antiparkinsonian effects.

Pharmacodynamics

Chlorpromazine primarily exhibits its effects at subcortical levels of the central nervous system. It is recognized for its strong antiadrenergic effects and weaker peripheral anticholinergic activity. The drug also shows slight antihistaminic and antiserotonin activity, contributing to its broad spectrum of effects on mood, behavior, and various physiological functions.

Pharmacokinetics

Chlorpromazine is well-absorbed following oral administration and is extensively metabolized in the liver. The drug's half-life varies significantly among individuals, typically ranging from 30 to 50 hours, but can be longer in some patients. It is primarily excreted in the urine as metabolites, with minimal unchanged drug being eliminated. The pharmacokinetics of chlorpromazine may be influenced by factors such as age, liver function, and concurrent medications.

Contra-indications

• Hypersensitivity to chlorpromazine or any of its components
• Comatose states
• Severe central nervous system depression
• Bone marrow depression
• Porphyria
• Severe liver dysfunction
• Pheochromocytoma

Adverse effects

• Sedation
• Weight gain
• Orthostatic hypotension
• Extrapyramidal symptoms
• Dry mouth
• Blurred vision
• Constipation
• Urinary retention
• Tachycardia
• Sexual dysfunction
• Akathisia
• Neuroleptic malignant syndrome

Interactions

• CNS depressants (e.g., alcohol, benzodiazepines) may enhance sedative effects
• Antihypertensive agents may have additive hypotensive effects
• Anticholinergic drugs may exacerbate anticholinergic effects
• Dopamine agonists may have reduced efficacy

Precautions

• Use with caution in patients with a history of seizures
• Monitor for signs of tardive dyskinesia
• Use cautiously in elderly patients, particularly those with dementia-related psychosis
• Regular monitoring of blood pressure is advised
• Consider the risk of metabolic syndrome

Pregnancy

Chlorpromazine should only be used in pregnancy if the potential benefit justifies the potential risk to the fetus. It is categorized as a pregnancy category C drug.

Breast-feeding

Chlorpromazine is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets (various strengths)
• Oral solution
• Injectable solution

Indications

• Cancer treatment
• Severe infections requiring aggressive therapy
• Autoimmune disorders
• Certain chronic diseases

Dosage

Children: For paediatric patients, dosing must be determined on a case-by-case basis according to the specific medication and condition. Refer to the BNF for Children for detailed dosing information.

Adults: Dosage varies widely depending on the specific drug and condition being treated. Refer to the BNF for specific dosing guidelines.

Mechanism of action

High doses of drugs can enhance their pharmacological effects, potentially leading to increased efficacy. However, the specific mechanisms can vary widely depending on the drug in question. For instance, in chemotherapeutic agents, high doses may aim to saturate the target pathways or overcome resistance mechanisms in cancer cells.

Pharmacodynamics

Pharmacodynamics in high-dose therapy often involves the relationship between drug concentration and effect. At higher doses, the drug may produce a more pronounced response, but it also increases the likelihood of side effects. The therapeutic window may be narrower, necessitating careful monitoring of patient response and adverse effects.

Pharmacokinetics

The pharmacokinetics of drugs can be altered at high doses, affecting absorption, distribution, metabolism, and excretion. High doses may lead to saturation of metabolic pathways, prolonged half-lives, and accumulation of the drug in tissues. This can result in variable patient responses and necessitate dose adjustments based on therapeutic drug monitoring.

Interactions

• tamoxifen+high-dose: Unknown (increases concentration)
• corticosteroids+high-dose: Unknown (decreases concentration)
• erlotinib+high-dose: Unknown (increases risk of gastrointestinal perforation)
• live vaccines+high-dose: Unknown (increases risk of generalized infection (possibly life-threatening))
• atazanavir+high-dose: Unknown (increases exposure)

Indications

• Jaundice
• Hemorrhagic disorders
• Liver dysfunction
• Hemolytic anemia
• Coagulopathy

Dosage

Children: Refer to specific treatment guidelines for underlying conditions, as icterhaemorrhagia is a syndrome requiring targeted therapy.

Adults: Refer to specific treatment guidelines for underlying conditions, as icterhaemorrhagia is a syndrome requiring targeted therapy.

Mechanism of action

The exact mechanism of action of icterhaemorrhagia is not well-defined as it is a clinical syndrome rather than a specific pharmacological agent. However, the management often involves the use of medications that enhance bilirubin clearance, promote liver function, or manage bleeding risk. For instance, vitamin K may be administered to correct coagulopathy, and agents that support liver health can be utilized.

Pharmacodynamics

Pharmacodynamics in the context of icterhaemorrhagia generally involves understanding the balance of bilirubin metabolism and the hemostatic processes in the body. Bilirubin is produced from the breakdown of hemoglobin, and its levels can increase due to hemolysis or impaired hepatic processing. The clinical management aims to restore normal levels of bilirubin while addressing any bleeding tendencies through appropriate interventions.

Pharmacokinetics

Pharmacokinetics will vary based on the specific treatments used for icterhaemorrhagia. For instance, bilirubin is primarily processed in the liver, where it is conjugated and excreted in bile. Medications used to treat underlying conditions will have their own absorption, distribution, metabolism, and excretion profiles that can influence their effectiveness and safety in managing this syndrome.

Pregnancy

There is limited data on the safety of icterhaemorrhagia during pregnancy. It is advised to consult healthcare professionals before use.

Breast-feeding

The effects of icterhaemorrhagia on breastfeeding are not well studied. Caution is advised and consultation with healthcare professionals is recommended.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Indications

• Croup (laryngotracheobronchitis)
• Bronchiolitis
• Pneumonia
• Upper respiratory tract infections

Mechanism of action

Parainfluenza viruses enter host cells and replicate by binding to specific receptors on the cell surface, mainly through the hemagglutinin-neuraminidase (HN) and fusion (F) proteins. Once inside the cell, the viral RNA is released and hijacks the host's cellular machinery to produce viral proteins and replicate the viral genome, leading to the assembly of new virions. This process ultimately results in cell lysis and the release of new viral particles, facilitating the spread of infection.

Pharmacodynamics

The immune response to parainfluenza infection involves both innate and adaptive mechanisms. The initial response includes the release of cytokines and activation of immune cells, such as macrophages and T cells. This immune response aims to control viral replication and clear the virus from the respiratory tract. Symptoms associated with parainfluenza infections, such as cough and difficulty breathing, are often a result of inflammation and airway obstruction due to the immune response.

Pharmacokinetics

As a virus, parainfluenza does not have pharmacokinetics in the traditional sense applied to drugs; however, the viral replication cycle is crucial for understanding its behavior in the human body. Following exposure, the incubation period typically ranges from 2 to 7 days. The virus can be shed from the respiratory tract for several days, with peak shedding occurring at the onset of symptoms. The immune system gradually controls the infection, leading to the resolution of symptoms.

Adverse effects

• Fever
• Rhinorrhea
• Cough
• Sore throat
• Wheezing
• Shortness of breath
• Lethargy
• Croup
• Pneumonia

Precautions

• Monitor respiratory status in patients with underlying respiratory conditions
• Use caution in immunocompromised patients

Pregnancy

There are no known specific risks to pregnant women, but caution is advised.

Breast-feeding

Generally considered safe, but consult a healthcare provider.

Storage

Store in a cool, dry place away from direct sunlight.

Indications

• Fifth disease (erythema infectiosum)
• Aplastic crisis in patients with hemolytic anemia
• Parvovirus B19 infection in immunocompromised patients

Dosage

Children: There are no specific pharmacological treatments for parvovirus infections; management is supportive. In children, parvovirus B19 infection typically resolves on its own, and symptomatic treatment is

Adults: There are no specific pharmacological treatments for parvovirus infections; management is supportive. Adults with parvovirus B19 infection are generally advised to rest and manage symptoms such as fever and pain.

Mechanism of action

Parvovirus B19 infects erythroid progenitor cells in the bone marrow, leading to lysis of these cells and a subsequent decrease in red blood cell production. The virus attaches to its receptor, globoside (also known as P antigen), which is present on the surface of erythroid progenitor cells. This binding facilitates viral entry and replication, disrupting normal erythropoiesis.

Pharmacodynamics

Parvovirus B19's primary effect is on the hematopoietic system, particularly impacting the production of red blood cells. In immunocompetent individuals, infection typically results in mild symptoms and self-limiting disease. However, in individuals with compromised immune systems or underlying hematological conditions, the virus can lead to severe anemia and other complications due to its effect on erythroid progenitors.

Pharmacokinetics

Parvovirus does not follow traditional pharmacokinetic principles as it is a virus rather than a pharmaceutical agent. Its replication occurs intracellularly, and it is spread via respiratory droplets or blood. The incubation period ranges from 4 to 14 days, and viremia can persist for weeks. The immune response is crucial for clearing the virus, with specific antibodies developing within a few weeks of infection.

Adverse effects

• Fever
• Malaise
• Rash
• Joint pain
• Anemia
• Lethargy

Precautions

• Immunocompromised patients may experience more severe symptoms.
• Pregnant women should be cautious due to potential risks to the fetus.

Pregnancy

Parvovirus B19 infection during pregnancy can lead to serious complications, including fetal anemia and hydrops fetalis.

Breast-feeding

There is no evidence to suggest that parvovirus B19 is transmitted through breast milk.

Storage

Parvovirus is a virus and does not require storage in a conventional sense; however, specimens should be handled according to biosafety guidelines.

Dosage

Children: Refer to the specific drug's prescribing information or BNF for Children for appropriate dosing guidelines.

Adults: Refer to the specific drug's prescribing information or BNF for appropriate dosing guidelines.

Mechanism of action

The mechanism of action for a drug typically involves the interaction with specific receptors or enzymes in the body that leads to a pharmacological effect. Understanding the passage of a drug through biological systems can involve mechanisms such as passive diffusion, facilitated diffusion, or active transport.

Pharmacodynamics

Pharmacodynamics involves the study of the biochemical and physiological effects of drugs and their mechanisms of action. It encompasses the relationship between drug concentration and effect, including the drug's therapeutic effects and potential side effects. The specific pharmacodynamic properties would depend on the particular drug in question.

Pharmacokinetics

Pharmacokinetics is the branch of pharmacology concerned with the movement of drugs within the body, which includes absorption, distribution, metabolism, and excretion (ADME). Factors affecting pharmacokinetics include drug formulation, route of administration, and patient-specific variables like age, weight, and organ function.

Pregnancy

Consult a healthcare provider before use. The safety of this drug during pregnancy has not been well established.

Breast-feeding

Consult a healthcare provider before use. It is not known if this drug is excreted in human milk.

Storage

Store in a cool, dry place away from direct sunlight and out of reach of children.

Indications

• Assessment of immune status
• Monitoring vaccine efficacy
• Diagnosis of infections
• Determining need for booster vaccinations

Dosage

Children: Refer to specific guidelines or protocols for the context of use, as titre is a measurement rather than a drug requiring dosing.

Adults: Refer to specific guidelines or protocols for the context of use, as titre is a measurement rather than a drug requiring dosing.

Mechanism of action

The mechanism of action for titre is not applicable as it is a measurement rather than a drug. However, it reflects the immune response, which involves the binding of antibodies to specific antigens, leading to neutralization of pathogens or marking them for destruction by other immune cells.

Pharmacodynamics

Pharmacodynamics is not directly applicable to titre since it is a measurement of concentration rather than a pharmacological agent. However, the presence and concentration of antibodies can indicate the body's immune status and responsiveness to pathogens, with higher titres generally signifying a stronger immune response.

Pharmacokinetics

Pharmacokinetics is not relevant to titre measurements, as titre does not describe a substance that is metabolized or eliminated. Instead, it represents the stable concentration of antibodies in the serum following exposure to an antigen, whether through infection or vaccination.

Pregnancy

There is limited data on the safety of titre during pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised when using titre during breastfeeding. It is recommended to monitor the infant for any adverse effects.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Indications

• Influenza
• HIV/AIDS
• Hepatitis B and C
• Herpes simplex virus infections
• Cytomegalovirus infections
• COVID-19
• Respiratory syncytial virus infections

Dosage

Children: Refer to specific antiviral agents for dosing guidance.

Adults: Refer to specific antiviral agents for dosing guidance.

Mechanism of action

Viruses infect host cells by attaching to specific receptors on the cell surface. Once inside, they hijack the host cell's machinery to replicate their genetic material and produce viral proteins. New viral particles are assembled and released from the host cell, often destroying the cell in the process. The specific mechanism can vary depending on the virus type, including integration into the host genome in retroviruses or utilizing specific pathways for replication.

Pharmacodynamics

The pharmacodynamics of antiviral agents depend on the specific virus and the mechanism of action. Antiviral drugs may inhibit viral entry into host cells, block viral replication, or prevent the assembly of new virions. The effectiveness of antiviral therapy often relates to the stage of viral replication and the immune response of the host.

Pharmacokinetics

Pharmacokinetics of antiviral drugs varies widely based on the specific medication used. Generally, antiviral agents are absorbed through the gastrointestinal tract and distributed throughout the body. They may undergo hepatic metabolism and are often excreted through the kidneys. The half-life of these drugs can range from a few hours to several days, influencing dosing schedules.

Mechanism of action

Chlorpromazine acts as an antagonist (blocking agent) on different postsysnaptic receptors -on dopaminergic-receptors (subtypes D1, D2, D3 and D4 - different antipsychotic properties on productive and unproductive symptoms), on serotonergic-receptors (5-HT1 and 5-HT2, with anxiolytic, antidepressive and antiaggressive properties as well as an attenuation of extrapypramidal side-effects, but also leading to weight gain, fall in blood pressure, sedation and ejaculation difficulties), on histaminergic-receptors (H1-receptors, sedation, antiemesis, vertigo, fall in blood pressure and weight gain), alpha1/alpha2-receptors (antisympathomimetic properties, lowering of blood pressure, reflex tachycardia, vertigo, sedation, hypersalivation and incontinence as well as sexual dysfunction, but may also attenuate pseudoparkinsonism - controversial) and finally on muscarinic (cholinergic) M1/M2-receptors (causing anticholinergic symptoms like dry mouth, blurred vision, obstipation, difficulty/inability to urinate, sinus tachycardia, ECG-changes and loss of memory, but the anticholinergic action may attenuate extrapyramidal side-effects). Additionally, Chlorpromazine is a weak presynaptic inhibitor of Dopamine reuptake, which may lead to (mild) antidepressive and antiparkinsonian effects. This action could also account for psychomotor agitation and amplification of psychosis (very rarely noted in clinical use). The principal pharmacologic effects of chlorpromazine are similar to those of other propylamino derivatives of phenothiazine. Chlorpromazine has strong anticholinergic and sedative effects and moderate extrapyramidal effects. Chlorpromazine has strong antiemetic and adrenergic blocking activity and weak ganglionic blocking, antihistaminic, and antiserotonergic activity. The development of phenothiazine derivatives as psychopharmacologic agents resulted from the observation that certain phenothiazine antihistaminic compounds produced sedation. In an attempt to enhance the sedative effects of these drugs, promethazine and chlorpromazine were synthesized. Chlorpromazine is the pharmacologic prototype of the phenothiazines. The pharmacology of phenothiazines is complex, and because of their actions on the central and autonomic nervous systems, the drugs affect many different sites in the body. Although the actions of the various phenothiazines are generally similar, these drugs differ both quantitatively and qualitatively in the extent to which they produce specific pharmacologic effects. /Phenothiazine General Statement/ In the CNS, phenothiazines act principally at the subcortical levels of the reticular formation, limbic system, and hypothalamus. Phenothiazines generally do not produce substantial cortical depression; however, there is minimal information on the specific effects of phenothiazines at the cortical level. Phenothiazines also act in the basal ganglia, exhibiting extrapyramidal effects. The precise mechanism(s) of action, including antipsychotic action, of phenothiazines has not been determined, but may be principally related to antidopaminergic effects of the drugs. There is evidence to indicate that phenothiazines antagonize dopamine-mediated neurotransmission at the synapses. There is also some evidence that phenothiazines may block postsynaptic dopamine receptor sites. However, it has not been determined whether the antipsychotic effect of the drugs is causally related to their antidopaminergic effects. Phenothiazines also have peripheral and/or central antagonistic activity against alpha-adrenergic, serotonergic, histaminic (H1-receptors), and muscarinic receptors. Phenothiazines also have some adrenergic activity, since they block the reuptake of monoamines at the presynaptic neuronal membrane, which tends to enhance neurotransmission. The effects of phenothiazines on the autonomic nervous system are complex and unpredictable because the drugs exhibit varying degrees of alpha-adrenergic blocking, muscarinic blocking,

Pharmacodynamics

Chlorpromazine is a psychotropic agent indicated for the treatment of schizophrenia. It also exerts sedative and antiemetic activity. Chlorpromazine has actions at all levels of the central nervous system-primarily at subcortical levels-as well as on multiple organ systems. Chlorpromazine has strong antiadrenergic and weaker peripheral anticholinergic activity; ganglionic blocking action is relatively slight. It also possesses slight antihistaminic and antiserotonin activity.