This document discusses key concepts regarding pharmaceutical formulation and biopharmaceutics, with a focus on dosage form design and factors influencing drug absorption. It describes the various routes and mechanisms by which drugs can be absorbed through biological membranes in the gastrointestinal tract, including passive diffusion and active transport. Several physiological factors are also summarized that can impact drug absorption, such as gastric emptying time, gastrointestinal pH, effect of food, and how different disease states and drugs can influence absorption.
FORMULATION FACTORS EFFECTING BIOAVAILABILITY OF DRUGSN Anusha
Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action.
When the drug is given orally, only part of the administered dose appears in the plasma.
By plotting plasma concentrations of the drug versus time, one can measure the area under the curve (AUC).
This curve reflects the extent of absorption of the drug.
Bioavailability & Bioequivalence ppt, Objectives, Improving bioavailability, Assessment of bioavailability, Urinary excretion studies, Blood serum studies, in vitro drug dissolution testing, need for dissolution testing, in vitro drug dissolution testing models, Bioequivalence, Therapeutic equivalence, Types of bioequivalence studies, Pharmacokinetic studies, Methods to enhance dissolution rate.
FORMULATION FACTORS EFFECTING BIOAVAILABILITY OF DRUGSN Anusha
Bioavailability means the rate and extent to which the active ingredient is absorbed from a drug product and becomes available at the site of action.
When the drug is given orally, only part of the administered dose appears in the plasma.
By plotting plasma concentrations of the drug versus time, one can measure the area under the curve (AUC).
This curve reflects the extent of absorption of the drug.
Bioavailability & Bioequivalence ppt, Objectives, Improving bioavailability, Assessment of bioavailability, Urinary excretion studies, Blood serum studies, in vitro drug dissolution testing, need for dissolution testing, in vitro drug dissolution testing models, Bioequivalence, Therapeutic equivalence, Types of bioequivalence studies, Pharmacokinetic studies, Methods to enhance dissolution rate.
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
Pharmaceutical film coating is considered a key part in the production of solid pharmaceutical dosage forms since it gives superior organoleptic properties products. In addition, it can improve the physical and chemical stability of dosage forms, and modify the release characteristics of the drug. Several troubleshooting problems such as twinning mottling, chipping, etc., may arise during or after or even during the shelf life of the film coated dosage forms. These troubleshooting problems may be due to tablet core faults, coating formulation faults and/or coating process faults. These problems must be overcome to avoid unnecessary product problems. Film coating as well as other parts of the pharmaceutical technology is subjecting to continuous innovation. The innovation may be at different levels including pharmaceutical excipients, processes, software, guidelines and equipment. In fact, of particular note is the growing interest in process analytical technology, quality by design, continuous coating processing and the inclusion of new ready for use coating formulations. In this review, we tried to explore and discuss the status of pharmaceutical film coating, the challenges that face this manufacturing process and the latest technological advances in this important manufacturing process.
United State Pharmacopoeia (USP)The establishment of a rational relationship between a biological property, or a parameter derived from a biological property produced by a dosage form, and a physicochemical property or characteristic of the same dosage form.
Food and Drug Administration (FDA) definitionIVIVC is a predictive mathematical model describing the relationship between an in vitro property of a dosage form and a relevant in vivo response. Generally, the in vitro property is the rate or extent of drug dissolution or release while the in vivo response is the plasma drug concentration or amount of drug absorbed.
Pharmaceutical film coating is considered a key part in the production of solid pharmaceutical dosage forms since it gives superior organoleptic properties products. In addition, it can improve the physical and chemical stability of dosage forms, and modify the release characteristics of the drug. Several troubleshooting problems such as twinning mottling, chipping, etc., may arise during or after or even during the shelf life of the film coated dosage forms. These troubleshooting problems may be due to tablet core faults, coating formulation faults and/or coating process faults. These problems must be overcome to avoid unnecessary product problems. Film coating as well as other parts of the pharmaceutical technology is subjecting to continuous innovation. The innovation may be at different levels including pharmaceutical excipients, processes, software, guidelines and equipment. In fact, of particular note is the growing interest in process analytical technology, quality by design, continuous coating processing and the inclusion of new ready for use coating formulations. In this review, we tried to explore and discuss the status of pharmaceutical film coating, the challenges that face this manufacturing process and the latest technological advances in this important manufacturing process.
First pass effect
Gastric emptying time
Gastrointestinal motility
Short note on Gastric emptying and motility
Physicochemical factors affecting drug absorption
A. Drug solubility and dissolution rate
B. Particle size and surface area of drugs
C. Polymorphism and amorphism
D. Hydrate or solvates
Biopharmaceutical classification system of drug
Pharmacokinetics is the study of the movement of drug molecules in the body. It includes absorption, distribution, metabolism, and excretion of drugs. Pharmacokinetics is the study of what happens to drugs once they enter the body (the movement of the drugs into, within, and out of the body). For a drug to produce its specific response, it should be present in adequate concentrations at the site of action. This depends on various factors apart from the dose.
Four pharmacokinetic properties determine the onset, intensity, and the duration of drug action (Figure 1.6.1):
• Absorption: First, absorption from the site of administration permits entry of the drug (either directly or indirectly) into plasma.
• Distribution: Second, the drug may then reversibly leave the bloodstream and distribute it into the interstitial and intracellular fluids.
• Metabolism: Third, the drug may be biotransformed by metabolism by the liver or other tissues.
• Elimination: Finally, the drug and its metabolites are eliminated from the body in urine, bile, or feces.
In short, pharmacokinetics means what the body does to the drug.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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3. For a drug to exert its biological effect, it must be
o Transported by the body fluids,
o Traverse the required biological membrane
barriers,
o Escape widespread distribution to unwanted areas,
o Endure metabolic attack,
o Penetrate in adequate concentration to the sites of
action,
o Interact in a specific fashion,
o Causing an alteration of cellular function.
4.
5. General principles of drug absorption
Body membranes are generally classified as three
main types:
- those composed of several layers of cells, as the skin,
- those composed of a single layer of cells, as the
intestinal epithelium,
- those of less than one cell in thickness, as the
membrane of a single cell.
In most instances a drug substance must pass
more than one of these membrane types before it
reaches its site of action.
6. Drugs are thought to penetrate these
biologic membranes in two general ways:
1. By passive diffusion
2. By active transport
7. Passive diffusion
• Passive diffusion is used to describe the passage of
(drug) molecules through a membrane which behaves
inertly in that it does not actively participate in the
process.
• The absorption process is driven by the concentration
gradient existing across the membrane, with the
passage of drug molecules occurring from the side of
high drug concentration.
• A major source of variation is membrane permeability,
which depends on the lipophilicity of the drug molecule
(logP). The lipid solubility of a drug, therefore, is a
very important physicochemical property governing the
rate of transfer through a variety of biologic
membrane barriers.
8.
9. Fick’s law: the rate of diffusion or transport across a
membrane (dc/dt) is proportional to the difference in
drug concentration on both sides of the membrane.
=dc/dt=P(C1-C2)
Where dc/dt = rate of diffusion,
C1 and C2 refer to the drug concentrations on each side of the
membrane
P is a permeability coefficient or constant.
For practical purposes the value of C1-C2 may be taken
simply as that of C1 and the equation written in the
standard form for a first order rate equation:
-dc/dt=PC1
10. The gastrointestinal absorption of most drugs
from solution occurs in this manner in accordance with
first order kinetics in which the rate is dependent on
drug concentration.
The magnitude of the permeability constant, depends on
• the diffusion coefficient of the drug
• the thickness and area of the absorbing membrane
• the permeability of the membrane to the particular
drug.
11. Biologic Membrane
• GI membrane is consists of a bimolecular lipoid layer covered
on each side by protein, with the lipid molecule oriented
perpendicular to the cell surface, approximately 70 to 100 Å
in thickness.
• The lipid layer is interrupted by small, water-filled pores with
a radius of approximately 4 Å. A molecule with a radius of 4
Å or less can easily pass through these water-filled pores
known as “convective absorption.”
• When permeation through the membrane occurs, the
permeating substance is considered to have transferred from
solution in the luminal aqueous phase to the lipid membrane
phase, then to the aqueous phase on the other side of the
membrane.
• Biologic membranes have a hydrophilic exterior and a
hydrophobic interior.
12. • Because of the lipoid nature of the cell membrane, it
is highly permeable to lipid soluble substances.
• Aqueous pores vary in size from membrane to
membrane and thus in their individual permeability
characteristics for certain drugs and other
substances.
13. • Although most drugs are absorbed from the
gastrointestinal tract by passive diffusion, some
drugs of therapeutic interest and some chemicals of
nutritional value, such as amino acids, dipeptides and
tripeptides, glucose, and folic acid, are absorbed by
the action of transporter proteins (i.e., a carrier-
mediated transport mechanism).
• The usual requirement for active transport is
structural similarities between the drug and the
substrate normally transported across the membrane.
Carrier-Mediated or Active Transport
14. Active transport
Active transport differs from passive diffusion in the
following ways:
1) The transport of the drug occurs against a concentration
gradient;
2) Limited to drugs structurally similar to endogenous
substances (eg, ions, vitamins, sugars, amino acids).
3) Requires energy
4) The transport mechanism can become saturated at high
drug concentration; and
5) A specificity for a certain molecular structure can
promote competition in the presence of a similarly
structured compound. This, in turn, can decrease the
absorption of a drug.
15. Gastrointestinal Physiology
• Drugs, via drug delivery systems, are most often
administered to human subjects by the oral route.
Compared to other routes of drug administration,
especially the intravenous route, the oral route is unusually
complex with respect to the physicochemical conditions
existing at the absorption site. Therefore, before we
discuss how the biopharmaceutical properties of a drug in
a dosage form can affect the availability and action of
that drug, it is prudent to review gastrointestinal
physiology.
16.
17. o If dissolution is rapid or if the drug is
administered as a solution the rate at which the
drug becomes absorbed depends mainly on its
ability to traverse the membrane barrier.
o If dissolution slow because of the
physicochemical characteristics of the drug
substance or dosage form, dissolution is a
rate-limiting step in absorption.
o Drug remain in stomach :2 to 4 hours.
o In small intestine: 4 to 10 hours.
18. Oral cavity
• Saliva is the main secretion of the oral cavity
• pH 7
• Contains ptyalin which digests starch.
e.g fentanyl citrate, nitroglycerin etc (lipid soluble
drug)
Esophagus
• It connects the pharynx and the cardiac orifice of
stomach
• pH 5-6
• Very little drug dissolution occurs in it
Anatomy of GI tract
19. Stomach
• Fasting pH 2-6
• pH in presence of food is 1.5-2
• Intrinsic factor enhances vit B-12 absorption &
gastric enzymes initiate digestion.
• Basic drugs are solubilized rapidly in presence of acid
• pH may be increased due to certain drugs e.g
omeprazole.
• Ethanol easily crosses cell membrane & efficiently
absorbed from the stomach.
• e.g ibuprofen, aspirin etc absorbed here.
20. Intestine
• pH 5-7.5
• Large area for drug absorption due to presence of
villi, faster drug absorption.
• pH is optimum for enzymatic digestion of protein and
peptide containing food. Hence protein type drug (e.g
insulin) can’t be administered orally.
• The influence of absorptive surface area is much
prominent than pH.
• Most of the drugs absorb here.
21. Colon and Rectum
• pH 5.5-7
• Colon promotes melting of oily drugs to form
emulsion.
• Rectums pH is 7 and virtually has no buffer capacity
• Oral sustained release drug delivery system are well
absorbed in colon (e.g theophylline)
• Suppositories are well absorbed in rectum
23. o The gastric emptying time for a drug is rapid with fasting
stomach.
o Slower as food content is increased, temperature and viscosity
of food also influence. Fats inhibit gastric secretion and gastric
emptying.
o Anticholinergic drug slows gastric emptying. Which increases
drugs absorption from stomach and reduce drugs absorption from
small intestine.
o Drugs that enhance gastric motility, for example, laxatives,
reduce amount of drug absorbed.
o Aging decrease absorption (geriatrics)
o Decrease in gastric emptying rate is advantageous for drugs
absorbed from stomach but disadvantage for drugs prone to
acid degradation, like penicillins and erythromycin, or inactivated
by stomach enzymes, like L-dopa.
Gastric Emptying Time
24. o If acidic drugs remain for long time into stomach,
they get absorbed at a faster rate.
o If basic drug remains for a short time in stomach
and being more time in small intestine, they get
easily absorbed.
o For acidic drug gastric emptying time should be
more and for basic drug less.
o Example: penicillin is unstable in acid and
decomposes if stomach emptying is delayed. Other
drugs, such as aspirin, may irritate the gastric
mucosa during prolonged contact.
25. Factors Influencing Gastric Emptying Time
Factors Influence on Gastric Emptying
Volume The larger the starting volume, the greater the initial
rate of emptying, after this initial period, the larger
the original volume, the slower the rate of emptying.
Type of meal Reduction in rate of emptying to an extent directly
dependent upon concentration of carbohydrate, lipid
and protein type food
Osmotic
pressure
Reduction in rate of emptying dependent upon
concentration for salts and nonelectrolytes
Physical state
of gastric
contents
Solutions or suspensions of small particles empty
more rapidly
Body position Rate of emptying is reduced in a patient lying on
left side.
Viscosity Rate of emptying is lower for viscous solutions.
26. Contd.
Factors Influence on Gastric Emptying
Temperature
of Food
Increase in temperature, increase in empyting
rate
Emotional
states
Aggressive or stressful emotional states increase
stomach contractions and emptying rate; depression
reduces stomach contraction and emptying.
Disease
states
Rate of emptying is reduced in some diabetics and in
patients with local pyloric lesions and
hypothyroidism; gastric emptying rate is increased in
hyperthyroidism.
Drugs Anticholinergic, narcotic analgesic etc decrease
emptying; Metoclopramide, Domperidone,
Erythromycin, Bethanchol increase emptying.
27. Interaction between drugs and GI components
Different enzymes affect drug absorption in different ways –
o Esterase transform ester drugs into parent compounds
o Pancreatic enzymes convert Chloromycetin palmitate into
chloromycetin
Various proteins reduce activity of aluminum antacids by
complexation
Bile salts enhance dissolution of sparingly soluble drugs and improve
absorption
Bile salts can also decrease absorption of Neomycin and Kanamycin
by forming insoluble complex
Mucin, the polysaccharide covering of the GI tract can also alter
absorption
o During trauma or irritation, mucin layer thickness increases
leading to decrease in absorption.
o They can form complex with different drugs – quaternary
ammonium compounds, anticholinergic and hypotensive drugs. Also
streptomycin.
28. Effect of Food
The presence of food in the GI tract affects the bioavailability
of oral drugs.
Some effects of food on the bioavailability of the oral drugs
include:
• Delay in gastric emptying time
• Stimulation of bile flow
• Change in the pH of GI tract
• Increase in splanchnic blood flow
• Change in luminal metabolism of drug substances
• Physical/chemical interaction of metal with drug
substances
29. o Absorption of some antibiotics decreases when administered
with food (e.g. penicillin, tetracycline)
o Absorption of some lipid soluble drugs increases when
administered with food. e.g. metazalone.
o The presence of food in the GI lumen stimulates the flow of bile
which increases the solubility of fat soluble drugs by forming
micelle.
o The presence of food in the stomach lowers the pH which causes
acidic drugs to remain in non-ionized form – helps in absorption.
They may help some basic drug in dissolution as well.
o Drugs irritating to GI mucosa (e.g: erythromycin, aspirin,
NSAIDs etc) given with food to reduce the irritation by
decreasing the rate of drug absorption.
o In the presence of food, enteric coated and non disintegrating
drug products can not reach the duodenum rapidly, thus they
delay drug release & systemic drug absorption.
30. Effect of nutrients on drug absorption
• Absorption of water soluble vitamins (e.g. B-12, folic
acid) in the stomach are facilitated by forming
complex with intrinsic factors.
• Absorption of calcium in the duodenum is facilitated
by vitamin-D by increasing calcium binding protein
which binds calcium in the intestinal cell & transfer it
to the blood circulation.
• Grape juice contains various flavonoids e.g. naringin
which inhibits cytochrome P-450 enzymes. Thus it
increases bioavailability of certain drugs.
31. In children & infants: Gastric pH is high,
membrane permeability & BBB permeability is
high, protein binding is less therefore it helps
drug absorption.
While in elderly patient there is altered gastric
emptying, decrease intestinal surface area,
decrease gastric blood flow & higher incidence
of achlorhydria so it inhibits drug absorption.
Age
32. Effect of Disease States
• Drug absorption differs in any disease which causes
changes in –
• 1. Intestinal blood flow
• 2. Gastrointestinal motility
• 3. Changes in stomach emptying time
• 4. Gastric Ph
• 5. Intestinal pH
• 6. Permeability of gut wall
• 7. Bile secretion
• 8. Digestive enzyme secretion
• 9. Alteration of normal GI flora
33. • Patient with Parkinson’s disease have difficulty
swallowing & greatly diminished GI motility
• Patient on tricyclic antidepressants & antipsychotic
drugs reduce GI motility which delay drug absorption
• In achlorhydric patient weak-base drugs remain
undissolved in stomach because no adequate acid
• In patient with acid reflux disorder, Proton Pump
Inhibitor such as omeprazole, render stomach
achlorhydric, may affect drug absorption
• HIV-AIDS patients are prone to a number of GI
disturbances e.g. increased gastric transit time,
diarrhea
34. • Crohn’s disease causes impaired absorption due to
reduce surface area & thicker gut wall e.g. higher plasma
propranolol conc. observe in crohn’s disease
• Patient with Celiac disease increase rate of stomach
emptying & permeability of small intestine
• Cephalexin absorption increase in Celiac disease
• Cardio-vascular diseases: Several changes associated
with congestive cardiac failure influence the bio-
availability of the drug viz., edema of the intestine,
decreases blood flow to GIT, etc.
• Hepatic diseases: Disorders such as hepatic cirrhosis
influence bio-availability mainly of drugs that undergo
considerable first-pass hepatic metabolism e.g.
Propranolol
35. Drugs that Affect Absorption of other Drugs
• Metoclopramide (antiemetic) stimulates stomach contraction
& increases intestinal peristalsis : Decrease the peak drug
conc. by reducing effective time for absorption
• Anticholinergic drug (propantheline bromide) may slow
stomach emptying &motility of small intestine
• Tricyclic antidepressants & phenothiazines with
anticholinergic side effects cause slower peristalsis &
stomach emptying may delay in drug absorption
• Cholestyramine is a non-absorbable ion- exchange resin for
the treatment of hyperlipemia : It binds warfarin, thyroxine,
thereby reducing absorption of these drugs.
• Erythromycin inhibits the hepatic metabolism of a number of
drugs e.g. Digoxin. : Antibiotic eliminates a species of
intestinal flora that inactivates digoxin, thus leading to
greater reabsorption of drug from the enterohepatic
circulation.