A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
A Powerpoint presentation on drugs excretion and elimination suitable for UG medical students. This ppt is already presented to my students in one of the theory classes.
Introduction to dosage regimen and Individualization of dosage regimenKLE College of pharmacy
Introduction of Dosage regimen, Approaches for design of dosage regimen, Individualization, Advantages, Dosage in neonates, Geriatrics, Renal and Hepatic impaired Patients.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
Pharmacokinetics (PK) is the study of how the body interacts with administered substances for the entire duration of exposure (medications for the sake of this article). This is closely related to but distinctly different from pharmacodynamics, which examines the drug’s effect on the body more closely. The four main parameters generally examined by this field include absorption, distribution, metabolism, and excretion (ADME). Wielding an understanding of these processes allows practitioners the flexibility to prescribe and administer medications that will provide the greatest benefit at the lowest risk and allow them to make adjustments as necessary, given the varied physiology and lifestyles of patients.
When a provider prescribes medication, it is with the ultimate goal of a therapeutic outcome while minimizing adverse reactions. A thorough understanding of pharmacokinetics is essential in building treatment plans involving medications. Pharmacokinetics, as a field, attempts to summarize the movement of drugs throughout the body and the actions of the body on the drug. By using the above terms, theories, and equations, practitioners can better estimate the locations and concentrations of a drug in different areas of the body.
The appropriate concentration needed to obtain the desired effect and the amount needed for a higher chance of adverse reactions is determined through laboratory testing. Using the equations given above, a clinician can easily estimate safe medication dosing over a period of time and how long it will take for a medication to leave a patient’s system. These are, however, statistically-based estimations, influenced by differences in the drug dosage form and patient pathophysiology. This is why a deep understanding of these concepts is essential in medical practice so that improvisation is possible when the clinical situation requires it.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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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!
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
2. Pharmacokinetics:
• It deals with the
»Absorption
»Distribution
»Metabolism of DRUGS.
»Excretion
• It is a branch which deals with “ What the
BODY DOES to the DRUG.
2
4. Absorption:
A drug can be absorbed from the following sites:
1. GI tract
Mouth
Stomach
Intestine
Large Intestine or Colon
2. Parenteral Sites : iv> im> sc
3. Lungs.
4. Topical Sites. eg. Eye drops.
Sublingual Rectal Oral
Rate of absorption, fastest to lowest
4
5. From mouth:
Lipid soluble basic/neutral drugs absorbed.
1st pass metabolism bypassed.
eg. Isosorbide dinitrate given sublingually
5
6. Stomach:
Lipid soluble acidic/neutral drugs absorbed.
Drug undergo First pass metabolism after
absorption.
6
7. Intestine:
Lipid soluble basic/neutral drugs absorbed.
eg. Morphine.
Major site of absorption.
First-pass effect.
Enterohepatic circulation- Drug secreted in
intestine through bile are reabsorbed back. eg.
Ezetimibe, Morphine.
7
8. Large intestine or Colon:
Basic/ Neutral Drugs absorbed.
Absorption from External Haemorrhoidal
vein have minimal first-pass effect.
8
10. Absorption via Lungs:
Simple diffusion.
Rapid---> large surface area, high vascularity.
Absorption increases due to +ve pressure.
First pass metabolism avoided.
eg. Salbutamol spray.
10
11. Absorption via Topical Sites:
Poor absorption in intact Skin.
Mucous membrane Highly vascular.
Ophthalmic drop Cornea
eg: Nitroglycerin patch, pilocarpine
containing ocular inserts.
11
12. Absorption and its Clinical importance:
• Do we need to increase/facilitate the
Absorption of a Drug?
• Do we need to delay the Absorption of a
Drug?
12
13. Facilitate Absorption Delay Absorption
1. Adding Hyaluronidase
to injection fluid.
1. Using Appropriate
dosage forms. Eg. S/c
implants, Retard tablets
2. Changing Physical
Characteristics of Drugs
2. Increase local blood
flow by hot fomentation
3. Adding a
Vasoconstrictor Drug or
applying a Tourniquet
13
14. Bioavailability:
Rate and extent to which the active concentration
of the drug is available at the desired site of
action after non-vascular route of administration.
It is an absolute term.
AUC (oral)
Drug Bioavailability(%) = -------------- x 100
AUC (iv)
14
15. Equivalence:
Comparison of two brand products of the same
drug with a set of established standards.
It is a relative term.
It can be of several types:
Bioequivalence.
Chemical Equivalence.
Clinical Equivalence.
Therapeutic Equivalence.
15
19. Factors Influencing Absorption & Bioavailability:
19
Pharmaceutical Factors Pharmacological factors
Particle Size Gastric Emptying & Motility
Salt Form GI Disease
Crystal Form Food & other substance
Water of Hydration First pass effect
Nature of Excipients & Adjuvants Drug-Drug Interactions
Degree of Ionization Pharmacogenetic Factors
21. After absorption of a drug it may:-
Reversibly attached with its site of action.
Bound to plasma Proteins.
Accumulate in various storage sites.
Enter into tissues.
21
22. Barriers to Drug Distribution:
• Blood-Brain Barrier [BBB] (by glial cells)
• Blood-CSF and CSF-Brain Barrier.
• Placental Barrier.
22
23. Clinical Importance of The Barriers:
• BBB Protects brain tissue from toxic
substances.
• Inflammatory conditions like cerebral
meningitis alter permeability of BBB
Drugs like Penicillin, Chloramphenicol exhibit
increased permeability.
23
24. • CSF-Brain barrier permeable to drug molecules
If drug given by intrathecal route it reach the brain
in sufficient concentrations.
eg: Penicillin in Brain Abscess.
• Hypoxia increases permeability of drugs through
placental barrier.
24
Clinical Importance of The Barriers (contd):
25. Special Compartments for Drug Distribution:
Cellular Reservoir. eg. Digoxin
Fat as Reservoir. eg. Thiopentone
Transcellular Reservoir. eg. Chloramphenicol in aqueous
humour
Bones & Connective Tissue as Reservoir. eg. Griseofulvin
in Keratin precursor cells.
Plasma protein binding as Drug Reservoir.
Free Drug + Protein Drug-Protein complex
25
26. Important proteins that contribute
to Drug Binding:
1) Plasma Albumin. [acidic drugs]
2) α1-Acid Glycoproteins (α1-AGP). [basic drug]
3) Tissue Proteins & Nucleoproteins. [drugs with high
aVd]
4) Miscellaneous Binding Proteins. [thyroxin to α
globulin, antigens to gamma globulins]
26
27. Clinical Importance of Plasma Protein Binding:
1. Plasma α1-AGP = acute phase reactant protein.
Increases in MI, Crohn’s disease etc. Binding of
basic drug increases. eg. Propanolol
2. Highly protein bound drugs
i) Restricts to vascular compartment and have
lower Vd.
ii) Difficult to remove by Dialysis
3. In diseases causing hypoalbuminemia therapeutic
dose can lead to higher conc. of drug.
27
28. 4. Displacement interactions increase free drug
concentration (of the displaced drug) causing
adverse effects.
Displacement is significant when:-
Clinical Importance (contd.)
Displaced drug is more than 95% protein bound
Displaced drug with extensive protein bounding but lower aVd
28
30. The volume of each of these compartments can be
determined by use of specific markers or tracers.
The intracellular fluid volume can be determined as the
difference between total body water and extracellular
fluid.
Physiological Fluid
Compartments the
Markers Used Approximate
volume (liters)
Plasma Evans Blue 4
Extracellular fluid Inulin 14
Total Body Water D2O 42
30
31. Apparent Volume of Distribution (aVd):
aVd = Total amount of drug in body (mg/kg)_
Conc. Of the Drug in the Plasma (mg/L)
It is the total space which should apparently be
available in the body to contain the known
amount of the drug.
31
33. Drugs which bind selectively to Plasma proteins
e.g. Warfarin have Apparent volume of
distribution smaller than their Real volume of
distribution. Vd between 6 to 42 liters.
Drugs which bind selectively to Extravascular
Tissues: e.g. Chloroquine have Apparent volume
of distribution larger than their Real volume of
distribution. Vd greater than 42 liters.
33
34. Redistribution of Drugs:
Typical mode of drug distribution
observed with highly Lipid-soluble
drugs.
eg: Anaesthetic effect of Thiopentone is
rapid but effect get terminated due to
redistribution in muscle and fat.
34
36. Metabolism:
• Drug molecules are processed by enzymes
evolved to cope with natural compounds
• Drug may have actions increased or
decreased or changed
• Not constant - can be changed by other
drugs.
36
38. Biotransformation results in formation of:
An inactive metabolite from an active drug.
eg: Phenobarbitone to hydroxyphenobarbitone
Active metabolite from prodrug.
eg: L-dopa to dopamine.
Active metabolite from an equally active drug.
eg: Codeine to morphine.
38
39. First pass metabolism:
• It means drug metabolism occurring before
the drug enters the systemic circulation.
• Results is decreased bioavailability.
• Decreased therapeutic response.
Bypass First pass
metabolism:
• IV route
• Sublingual route
39
41. i) Microsomal Enzymes:
Primarily present in LIVER.
Also present in intestinal mucosa, lungs, kidney.
Principal enzyme is Cytochrome P -450.
Non-specific in action.
Concerned primarily with Phase I reactions [&
Phase II Glucuronyl conjugations]
Eg. CYP2D6
41
42. ii)Non-Microsomal Enzymes:
Present in Cytoplasm, Mitochondria of hepatic
cells & Plasma.
Catalyse Phase II reactions (except Glucuronide
conjugations).
Eg. Monoamine oxidase, Transferase.
42
43. iii) Non-enzymatic Biotransformation:
No involvement of any enzyme action
Drugs metabolized in Plasma through
Molecular Rearrangement.
Eg. Atracurium (Hoffmann Elimantion)
43
44. CYP:
Haemoproteins
In reduce form combine with CO whose
product’s absorption peak at 450.
Classification of CYP:
Families designated by numbers. Eg. 1,2,3,4 etc.
Subfamilies by letters A,B, C, D etc.
Another number is added, indicating specific
isoenzymes.
Eg. CYP2D6
44
45. CYP (contd.):
In humans 12 CYPS responsible for drug metabolism
CYP1A1, CYP1A2, CYP1B1, CYP2B1,
CYP2A6,CYP2B6,CYP2C8,CYP2C9,CYP2C19,CYP2D6,
CYP2E1, CYP3A4,CYP3A5.
Most important of CYPs for drug metabolism are
belong to 3 subfamilies CYP3A,CYP2D, CYP2C.
45
47. CYP3A4 & CYP3A5:
50 % of drugs are metabolised.
Present in Liver, intestine, kidney.
47
Inducers: Inhibitors:
Barbiturates Ketoconazole
Rifampicin Erythromycin
Phenytoin Verapamil
Carbamazepine Diltiazem
Ritonavir
48. CYP2D6:
Metabolise 25-30% commonly used drugs.
Inhibitors: Quinidine & Fluoxetine
Inducers: Unknown
Exhibit Genetic Polymorphism.
CLINICAL IMPORTANCE:
Some person may be genetically deficient to CYP2D6.
Such persons are poor responders to analgesic action
of Codeine.
They are unable to metabolise Codeine to Morphine
48
49. Chemical Pathways of Drug
Biotransformation:
1) Phase I Reactions
- Degradative reactions
- Introduction of new group
2) Phase II Reactions
- Conjugation reactions
- Originally contains NH2, OH, COOH
reactive group.
49
50. Phase I Reactions:
a) Oxidations [uses enzyme oxidases]
1) Microsomal Oxidations (CYP dependent)
2) Non Microsomal (CYP Independent)
b) Reductions
1) Microsomal Reductions
2) Non-Microsomal Reductions.
c) Hydrolysis
1) Microsomal Reductions
2) Non-Microsomal Reductions.
50
53. Phase II Reactions:
Conjugations Reactions
Types - i) Microsomal.
ii) Non- microsomal.
Enzymes used:
UDP Glucuronyl Transferase
N-acetyl Transferase
Sulfotransferase (in cytosol)
Eg. Drug + UDPGA Drug glucuronide + UDP
Drugs like Morphine, Diazepam, Aspirin etc.
53
54. Enzyme Induction:
Several drugs induce growth of smooth ER.
Leads to enhance microsomal enzyme
activity.
Accelerated metabolism.
Decrease pharmacological response.
54
55. Clinical Importance of Enzyme Induction:
1.Clinical consequence of increases drug
metabolism:
a) Decreased plasma levels & decrease
therapeutic effect.
b) Decreased drug effect if metabolite is
inactive.
c) Increased drug effect if metabolite is active.
Eg. OCP & Rifampicin Unwanted Pregnancy.
55
56. Clinical Importance of Enzyme Induction:
(contd.)
2. Drug toxicity.
eg. Ethanol drinkers have more probability of
developing drug toxicity.
3. For therapeutic benefit.
Eg. For Rx neonatal jaundice phenobarbitone is
used in pregnant mother or in new born.
56
57. Enzyme Inhibition:
One drug may inhibit metabolism of another drug
Increase in circulating levels of slowly metabolised
drug.
Prolongation & Potentiation of effects.
Enzyme inhibition can be either
Hepatic Microsomal Mixed function oxidase
Enzyme with specific functions. Eg Xanthine oxidase.
57
58. Clinical Importance of Enzyme Inhibition:
1) Potentially adverse Consequences:
* Theophylline co-administered with
Chloramphenicol Nausea, Tremors,
Vomiting.
* Dicumarol with Cimetidine Increased
bleeding tendency.
58
59. Clinical Importance of Enzyme Inhibition:
(contd.)
2) Therapeutically beneficial Consequences:
* Increased accessibility of L-dopa in brain
when given with Carbidopa .
* Aversion to alcohol after prior disulfiram
therapy. Further conversion of acetaldehyde to
acetic acid prevented vomiting, nausea
headache etc. 59
60. Factors Affecting Drug Metabolism:
Age
Sex
Species
Race
Genetic Variation
Nutrition and Diet
Disease
Drug-drug Interactions.
60
63. Renal Excretion:
Most important organ for Elimination.
Free drugs (eg. Frusemide, gentamicin)
Drug Metabolites.
63
64. Processes that determine renal excretion:
i. Glomerular filtration.
ii. Active tubular Secretion.
iii. Passive tubular reabsorption.
64
65. Factors of Glomerular filtration:
i. Molecular size.
ii. Plasma protein binding
iii. Renal Blood Flow.
65
66. Tubular Secretion:
Non-selective Active transport
Two independent carrier systems
For acidic drug (eg. Penicillin, salicylic acid)
For basic drugs (eg. Morphine)
Clinical Importance:
Weakly acidic drug (salicylic acid) interfere with secretion of Uric
Acid
Increase plasma Uric acid Level
Precipitates GOUT
66
67. Tubular Reabsorption:
Passive diffusion.
Factors :
Lipid solubility.
Ionisation constant (pKa)
pH of Urine.
Clinical Importance:
Alkalisation of Urine in Salicylate or barbiturate
poisoning.
67
68. Biliary Excretion & Enterohepatic circulation:
Drugs excreted in Bile:-Quinine, Colchicines,
Corticosteroids.
Some drugs secreted through bile but after being
delivered to intestine, are reabsorbed back and
the cycle is repeated. Eg: Digitoxin.
Other drugs with enterohepatic circulation:
Morphine, Chloramphenicol, Tetracycline etc.
68
69. Clinical Importance of Biliary excretion and
Enterohepatic circulation:
In morphine poisoning Gastric lavage is done
to prevent Enterohepatic Circulation.
Rifampicin drug action is prolonged.
69
70. Fecal Elimination:
Orally ingested drug not absorbed in Gut
eg. MgSO4, Neomycin, Certain purgatives
Drugs excreted in bile & not absorbed from
intestinal tract.
eg. Erythromycin, Corticosteroids.
70
71. Alveolar Excretion:
Gases & Volatile liquids
eg: General Anaesthetics, Ether, Alcohol
Depends on partial pressure in the blood.
Eucalyptus oil and garlic oil eliminated through
expectoration.
71
72. Elimination through Breast Milk:
May cause unwanted effect in Nursing infant.
Drugs transferred to breast milk according to pH
partition principle.
Basic drugs not ionised at plasma alkaline pH, get
accumulated in Milk.
Eg: Chloramphenicol, Tetracycline, Morphine etc.
72
73. Excretion through Skin, Hair, Sweat & Saliva:
Griseofulvin is secreted through keratin
precursor cells.
Arsenic, Mercury salts & Iodides Hair
Follicles.
Iodine, KI, Li & Phenytoin Saliva.
Amines & Urea derivatives Sweat.
73
74. Kinetics of Drug Elimination:
First order kinetics.
Zero order kinetics.
Mixed order kinetics.
74
75. First order kinetics:
Majority of the drugs follow this type of
elimination.
A constant fraction of the drug is eliminated
at a constant interval of time.
eg: Plasma concentration declining at a rate
of 50% per two hours:
100 µg/ ml 50 µg/ml 25 µg/ ml
12.5 µg/ml and so on.
75
76. First order kinetics: (contd.)
The rate of drug elimination is directly
proportional to the plasma concentration.
eg: 200-> 100-> 50-> 25-> 12.5 so on.
The t ½ of any drug would always remain
constant irrespective of the dose.
76
77. First order kinetics: (contd.)
Plasma concentration is plotted against time , the
resultant “ plasma fall-out curve” curvilinear,
Log of plasma concentration are plotted against
time , the resultant curve linear.
77
78. (contd.)
After a single dose, about 97% of the drug gets
eliminated after 4-5 half-lives (t ½) interval.
Steady state Concentration:
78
79. (1st order kinetics:contd)
If the dose of the drug is doubled, its duration
of action is prolonged for one more half-life.
The “log plasma concentration fall-out curve” of
a drug having high aVd, exhibits 2 slopes.
• An initial rapid declining phase due to distribution
(called as α phase)
• Later linearly declining phase due to elimination
(called as β phase)
79
81. Zero Order Kinetics:
A constant or a fixed quantity of drug is
eliminated per unit time.
Ethyl alcohol exhibit zero order at virtually all
plasma concentrations.
For eg: if plasma concentration falls at a rate of
25 µg per hour then 50 25 nil
81
82. The rate of elimination is independent of the
concentration of the drug in the plasma. So
increasing the dose does not result in a
proportionate rise in the extent of elimination.
100 75 50 25 Nil
The t ½ of a drug following zero order is never
constant.
Zero Order Kinetics: (contd.)
82
83. If such a fall in plasma concentration is plotted
against time, the resultant “plasma fall-out
curve” is steeply linear, but if logarithm of
plasma concentration are plotted against time ,
then the curve becomes curvilinear.
83
84. Mixed Order Kinetics/ Saturation
Kinetics / Michaelis-Menten Kinetics:
Dose-dependent kinetics where smaller doses
are eliminated by first order kinetics but as the
plasma concentration reaches higher values ,the
rate of drug elimination becomes zero order.
Phenytoin, warfarin, digoxin, dicumarol.
84
85. After a single dose administration, if the plasma
concentrations are plotted against time, the
resultant curve remains linear in the beginning
(zero order) and then become predominantly
exponential ( curvilinear i.e. first order).
Fig : Plasma concentration fall-out curve in mixed order kinetics.
85
86. Clinical Importance:
Drugs having very short half-life are given by
constant i.v. infusion to maintain steady state
concentration.
For drugs having longer t ½, with high Vd & slow
rate of clearance also are cumulative in nature. To
reach steady state Loading dose given
Maintenance dose.
Loading dose= Desired plasma conc. x aVd.
86
87. Digoxin , 0.25 mg given/24 hour, 5 days a week,
considering its nature of accumulation.
Lignocaine in cardiac arrhythmia- loading dose
given irrespective of shorter t ½.
Loading dose also necessary in case of certain
antibiotics to keep the plasma conc. higher than
MIC.
87
88. Fixed-Dose Drug Combination:
Rationale fixed-drug formulation of two drugs can
be advantageous.
The drug should have equal t ½. Eg. Cotrimoxazole
(Sulfamethoxazole [t½ 11 hr]) & Trimethoprim [t ½ 10 hr] )
Ratio of dose depends on aVd & plasma conc. Of
individual drug. eg. t ½ & aVd of Amoxycillin (1-2hr;
0.21 L/kg) matches with t ½ & aVd of Clavulanic acid
(1-1.5hr; 0.20 L/kg ).
88
90. Disadvantage of Fixed-dose formulation:
Dose of component drug can’t be
adjusted independently.
Difficult to identify which component
cause harmful or beneficial effect.
90