Absorption Cont. Flashcards
Bulk flow
Substances are transported in the body along with the movement of air in the respiratory system during breathing and the movements of blood, lymph or urine
Bulk flow
Substances are transported in the body along with the movements of air in the respiratory system during breathing and the movements of blood, lymph, or urine
Filtration
Due to osmotic pressure water flows in bulk through pores in the endothelium
Types of absorption
- Pulmonary
- Percutaneous
- GIT
- Other routes : IV,IM,SC,IP
Effectiveness of route of exposure
IV > inhalation > IP > IM > ingestion > topical
Effectiveness of route exposure
IV > inhalation > IP > IM > ingestion > topical
Volume of distribution
D/Co*K
Where D : amount of substance in the body at a given time
Co: concentration in blood, plasma /serum at that time
K: body weight
Vd of < 1 kg body weight
Indicates preferential distribution in the blood
Vd > 1 kg body weight
Indicates a preference for peripheral tissues such as adipose tissue for fat soluble substances
Factors determining the rate of distribution of chemicals in the body
- Accumulation: build up of a substance in a tissue or organ to higher levels than in blood and plasma
- Physiological barriers: the blood vessels in the brain , testes and placenta have special anatomical features that inhibit passage of large molecules like protein
- Plasma concentration: substances may be bound to RBC or plasma components or occur unbound in blood
- Protein binding : chemicals highly bound to proteins have small Vd
- Affinity of chemicals to certain tissues: concentration of a chemical in certain tissues after a single may persist even when plasma concentration is reduced eg: lead concentrate in bone tissue
Elimination half-life
The time required for the concentration of the drug to reach 1/2 of its original value
T1/2 = ln 2/Ke
Elimination half-life
The time required for the a drug to reach 1/2 of its original value
T1/2= ln 2/Ke
The effectiveness of any drug depends on
Its half life
Elimination rate constant (Ke)
The rate at which a drug is removed from the body
Ke= ln2/ t1/2
Ke = CL/Vd
Clearance
The vol of blood per unit time completely cleared of a substance
Intrinsic clearance
The capacity of metabolites to transform a substance
Concentration time curve
Curve of concentration in blood vrs time
Routes of excretion
- Urinary excretion
- Exhalation
- Biliary excretion via faecal excretion
- Milk
- Saliva
- Sweat
Why would a body try to form metabolites of a substance which accidentally enters the body?
For elimination
To reduce toxicity of a substance
Target organs
Greater susceptibility of the target organ
Higher concentration of active compound
Metabolism
Process by which the administered chemical are modified by the organisms by enzymatic reactions
Primary objectives of metabolism
Make chemical agents more water soluble and easy to excrete
Decrease lipid solubility thus decreasing the amount at target sites
Increase ionization this increasing excretion rate this decreasing toxicity
Mechanism of toxicity
- Delivery
- Reaction of the ultimate toxicant with the target molecules
- Cellular dysfunction and resultant toxicity
- Repair / disrepair
Forms of cell death
Apoptosis
Necrosis
Unprogrammed death ( necrosis)
Passive form of cell death induced by accidental damage of tissue and doesn’t involve activation of any cellular program
Characteristics of necrosis
Early loss of plasma membrane integrity and swelling of the cell body followed by bursting of cell
Mitochondria and various cellular processes contain substances that can be damaging to the surrounding cells and are released upon bursting and cause inflammation
Cells necrotize in response to tissue damage
Programmed cell death (apoptosis)
Active form of cell death enabling individual cells to commit suicide
Casepase dependent
Characteristics of apoptosis
Dying cells shrink and condense then fragment to release macrophages
Intracellular constituents not released may have adverse effects on neighboring cells
Cell blebbing: presence of spherical bubbles distorting the shape of the cell
Characteristics of apoptosis
Dying cells shrink then condense then fragment releasing macrophages
Intracellular constituents which are not released might have adverse effect on neighboring cells
Presence of cell blebbing : spherical bubbles distorting the cell’s shape
Phenotypes of apoptosis
Overall shrinkage in volume on its nucleus
Loss of adhesion to neighboring cells
Formation of blebs on the cell surface
DNA fragmentation
Rapid engulfment if dying cells by phagocytosis
Factors that induce apoptosis
Internal stimuli: abnormalities in DNA
External stimuli: removal of growth factors, addition of cytokines
Signal transduction pathways leading to apoptosis
Intrinsic pathway: mitochondria dependent
Extrinsic pathway : mitochondria independent
Primary metabolic disorders jeopardizing cell survival
ATP depletion
Sustained rise in Intracellular Ca
Overproduction of reactive oxygen species and reactive nitrogen species
