Drug Excretion, Bioavailability And Bio equivalence Flashcards
Drugs excretion is the irreversible __________ of unchanged _________ ________or their __________ from the body via various organs of which the __________ is major and most important
Elimination
Parent drugs
Metabolites
Kidney
Organs of drug excretion and their product (8)
Kidney: urine
Tongue : saliva
Skin: sweat
Breast: breast milk
Lungs: breathe
Rectum/intestine: bile- faeces
Eye: tears
Hair
Large intestine excreted drugs include 2
Vancomycin (Antibiotic)
Vincristine (chemotherapy)
________ drugs are excreted in saliva as a result of __________ diffusion of drug across the cells of the salivary glands and oral ___________.
Basic
Passive
Epithelium
Saliva has a pH of
5.8-8.4
Examples of tongue excreted saliva
Phenytoin (anti- epileptic/ anti- convulsant)
diazepam (anxiolytic)
theophylline (bronchodilator: asthma, COPD)
caffeine (stimulant)
lithium (mood stabilizer)
Eye excretion occurs by ________ diffusion of __________, non-protein bound and _________ molecules from plasma across the _________ and ___________ glands.
Passive
Lipophilic
Unionized/ non- ionized
Eccrine & Lacrimal
In eye excretion, variations in __________affects movement of unbound drugs between plasma and tear.
pH of tears
Examples of drug excreted by tears
Cytarabine : chemotherapy
Lung excretion occurs mainly with
Anaesthetics
Drugs excreted by the skin include (7)
Alcohol
antipyrine
benzoic acid
cocaine
salicylic acid
lead
mercury
Most drugs are excreted through breast milk T/F
True
The exact mechanism by which drugs enter hair is known. They may be deposited from the capillaries, which supply blood to the follicles, or they may be excreted in the ________, _________ or __________ that coat the hair shafts
T/F
False. It is unknown
sebum, oil, or sweat
Examples of drugs excreted from hair is
phenobarbital (barbiturates and anticonvulsant)
methamphetamine (CNS stimulant)
methoxyphenamine(bronchodilator)
The _________ is the most important organ involved in the elimination of via its functional unit
Kidney
Drugs and their metabolites
nephron= __________ + ________
Glomerulus + Tubules
Renal excretion = __________- _________+ ___________
Glomerular filtration (GF) – tubular reabsorption (TR) + tubular secretion (TS).
Glomerular filtration filters small molecules. Less than
20,000
Tubular reabsorption: Occurs by _______ diffusion from the _________ into the _________ capillaries, and requires _________ ______________
Passive
Tubules
Peritubular
Lipid solubility
Tubular secretion: Carrier mediated, independent of ____ nor _________ ________.
Excretes most drugs (~ ___%) and occurs at both proximal and distal convoluted tubules.
size nor protein binding.
80%
Most of which drugs are not excreted by glomerular filtration.
drugs with high molecular weight like heparin
high molecular weight plasma protein such as albumin (68000)
highly protein-bound drugs such as warfarin (98%)
Water, lipid soluble drugs and other lipid soluble substances are _________ at the distal tubule by _________ across the renal tubule into the bloodstream. Hence they are ______ excreted via the urine.
Reabsorbed
Diffusion
Poorly
ACT means
Artemisinin- based Combination therapy
Define renal clearance
is the volume of plasma containing
the amount of substance that is excreted by the kidney per unit time.
Formulae for renal clearance
Urine volume * urine concentration
/
Plasma concentration
The types of half life are
T1/2
Biological half time
Plasma half time
Biological half life is the time taken for a substance to lose half of its __________, __________ or __________ activity
physiological
pharmacological
radioactive
Plasma t1⁄2 is the time required for?
the plasma concentration of a drug to be reduced to half.
Plasma half time depends on what & what
Rate of excretion and
Metabolism of the drug
Plasma t1⁄2 varies between drugs. It may be very short requiring repeated administration e.g.?
or long requiring administration once daily e.g. ?
Or very long requiring once weekly intake eg?
Noradrenaline 2 minutes (increase blood pressure)
Methadone 15 hours (pain relief and treat drug addiction)
Fluoxetine 6 days (antidepressant)
7 Factors affecting Drug Excretion
Lipid Solubility
pH
Enterohepatic cycling
Particle size
Protein binding
Drug interaction
Renal disease
About lipid solubility
Excretion is decreased except for drugs exerted via the lungs
About pH,
acidic drug becomes polar in ________
alkaline urine
Alkaline drug becomes polar (ionized) in acidic urine
Thus increasing excretion
Therefore for abosorption acid?
While for excretion
Acid should be in acidic solution
Acid should be in alkaline medium
Drugs for alkalization of urine
sodium bicarbonate
acetazolamide
potassium citrate
Drugs for acidification of urine
ammonium chloride
sodium phosphate
potassium phosphate
Basic drugs include
quinine
probenecid
morphine
histamine
serotonin
dopamine
pethidine
Acidic drugs are
aspirin
penicillin
methotrexate
indomethacin
frusemide
thiazide diuretics
Enterohepatic cycling does 2 things
reduces drug excretion
may increase half life.
Enterohepatic recycling involves return of drugs from (through the portal vein) liver where they were originally metabolized, secreted and transported in the bile to the intestine which contain enzymes that _________ the metabolites to form ___________ that are carried to the liver again and the cycle is repeated
Hydrolyze
Parent drug
enterohepatic recycling (or enterohepatic circulation) involves the circulation of metabolized and non-metabolized compounds (including physiologic compounds and xenobiotics) between the intestine and the liver.
Some xenobiotics and some endogenous substances (e.g., bile acids) can be reabsorbed after their elimination into the intestine by the liver, entering an enterohepatic cycle
Examples of drugs that go through enterohepatic recycling because they are secreted by the liver into bile
tetracycline
chloramphenicol
flurbiprofen
leflunomide
colchicine
digitoxin
phenytoin
oestradiol
Which drug is a macromolecule and can’t be easily excreted
Heparin
most drugs, their metabolites and other substances with molecular weight below _________ pass freely through the glomerular capillary and are excreted
20,000
plasma albumin has a molecular weight of ________ and cannot pass freely through the glomerular capillary.
Hence ____________ which is highly protein bound __%has very small concentration ___% in the filtrate compared to plasma.
68,000
Warfarin
98
2
____________ inhibits the excretion of penicillin
Probenecid
by competing with it for tubular secretion at the proximal tubule thereby prolonging its action
How does renal disease affect renal excretion of drugs
It reduces excretion
Risk factors for kidney disease include
diabetes
high blood pressure
family history
older age
ethnic group
smoking.
Normal kidney function can be determined by?
Glomerular Filtration rate
GFR is ?
the volume of fluid filtered through the renal glomerular capillaries into the Bowman’s capsule per unit time
GFR in
Normal kidney
Kidney disease
Kidney failure
100-130
Less than 60
Less than 15
Unit of GFR
ml/min/1.73m2
Body surface
Bioavailability is a measurement of the ________ & __________ to which the active ingredient in a drug product becomes available at the site of action or in _________ ____________
Rate & extent
Systemic circulation
Absolute bioavailability is the _________ of an active ingredient of an ___________ administered drug that reaches _________ ___________ as an intact drug (unchanged)
fraction
orally
systemic circulation
unchanged)
Absolute bioavailability of drugs administered
intravenously is ______% but it is less for drugs administered through other routes due to __________________ and _______________
100%
Incomplete absorption
First pass metabolism
AUC means
Area under plasma conc vs time curve
Absolute bioavailability (F) formula if doses are the same
▪ F= AUCoral / AUCiv x 100%
F formula for different doses is
F= AUCoral X DOSEiv / AUCiv X DOSEoral X 100%
The plasma concentration vs time curve has the shape of?
and the AUC is calculated using?
A trapezium
Trapezoidal rule which is
Area= 1⁄2 (length + breath) x height.
Factors that affect bioavailability also affect absorption T/F
True
Factors that affect bioavailability is
Variations in enzyme activity of the gut wall ;
gastric pH;
intestinal motility
What is relative bioavailability?
Relative bioavailability is a measure of the systemic availability of a generic or test drug product in comparaism to that of a Reference standard drug product containing the same active ingredient when they are administered through the same route in the same dosage form.
Relative bioavailability = AUC test/ AUC standard
In bio equivalence,
A generic drug is bioequivalent to a reference standard drug if their relative bioavailability do not show SSD when both drug products containing the same active ingredient in the same chemical and dosage forms are administered at the same dose through the same route and under the same experimental conditions.
SSD?
To be bioequivalent the difference in relative bioavailabilities of two related drugs must not exceed +|- ?
20%
