Drug Excretion Flashcards
Large intestine/rectum (biliary and faecal excretion):
Drugs secreted into ___ will ultimately pass through the large intestine and be excreted in _____. Examples include ________ and ________.
bile
faeces
vancomycin & vincristine
Tongue (excretion in saliva) : (acidic or Basic?) drugs are excreted in saliva (pH __-__) as a result of _______ of drug across the cells of the salivary glands and oral epithelium. E.g. ____,_____,_____,_____,_____
BASIC ; 5.8-8.4
passive diffusion
Phenytoin, diazepam, theophylline, caffeine & lithium
Eyes (tears)- occurs by __________ of lipo___, (protein or non-protein?) bound and (ionized or unionized?) molecules from plasma across the _____ and _____ glands.
Variations in tear pH affects movement of unbound drugs between plasma and tear. E.g. ______
passive diffusion
philic; non-protein
Unionized
eccrine and lacrimal
cytarabine
Lung: excretion occurs mainly with _______.
anaesthetics
Skin (sweat): e.g. _____, antipyrine, benzoic acid, _______, ________, _____ and ________.
Alcohol
Cocaine
Salicylic acid
Lead
Mercury
Hair: The exact mechanism by which drugs enter hair is ______. They may be deposited from the ______, which supply blood to the ______, or they may be excreted in the ___________ that coat the _______. E.g. ______,_______ & methoxyphenamine.
unknown
Capillaries; follicles
follicles; hair shafts
phenobarbital, methamphetamine
: The __________ is the most important organ involved in the elimination of drugs and their metabolites via its functional unit
kidney
nephron: _____ + ______
glomerulus + tubules
GF: filter small molecules (<_______) such as water, sugar, salt and unbound drugs via pores at the base of the glomerulus.
20000
Tubular reabsorption: Occurs by (passive or active ?) diffusion from the ____ into the _______
Tubular secretion: ____ mediated, (dependent on or independent of?) size nor protein binding. Excretes most drugs (~___%) and occurs at ______ and ______ of the nephron
Passive ; tubules ;peritubular capillaries
Carrier; independent of
80
both proximal and distal convoluted tubules.
Tubular reabsorption doesn’t require lipid solubility.
T/F
F
It requires lipid solubility.
Most of the drugs with high molecular weight like heparin, high molecular weight plasma protein such as albumin (68000) and highly protein-bound drugs such as warfarin (98%) are not excreted by glomerular filtration.
T/F
T
Water, lipid soluble drugs and other lipid soluble substances are not reabsorbed at the distal tubule by diffusion across the renal tubule into the bloodstream. Hence they are well excreted via the urine.
t/F
F
They are reabsorbed leading to poor excretion
Renal clearance (CLr) - is the ________________________________
volume of plasma containing the amount of substance that is excreted by the kidney per unit time.
Renal clearance is calculated from the ____________, ____________ and the _________ by the equation:
CLr = ________
plasma concentration, Cp
the urinary concentration, Cu,
volume of urine, Vu,
Cu/Cp x Vu
Half life (t½) – 2 types: _______ and _______ t½.
biological and plasma
Biological t½ is the time taken for ______________________________
a substance to lose half of its physiological, pharmacological or radioactive activity.
Plasma t½ is the time required for _______________
the plasma concentration of a drug to be reduced to half.
Plasma t½ - depends on _______ and _______ of the drug.
rate of excretion and metabolism
Plasma t½ varies between drugs. It may be very short requiring repeated administration (e.g. noradrenaline [____]) or long requiring administration once daily (e.g. methadone [____]). It may also be very long requiring once weekly intake (fluoxetine [____]).
2mins
15hrs
6days
Factors affecting drug excretion
Lipid solubility- ___eases excretion except for drugs excreted vial the ____.
Decr
lungs
Factors affecting drug excretion
pH- ____ drug becomes polar in _____ urine and vice versa resulting in increase in their excretion.
acidic
alkaline
Morphine
Serotonin
Thiazide diuretics
Serotonin
Aspirin
Indomethacin
Penicillin
Dopamine
Histamine
Quinine
Methotrexate
BASIC
Basic
Acidic
Basic
Acidic
Acidic
Acidic
Basic
Basic
Basic
Acidic
Factors affecting drug excretion
Enterohepatic cycling: (increases or reduces?) drug excretion and may (increase or decrease ?) half life.
Reduces
Increase
Enterohepatic cycling:
It involves ____ of drugs from the ____ through the _______ to the ____ where they were originally metabolized, secreted and transported in the ____ to the ______ which contain enzymes that _____ the metabolites to form _________ that are carried to the _____ again and the cycle is repeated
return; intestine; portal vein; liver
Bile ; intestine; hydrolyse
parent drug ; liver
Examples of drugs that undergo enterohepatic cycling?
tetracycline, flurbiprofen, digitoxin, phenytoin
Factors affecting drug excretion
Particle size- Except for _____ which is a macromolecule, most drugs, their metabolites and other substances with molecular weight below _____ pass freely through the glomerular capillary.
heparin
20000
Factors affecting drug excretion
Drug interaction- probenecid inhibits excretion of _____ by competing with it for tubular _____ at the _____ tubule thereby prolonging its action.
penicillin
secretion
proximal
Warfarin is mildly protein bound
T/F
F
Highly (98%)
warfarin has very small concentration in the filtrate compare to plasma.
T/F
T
Renal disease- (increases or reduces?) renal excretion of drugs.
Reduces
Normal kidney’s function can be determined by ____ which is the volume of fluid filtered through the renal glomerular capillaries into the Bowman’s capsule per unit time.
GFR
GFR: Normal ___-____
kidney disease < ___
Kidney failure < ___ [ml/min/1.73m2].
100-130
60
15
Absolute bioavailability of drugs administered intravenously is ___% but it is less for drugs administered through other routes due to ______ and _____
100
incomplete absorption and first pass metabolism.
Absolute bioavailability can be determined by measuring the _____ of a drug at different time when the drug is administered ________ and _______ on (same or different?) occasions.
plasma concentrations
orally and intravenously
Different
Formula for bioavailability
1) when dose is the same
_______________________
2)when dose are different
_______________________
AUCORAL x 100% / AUCIV
AUCORAL X DOSEIV X 100% / AUCIV X DOSEORAL
The plasma concentration vs time curve has the shape of a ______ and the AUC is calculated using _____ rule:
AUC= ______________
trapezium; trapezoidal
½ (length + breath) x height.
Variations in enzyme activity of the gut wall ; gastric pH; intestinal motility and other factors that affect drug absorption also affect its bioavailability.
T/F
T
Relative bioavailability is a measure of the _______________________
Relative bioavailability formula =
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.
AUC TEST
_________________
AUCSTANDARD
To be bioequivalent the difference in relative bioavailabilities of two related drugs must not exceed ___%.
+/- 20
alkalization of urine (using _______, acetazolamide or _______) and acidification (using ________, _________ or _________)
sodium bicarbonate; potassium citrate
ammonium chloride
sodium phosphate or potassium phosphate
Phenytoin is an ________ drug
Anti-comvulsant
Absolute availability can be equal to 1
T/F
F
It’s always less than 1
AUC of oral takes the shape of a ?
AUC of IV takes the shape of a ??
Trapezium
Triangle
In patent period- the drug is branded and marketed by the company that __________
does the research of the drug
When patent period expires, can other brands market the drug?
Yeah
Relative bioavailability is used to determine if 2 brands are _______
Bio equivalent
Relative bioavailability can be equal to 100
T/F
F
Less than 100
A drug interaction is only clinically significant if ________?
If the interaction affects the efficacy of one or more drugs
Mechanism of action of Artemisinin
Causes radical oxidation of plasmodium to destroy it !!!
Full meaning of ACT
Artemisinin based combination therapy
Lipid solubility and pH influence the passage of drugs into the glomerular filtrate.
T/F
F
Lipid solubility and pH
do not influence the passage of drugs into the glomerular filtrate.
As a general rule, weak acids can be eliminated by ______ of the urine,
whereas elimination of weak bases may be increased by ______ of the urine.
alkalinization
acidification
P-glycoprotein is a transmembrane transporter protein responsible for transporting various molecules, including drugs, across ______
It is expressed in tissues throughout the body, including the liver, kidneys, placenta, intestines, and brain capillaries, and is involved in transportation of drugs from _____ to ______ That is, it “pumps” drugs _______.
cell membranes
tissues to blood.
out of the cells
Thus, in areas of high expression,
P-glycoprotein (increases or reduces?) drug absorption.
In addition to transporting many drugs (into or out of ?) cells, it is also associated with ___________
Reduces
Out of
multidrug resistance
Pharmacokinetic DI: occurs when one or more drug alters the _____________________ of another drug such that its plasma concentration is altered.
absorption, distribution, metabolism or excretion
Pharmacodynamic DI: occurs when one or more drugs alter the _________________ of another drug.
pharmacological or toxic effects
Pharmacokinetic drug interaction
• Alteration of absorption
– Calcium containing drugs (Antacids) vs tetracycline: Calcium _____ tetracycline to form a complex and (aid or prevent?) its absorption thereby reducing its plasma conc
chelate; prevent
Pharmacokinetic drug interactions
Alteration of metabolism
– Efavirenz vs artemether/lumefantrine: efavirenz induces _________ enzyme which metabolises the _____ drug thereby reducing their plasma
concentration.
cytochrome P3A4
antimalarial
Pharmadynamic drug interaction
• Additive toxicity
– Concomitant use of _______ and _____
increases the risk of ________ and
worsens _____ disease
NSAIDs and glucocorticoids
Gastric bleeding
peptic ulcer
Pharmacodynamic drug interactions
Therapeutic failure/Reduction in efficacy
– Concomitant administration of ______ or other antioxidants with ________________________ in the treatment of malaria
ascorbic acid
artemisinin based combination therapy (ACT)
Where is vancomycin Excreted from ?
Large intestine/ rectum
Where is vincristine excreted from?
Large intestine /rectum
Where is Phenytoin excreted from?
Saliva
Where is diazepam excreted from?
Saliva
Where is theophylline excreted from?
Saliva
Where is caffeine secreted from ?
Saliva
Where is lithium excreted from?
Saliva
Where is cytarabine excreted from ?
Tears
Where is Alcohol excreted from ?
Sweat
Where is antipyrine excreted from?
Sweat
Where is benzoic acid excreted from?
Sweat
Where is cocaine excreted from?
Sweat
Where is salicylic acid excreted from?
Sweat
Where is lead excreted from?
Sweat
Where is mercury excreted from?
Sweat
Where is aspirin excreted from?
Breast milk
Where is phenobarbital excreted from?
Hair
Where is methamphetamine excreted from?
Hair
Where is methoxyphenamine excreted from?
Hair
Plasma half life of methadone is _____
15hrs
Plasma half life of fluoxetine is ______
6days
alkalization of urine using _______,_______, or ________
sodium bicarbonate, acetazolamide or potassium citrate
acidification of urine using ______,_______, or _______
ammonium chloride, sodium phosphate or potassium phosphate
quinine
Acidic or basic
BASIC
probenecid
Acidic or basic
BASIC
morphine
Acidic or basic
Basic
histamine
Acidic or basic
BASIC
serotonin
Acidic or basic
BASIC
dopamine
Acidic or basic
BASIC
pethidine
Acidic or basic drug?
BASIC
aspirin
Acidic or basic
Acidic
penicillin
Acidic or basic
Acidic
methotrexate
Acidic or basic
Acidic
indomethacin
Acidic or basic
Acidic
frusemide
Acidic or basic drug?
Acidic
thiazide diuretics.
Acidic or basic drugs
Acidic drugs
tetracycline
Undergoes enterohepatic cycling
T/F
T
chloramphenicol
Undergoes enterohepatic cycling
T/F
T
digitoxin
Undergoes enterohepatic cycling
T/F
T
phenytoin
Undergoes enterohepatic cycling
T/F
T
oestradiol
Doesn’t undergo enterohepatic cycling?
T/F
F
First pass effect can occur in;
- ___ (when drug is taken _____)
- ___ (through ______)
- ____ (_______ drugs)
GI; orally
Skin; transdermal patch
Lungs; inhalational
