Drug Excretion Flashcards by Iseoluwa Ojo

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

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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

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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

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Lung: excretion occurs mainly with _______.

anaesthetics

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Skin (sweat): e.g. _____, antipyrine, benzoic acid, _______, ________, _____ and ________.

Alcohol
Cocaine
Salicylic acid
Lead
Mercury

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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

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: The __________ is the most important organ involved in the elimination of drugs and their metabolites via its functional unit

kidney

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nephron: _____ + ______

glomerulus + tubules

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GF: filter small molecules (<_______) such as water, sugar, salt and unbound drugs via pores at the base of the glomerulus.

20000

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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

both proximal and distal convoluted tubules.

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Tubular reabsorption doesn’t require lipid solubility.
T/F

F
It requires lipid solubility.

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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

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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

They are reabsorbed leading to poor excretion

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Renal clearance (CLr) - is the ________________________________

volume of plasma containing the amount of substance that is excreted by the kidney per unit time.

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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

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Half life (t½) – 2 types: _______ and _______ t½.

biological and plasma

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Biological t½ is the time taken for ______________________________

a substance to lose half of its physiological, pharmacological or radioactive activity.

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Plasma t½ is the time required for _______________

the plasma concentration of a drug to be reduced to half.

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Plasma t½ - depends on _______ and _______ of the drug.

rate of excretion and metabolism

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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

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Factors affecting drug excretion

Lipid solubility- ___eases excretion except for drugs excreted vial the ____.

Decr

lungs

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Factors affecting drug excretion

pH- ____ drug becomes polar in _____ urine and vice versa resulting in increase in their excretion.

acidic

alkaline

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Morphine
Serotonin
Thiazide diuretics
Serotonin
Aspirin
Indomethacin
Penicillin
Dopamine
Histamine
Quinine
Methotrexate

BASIC
Basic
Acidic
Basic
Acidic
Acidic
Acidic
Basic
Basic
Basic
Acidic

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Factors affecting drug excretion

Enterohepatic cycling: (increases or reduces?) drug excretion and may (increase or decrease ?) half life.

Reduces
Increase

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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

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

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

chloramphenicol Undergoes enterohepatic cycling T/F

digitoxin Undergoes enterohepatic cycling T/F

phenytoin Undergoes enterohepatic cycling T/F

oestradiol Doesn’t undergo enterohepatic cycling? T/F

First pass effect can occur in; - ___ (when drug is taken _____) - ___ (through ______) - ____ (_______ drugs)

GI; orally Skin; transdermal patch Lungs; inhalational