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Pharmacology > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Metabolism and excretion can collectively be called?

A

Elimination

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2
Q

What is first pass effect

A

This is when a drug is metabolized by the liver . When this occurs the drug has passed thru the liver

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3
Q

Define absorption

A

This when a drug moves from the site of administration into the systemic circulation

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4
Q

What is a route of admins

A

How a drug gets into the body

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5
Q

Absorption depends on

A

The rate - how fast or slow or how long it takes for a drug to get into circulation and
The extent- how much of the drug is getting into the body
It is directly related to bioavailability

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6
Q

Define bioavailability

A

The amount or fraction of the drug that passes through first pass effect into the systemic circulation in the unchanged state

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7
Q

Drugs given by IV route have how much bioavailability and why

A

100percent
Because drugs given intravenously do not pass through first pass effect. They go straight into the blood stream so all the amount of drug given will be in circulation

Unlike in other drugs. Because they’re given by oral route or something so they have to get thru first pass effect before they get into systemic circulation and by the time it gets into circulation the amount of drug will be reduced as compared to the amount that was given

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8
Q

How to increase the effect of a drug with regards to bioavailability

A
  1. Increase the drug’s dose.
    If you know that a drug A has 30 percent bioavailability and you want to give 400 mg. You can increase the amount you give knowing that since 30 divided by 100 times 400 will give 120mg meaning only 120 mg will be in circulation then you can increase the amount of the drug
  2. Change the route of administration: instead of giving the drug as an oral drug you can give it as an IV so it works faster and bioavailability will increase or the full amount of the drug will be in circulation
  3. Reformulate the drug as a prodrug- if you want to give 400 mg of a drug but bioavailability is 30 percent then you can coat the drug so that the coat will go thru first pass metabolism and after it has metabolized it will release the actual drug so that that drug will be in systemic circulation. Example- aciclovir and valaciclovir(prodrug)
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9
Q

What is a prodrug

A

A drug which is inactive and only releases the active form or agent
when it has been metabolized
Example Valaciclovir.
Valine is a valyl ester of aciclovir. When valaciclovir undergoes metabolism , the bond in the drug is broken and aciclovir is released or becomes a metabolite
So the amount of aciclovir you want then you incorporate it into valaciclovir so when it breaks down you’ll get the exact amount of aciclovir you want

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10
Q

What factors affect absorption of a drug

A

Size of the drug
Small molecules are easily absorbed
2. Ionization - if drug is ionized it will not be easily absorbed but if it’s non ionized it’ll be easily absorbed
3. Surface area of the receptors

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11
Q

Drugs are either strong acids or weak bases true or false

A

False

Drugs are either weak acids or weak bases

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12
Q

State and explain three ways by which drugs cross membranes

A

Passive diffusion- free moment of drugs from a region of high concentration to a region of low concentration so drug is evenly distributed (downhill)
Facilitated diffusion- movement of drug is facilitated or occurs with the help of a carrier molecule from a region of high concentration to a region of low concentration(downhill)
Active transport- drug moves from low concentration to high concentration against a concentration gradient using energy in the form of ATP from the cell. (Uphill transport)

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13
Q

Drugs that are ionized are easily

A

Excreted instead of absorbed

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14
Q

Drug must be in the lipid soluble form to be absorbed true or false

A

True

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15
Q

What can help you find the ratio of unionized drug to ionized drug to see if a drug will be absorbed

A

Henderson hasselbach equation
Ph=pka-log conc of ionized divided by conc of non ionized

And how to find percentage of ionized = ionized divided by total ratio times 100

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16
Q

What is distribution

A

The movement of drugs into the tissues

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17
Q

Extent of Distribution of a drug depends on

A

Pka of the drug
Lipid solubility
Blood flow: well perfumes organs receive lots of blood so if an organ is well perched it’ll be more exposed to the drug or the drug will easily be distributed there
Degree of plasma protein binding- some drugs bind to proteins mainly albumin . This means they have affinity for the protein so if a drug had 90 percent affinity for a protein then less of the drug will be free enough to move about in circulation .

Membrane permeability
●For a drug to enter an organ (tissue), it must permeate all membranes that separate the organ from the site of drug administration

Storage Depots (Tissue binding)
●Drugs may collect in certain body tissues
●A. Fat – lipophilic drugs accumulate here and are released slowly (due to low blood flow)
●Ex: thiopental (or other anesthetic) – causes ↑ sedation in obese patients
●B. Bone – Ca++ binding drugs accumulate here
●Ex: tetracycline can deposit in bone and teeth → will cause mottling or discoloration of teeth
●C. Liver – many drugs accumulate in the liver due to an affinity for hepatic cells
●Ex: quinacrine (antimalarial agent) – has higher conc (22,000 times) in the liver than in plasma due to long term administration

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18
Q

EhT are the factors that affect protein binding

A

Affinity of drug for plasma proteins
Number of binding plasma proteins or something
Conc of protein sites available
Level of tissue binding

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19
Q

When does a protein binding something serve as a storage

A

When the drug is bound. It is being stored till it is released

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20
Q

Weak acid plus alkaline medium in the body will produce what

A

Ionized

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21
Q

Weak acid plus acidic medium will give what result

A

Non ionized

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22
Q

What is symport and antiport

A

Symport- when molecules move in the same direction

Anti port- when molecule move in one direction and some move in the other direction or a differ direction

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23
Q

Albumin can bind to what kind of drugs

A

Weak acid drugs example- phenytoin, disopyramide,salicylates

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24
Q

What kind of drugs have affinity for alpha-1 acid glycoprotein or in general serum globulins and give examples

A

Weak base drugs- quinidine, lidocaine,propanolol

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25
Q

Give theee example of highly bound drugs

A
  1. Diazepam
    Warfarin- anticoagulant
    Phenytoin
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26
Q

What is volume of distribution or apparent volume which is a way of calculating how much of a drug is distributed

A

This is estimated
It tells if a drug is well distributed or not
It is the volume of fluid into which a drug distributed based on the amount in the body and the concentration in the plasma

Vd is equal to dose that has been given or is in the body ,Q. Divided by plasma concentration,Cp

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27
Q

If the concentration in the plasma is what will the concentration in the tissues be and why

A

It’ll be low because it means Vd is low. Vd being low here means most of the drug was not well distributed into the tissues so majority of the drug is still in the plasma

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28
Q

When are drugs said to be bio equivalent

A

Two drugs are said to be bioequivalent when they have almost the same bioavailability or are similar when compared

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29
Q

Small, non-ionized, lipid soluble drugs permeate plasma membranes most readily
●The plasma membrane is impermeable to polar, water-soluble substances true or false

A

True

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30
Q

A drugs rate and efficiency depends on a drug´s route of administration true or false

A

True

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31
Q

What are the main routes of administration for drugs

A

Enteral route ▬ oral ingestion, sub-lingual and rectal (into the GIT)
➢Parenteral route ▬ Intravenous, intra arterial, subcutaneous, intramuscular, intraperitoneal and intrathecal (by inj.)
➢Topical route (i.e. application to epithelial surfaces or mucous membranes → skin, cornea (eye), vagina and nasal mucosa etc.),-usually local effects
➢Inhalational (lungs)- usually local or systemic effects

9
absorption
Other classification:
●Oral:→Drugs administered by mouth and swallowed.
●Transcutaneous:→ Us Oral:→Drugs administered by mouth and swallowed.
●Transcutaneous:→ Used when local effects on the skin is required.e.g. Topical creams, transdermal patches for nicotine withdrawal symptoms, fentanyl for analgesia & GTNT for angina.
●Transmucosal e.g. Sublingual, →absorption directly from the oral cavity [drug must have good taste], rectal(supp.) conj, vaginal (pess),nasal adm,
●Inhalational→Drugs administered this way to achieve much higher concentrations in the lungs than elsewhere in the body.e.g Inhalers, Inhalational anaesthethics etc.
●Parenteral

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32
Q

Drugs that’s re weak acids tend to be absorbed where and drugs that are weak bases tend to be absorbed where

A
  1. Stomach
    ●Drugs that are weak acids tend to be absorbed here
    ●Ex: aspirin, ethanol
    ●3. Small intestine
    ●Drugs that are weak bases tend to be absorbed here
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33
Q

What are the advantages of using the oral route of administration

A

Most convenient
●2. Least unpleasant method for most drugs
●3. No equipment required
●4. Safest (drug absorbed more slowly)

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34
Q

Drug absorption after oral administration has two (2) components name em
➢

A

The Rate of Absorption

➢Bioavailability of the drug

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35
Q

Bioavailability is Calculated from comparison of the area under the curve (AUC) relating plasma concentration to time for i.v. dosage compared with other route.
It
Says nothing about effectiveness.

True or false

A

True

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36
Q

●Bioavailability may be altered:
●By low solubility of the drug
●If drug is destroyed by the acid in the stomach (e.g.X’Pen).
●By the presence of food in the G.I.T.
●Co-administration with other drugs.
●e.g. Heavy metals in antacids can reduce the absorption of quinolones (e.g. Ciprofloxacin) and tetracyclines by binding them in the gut.

True or false

A

True

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37
Q

Drugs with very low lipid solubility such as strong acids: pKa ≤ 3 or strong bases pKa ≥ 10 (e.g.suxamethonium); are fully ionized in the GIT, may not be absorbed when administered orally. [administer parenterally]

True or false

A

True

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38
Q

Other highly polar molecules such as amino glycosides and vancomycin are also poorly absorbed from the G.I. (Very low oral bioavailability). These drugs are usually formulated as injections.
●Drugs such as levodopa and others are exceptions since they are absorbed by carrier mediated mechanisms

True or false

A

True

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39
Q

The small surface area of the stomach and its thick mucosa limits absorption.
●In contrast, as a result of the huge surface area of the intestines, the rate of absorption of ALL drugs is greater in the intestines.
●Changes in the rate of gastric emptying influence rate of presentation of drug to the intestine, and therefore influence rate of absorption
True or false

A

True

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40
Q

OVERALL RATE of absorption of a drug from the intestine > that from the stomach even if the drug is relatively more ionized in the intestine than in the stomach.
True or false

A

True

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41
Q

The prodrug of levodopa and enalapril is

A

Dopamine

Enalaprilat

42
Q

How long does it take for IV,IM and subcut to work

A

1-2 mins

10-15 minutes

20 minutes

43
Q

A. Inhalation
●Rapid absorption due to large surface area and large # of blood capillaries lining alveoli
●For gaseous/volatile drugs; Absorption rapid, local application, avoids first-pass metabolism.
● - local: in the case of respiratory disease offers delivery closest to the targer tissue
● - systemic: rapid absorption (large alveolar surface)

True or false

A

True

44
Q

When is rectal,topical,transdermal,nasal routes of administration used

A

Rectal (PR) – suppositories
●Useful for unconscious or vomiting patients or small children
●Absorption is unreliable:
●Lower rectum – enter vessels that drain into inferior vena cava and by-pass liver
●As a suppository moves upward in the rectum, access to superior hemorrhoidal vein is more likely and this leads to the liver
●C. Topical
●To maximize the drug concentration at the site of action and minimize it elsewhere, particularly for those drugs which have toxic effects if administered systemically
●Ex: dermatologic, ophthalmologic, nasal, vaginal, and otic
●D. Transdermal – drug seeps out of patch, through skin and into capillary bed
●Slow absorption
●To prolong the duration of drug absorption
●Convenient for self administration – increases compliance

Nasal→ (- for local effects ) Gonadotropin-releasing hormone and calcitonin
▬ administered as nasal spray [quickly destroyed in the G.I.T ▬ inactive when given orally]. Ephedrine nasal drops, desmopressin for patients with diabetes insipidus)

45
Q

Drugs can be transported by phagocytosis (engulfing the drug)example vaccines true or false

A

True

46
Q

Factors affecting oral absorption

A 
Disintegration of dosage form
●Dissolution of particles
●Chemical stability of drug
●Stability of drug to enzymes
●Motility and mixing in GI tract
●Presence and type of food
●Passage across GI tract wall
●Blood flow to GI tract
●Gastric emptying time
●FORMULATION
47
Q

very lipid soluble anaesthetic agent will transfer out of the blood more rapidly and to a greater extent than a drug with a low lipid solubility. True or false

A

True

48
Q

Body fluid is distributed into four main parts of the body name em

A 
THE PLASMA WATER,
•INTERSTITIAL FLUID,
•INTRACELLULAR FLUID and
•TRANSCELLULAR FLUID.
●Transcellular fluid include: C.S.F., intra ocular fluid, peritoneal fluid, pleural fluid, synovial fluid , digestive secretions etc.
•~Body fat (the fifth)
●ECF= Blood plasma + Interstitial fluid+ Lymph.
●ICF= sum of fluid contents of all cells in the body.

●To enter transcellular compartments, drug molecules must cross cellular barriers.

49
Q

What is the blood brain barrier?

A

Blood brain barrier (BBB) – lipid membrane located between plasma and the extracellular space in the brain
●The entry of drugs is restricted into the CNS and CSF (cerebrospinal fluid)
●Lipid solubility and cerebral blood flow limit permeation of the CNS
●Highly lipophilic drugs can pass the BBB (i.e. benzodiazepines)
●It is difficult to tx the brain or CNS, however, the difficulty of passage into the brain can also serve as a protective barrier when treating other parts of the body

50
Q

What is the blood placenta barrier

A

Blood-placenta barrier – the foetus is exposed to most drugs the mother ingests at anytime during the pregnancy.
Lipid soluble drugs may cross the placenta and cause developmental toxicity.
●Nicotine withdrawal symptoms in neonates,
●Down syndrome babies for alcoholic mothers.

●C. Mammary transfer of drugs – breast milk is acidic so basic drugs concentrate in this fluid
●Non-electrolyte drugs (do not depend on pH gradient – i.e. alcohol) readily reaches the same concentration as in the plasma, independent of the pH of breast milk

51
Q

What is redistribution

A

Redistribution – after a drug has accumulated in tissue, i.e. thiopental in fatty tissues, drug is gradually returned to the plasma

52
Q

Which drug stays in the tissue for a long time

A

Chloroquine

53
Q

The brain is inaccessible to many systemically acting drugs including the aminoglycosides ▬insufficiently lipid soluble to allow penetration into the blood-brain barrier.
●Inflammation of the meningis (as in meningitis) disrupt the integrity of the blood-brain barrier and allow such substances to pass through.
True or false

A

True

54
Q

Lipid insoluble drugs are mainly confined to the plasma or the interstitial fluids and could hardly enter the blood-brain barrier unless the meningis are inflamed.
True or false

A

True

55
Q

What affects volume of distribution

A

Small volume of distribution occurs when:
➢The Lipid solubility properties of the drug is low.
➢High degree of plasma protein binding
➢Low level of tissue binding

●High Vd however occurs when:
➢Lipid solubility properties of the drug is high
➢Low degree of plasma protein binding,
➢High degree of tissue binding

56
Q

Name some examples of drugs that are confine to the plasma,distributed in the ECF,distributed throughout body water

A

Drugs confined to plasma compartment
➢Heparin, insulin,→ molecule large, cannot cross the capillary wall.
● Drugs distributed in the ECF compartment
➢Aminoglycosides, Penicillins, suxamethonium, Tubocurarine etc.
●Drugs distributed throughout body water
➢Phenobarbitone, Phenytoin, Ethanol, Amitryptilline, Haloperidol, morphine et

57
Q

Increased plasma concentration of free drug may be clinically relevant if the drug is highly protein bound
OR
●not clinically relevant if the change in plasma concentration is a transient increase.
True or false

A

True

58
Q

e t a b o l i s m as a mechanism of:
● termination of drug action - inactive derivatives
● drug activation true or false

A

True

59
Q

Drugs are eliminated from the body by two principal mechanisms name them

A

By liver metabolism and
●By renal excretion.
●NB metabolism and elimination occurs in other parts of the body e.g. Billiary excretion, lungs etc.

60
Q

Lipid soluble drugs are not easily excreted by the kidneys why?

A

Lipid soluble drugs are not easily excreted by the kidneys because they are largely reabsorbed from the proximal tubules after glomerular filtration.
●such drugs have to undergo biotransformation before they could be excreted by the kidneys.

61
Q

Drugs that are water soluble may be excreted unchanged by the kidney.

●The first step in the elimination of lipid soluble drugs are metabolism to more polar cpds that are water soluble and excreted by the kidneys.
True or false

A

True

62
Q

What is biotransformation

A

Biotransformation
●Process of making a drug more polar and water soluble to be excreted out of the body (lead to termination)
●Drug metabolism often results in detoxification or inactivation of drugs where the metabolites are less active or inactive compared to the parent drug
●Some metabolites may be equally or even more active than the parent drug. Prodrug – inactive drug that is activated by metabolism (ex: enalapril)
●Some drugs can be metabolized to toxic compounds
●Ex: When acetaminophen exceeds therapeutic doses, it can deplete glutathione and accumulate a toxic metabolite which causes hepatotoxicity. N-acetylcysteine is given within 8-16 hours of overdosage to decrease toxicity

63
Q

What is xenobiotics,first pass effect,excretion ratio

A

Xenobiotics – are foreign compounds that can be absorbed across the lungs or skin or ingested in food or drinks or taken as “recreation drugs”
●Absorbed substance can be converted to active metabolite
●All drugs are foreign substances
●Every tissue has some ability to metabolize drugs (i.e. GI tract, lungs, skin, kidneys); however, the liver is the principal organ for drug metabolism

62
DRUG METABOLISM
●First-pass effect – some drugs go straight from the GI tract to the portal system where they undergo extensive metabolism in the liver (ex: morphine) before entering the systemic circulation
●This can limit the This can limit the bioavailability of certain drugs
●It can be greatly reduced by giving drug by other route of administration
●Extraction ratio – an expression of the effect of first-pass hepatic elimination on bioavailability. ER = Clliver/Q (hepatic blood flow)
●Highly extracted drugs: isoniazid, morphine, propranolol, verapamil, and several TCAs
●Poorly extracted drugs: phenytoin, theophylline, warfarin, diazepam

64
Q

What are the pathways of drug metabolism a ms explain

A

Phase I reaction – (oxidation, reduction, hydrolysis)
●Generally, the parent drug is oxidized or reduced to a more polar metabolite by introducing or unmasking a functional group (-OH, -NH2, -SH)
●The more polar the drug, the more likely excretion will occur
●This reaction takes place in the smooth (no ribosomes) endoplasmic reticulum in liver cells (hepatocytes)

●The smooth microsomes are relatively rich in enzymes responsible for oxidative drug metabolism
●Important class of enzymes – mixed function oxidases (MFOs)
●The activity of these enzymes requires a reducing agent, NADPH and molecular oxygen (O2)
●Two microsomal enzymes play a key role:
●1. NADPH-cytochrome P450 reductase, a flavoprotein
●2. Cytochrome P450, a hemoprotein, the terminal oxidase

This involves the addition or conjugation of endogenous molecules such as glucoronides, sulphates, acetyl, gluthathione etc to the phase 1 metabolites.

●This almost always lead to abolition of pharmacological activity or produces a pharmacologically inactive compound that is more water soluble and readily excreted in the urine mainly, or by the bile.

●The liver is the major site for phase II conjugation reactions but conjugation can also occur in the gut.

65
Q

Cytochrome P450
●Is a family of isoenzymes
●Drugs bind to this enzyme and are oxidized or reduced
●Can be found in the GI epithelium, lung and kidney
●Cyp3A4 alone is responsible for more than 60% of the clinically prescribed drugs metabolized by the liver true or false

A

True

66
Q

example of phase one metabolism is.

A

oxidation of ethanol to acetaldehyde

67
Q

phase 1 reactions convert the parent drug to a more polar (water-soluble), or a more reactive product
by unmasking or inserting polar functional group as
OH, SH,NH2
more polar, less active:
deamination: diazepam – nordiazepam
hydroxylation: phenytoin
activated:
O-dealkylation: codeine–morphine
The phase 1 metabolites are usually more reactive and sometimes more toxic than the parent compound.
True or false

A

True

68
Q

For phase 1 reactionsThe liver metabolic reactions are mostly catalyzed by the mixed function oxidases or the cytochrome P450 enzymes.
●( There are multiple iso-forms of the P450 enzymes which can act on numerous substrates)
●Different members of the iso-zymes have distinct but often overlapping substrate specificities.
●Some act on the same substrates as the other but at different rates. True or false

A

True

69
Q

For phase 2 reactions The endogenous substrates originate in the diet, so nutrition plays a critical role in the regulation of drug conjugation
●Drugs undergoing phase II conjugation reactions (glucuronidation, acetylation, methylation, and glutathione, glycine, and sulfate conjugation) may have already undergone phase I transformation
●Some parent drugs may already possess a functional group that may form a conjugate directly true or false

A

True

70
Q

Example of drugs that undergo glucuronidation,sulfate conjunction,acetylation are

A

glucuronidation: morphine
sulfate conjugation: acetaminophen
acetylation: sulphonamides

71
Q

All drugs metabolized by phase 2

all tend to be less lipid soluble and therefore better excreted (less well reabsorbed) true or false

A

True

72
Q

Factors affecting biotransformation

A

Age (reduced in aged patients & children)
●Sex (women more sensitive to ethanol?)
●Species (phenylbutazone 3h rabbit, 6h horse, 8h monkey, 18h mouse, 36h man); route of biotransformation can also change
●Race (fast and slow isoniazid acetylators, fast = 95% Eskimo; 50% Brits; 13% Finns; 13% Egyptians.
●Clinical or physiological condition
●First-pass (pre-systemic) metabolism

73
Q

Grapefruit juice inhibits the metabolism of Terfenadine where as cigarette smoke is an enzyme induce true or false

A

True

74
Q

Name five inducers of CP450 enzyme

A

phenobarbital, rifampin, phenytoin, carbamazepine, griseofulvin, cigarette smoking

75
Q

How does enzyme inhibition work

A

decreases drug metabolizing capacity
pl .concentrations cimetidine—warfarin,theophylline
effects erythromycin— astemizole

76
Q

A number of drugs e.g. rifampicin, ethanol, phenytoin, carbamazepine etc, increases the activity of liver microsomal enzymes by inducing the expression or synthesis of the enzymes. Many carcinogenic chemicals such as benzpyrene also have this effect.

●This is one of the major causes of drug interactions.

●Drugs such as alcohol, phenobarbitone and rifampicin induce their own metabolism true or false

A

True

77
Q

If two drugs which are metabolized by the same enzymes are administered together, one can influence the metabolism of the other
Give two examples

A

E.g. the anticonvulsants phenytoin, carbamazepine, and phenobarbarbitone are all metabolized by the same enzymes that metabolizes oestrogens and progesterone of oral contraceptives.

●If a woman taking an oral contraceptive concurrently takes one of the drugs mentioned above, the metabolism of the oestrogen and the progesterone in the contraceptive increases with the risk of contraceptive failure.

83
Enzyme induction
●Nicotine in cigarette induces the expression of the enzyme that metabolize theophylline, leading to decreased theophylline levels in the body when administered concur Other examples of enzyme inducers include, alcohol, phenobarbitone, griseofulvin, DDT, sodium valproate etc.

●Enzyme induction by accelerating phase I metabolism can increase or decrease drug effect or drug toxicity.

78
Q

Phase I metabolites of paracetamol and some polycyclic hydrocarbons are mainly responsible for their toxicity.
True or false

A

True

79
Q

Give two examples of ways drug metabolism can alter pharmacological function of drugs

A

Drug metabolism can alter the pharmacological action of a drug qualitatively.
●E.g. Aspirin to salicylate – has anti-inflammatory effect but no antiplatelet activity.
●Terfanidine causes serious cardiac arrhythmias but fexofenadine, an active metabolite lacks cardio-toxic effects. (Both are non- sedating anti histamines)

●Toxic metabolites: Acetaminophen, Phase I metabolite is hepatotoxic.
●Acrolein is a toxic metabolite (Bladder toxicity) of cyclophosphamide.
●Both methanol and Ethylene glycol exert their toxic effect through their active metabolites (By alcohol dehydrogenase)

80
Q

Example of pro drugs and their active metabolite

A 
Pro drugs to Active metabolites
●Azathioprine ▬ 6 Mecaptopurine
●Enalapril ▬   Enalaprilat
●Artemisinin ▬ dihydroartemisinin
●Sometimes designed to deliberately overcome the problem of drug deliver
81
Q

Name five enzyme inhibitors and give two examples of how the inhibitor is done

A 
seizures etc.
Other examples of microsomal enzyme inhitors include:
● Allopurinol
●Chloramphenicol
●Cimetidine
●Ketocornazole
●Erythromycin
●Ciprofloxacin
●Isoniazid
●NB Terfanidine + ketoconazole
●Cimetidine + metronidazole

●Cytochrome P450 enzyme inhibition
●Some drugs may decrease

Some drugs may decrease the activity of hepatic drug-metabolizing enzymes
●Could lead to increase levels of active drug in the body
●Ex of inhibitors: alcohol, allopurinol, grapefruit juice, cimetidine, amiodarone, ciprofloxacin, clarithromycin, erythromycin, fluoxetine, isoniazid, metronidazole, verapamil, omeprazole, oral contraceptives
●Two different mechanisms examples:
●Cimetidine binds tightly to Cyp450 and through competitive inhibition reduces metabolism of other drugs
●Erythromycin is metabolized at Cyp3A, its metabolite forms complex with enzyme and renders it catalytically inactive

82
Q

Elimination of unchanged drug or metabolite from the body – terminating its activity
●Urine is the principal but NOT the only route of excretion
M i n o r r o u t es :
●drugs may be excreted in saliva (phenytoin), sweat (salicylates), expired air (narcotics), breast milk (amiodarone, aspirin).
True or false

A

True

83
Q

Most products of phase I and II metabolism are more quickly cleared from the body by the kidneys than the parent compounds.
True or false

A

True

84
Q

Name the ways renal excretion occurs

A

Glomerular filtration – passive diffusion. is the most common route of renal elimination.
●Most drugs except those that are highly bound to plasma proteins cross freely into the glomerulus with the glomerular filtrate.

●The protein bound drug remains in the circulation where some dissociates to restore equilibrium,

● the free drug is cleared by filtration.
●Small nonionic drugs pass more readily. Drugs bound to plasma proteins do not
●Tubular secretion - drugs which specifically bind to carriers are transported (ex: penicillin). This occurs in the proximal tubules.
●Both weakly acidic (e.g. penicillins) and weakly basic drugs (e.g. procainamide) have specific secretory sites in the proximal tubular cells.

●The drug molecules are transported into the tubular lumen by some transport systems.

●The carriers can transport the drug molecules against electrochemical gradient, and can reduce the plasma concentration to nearly zero.
●Tubular reabsorption – Small nonionic drugs pass more readily (ex:diuretics)
This occurs with non-ionized and thus lipid soluble drugs in the distal tubule.

●Lipid soluble drugs are passively reabsorbed by diffusion across the renal tubules, and are not efficiently excreted in the urine.

●Whether or not weak acids or bases are reabsorbed depends on the pH of the urine, and the pKa of the drug.

93
Glomerular Filtration
●It is the most common route of renal elimination.
●Most drugs except those tha

85
Q

Unlike glomerular filtration, in active tubular sectretion,carrier mediated transport can achieve maximum drug clearance even when most of the drug is bound to plasma protein.
●Many of the drugs excreted by this route share the same transport system and competition can occur between them
True or false

A

True

86
Q

Weakly acidic drugs are excreted more rapidly in alkaline urine and weakly basic drugs in acidic urine.
●Many important drugs are removed or cleared from the body by renal excretion hence if the renal function is impaired, such drugs are liable to cause toxicity.
●( Usually the case in the elderly and in patients with renal disease)
True or false

A

True

87
Q

some drugs are mainly excreted by the kidney without prior metabolism -digoxin, gentamicin, lithium
● most drug metabolites are inactive and their rate of renal excretion is usually without clinical importance- neuroleptics

●if metabolites retain pharmacological activity, drug action may be terminated by excretion NOT by biotransformation- nordiazepam
True or false

A

True

88
Q

Hydrophilic drug conjugates may be concentrated in the bile and delivered to the intestine.

●The glucoronide could hydrolyze, releasing the free drug that can be reabsorbed and the cycle repeated. (Enterohepatic circulation)
●E.g. morphine, Propranolol, ethinylestradio
True or false

A

True

89
Q

Biliary route of excretion: parent drugs and metabolites with molecular weights greater than 350 may be actively excreted into the bile: ampicillin, rifampicin.
This process may be followed by loss of the drug in the faeces. However, drug conjugates may be hydrolysed by gut bacteria, releasing the parent drug which may be reabsorbed : enterohepatic circulation - oral contraceptive steroids, ergot alkaloids

●Vecuronium (Polar) – Excreted mainly unchanged in bile.
●Rifampicin is metabolized by deacetylation.
●Both parent drug and the metabolite are active and both forms are secreted into the bile.
●The deacetylated form is not reabsorbed, so excreted from the body through the faeces.
True or false

A

True

90
Q

What is first order elimination and zero

Order elimination

A

First-order elimination - implies that the rate of elimination is proportionate to the concentration, i.e., the higher the concentration, the greater the amount of drug eliminated per unit time.

●Zero-order elimination (saturation kinetics). Z-o elim. implies elimination at a constant rate regardless of concentration. As a result, the drug´s concentration in plasma decreases in a linear fashion over time.
●This is typical of ethanol, and of phenytoin and aspirin at high therapeutic or toxic concentration.

91
Q

Explain half life of a drug

A

The half life of a drug is the time required for the plasma concentration of the drug to fall to ½ of its original value.
●4 half-lives must elapse after starting a drug dosing regimen before full effects will be seen

●k = The elimination rate constant

●The plasma t1/2 is directly proportional to the volume of distribution and inversely proportional to the rate of clearance.
●It can be used to determine dosage interval to achieve a target concentration-time profile.

92
Q

Cytochrome P450 enzymes are promiscuous why

A

Cuz the group of enzymes metabolize different drugs

93
Q

Aspirin is metabolized to what in phase 1 and then metabolized to what in phase 2

A
  1. salycyclic acid

2. Glucuronide

94
Q

Absorption of a drug makes it go intro he CNs easily true or false

A

True

95
Q

What are antacids used for

A

Recurrent acid indigestion and are histamine receptor antagonists to prevent acid secretion a no are urine alkanizors

96
Q

Sometimes adverse effect of a drug is due to accumulation of the metabolite and not the parent drug true or false

A

True

97
Q

What enzyme does grapefruit juice contain that makes it so deadly

A

Contains furanocoumarins which disrupt the normal function of CYPS enzymes specifically the CYP3A4 enzyme which breaks down most drugs

98
Q

Mibefradil which is a calcium channel blocker is a potent enzyme inhibitor true or false

A

True

99
Q

Define a bioequivalent drug,therapeutic equivalent and pharmaceutical equivalence

A

Bioequivalent: the two drugs release active ingredients into bloodstream at the same amount ,same rate and have the same quality or it means two drugs have the same bioavailability

Therapeutic equivalenceor therapeutic equivalent 2 drugs have same clinical effect and safety profile, same active ingredients,concentration,dosage and route of administration

100
Q

If two drugs are bioequivalent they are therapeutically equivalent true or false

A

True

101
Q

so that 50% of the absorbed drug remains after one elimination half-life, 25% remains after two elimination

A

True

102
Q

so that 50% of the absorbed drug remains after one elimination half-life, 25% remains after two elimination

A

True

Pharmacology (11 decks)

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