Pharmacokinetic Flashcards by Muhammad ASR | Brainscape

Q

What is pharmacokinetics?

A

Is the effect of the body on the drug. Include: ADEM

Absorption
Distribution
Metabolism
Excretion

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Q

Elimination through liver is called

A

Metabolism

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Q

Elimination of lipophilic drug occur in

A

Hepatic liver

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Q

Elimination of hydrophilic drug occur in

A

Kidney

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Q

Absorption of the drug Occurs mainly by ______ which depends on degree of _______ of the drug

A

Lipid passive diffusion
Ionization

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Q

What is pka

A

• PKa (Dissociation constant): is the pH of medium at which 50% of drug molecules are ionized & 50 % unionized.

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Q

pH of medium = pKa of the drug—>

A

50% unionized (lipid soluble) and 50 % is ionized ( water soluble)

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Q

pH of medium < pKa of drug →

Weak acid :
Weak base :

A

ionization decrease (More unionized)
e.g aspirin [pka =3.5] exist mainly in non ionized (lipid soluble) form at gastric pH 1.5 -2.5

ionization ↑ (less unionized)

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Q

lonization of weak bases
decreases at

A

Ph>pka

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Q

E.g for lonization of weak bases

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

lonization of weak bases
decreases at pH > pka

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

lonization of weak bases
decreases at pH > pka

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

lonization of weak bases
decreases at pH > pka

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

lonization of weak bases
decreases at pH > pka

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

lonization of weak bases
decreases at pH > pka

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

lonization of weak bases
decreases at pH > pka

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

lonization of weak bases
decreases at pH > pka
Give e.g for that

A

e.g. Theophylline (pka = 8.8) is mostly non-ionized (lipid soluble) at alkaline pH of the intestine.

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Q

How peptic ulceration ouccr in GIT due taking aspirin orally ?

A

• Aspirin is acid → mostly unionized (non-polar) = Lipid soluble in the empty stomach → cross the cell membrane of gastric mucosa to be trapped inside these cell(mucosa cells) (acid trap) > death of the cells (peptic ulcer).

• Aspirin → Peptic ulcer (PU) due to acid trap + inhibition of Cyclooxygenase (cox) enzyme → decrease PGs(prostaglandin) which is protective against PU in the stomach دا هو السبب الأهم

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Q

Aspirin is part of

A

NSAIDs

non-steroidal anti-inflammatory drugs

هي انزيمات وحشه تضرب prostaglandin

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Q

How to inhibit tubular reabsorption during drug poisoning in kidney?

A

In drug poisoning, Renal drug elimination can be increased by changing urinary pH

↑ drug ionization→ decrease tubular reabsorption of the drug →↑ its renal excretion

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Q

How to inhibit tubular reabsorption during drug poisoning in kidney?

A

In drug poisoning, Renal drug elimination can be increased by changing urinary pH

↑ drug ionization→ decrease tubular reabsorption of the drug →↑ its renal excretion

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Q

How to inhibit tubular reabsorption during drug poisoning in kidney?

A

In drug poisoning, Renal drug elimination can be increased by changing urinary pH

↑ drug ionization→ decrease tubular reabsorption of the drug →↑ its renal excretion

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Q

How to inhibit tubular reabsorption during drug poisoning in kidney?

A

In drug poisoning, Renal drug elimination can be increased by changing urinary pH

↑ drug ionization→ decrease tubular reabsorption of the drug →↑ its renal excretion

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Q

How to inhibit tubular reabsorption during drug poisoning in kidney?

A

In drug poisoning, Renal drug elimination can be increased by changing urinary pH

↑ drug ionization→ decrease tubular reabsorption of the drug →↑ its renal excretion

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Q

How to inhibit tubular reabsorption during drug poisoning in kidney?

A

In drug poisoning, Renal drug elimination can be increased by changing urinary pH

↑ drug ionization→ decrease tubular reabsorption of the drug →↑ its renal excretion

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Q

During Acidic drugs poisoning in renal , the urine should be ____ for treatment

A

Alkalized

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Q

E.g for Acidic drug

A

Aspirin, phenobarbital

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Q

During basic drugs poisoning in kidney, urine should be ____ to avoid reabsorption of it in blood

A

Acid

تذكر قصة دكتور خليفة مع الود إلي شرب صاحبه عصير برتقال عشان ينقذه من جرة amphetamine

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Q

E.g for basic drug

A

Amphetamine

اي مركب آخره mine هو قاعدي

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Q

What is bioavailabilty?

A

Definition: It is the percentage of drug that reaches the systemic circulation and becomes available for biological effect.

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Q

Bioavailability of IV

A

100%

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Q

↑ Absorption –> increase bioavailability

A

True

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Q

Increase of First pass metabolism–> Increase of bioavailability

A

False

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Q

How to calculate bioavailability?

A

(AUC oral/AUC IV) × 100

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Q

Factors affecting bioavailability (F)

A

Amount of drug absorbed = Factors affecting GIT absorption

2 First Pass Metabolism (FPM) = Pre-systemic elimination

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Q

E.g for parental

A

IV
IM
subcutaneous

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Q

What is bioequivalence?

A

2 dosage forms have the same (bioavailability & time to reach the peak)

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Q

What is Therapeutic equivalence?

A

2 drugs form have same bioequivalent drug + have similar efficacy & toxicity.

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Q

Name factors affecting absorption from GIT

A

. Factors related Dosage form: (affect disintegrationتفكك)

Factors related to Drug: (affect dissolutionنحلل)

Factors affecting drug Stability in GIT content

GIT pH & drug’s pKa

Factors related to Absorptive system

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Q

E.g for factors related to Dosage form

A

Synthesis techniques طرق التصنيع

& excipients added during preparation إضافات لتحسين الدواء

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Q

E.g for factor related to Drug

A

Molecular weight (MW)

lipid solubility

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Q

Factors affecting drug Stability in GIT content

GIT secretions (HCL) –> with e.g
Food–>

A

HCL can destruct some drugs : e.g. erythromycin

Dairy food منتجات الالبان decreases absorption of tetracyclines (ca++)

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Q

GIT pH& drug’s pKa example

A

Affect degree of drug ionization → affect lipophilicity

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Q

Factors related to Absorptive system
•GIT motility:
Surface area:
• GIT disease:

A

Prokinetics (↑) & anticholinergics (decrease) motility of GIT

Intestine&raquo_space;> stomach معظم كمية الدواء تمتص في الأمعاء

e.g. Mal absorption syndrome

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Q

What is pre systematic elimination or FPM?

A

It is the metabolism of the drug through the liver, GIT wall or lung before reaching systemic circulation

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Q

E.g for FPM drug in
Hepatic:
Pulmonary:
Intestine:

A

Nitroglycerine يؤخذ sublingualافضل & propranolol

اي دواء آخره lol هو beta bloker يعمل VC فيوقلل Hepatic blood flow

Nicotine

Estrogen

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Q

Portal hypertension cause ____ by a drug called ____

A

Decrease Hepatic blood flow (الجسم يفتح قنوات اسمها porto-systimic shunt تقلل ضغط الدم)

Propranolol ,it’s a beta blocker –>VC

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Q

Liver failure cause _____ by drug called enzymes inhibitor or ___

A

Decrease Hepatic enzymes

Erythromycin

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Q

How to avoid (bypassing) FPM ?

A

Change the route into Sublingual or Parenteral (injection) / Rectal

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Q

Drugs with variable Bioavailability (F) in their different dosage forms:

A

Digoxin(treatment of heart failure) & Phenytoi(treatment of epilepsy)

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Q

What distribution?

A

The drug passes through body compartments (plasma, interstitial & intracellular fluids) = 42L/70kg

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Q

What is volume of distribution (Vd) ?

A

Apparent volume of fluids that would تستوعبaccommodate total dose of the drug if(الحرف دا مشكلة🤣) its concentration in body equal to that in plasma

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Q

Importance of Vd

A

It is an estimate of the extent of tissue uptake of drugs

In cases of treatment of drug toxicity by hemodialysis
1.
2.

Vd can be used to calculate the loading dose (LD):

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Q

If Volume of distribution is smal , then tissue uptake is___

A

Low

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Q

High tissue up take means high Vd

A

True

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Q

E.g for small Vd in tissue

A

Frusemide

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Q

E.g for high large Vd in tissue uptake

A

Digoxin

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Q

Why dialysis is not useful for high Vd?

A

most of drug is in the tissues)

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Q

Why is dialysis useful for low Volume of distribution?

A

most of drug is in blood and ECF(plasma and ISF)

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Q

How is loading dose calculated?

A

LD = Vd x Steady state plasma concentration (Css)

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Q

Vd is affected by:

A

Vd is affected by:
Perfusion
Lipophilicity (diffusion)
Binding to plasma protein
Binding to tissues
Degree of tissue uptake
Loading dose

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Q

What is perfusion ?

A

↑ blood flow → ↑ Distribution

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Q

What is diffusion ?

A

↑ lipophilicity → ↑ Distribution

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Q

Perfusion and diffusion have a relationship, name it

A

Direct relationship

Q

Name Drugs and there Binding to cell and tissue constituents

A

Chloroquine: Liver
Tetracyclineيحب Ca++: Bone & Teeth
lodides: Thyroid & salivary glands

Q

Significance of HIGH lipophilicity:
Or
Q. Mention pharmacokinetic characters of lipophilic drugs

A

↑ Absorption
↑ Vd
↑ Hepatic elimination (lipophilic drugs can enter hepatocytes)
Dec. Renal elimina tion (due to ↑ renal reabsorption)

Q

Binding to Plasma protein (pp): → Drug Mainly binds to ____

A

Albumin

Q

Drug in blood exists in 2 forms in equilibrium:

A

Free form
Bounded form

Q

Bound form is

A

is inactive, non-diffusible, cannot be metabolized or excreted. Acts as reservoir

Q

Free Form is:

A

is active, diffusible and can be metabolized and excreted.

Q

Significance of binding to plasma protein: Highly bound drugs ->

A

Affect pharmacokinetics:
↑ absorption (by Decrease free concentration of the drug in plasma)

Decreases Distribution ( Vd tissue uptake and penetration)

Decreases elimination (Prolong ti/2). The bound drug can not be elimina releases the free part.

Q

Significance of binding to plasma protein: Highly bound drugs ->

A

Affect pharmacokinetics:
↑ absorption (by Decrease free concentration of the drug in plasma)

Decreases Distribution (Decreases Vd tissue uptake and penetrationالإختراق او التغلغل)

Decreases elimination (incerse Prolong t1/2). The bound drug can not be eliminated and acts as reservoir which continuously releases the free part.

Q

Significance of binding to plasma protein: Highly bound drugs ->

A

Affect pharmacokinetics:
↑ absorption (by Decrease free concentration of the drug in plasma)

Decreases Distribution ( Vd tissue uptake and penetration)

Decreases elimination (Prolong ti/2). The bound drug can not be elimina releases the free part.

Q

Significance of binding to plasma protein: Highly bound drugs ->

A

Affect pharmacokinetics:
↑ absorption (by Decrease free concentration of the drug in plasma)

Decreases Distribution ( Vd tissue uptake and penetration)

Decreases elimination (Prolong ti/2). The bound drug can not be elimina releases the free part.

Q

Plasma protein Not effective against ___

A

dangerous infections
لأنها اغلبها تمسك (albumin ) ومش رح تكون free form

Q

E.g Site of drug interaction (خناقة الادوية) on acidic binding sites of albumin:

A

NSAIDS displace Warfarin from binding sites → ↑Free form of warfarin>↑warfarin effect (bleeding من الانف ): see drug interaction

Q

Why NSAID drugs could take the place of wafrine?

A

Drugs with high Affinity to bind to pp → DISPLACEMENT of drugs with low affinity

Q

toxicity from low affinity drug if it is _____ to plasma protein

A

Higley bound

Q

Aim of Biotransformation (metabolism)

A

Aim: Change the drug into more H20 soluble (polar= ionized) metabolites —> easily excreted in urine

Q

Consequences of biotransformation(metabolism)

A

Inactive drug (prodrug)—>converte to active drug which take two pathway
1.active metabolism
2. Toxic “

Or it may take another pathway, to be inactive metabolites) most of drug ) with no adverse effects

Q

E.g for pro drugs

A

Enalapril (ACED) –>active form enalaprilat
Prednisone (Cortisone)–> active form prednisolone

Q

E.g for active metabolism

A

Codeine(دواء الكحة) changes to morphine
الناس المدمنة تشربوا كامل عشان الجسم رح يحوله ليمورفين

Q

E.g for toxic metabolism

A

Paracetamol metabolized to toxic epoxide which then conjugated with SH (Glutathione) to non- toxic metabolites.

Q

Types of biotransformation reaction

A

Phase I (Non synthetic)
Phase ll (synthetic)

Q

Phase 1 (Non synthetic)

A

Include: Oxidation (by cytochrome P450), reduction & hydrolysis
اي يزيل جزء من الدواء

Unmasking of a polar group (-0H,-SH, - NH2)

Converting the drug to an H20 soluble the can be excreted

Q

What is phase 2 (synthetic)

A

Include: Conjugation with: glucuronic acid, Glutathione,
Glycine, Sulfate,..
(addition: —ation ?)

يضيف جزء للدواء

Q

Types of metabolizing enzymes

A

Microsomal enzyme
Non-Microsomal enzyme

Q

Microsomal enzyme Bound to ____

A

endoplasmic reticulum

Q

E.g for Microsomal enzyme

A

Cytochrome P450(phase1)
Glucuronyl transferase(phase 2)

Q

Non Microsomal enzyme : found in ___or ____

A

Plasma
Cytoplasm

Q

E.g for non microsomal enzyme in plasma and cytoplasm

A

Plasma: Choline esterase
Cytoplasm: Xanthine oxidase

Q

Not liable

A

Non-microsomal enzyme

Q

Factors affecting drug metabolism

A

1) Physiological: Age, Sex
2) Pathological
3) Pharmacogenetic variation
4) Enzyme induction & enzyme inhibition

Q

Factors affecting drug metabolism
E.g for physiological
Age:
Sex:

A

extreme of age (newborn, very old) →decrease metabolism

testosterone ↑ metabolism while
Estrogen decreases “

Q

E.g for pathogenesis factor effecting metabolism

A

2) Pathological: Liver diseases > decraes metabolism

Q

E.g for 3) Pharmacogenetic variation

A

3) Pharmacogenetic variation: Slow acetylators > decrease metabolism of isoniazid

تذكر acetylation polymorphism

Q

What are enzyme induction

A

•Enzyme inducer →↑ metabolism → dec. effect
Increase dose

Q

Enzyme inhibitor function

A

•Enzyme inhibitor → decrease metabolism-> ^ effect

Q

Importance of enzyme induction, with e.g for each

A

Increase its own metabolism > tolerance e.g. phenobarbitoneدواء غبي
↑ metabolism of other drugs → drug interactions e.g. Rifampicin →↑ Oral contraceptive pills (0CP) metabolism > dec
effect of OCP → pregnancy. Also rifampicin > ↑ Warfarin metabolism >dec. its effect
↑ metabolism of Endogenous substrates → (e.g. phenobarbitone enzyme inducer >ink. metabolism of bilirubin(on plasma protein) in case of drug therapy of neonatal jaundice or kernicterus) ) يستخدم في علاج الصفرة عند حديثي الولادة

Q

*Enzyme inducers→ ↑ activity of___

A

Cytochrome P450

Q

Enzyme induction is reversible/irreversible. occurs over a few/many days & disappears over 2-3/6-8 weeks after withdrawal of the indu

A

Reversible
Few
2-3

Q

Importance of Enzyme Inhibition

A

Enzyme inhibitors >dec. activity of Cytochrome P450 and other microsomal enzymes –> dec. metabolism of drugs.
This can lead to significant drug interactions.

It occurs faster than enzyme induction.

Q

E.g for enzyme inducer

A

Carbamazepine treat epilepsy
Phenytoin(T.B)
Phenobarbitone , same
Rifampicin , same in CNS
Nicotine

Q

E.g for enzyme inhibitors

A

• Chloramphenicol
•Erythromycin
•Ciprofloxacinسيبروفلوكساسين
Ketoconazole

Q

Kidney is the main site of drug excretion by:

A

Filtration
Active tubular secretion
(e.g. Penicillin, Amphetamine)

Q

Factors affecting Renal elimination (Excretion) or _____

A

Glomercular filtration : Glomerular filtration rate (GFR) علاقة طريقة بالنسبة للإخراج

• Plasma protein binding (PPB)→ prevent filtration علاقة عكسية

• Drug Lipophilicity (affected by Pka of the drug & pH of the urine) → enhances reabsorption of the drug after being filtrated غلاقة عكسية

Q

Elimination half life (t1/2) is

A

is the time needed to dec. Drug con. In plasma to half the initial concentration

Q

Calculation of t1/2

A

t1/2=0.693 X Vd/CLs

Q

0.693 =
Vd =
CLS =

A

0.693 = Constant
Vd = Volume of distribution
CLS = Systemic clearance

Q

Values (significance) of elimination t1/2 are

A

Determination of dosage intervals (t)المسافة بين الجرعات
Determination of Tss (time needed to reach Css) = 4-5 t1/2

Q

If t= tı/2 then

A

Body stores twice the dose. Accepted choice for most of drugs

Q

Ift < tı/2 then

A

Drug accumulation occurs –>
adverse effects هنا يعمل مشكلة

Q

If t> t1/2 then

A

Dec. drug concentration between the doses مش حيشتغل كويس

Q

if the t1/2 is very short the drug is taken

A

IV infusion الحقن بالتقطير

Oral slow release (SR) preparation

Q

Steady state concentration (Css) is

A

Definition:
It is the concentration of the drug at which rate of drugs administration = rate of drug elimination

Q

Time needed to reach Css (Tss) is

A

4 to 5 t1/2 if fixed dose is taken every t1/2

Q

Calculate LD

A

Loading Dose = Vd X Css

Q

Maintenance dose is
And calculate it

A

is the dose needed to maintain Css
Mantainance dose = Clearance × Css

Q

Css is reached only in

A

first order kinetic drugs

Q

Factors affecting elimination t1/2

A

The state of elimination organs: i.e. Liver & Kidney function
The delivery of the drug to elimination organ:
a. Plasma protein binding limits renal filtration
b. Drugs with very high Vd may escape in the tissue from elimination

Q

1 order kinetics Elimination (EL)

A

proportional to plasma concentration (El a Cp)

Q

Kinetic orders are

A

1st order kinetics
Zero-order kinetics
Saturation kinetics

Q

Zero order kinetics elimination is

A

Constant , طالب كسلان

Q

drug eliminated/unit time in 1st order kinetics

A

Constant fraction (%) of the doses

Q

drug eliminated/unit time in zero unit elimination

A

Constant amountكمية من الجرعة

Q

1st order kinetics
Metabolizing enzymes:

A

Unlimited

Q

Zero-order kinetics
Metabolizing enzymes:

A

Limited

Q

In 1st order kinetics
Modest changes in doses or Bioavailability

A

Tolerance الجسم ممكن يتحمل التغير

Q

Zero-order kinetics
Modest changes in doses or F

A

Toxicity

Q

In 1st order kinetics
T1/2:

A

Constant

Q

In Zero-order kinetics
T1/2

A

Variable, not constant

Q

Css in 1st order kinetics

A

is reached on repeating the doses
Tss = 4-5 t/2
↑ Dose → ↑Css

Q

Css in Zero-order kinetics

A

No Css.

Repeating the doses →
overshooting of drug Concentration (Cp)

Q

Drug metabolized in 1st order kinetics

A

Fixed

Q

Drug metabolism in Zero-order kinetics

A

May vary with increasing the doses

Q

Most drug are

A

1st order kinetics

Q

E.x for Zero-order kinetics drugs

A

Ethanol

Q

What is saturation kinetics ?

A

Definition: The drugs follow 1* order kinetics in low doses and follow zero order kinetics in higher doses.
Elimination mechanism is saturable in higher doses.

طالب نص نص

Q

Significance of saturation kinetics:

A

• Modest changes in dose or F of the drug → unexpected toxicit

Drug interaction are more common and important clinically

Q

E.g for saturation kinetics

A

Phenytoin , enzyme inducer
Theophylline

Q

Extraction ratio (ER) is

A

It is the fraction of the drug eliminated by the liver.

Q

How to calculate ER

A

ER = (Arterial drug conc.) - (Venous drug conc.) / (Arterial drug conc.) =
Amount extracted/amount entered

Maximum is 1 (100%),0.4[40%]
Least is 0

Q

Types of extraction ratio

A

Low: <0.2
High > 0.7
Moderate: 0.2 - 0.7

Q

Low ER clearance in liver

A

Enzyme dependent

Q

High ER clearance in liver

A

Flow depend enzyme

Q

Moderate: 0.2- 0.7 clearance in liver

A

Both enzyme & flow dependent

Q

E.x for low elimination ratio

A

Wafrine

Q

E.g for high ER drug

A

Phenobarbitone

Q

E.g for moderate ER drug

A

Paracetamol(acetaminophen), chloramphenicol

Q

F in low ER drugs

A

High

Q

F in high Elimination ratio is

A

Low

Q

Bioavailability in moderate elimination ratio drug is

A

Moderate

Q

Hepatic clearance:

A

Hepatic clearance: Volume of the blood cleared by the liver per unit time

Q

Calculate Hepatic clearance

A

CL liver = Extraction ratio × hepatic blood flow (Q)

Q

. Systemic clearance (Cls)

A

Volume of fluid cleared from the drug per unit time.

لو جبتلكم في ام سي كيو دراج ، خطأ

Q

Calculate systemic Cls

A

Renal clearance (Clr) + non-renal clearance (Clr)

Like lung , liver ….

Q

Factors affecting drug clearance

A

Factors affecting drug clearance 1. Blood flow to the clearing organ(direct relationship)

Activity of processes responsible for drug removal as hepatic enzymes, glomerular filtration rate (direct relationship)
Binding of the drug to plasma proteins(inverse relationship)

Q

Significance of Drug clearance

A

Calculation of the maintenance dose (MD)

2.The dosing regimen of drugs eliminated by glomerular filtration can be guided by creatinine clearance e.g (دواء هايلي هيدروفيليك ومش مهم حفظ اسم الدواء بس احفظه محمد سان)Gentamicinيساعد في إعادة ضبط جرعة في حالات قصور وظائف الكلى

Q

Calculate Mantainance dose

A

Maintenance Dose= CLs x Steady state plasma concentration (Css)