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ICPP Lecture Summaries > Pharmokinetics > Flashcards

Pharmokinetics Flashcards

1
Q

Why is pharmokinetics clinically relevant?

A

Understanding if the drug is getting to the target at the therapeutic dose

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2
Q

What are the main routes of drug admisistration?

A

Enteral- absorbed via GI tract

Parenteral- via routes that aren’t GI tract

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3
Q

What are the main methods of drug delivery?

A

Orally

Iv
Intramuscular 
Transdermal 
Intranasal 
Subcutaneous 
Inhilation 
Rectal
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4
Q

How are drugs absorbed via the oral route?

A

Only small amount in stomache (thick muscosa)

Mainly in small intestine (due to large SA)

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5
Q

What are the methods of drug absorbtion at cellualr levels?

A

Passive diffusion
Facilitated diffusion
Secondary active transport

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6
Q

How does passive diffusion absorbtion occour?

A 
In lipophilic (steroids) and weak acid/basic drugs 
Direcetly down conc grad
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7
Q

How does

A
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8
Q

How does absorbtion of weak acids/bases occour?

A

Pka determines drugs in non ionsed form
In ionised from can’t pass through
Only drugs not protented eg, HA or B can move through

Once some drugs absored others get converted from BH+/A- to non ionsed from
Can now be absorbed

This due to restablishing the equilibrium between ionised and non ionised dictated by the PKa

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9
Q

How are drugs absorbed via facilitated diffusion?

A

Via Solute carrier transporters (SLTs)
These are either OATs or OCTs

Due to electrochemical gradient of molecule

SLTs can aid in both absorbtion and elimination

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10
Q

What type of drugs are absorbed via facilitated diffusion?

A

Nett ionic charge within GI pH range so can be transported across its epithelia

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11
Q

How does absorbtion via secondary active transport occour?

A

Transport driven by electrochemical gradient across GI epithelia using SLCs of other molecules

Eg, Penicillins cotransported with H+ ion

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12
Q

What physicochemical factors affect drug absorbtion?

A

GI length/SA
Drug lipophilicity/ pKa (more lipophilic pass more)
Density of SLC expressed

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13
Q

What GI physiology factors affect absorbtion?

A

Blood flow- if increased carry drug away more rapidly so conc grad steeper

GI motility- if slower more absorbtion time

Food- lipophilic drugs absorbed better with fatty foods (dissolve in fats)

PH- destroys some drugs

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14
Q

How can first pass metabolism affect absorbtion?

A

Can metabolise some of the drug before it has chance to reach its target, reducuing availabilty of drug

Phase 1( cytocrome P450) and Phase 2 (Conjugating) enzymes both in liver

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15
Q

What is bioavaliabilty?

A

The fraction of defined dose that reaches a specific body compartment eg, CVS circulation

Other routes compared to IV as reference

Determined by absorbtion and distribution factors

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16
Q

What is the bioavaliabilty equation?

A

F= amount reaching systemic circulation / total drug given by Iv

Eg, drug given orally/ drug given by IV

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17
Q

How do drugs pass through the body?

A

Interat with therapeutic and non therapeutic targets (toxic/non toxic effects)
Interact with other molecules eg, proteins

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18
Q

How does drug lipophilicity/ hydrophilicity affect distribution?

A

If lipophilic more more freely across memb

If hydrophilic more dependant on factors affecting absorbtion
Eg, cap permabilty, drug pKa, local pH, OTCs & OATs

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19
Q

How does binding to plasma proteins effect drug distribution?

A

Only the free drug can bind to targets and binding to plasma prot decreases free drug available

Binding is dynamic equilibrium

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20
Q

How can giving multiple drugs at once alter drug distributon?

A

May compete for same binding site on plasma proteins (eg, Albumin)

Alters the free plama conc available to give therapeutic effect

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21
Q

What is apparent volume of distribution?

A

Modles 3 main fluid compartments as all one in referenece to plasma concentration

Summary measure of movemnt from Plasma- Interstitial- Intracelluar

Vd depends on push/ pull factors

22
Q

What does a small Vd mean?

A

Less penetration of interstitail/ intracellualr fluid compartment

23
Q

What does a large Vd mean?

A

Greater penetration of interstitial/ fluid compartment

24
Q

What is the Vd equation?

A

Vd= drug dose/ plasma dose conc

25
Q

What factors can affect Vd?

A
  • Regional blood flow changes
  • Low Albumin
  • Extremes of weight (high BMI and adipose= more lipophilic drug distributed into adipose rather than target need higher dose)
  • Drug interaction
  • Renal failure (removed more slowley)
  • Pregnancy
  • Paeds (diff h20 weights amd pharmokinetics)
  • Cancer patients
  • Anaestherics
  • Geriatrics
26
Q

What is drug elimination?

A

The combination of drug metabolism and drug excretion

Has both protective and homeostatic functions

27
Q

What are the 2 phases of drug metabolism?

A

Phase 1 and 2

Both increase iconic charge so enhance renal elimination
One metabolised drug normally inactive
Mainly in liver

28
Q

How is phase 1 metabolism carried out?

A

Cytochrome P450 enzymes (Cyps)

  • are versatile generalists, increase ionic charge
  • catalyse redox/ dealkylation/ hydroxilation
  • many different subtypes
  • active some pro drugs into active form eg, codine
29
Q

What happens in phase 2 drug metabolism?

A

By hepatic enzymes (cytostolic)

-generalists but more rapid than phase CYP450s
-enhance ionic charge via conjugation
(Adding glutathione, glucorinadation ect)

30
Q

What are the different types of cytochrome P450s?

A

Superfamily type 1,2 and 3

6 main I zoomed that metabolise most drugs
-each has drugs optimally metabolises but some overlap

31
Q

What factors affect drug metabolism?

A

Age- (young= kidney and liver maturation, old= decrease in funct reserve0

Sex- (eg. Women metabolism alcohol slower)

General health/ disease ect- (HRH factors)

Induction/ inhibition of CYPs 450s

32
Q

What is the HRH acronym for drug metabolism?

A

Heart
Renal
Hepatic

Decreases function of these decreases functional reserve

33
Q

How is CYP450 induction?

A

When there is concurrent administration of multiple drugs

Induction can increase transcription, translation and slow degradation of CYP450s

Rate of elimination of drug increases = plasma levels fall

34
Q

How does CYP450 inhibition work?

A

Concurrent administration of certain drugs

Via competitive/ non competitive inhibition
(May both have same isozyme that metabolise it)

Rate of elimination slower
Plasma levels of drugs rise=side effects

35
Q

What is the importance of genetic factors in drug metabolism?

A

Genetic variation in the type of CYP450 enzymes expressed

Need to be aware of how this effects the type of drugs that can be metabolised by patients

May mean that certain prodrugs aren’t effective

36
Q

What is the main route of renal excretion?

A

Via the kidneys

Fenestrations in capillaries allows drugs to pass across

37
Q

What are the 3 processes in renal excretion?

A

Glomerular filtration
Active tubular secretion
Passive tubular reabsorption

38
Q

What happens in Glomerular filtration?

A

Unbound drugs leaves via glomerular

39
Q

What happens in active tubular secretion?

A

In both the proximal tubular

Have OATs/OCTs with low affinity/ high capacity
Can act as competitive transporters
Ionised molecules out

The reverse of small intestine

40
Q

What happens in passive tubular reabsorption?

A

Distal tubular

Along tubule h20 reabsorbed, drug conc increase
If drug still lipophilic will move back into blood

Depends on weak acid/ base characteristics of drug (follows the proton!)

41
Q

What is drug clearance?

A

The rate of elimination of drug from the body

CL (assumed at total clearance= hepatic + renal)

42
Q

What is CL?

A

The volume of plasma this is completely cleared of the drug per unit time

In ml/min

Use apparent volume of distribution Vd (as drug can’t be completely eliminated)

43
Q

Why is the CL important?

A

To know decide:

  • dosing schedules
  • therapeutic levels
  • minimise ADRs (adverse drug responses)
44
Q

What is half life?

A

The amount of time over which a concentration of drug in plasma decreases to one half of that concentration value it had when it was first measured

45
Q

What happens if clearance increased but Vd stays the same?

A

Half life would decrease

46
Q

What happens if clearance stays the same but Vd increases?

A

Half life would increase

47
Q

What is linear elimination kinetics?

A

When log of plasma conc vs time gives a linear graph

Rate of excretion is proportional to plasma concentration of a drug

Means there is a large functional reserve

48
Q

What is a functional reserve?

A

When there are plenty of:

  • phase 1/2 enzymes
  • OAT/OCT carriers
49
Q

What is zero order kinetics?

A

When all elimination processes become saturated

As plasma drug conc increases rate of excretion no longer increases

Rate remains constant

50
Q

Whey are zero order drugs clinically important?

A

Can’t predict half life of them as exponentially increase in conc
This gives a narrow therapeutic window and high chance of ADRs

Need to monitor in elderly/ infants/ poly pharmacy cases

ICPP Lecture Summaries (4 decks)

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