Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Phamacokinetics/dynamics > Flashcards

Phamacokinetics/dynamics Flashcards

1
Q

Explain Bioavailability (F)

A

Proportion of administered dose that reaches systemic circulation, nothing to do with extent of drug that reaches effective therapeutic concentrations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Explain parenteral

A

Administered outside of alimentary tract

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Explain steady state

A

Rate of drug administration = rate of drug elimination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Explain Tachyphylaxis

A

Rapidly decreasing response to drug after administration of a few doses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Explain Therapeutic Index (TI)

A

Ratio of drug plasma concentration producing toxic (TD50) vs therapeutic (ED50) effects in 50% of patients (high TI is beter than lower TI)

Toxic Dose
Effective Dose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Define pharmacokinetics

A

Pharmacokinetics- Body’s reaction to a drug. ADME
Absorption-process by which drug enters bloodstream
Liberation-drugs release from pharmaceutical form
Distribution-dispersion/dissemination of drug
throughout fluids/tissues in body
Metabolism-biotransformation/inactivation
Elimination-removal of substance from body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Explain pharmacodynamics

A

Pharmacodynamics- drugs reaction on body
Biochemical and physiologic effects of drug on
the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Explain pharmacotherapeutics

A

Pharmacotherapeutics- Drug on disease
Biochemical and physiologic effects of the drug on
a specific disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

*Factors affecting interpretation of drug concentrations

A
  • Tachyphylaxis-response doesn’t corrolate with drug levels
  • Desensitization-decreased response over seconds/min in absence of change in agonist
  • Aberrant metabolites-may produce unexpected effects
  • Active metabolites- need to be measured in addition to parent compound

(Plasma drug level is assumed to reflect drug concentration at it’s target receptors)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Explain mechanism of desensitization and downregulation

A
  1. Agonist binding promotes Intracellular binding of a Gs protein
  2. When excessive stimulation is sensed by cell,a Beta-arrestin molecule binds to receptor to promote its internalization
  3. Once internalized, receptor is either:
  4. Recycled and it’s agonist is discarded
  5. The recycled receptor is placed back into the membrane as a step of resensitization
  6. If excess agonist stimulation continues, receptor is degraded as a means of downregulation, leaving the cell with less receptors than before

eg narcotics-later need more to get same effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Give an example of drug synergism

A

Antibiotics represent synergism:
*blockage of sequential steps in a
microbe’s metabolism
*Beta-lactamase inhibitors prevent inactivation of
Beta-lactam antibiotics
*Antibiotics that can disrupt cell wall integrity
increase the likelihood of affected bacteria to
absorb a second antibiotic

(When one drug’s activity is enhanced in the presence of another drug)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Distinguish drug activity of agonist from antagonist

A

Agonist stimulates
Antagonist inhibits

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Give exaple of drug synergism

A

Antibiotics
- Beta-lactam inhibitors prevent inactivation of beta-lactam antibiotics

  • blockage of sequential steps in microbe’s metabolism
  • antibiotics that can disrupt cell wall integrity increase the likelihood of affected bacteria to absorb a second antibiotic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Explain EC50 and Kd

A

EC50 is the amount of drug that causes 50% of effect

Kd measure of affinity of drug for a receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Agonist subtypes

A

Direct eg isoproterenal
Indirect eg cocaine
Mixed eg tamoxifen
Inverse eg antihistamines
Partial eg buspirone

Alosteric inhibitor/activator can change the sensitivity of a receptor for a specific agonist

Competitie inhibitor can be overcome by increasing the agonist concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Direct agonist vs indirect agonist

A
  • Direct- Binds to receptor and produces max effect
  • Indirect- enhances release/action of neurotransmitter but has no specific agonist activity at the neurotransmitter receptor itself
  • can cause receptor block/induction of transmitter release/inhibits receptor breakdown
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Mixed agonist

Partial agonist

A
  • Mixed - Both agonist and antagonist activity
  • Partial - trigger a response that is lower than that of full agonist ( touted forthwir reduced dependency and withdrawal effects)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Inverse agonist

A

Reverse activity of receptor

Produces effect less than the contstitutive effect(baseline effect/response normally found in body)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Functionally selective drug

A

Can act as full or partial agonist/antagonist depending on its interaction with receptors

Can act as full/partial agonist or antagonist through induced structural changes in G-protein coupled receptors which affect actions of Intracellular G-proteins depending on specific cellular milieu

20
Q

Antagonist binding site selectivity

A
  • Competitive-competes with agonist for binding (reversable/irreversible)
  • Non-competitive -allosteric, unaffected by agonist dose. Binds to site distinct from agonist binding site, causes changes in agonist binding site
  • Uncompetitive -require agonist. Locks receptor with agonist attached so agonist cannot disassociate and restimulate
21
Q

Spare receptor theory

A

Therapeutic effect vs drug dose

Body has many extra receptors, to overcome competitive antagonists- increase agonist dose. Max effect can still be reached up until the critical nr of receptors are are bound by antagonists. Then only the max effect starts to decrease

Only with noncompetative agonists can agonists not produce full effect

22
Q

How can you modify a patient’s drug plasma level with regard to dosing

A

Dose modulation(increase amou tof drug)
Dose frequency
Or both

With appropriate dosing the trough should meet the MEC (min effective concentration)

Dose before levels are too low

23
Q

Drug metabolism

A

Most drugs metabolised after entering circulation, becoming highly polarised molecule eliminated via kidneys

Liver(main), GIT,skin.,kidneys,brain can contribute to metabolism

Bio transformation of drugs involves 2 phases
Phase 1 converts drug into more polar metabolite
When phase 1 does not produce highly polarised molecule, phase 2 reaction follows

24
Q

Cytochrome P450 based drug metabolism

A

CYP450 cytochromes form versatile group of biocatalysts that are not involved in electron transport

Found throughout body but concentrated in liver
Recognised for hormone synthesis and xenobiotic metabolism (xenobiotic-foreign chemicals,drugs, pollutants that have been introduced in the body

Carries out phase 1and 2 reactions

25
Q

Which is the isoform of P450 that is the most important in drug metabolism

A

CYP3A4

Renal&liver function key in metabolism

Metabolites of phase1 do not alway become inactivated

Many drugs inhibit/enhance specific isoforms of CYP450 eg grapefruit inhibits resulting in increased accumulation of drug

26
Q

Schild equation

A

In absence of competitive antagonist, agonist will produce an effect at designated concentration

In presence of fixed concentration of competitive antagonist, agonist can overcome effect of antagonist by increasing its concentration to critical level

27
Q

hepatic portal circulation

A

All GIT nutrients are shunted to liver via hepatic portan vein for inspection and initiation of metabolism

Prodrugs commonly taken orally to achieve activation via first pass metabolism

First pass effect protects body from harmfull substances, but also reduces level of beneficial substances

28
Q

Enterohepatic circulation

A

Circulation of biliary acids, bilirubin, drugs and other substances from liver to bile to small intestine and back to liver
Lipophyllic xenobiotic drugs follow this path

Hepatotoxic substances produce continuous liver damage through their circulation

29
Q

Parenteral administration normally results in 100% bioavailability. i.e F=1.0

Exception eg:

A

Parenteral Chloramphenicol succinate ester is a prodrug. Ranges from 0.55 to 0.95 becuase variable degrees of renal elimination can occur before drug activation

Bioavailability factor F

Plasma drug levels =F x dose

30
Q

Digoxin comes in tablets F= 0.7 and elixer = 0.8. Tablets usually dosed at 250ug. Dose of syr?

A

Dose b = dose a x Fa / Fb

Dose a x Fa = dose b x Fb

0.7 x 250 / 0.8 = 219ug

31
Q

Bioavailability and plasma drug levels depend on:

A

-Inherent dissolution & absorption characteristics eg px with inflammatory bowels disease
-dosage form(tablet, capsule, syr…
- route of administration
-stability of drug in GIT
-extent of drug metabolism
GI bacteria-dramatically altered by antibiotics
GI mucosa -CYP3A4
Liver- first pass metabolism
Age- pharmacokinetics differ in old vs young
Health- integrity of organs
Genetic variations

32
Q

Routes of drug administration

A
  • Enteral- oral ,sublingual, rectal
  • Parenteral - IV, intraarterial, intramuscular, opthalmic, intranasal
  • respiratory
  • topical/transdermal

Iv admin avoids first pass effect

33
Q

Oral administration of drugs varies in success due to

A

Lipid solubility
GIT ph- may affect stability
First pass effect- results indrug metabolism before they reach systemic circulation
Sustained release drugs result in uniform absorption
Sublingual admin avoids first pass metabolism

34
Q

Example ofsingle dose absorption

A

IV - instant absorption with 100% bioavailability

IM- intermediate absorption

Oral- slowest rate

35
Q

Drug administration rate

Calculate Ra for digoxin tablets F=0.7, S=1, commonly dosed at 250ug

A

Ra= average rate at which absorbed drug reaches systenic circulation over dosing interval
S=fraction of drug total molecular weight that consists of the active moiety

Ra= S x F x dose / dosing interval

0.7x1x350/1day = 175ug/ day

36
Q

Most abundant plasmaprotein

A

Albumin

Acidic drugs commonly santurate albumin binding sites

37
Q

Volume of distribution

A

Vd- Estimate of fluid volume required to allow the drug in healthy body to exist in the same concentration as that found in the plasma
Helps determine amount of drug to give a px to reach therapeutic concentration
Plasma volume about 3.2L in 70kg adult(0.046l/kg)
Drug with Vd >3 expected to exist outside of plasma compartment in tissues or fluids
Vd is lower(drug plasma levels increased) in drugs with low lipid solubility, increased plasma protein binding,decreased tissue binding. (Opposite conditions could raise Vd)

38
Q

Vd (volume of distribution) will be increased or decreased in the following instances:
1. Renal failure
2 Liver failure
3 Uremic patient
3 Reduced plasma protein levels
4 Dehydration

A 
1 increased (due to fluid retention)
2 increased (due to changes in body fluid and plasma proteins
3 reduced (due to decreased tissue binding)
4 reduced

Vd correlates with lipid solubility, only lipid soluble drugs cross BBB

Vd is based on total drug in body(A”mg”) and plasma concentration (C”mg/L”)
Vd= A/C

39
Q

Loading dose

A

Cases where rapid achievement of desired plasma concentration is needed, calculation of loading dose is necessary

Vd important in determining loading dose

Bolus dose is considered almost instantaneous often in loading dose concentration

40
Q

Two compartment models

A
  • Therapeutic drug monitoring requires use of computer models
  • Vi -initial smaller region of a drugs rapidly equilibrating distribution:plasma and highly perfused tissues and organs
  • Drug admin and elimination occur here
  • When target organs are in Vi and if loading dose were based on the Vd, high plasma concentration preceding distribution would be dangerous
  • Vt refers to larger tissue compartments which requires a longer time for distribution
  • When target organs are in Vt, high plasma concentration preceding distribution are not dangerous nor can they predict therapeutic/toxic response
41
Q

What does Vi and Vt refer to regarding rhe two compartment model

A

Vi regers to the initial, smaller region of a drug’s rapidly equilibrating distribution: plasma and highly perfused tissues and organs. Drug administration and elimination occur here

Vt refers to the larger, tissue compartment which requires a loger time of distribution

If target organs in Vi + loading dose based on Vd, high plasma concentration preceding distribution =dangerous

If target organs in Vt, high plasma concentration preceding distribution are not dangerous nor can they be used to predict therapeutic/toxic response

42
Q

Explain intrinsic activity

A

Capacity to produce vs inhibit a biological effect

43
Q

Explain intrinsic activity

A

Capacity to produce vs inhibit a biological effect

44
Q

1st order vs zero order kinetics

A

pic

45
Q

l

A
46
Q
A

Pharmacology (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions