Describes principles of Pharmacokinetics as a basis of Pharmacological principles of therapeutics., ADME PRINCIPLES ,

1. . 1IMS PATKI
Super world of
PHARMACOLOGY
welcomes you

2. After attending this session, students will
be able to
• Define drug with two examples
• Define Pharmacology and name at least
three of its sub branches
• Enumerate different nomenclatures of drug
with one example each.
• Discuss three different sources of drugs
with one example each
• Discuss at least four different routes of drug
administrations with their advantages and
disadvantages.
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3. Pharmacology
• Pharmacon, logos. Science of drugs.
• What is drug ?
• Any substance used or intended to be
used to modify or explore
physiological systems or pathological
state.
• Treatment, cure, diagnosis, prevention
of a disease.
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5. Branches
• Pharmacokinetics
• Pharmacodynamics
• Pharmacy
• Pharmacognosy
• Pharmacogenetics
• Therapeutics
• Chemotherapy
• Toxicology
• Clinical pharmacology
• Posology PATKI 5

6. Sources of drugs
• Plants , Alkaloids, Glycosides, Oils,
• Animal sources
• Microorganisms
• Chemicals , Organic, Inorganics,
• DNA technology
• Radioisotpes
• Monoclonal antibodies.
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7. Nomenclatures
• Chemical name
• Generic name, Pharmacological name. Non
proprietary name
• Brand name
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8. Pharmacology Basics- Kinetics
ADME
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9. At the end of the session, student will be
able to
• Define Pharmacokinetics with example of movement of a
drug across membranes.
• Enumerates three routes of drug administrations with two
advantages and two disadvantages.
• Defines First pass effect with suitable examples.
• Explains the importance of Bioavailability of a drug with
examples.
• Defines bioequivalence, area under curve , onset and
duration of activity of a drug using kinetic graphs.
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10. Definitions
• Pharmacokinetics
– The process by which a drug is absorbed, distributed,
metabolized and eliminated by the body
– Quantitative study of drug movement in, through and out of the
body.
– It determines – the route of administration, dose, onset, time to
peak, duration of action, and frequency of drug administration.
– Absorption, Distribution, Metabolism and Excretion of a drug.
– Transport mechanism- Pass through biological barriers
– Intestinal epithelium, Renal filtration mechanism, Capillary
barriers
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11. The Life Cycle of a Drug
(pharmacokinetics)
• Absorption
• Distribution
• Degradation
• Excretion
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12. Movement of drugs across cell
membranes
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13. Is the passage of drug through cell
membranes to reach its site of action.
Mechanisms of drug absorption
1. Simple diffusion = passive diffusion.
2. Active transport.
3. Facilitated diffusion.
4. Pinocytosis (Endocytosis).
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16. water soluble drug (ionized or polar) is readily
absorbed via aqueous channels or pores in cell
membrane.
Lipid soluble drug (nonionized or non polar) is
readily absorbed via cell membrane itself.
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17. Patki

18. Characters
 common.
Occurs along concentration gradient. Non
selective
 Not saturable
 Requires no energy
 No carrier is needed
Depends on lipid solubility.
 Depends
pka of drug - pH of medium.
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19. PKa of the drug
(Dissociation or ionization constant):
pH at which half of the substance is ionized &
half is unionized.
pH of the medium
Affects ionization of drugs.
– Weak acids → best absorbed in stomach.
– Weak bases → best absorbed in intestine.
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20. Drugs exist in two forms ionized (water soluble &
nonionized forms (lipid soluble) in equilibrium.
Drug ionized + nonionized
• Only nonionized form is absorbable.
• Nonionized / ionized fraction is determined
by pH and pKa according to Henderson-
Hasselbach
pKa- pH= log protonated / non-protonated
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21.  Relatively unusual.
Occurs against concentration gradient.
Requires carrier and energy.
Specific
Saturable.
 Iron absorption.
Uptake of levodopa by brain.
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22. Patki

23.  Occurs along concentration gradient.
 Requires carriers
 Selective.
 Saturable.
 No energy is required.
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24. Patki

25. Active transport Carrier-mediated
facilitated diffusion
Against concentrationAgainst concentration
gradientgradient
(From low to high)(From low to high)
along concentrationalong concentration
gradientgradient
(From high to low)(From high to low)
Needs carriersNeeds carriers Needs carriersNeeds carriers
Selective, saturableSelective, saturable Selective, saturableSelective, saturable
Energy is requiredEnergy is required No energy is requiredNo energy is required
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26. Endocytosis: uptake of membrane-bound particles.
Exocytosis: expulsion of membrane-bound particles.
High molecular weight drugs or
Highly lipid insoluble drugs
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27. Patki

28. Routes of Administration
©2006 Twentieth Century Fox Film Corporation
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29. Patki

30. Oral Absorption
• Passive non-ionic diffusion
– Majority of drugs
• Specialised transporters
– Large neutral amino acid transporter
• L-dopa, Methyldopa, Baclofen
– Oligopeptide transporter (PEPT-1)
• Amino beta lactams, ACE inhibitors
– Monocarboxylic acid transporter
• Salicylic acid, pravastatin
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31. Oral (enteral): absorption from mouth,
stomach and small intestine
• Stomach: minority
• Small Intestine: majority
– Passive > Active
– Rate ~ 75% in 1-3 hours. Depends on:
• Motility eg diarrhoea decreases absorption
• Blood flow
• Food – enhance or impair
• Particle size and formulation
• Physico-chemical factors
– Unionised
– Lipid soluble
• Rate of gastric emptying rate limiting step
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32. Gastric Emptying Rate Affects
Paracetamol Absorption
Nimmo et al., Br Med J, 1973
Gastric emptying is:
-Delayed by
propantheline
-Stimulated by
metaclopramide
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33. Effects of Food on Oral Drug Absorption
• Poor acid stability: prolonged gastric exposure →
degradation
– eg erythromycin, azithromycin, isoniazid
• Require acid environment
– eg itraconazole, ketoconazole
• Fat or bile acids enhance absorption
– eg tacrolimus, carbamazepine
• Bind to fibre, reducing absorption
– eg digoxin
• Bind to calcium (chelate), reducing absorption
– eg tetracyclines, quinolones
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34. Formulation
• Rate of disintegration of tablet
– Tablet compression
– Bulk excipients
• Rate of dissolution of drug particles in intestinal fluid
– Particle size: smaller dissolve quicker
• Modified Release
– Reduce frequency of oral administration
• eg morphine, nifedipine, paracetamol extend
– Deliver contents to site of action
• eg mesalazine: pH sensitive coating – 5-ASA released in distal small
bowel and colon
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35. Advantages Disadvantages
EasyEasy
Self useSelf use
SafeSafe
ConvenientConvenient
cheapcheap
No need forNo need for
sterilizationsterilization
Slow effectSlow effect
No complete absorptionNo complete absorption
(Low bioavailability).(Low bioavailability).
Destruction by GITDestruction by GIT
First pass effectFirst pass effect
GIT irritationGIT irritation
Food–Drug interactionsFood–Drug interactions
Drug-Drug interactionsDrug-Drug interactions
Not suitableNot suitable for vomiting,for vomiting,
unconscious, emergency.unconscious, emergency.
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36. Sublingual Administration
• From blood vessels at base of tongue
• Lipid soluble drugs only
– nitroglycerin
• Small surface area
– potent drugs only
• Avoids first pass metabolism
• Rapid absorption: minutes
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37. Rectal Formulations
• Avoid first pass metabolism
• Erratic absorption because of rectal contents
• Acceptable to patients?
• Useful if unable to take oral medications
– eg paracetamol, oxycodone, NSAIDS
• Useful if unable to get IV access
– eg diazepam in status epilepticus
• Direct effect on large bowel
– eg corticosteroids in Inflammatory Bowel Disease
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38. Inhaled Medications
• Formulations:
– Powders
– Aerosol solutions
– Nebulised solutions
• Delivery to bronchioles
– ~10%
– Depends on type of inhaler and how used
• Local effects
– eg oral candida
• Some systemic absorption
– Salbutamol: tremor
– Corticosteroids: osteoporosis
– Ipratropium bromide: anticholinergic ‘dry mouth’ in 15% patients
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39. Topical: Intranasal Formulations
• Direct therapeutic effect
– Sodium chromoglycate for rhinitis
• Systemic effect
– Sumatriptan in migraine (vomiting)
• Local toxicity
– Cocaine – necrosis of nasal septum
Saddle-nose deformity
Villa, J Can Dent Assoc, 199939PATKI

40. Routes of Administration
©2006 Twentieth Century Fox Film Corporation
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41. Topical: Eye Drops
• Absorption through conjunctival sac
epithelium
• Local effects in eyes with minimal systemic
effects
• Some systemic absorption
– eg timolol for glaucoma may precipitate
bronchospasm in asthma
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42. Routes of Administration
©2006 Twentieth Century Fox Film Corporation
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43. Topical: Cutaneous Administration
• Local effect on skin
– Steroids
• Slow systemic absorption (patch)
– Lipid soluble drugs only
• Oestrogen
• Opioids – Fentanyl, Buprenorphine
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44. PATKI 44
https://youtu.be/rKOyNSR4ByA
https://youtu.be/fgpwIfj1A5w?t=38

45. • 77 year old woman found dead
• Applied heating pad over fentanyl patch,
which was also site of her pain
• Increased fentanyl absorption due to heat
• Possible application of 2nd
patch without
removing 1st
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46. First pass metabolism of oral drugs
Gu
t
Liver
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47. First Pass Metabolism in Gut Lumen
– Gastric acid inactivates benzylpenicillin
– Proteolytic enzymes inactivate insulin
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48. First Pass Metabolism in Gut Wall
– Monoamine oxidase – metabolises monoamines
• Irreversible MAO inhibitors + amine-containing foods
– Tyramine not metabolised by MAO in gut wall
» enters systemic circulation
» releases NAd from stores in nerve endings causing hypertensive
crisis
Microsoft Clip Art
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49. First Pass Metabolism in Gut Wall
• CYP 3A4
• Blocked by grapefruit juice
• Many drugs inducers, inhibitors, substrates
PlasmaSimvastatinConcentration(ng/ml)
Water
Grapefruit juice
Administration of 40mg
Simvastatin with
Lilja et al., Br J Clin Pharmacology, 1994
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50. First Pass Metabolism in Gut Wall
• P-glycoprotein (enterocytes to gut lumen)
– Interactions b/w inhibitors (eg verapamil,
macrolides) and substrates (eg digoxin)
Administration of
0.75mg digoxin
withplacebo
clarithromycin
Rengelshausen et al., Br J Clin Pharmacol, 2003
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51. Hepatic First Pass Metabolism
• Reduced amount of parent drug
• Metabolites
– More water soluble - facilitates excretion
– Activity
• Decreased
• Increased: Pro-drugs
– Inactive precursors, metabolised to active metabolites
– eg cyclophosphamide, simvastatin, ramipril, perindopril
– Reduced first pass metabolism – reduced bioavailability of pro-
drugs
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52. Oral availability
Bioavailability: the % of an
ingested dose of a drug that
enters systemic circulation
www.icp.org.nz
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53. Bioavailability: implications for oral
and parenteral dosing
• High bioavailability, dose same for IV and po
routes
– eg metronidazole, fluconazole, amoxicillin
• Low bioavailability, lower dose for parenteral
than po routes
– eg morphine: 10 mg s/c or IM = 30 mg po
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54. Patki

55. Bioavailability after oral administration
of different formulations
Burkitt, Australian Prescriber, 2003
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56. Factors Affecting Bioavailability:
 Molecular weight of drug.
Drug Formulation (ease of dissolution).
(solution > suspension > capsule > tablet)
 Drug solubility of the drug
 Chemical instability in gastric pH
(Penicillin & insulin )
 First pass metabolism reduces bioavai
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57. Factors Affecting Bioavailability (BAV):
 Blood flow to absorptive site
• Greater blood flow increases bioavailability
• Intestine has greater blood flow than stomach
 Surface area available for absorption.
• Intestinal microvilli increases it
Rate of gastric emptying
• rapid gastric emptying fast transit to
intestine
 pH of gut
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58. Intestinal motility (Transit Time)
• Diarrhea reduce absorption
Drug interactions
Food
• slow gastric emptying
• generally slow absorption
• Tetracycline, aspirin, penicillin V
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59. Bioequivalence
• Pharmaceutically equivalent and equal systemic
bioavailability
• Generics
– must be bioequivalent to innovator (80-125%)
• Phenytoin toxicity outbreak (Australia 1968)
– ‘Inert’ excipient changed: CaSO4 to lactose
– Increased solubility and systemic availability
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60. Change in phenytoin excipients
results in epidemic toxicity
F Bochner, Proc Aust Assoc Neurol, 1973
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61. AUC A > B: Therapeutic Significance?
0
1
2
3
4
5
6
7
8
9
0 5 10 15 20 25
Time after drug administered (hours)
serumconcentration
Drug A
Drug B
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62. AUC A > B: B Ineffective
MEC
MEC = Minimum Effective Concentration
0
1
2
3
4
5
6
7
8
9
0 5 10 15 20 25
Time after drug administered (hours)
serumconcentration
Drug A
Drug B
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63. AUC A > B: Equally Effective
MEC
MEC = Minimum Effective Concentration
0
1
2
3
4
5
6
7
8
9
0 5 10 15 20 25
Time after drug administered (hours)
serumconcentration
Drug A
Drug B
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64. Drug Binding and Distribution
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65. Protein Binding
Reversible and rapid
Depends on [free drug], affinity for binding sites, [protein]65PATKI

66. Protein binding
• Many drugs bind to plasma proteins
– Albumin (acidic drugs, eg warfarin, NSAIDs)
– Alpha-1 acid glycoprotein (basic drugs, eg
quinine)
– Lipoproteins (basic drugs)
– Globulins (hormones)
• Only free drug can bind to receptors
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67. Clinical implications of changes in
protein binding
• Changes in protein binding
– Disease and nutrition
– Protein binding displacement interactions
• eg valproate displaces phenytoin – increases free
phenytoin, compensate with increased clearance
• Clinically relevant effects if
– >90% of drug is protein bound
• eg phenytoin, warfarin
– Small volume of distribution 67PATKI

68. High protein binding, low clearance
• [Free drug] depends on clearance of free drug
• [Total drug] depends on protein binding
0
10
20
30
40
50
60
70
80
90
100
1 2
patient
drugplasmaconcentration
free
bound
Birkett et al., 1979
Same drug
Same dose
Same clearance
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69. Tissue Binding
• Body Fat
– Lipid soluble drugs
– Stable reservoir
– eg anaesthetics
• Bone
– Adsorption onto bone-crystal surface
– Reservoir – slow release
– eg tetracyclines, heavy metals
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70. Distribution: body fluid compartments
Plasma
Water
5%
Interstitial
Water
16%
Fat
20%
Intracellular
Water
35%
Transcellular
Water
2%
Free drug can move between compartments. Depends on:
- permeability
- binding
- pH partition 70PATKI

71. Apparent distribution volumes of some
common drugs
Volume
(L/kg body weight)
Compartment Vd
(L/kg body weight)
Examples
0.05 Plasma 0.05-0.1
0.1-0.2
Heparin
Insulin
Warfarin
Atenolol
0.2 Extracellular fluid 0.4-0.7 Theophylline
0.55 Total body water
1-2
2-5
Ethanol
Phenytoin
Methotrexate
Paracetamol
Diazepam
Morphine
Digoxin 71PATKI

72. Apparent Volume of Distribution (Vd)
• Vd: volume of fluid required to contain the total amount
of drug in the body at the same concentration as that in
the plasma
• Vd = amount of drug in body
plasma concentration
• Loading dose = Vd x desired plasma concentration
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73. Gentamicin
• Absorption
– Oral: <1% - highly polar cation, ↑ disease
– Topical: ↑ large wound/burn/ulcer
– IMI: rapid, peak 30-90 mins, ↓ shock
• Distribution
– Apparent Vd 25% lean body weight (~ECF)
– Loading dose = Vd x desired plasma concentration
= 0.25 L/kg x 12-20 mg/L
= 3-5 mg/kg
Apparent Vd increases in sepsis – ? higher loading dose
Adjust interval or maintenance dose in renal impairment – clearance
next lecture!
– High concentrations in renal cortex and endolymph/perilymph
inner ear – toxicity
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74. Barriers to Drug Distribution
• Blood brain barrier
– Only lipid soluble drugs can enter brain and
CSF
– ‘Leaky’ in disease – eg penicillin in meningitis
• Placenta
– Allows passage of lipid and some water soluble
drugs - eg opioids, antiepileptics
– Enzymes in placenta inactivate some drugs
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75. Faster Absorption
• Parenterally (injection)
– Intravenous (IV)
– Intramuscular (IM)
– Subcutaneous (SC)
– Intraperitoneal (IP)
• Inhaled (through lungs)
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76. Fastest Absorption
• Directly into brain
– Intracerebral (into brain tissue)
– Intracerebroventricular (into brain
ventricles)
General Principle: The faster the absorption, the quicker the
onset, the higher the addictiveness, but the shorter the duration
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77. (hydroxyl group)
(amine group) 77PATKI

78. Distribution: Depends on Blood Flow and
Blood Brain Barrier
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79. Bioavailability
• The fraction of an administered dose of drug that reaches the
blood stream.
• What determines bioavailability?
– Physical properties of the drug (hydrophobicity, pKa, solubility)
– The drug formulation (immediate release, delayed release, etc.)
– If the drug is administered in a fed or fasted state
– Gastric emptying rate
– Circadian differences
– Interactions with other drugs
– Age
– Diet
– Gender
– Disease state
79PATKI

80. Depot Binding
(accumulation in fatty tissue)
• Drugs bind to “depot sites” or “silent receptors” (fat,
muscle, organs, bones, etc)
• Depot binding reduces bioavailability, slows elimination,
can increase drug detection window
• Depot-bound drugs can be released during sudden weight
loss – may account for flashback experiences?
80PATKI

81. Degradation & Excretion
• Kidneys
– Traps water-soluble (ionized)
compounds for elimination via urine
(primarily), feces, air, sweat
• Liver
– Enzymes(cytochrome P-450)
transform drugs into more water-
soluble metabolites
– Repeated drug exposure increases
efficiency  tolerance
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82. Excretion: Other routes
• Lungs
alcohol breath
• Breast milk
acidic ---> ion traps alkaloids
alcohol: same concentration as blood
antibiotics
• Also bile, skin, saliva ~~
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83. Metabolism and Elimination (cont.)
• Half-lives and Kinetics
– Half-life:
• Plasma half-life: Time it takes for plasma concentration of a
drug to drop to 50% of initial level.
• Whole body half-life: Time it takes to eliminate half of the
body content of a drug.
– Factors affecting half-life
• age
• renal excretion
• liver metabolism
• protein binding
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84. First order kinetics
A constant fraction of drug is eliminated per unit of time.
When drug concentration is high, rate of disappearance
is high.
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85. Zero order kinetics
Rate of elimination is constant.
Rate of elimination is independent of drug concentration.
Constant amount eliminated per unit of time.
Example: Alcohol
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86. Comparison
• First Order Elimination
– [drug] decreases
exponentially w/ time
– Rate of elimination is
proportional to [drug]
– Plot of log [drug] or
ln[drug] vs. time are
linear
– t 1/2 is constant regardless
of [drug]
• Zero Order Elimination
– [drug] decreases linearly
with time
– Rate of elimination is
constant
– Rate of elimination is
independent of [drug]
– No true t 1/2
86PATKI

87. Drug Effectiveness
• Dose-response (DR) curve
– Depicts the relation between
drug dose and magnitude of drug
effect
• Drugs can have more than one
effect
• Drugs vary in effectiveness
– Different sites of action
– Different affinities for
receptors
• The effectiveness of a drug is
considered relative to its safety
(therapeutic index)
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88. ED50 = effective dose in 50% of population
100
50
0
DRUG DOSE
0 X
ED50
% subjects
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89. Therapeutic Index
• Effective dose (ED50) = dose at which 50% population shows response
• Lethal dose (LD50) =dose at which 50% population dies
• TI = LD50/ED50, an indication of safety of a drug (higher is better)
ED50 LD50
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90. Potency
• Relative strength of response for a given dose
– Effective concentration (EC50) is the concentration of an agonist needed to
elicit half of the maximum biological response of the agonist
– The potency of an agonist is inversely related to its EC50 value
• D-R curve shifts left with greater potency
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91. Efficacy
• Maximum possible effect
relative to other agents
• Indicated by peak of D-R curve
• Full agonist = 100% efficacy
• Partial agonist = 50% efficacy
• Antagonist = 0% efficacy
• Inverse agonist = -100% efficacy
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92. Average
Response
Magnitude
LO
DRUG DOSE
0 X
HI
A
B
C
Comparisons
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93. Tolerance
(desensitization)
• Decreased response to same
dose with repeated (constant)
exposure
• or more drug needed to achieve
same effect
• Right-ward shift of D-R curve
• Sometimes occurs in an acute
dose (e.g. alcohol)
• Can develop across drugs (cross-
tolerance)
• Caused by compensatory
mechanisms that oppose the
effects of the drug 93PATKI

94. Sensitization
• Increased response to same dose
with repeated (binge-like)
exposure
• or less drug needed to achieve
same effect
• Left-ward shift in D-R curve
• Sometimes occurs in an acute
dose (e.g. amphetamine)
• Can develop across drugs (cross-
sensitization)
It is possible to develop tolerance to some side effects AND sensitization
to other side effects of the same drug
94PATKI

95. Mechanisms of Tolerance and Sensitization
• Pharmacokinetic
– changes in drug availability at site of action (decreased bioavailability)
– Decreased absorption
– Increased binding to depot sites
• Pharmacodynamic
– changes in drug-receptor interaction
– G-protein uncoupling
– Down regulation of receptors
95PATKI

96. Other Mechanisms of
Tolerance and Sensitization
• Psychological
As the user becomes familiar with the drug’s effects, s/he learns tricks to
hide or counteract the effects.
Set (expectations) and setting (environment)
Motivational
Habituation
Classical and instrumental conditioning (automatic physiological change in
response to cues)
• Metabolic
The user is able to break down and/or excrete the drug more quickly due
to repeated exposure.
Increased excretion
96PATKI

97. • Pharmacokinetic and pharmacodynamic
– With pharmacokinetic drug interactions, one drug affects the
absorption, distribution, metabolism, or excretion of another.
– With pharmacodynamic drug interactions, two drugs have
interactive effects in the brain.
– Either type of drug interaction can result in adverse effects in
some individuals.
– In terms of efficacy, there can be several types of interactions
between medications: cumulative, additive, synergistic, and
antagonistic.
Drug-drug Interactions
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98. Response
Hi
Lo
Time
Cumulative Effects
Drug A
Drug B
The condition in which repeated administration of a drug may produce effects
that are more pronounced than those produced by the first dose.
98PATKI

99. Response
Hi
Lo
Time
A B
Additive Effects
A + B
The effect of two chemicals is equal to the sum of the effect of the two
chemicals taken separately, eg., aspirin and motrin.
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100. Response
Hi
Lo
Time
A B
A + B
Synergistic Effects
The effect of two chemicals taken together is greater than the sum of their
separate effect at the same doses, e.g., alcohol and other drugs
100PATKI

101. Response
Hi
Lo
Time
A B
A + B
Antagonistic Effects
The effect of two chemicals taken together is less than the sum of their
separate effect at the same doses
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102. Pharmacodynamics
• Receptor
– target/site of drug action (e.g. genetically-coded proteins
embedded in neural membrane)
• Lock and key or induced-fit models
– drug acts as key, receptor as lock, combination yields response
– dynamic and flexible interaction
102PATKI

103. Pharmacodynamics (cont.)
• Affinity
– propensity of a drug to bind with a receptor
• Selectivity
– specific affinity for certain receptors (vs. others)
103PATKI

104. Agonism and Antagonism
Agonists facilitate receptor
response
Antagonists inhibit receptor
response
(direct ant/agonists)
104PATKI

105. Modes of Action
• Agonism
– A compound that does the
job of a natural substance.
– Does not effect the rate of
an enzyme catalyzed
reaction.
• Up/down regulation
– Tolerance/sensitivity at the
cellular level may be due to
a change in # of receptors
(without the appropriate
subunit) due to changes in
stimulation
• Antagonism
– A compound inhibits an
enzyme from doing its job.
– Slows down an
enzymatically catalyzed
reaction.
105PATKI

106. Agonists/Antagonists
• Full
• Partial
• Direct/Competitive
• Indirect/Noncompetitive
• Inverse
A single drug can bind to a single
receptor and cause a mix of effects
(agonist, partial agonist, inverse agonist,
antagonist)
Functional Selectivity Hypothesis:
Conformational change induced by a
ligand-receptor interaction may cause
differential functional activation
depending on the G-protein and other
proteins associated with the target
receptor
106PATKI

107. Important implications of
drug-receptor interaction
• drugs can potentially alter rate of any bodily/brain function
• drugs cannot impart entirely new functions to cells
• drugs do not create effects, only modify ongoing ones
• drugs can allow for effects outside of normal physiological
range
107PATKI

108. Law of Mass Action
(a model to explain ligand-receptor binding)
• When a drug combines with a receptor, it does so at a rate which
is dependent on the concentration of the drug and of the
receptor
• Assumes it’s a reversible reaction
• Equilibrium dissociation (Kd) and association/affinity (Ka)
constants
– Kd = Kon/Koff = [D][R]/[DR]
– Ka = 1/Kd = Koff/Kon = [DR]/[D][R]
108PATKI