Pharmacodynamics

Anggun Rindang Cempaka, S.Gz, MS, RD.

Interaksi Obat dan Makanan 2024
Program Studi S1 Ilmu Gizi
Fakultas Ilmu Kesehatan Universitas Brawijaya
Objectives
Food-drug interactions are divided into two broad types:
(1) Pharmacodynamic interactions, which affect the activity at
the site of action in the body; and
(2) Pharmacokinetic interactions, which affect the absorption,
distribution, metabolism, and excretion of the drug.

Review basic principles of pharmacodynamics and

the quantification of drug and nutrient action

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 Pharmacodynamics

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Senturk A and Otles S. Food and Drug Interactions: A General Review. Acta Sci. Pol., Technol. Aliment.. 2014; 13 (1): 89-102
Pharmacodynamics

Pharmacodynamics is the term used to describe

a drug’s effect and how that effect is produced
(its mechanism of action).

❖ A drug–nutrient interaction is medically significant if

either the patient’s response to the drug or the
patient’s nutritional status is affected adversely.

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Boullata and Armenti. Handbook of Drug-Nutrient Interactions, 2nd Ed; 2010.
Pharmacodynamics

Pharmacodynamics is the study of the biochemical

and physiologic effects of a drug.

❖ The mechanism of action of a drug may include the binding of the

drug molecule to a receptor, enzyme, or ion channel, resulting in
the observable physiologic response.
❖ This response may be enhanced or attenuated by the addition of
other substances with similar or opposing actions.

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Mahan and Raymond. Krause's Food & the Nutrition Care Process, 14th Ed; 2017.
 Receptors
The effect of a drug present at the site of action is
determined by that drug’s binding with a receptor.

Cell Membranes

Receptors
= Regulatory Intracellular
Proteins

Drug-receptors are regulatory proteins which mediate

the actions of endogenous chemical signals such as
neurotransmitters, enzymes, and hormones.

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Kaztung BG. Basic and Clinical Pharmacology, 14th Ed; 2018.
Class of Proteins as
Drug-Receptors
Class of Proteins Receptor for
Antineoplastic drug
Enzymes Dihydrofolate reductase
methotrexate
3-hydroxy-3-methylglutaryl–
Statins
coenzyme A (HMG-CoA) reductase
Transport Cardioactive digitalis
Na+/K+-ATPase
proteins glycosides
Norepinephrine and serotonin
Antidepressant drugs
transporter proteins
Cocaine and a number of
Dopamine transporters
other psychostimulants
Structural Antiinflammatory
Tubulin
proteins agent colchicine

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Kaztung BG. Basic and Clinical Pharmacology, 14th Ed; 2018.
 Drug-Receptor Function
(1) Receptors as determinants of the quantitative
relation between the concentration of a drug
and the pharmacologic response

(2) Receptors as regulatory proteins and components

of chemical signaling mechanisms that provide
targets for important drugs

(3) Receptors as key determinants of the therapeutic

and toxic effects of drugs in patients.

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Kaztung BG. Basic and Clinical Pharmacology, 14th Ed; 2018.
Pharmacodynamics Principles
▪ Drug (D) + receptor-effector (R) → drug-receptor-effector complex →
effect

▪ D + R → drug-receptor complex → effector molecule → effect

▪ D + R → D-R complex → activation of coupling molecule → effector

molecule → effect

▪ Inhibition of metabolism of endogenous activator → increased activator

action on an effector molecule → increased effect

Note:
The final change in function is accomplished by an effector mechanism.
The effector may be part of the receptor molecule or may be a separate
molecule. A very large number of receptors communicate with their
effectors through coupling molecules.

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Kaztung BG. Basic and Clinical Pharmacology, 14th Ed; 2018.
Signaling Types of Receptors

1) Agonist gated trans-membrane channels

2) G-protein coupled
3) Ion channel-mediated response
4) Linked directly to tyrosine kinase
5) Nuclear receptors that regulate gene transcription

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Basic Mechanism of
Transmembrane Signaling

Na+
K+
Ca2+
CL-

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Kaztung BG. Basic and Clinical Pharmacology, 14th Ed; 2018.
General Mechanism
LIGAND
FIRST MESSENGER
Impact:
1. Increase the effects of ligand
2. Increase second messengers

RECEPTOR

Trigger physiological changes at cellular level

SECOND MESSENGER such as proliferation, differentiation, migration,
survival, apoptosis and depolarization.

CASCADE BIOCHEMICAL Examples: cyclic AMP, cyclic GMP, inositol

trisphosphate, diacyl glycerol, and calcium

EFFECT
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 GENERAL C- AMP MEDIATED CHANNEL-MEDIATED
MECHANISM RERSPONSE RESPONSE

EXT CELL SIGNAL GLUCAGON ACETYLCHOLINE

SURFACE GLUCAGON ACETYLCHOLINE RECEPTOR

RECEPTOR RECEPTOR ION Na+ COMPLEX

CONFORMATIONAL ACTIVATION OF INFLUX of Na+

CHANGE RECEPTOR G-PROTEIN EXTRA CELL

RELEASE SECOND C-AMP SYNTHESIS ACTIVATION of

MESSENGER Ca2+ CHANNEL

BIOLOGICAL INCREASE C-AMP INFLUX of Ca2+

RESPONSE CYTOPLASM INTO CYTOPLASM

STIMULATION of MUSCLE
GLYCOGEN DEGRADATION CONTRACTION
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Linked directly to Tyrosine Kinase

A tyrosine kinase is an
enzyme that can
transfer a phosphate
group from ATP to a
protein in a cell.

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Nuclear receptors that
regulate gene transcription

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 Speed of Responses
Non-genomic → cell-membrane; fast, direct Genomic → intracell; long duration

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Extracell Molecule Signals

HYDROPHILIC SIGNAL SECOND MESSENGER

HYDROPHILIC SIGNALING MOLECULE

NON GENOMIC EFFECT
CELL SURFACE
RECEPTOR

HYDROPHOBIC SIGNALING MOLECULE

GENOMIC EFFECT

HYDROPHOBIC SIGNAL

CARRIER PROTEIN
IN THE BLOOD

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Pharmacodynamic
Interactions
Adrenergic Neurotransmitter

ATP
G-protein → adenylate cyclase
NORADRENALINE
EPINEPRINE + reseptor cAMP
DOPAMIN
DAG
Pospolipase → pospolipid
IP3
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Continue

first adrenalin
messenger
adrenalin
receptor
OUT
receptor MEMBRANE

IN
transducer G protein
adenylate
amplifier cyclase

second cAMP
messenger
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Continue

first vasopressin
messenger

OUT
receptor MEMBRANE

IN
G protein phospholipase C
transducer
amplifier
IP3 & DAG

second
messenger
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G-Proteins and Adenylate Cyclase

adenylate cyclase
ATP cAMP
❖ adenylate cyclase (AC) is membrane-associated enzyme
❖ found in all eukaryotic cells
❖ cAMP must be degraded rapidly so signal does not linger
❖ enzyme phosphodiesterase breaks cAMP to AMP

phosphodiesterase
cAMP AMP
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Mechanism
LIGAND

RECEPTOR

G-PROTEIN

XANTHIN DERIVAT ADENYLAT CYCLASE

AMINOPHYLINE
ATP C AMP
CAFFEIN
PERUBAHAN
THEIN PHOSPHODIESTERASE x CONFORMATIONAL

AMRINON KANAL ION

CAMP 5 AMP
Cola ION KALSIUM MASUK

Coklat KONTRAKSI 23
How does coffee perk you up?
❖ The active component is caffeine
❖ Caffeine inhibits phosphodiesterase so cAMP levels
remain high
❖ Adrenalin’s effect on heart is prolonged by:
❖ Increasing heart rate & force
❖ More O2 to brain & tissues
❖ Gives a feeling of increased vitality and energy

Increase c-AMP levels → Increase risk of

tachycardia, arithmia, insomnia, and anxiety
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Brain Nervous System

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Brain Nervous System

TYRAMINE IPRONIAZIDE (MAO-I) MAO

(enzyme)
RELEASE INHIBIT MAO
NOREPINEPRINE (breaking down NT) Inhibit
dopamine,
NOREPINEPRINE NE, serotonin
NOREPINEPRINE
in the brain
ACCUMULATION ACCUMULATION

Anxiety and
INCREASE VASOCONSTRICTION OF depression
HEART AND BLOOD VESSEL

HYPERTENSION CRISIS 26
Brain Nervous System
Makananan mengandung TYRAMINE Direct vasoconstriction
❖ Keju yang lama and
❖ Daging yang disimpan lama
❖ Extract yeast
Release cathecolamine

Cheese Reaction
✓ Nyeri kepala hebat mendadak
✓ Pucat gemetar, leher kaku

✓ Terkait dengan sistem cardiovascular:

✓ Berdebar debar mendadak
✓ Hipertensi
✓ Nyeri dada, pucat, sakit kepala, collaps

✓ Terjadi perdarahan intra-serebral

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 Thank You
Happy Studying