PHARMACOLOGY 1 (PRPM147)

ADDITIONAL NOTES
These are the principles and assumptions that the drugs is
already at the site of action.

• STIMULATION – ex. of the drug that can cause

stimulation of the central nervous system is
caffeine (widely abused CNS stimulant where it
increases the activity of the brain or the CNS which
makes us awake or stimulated) the molecular
Pharmacodynamics came from two words which are action- it generally blocks the adenosine
PHARMACON meaning Drug and DYNAMO meaning receptors leads to CNS stimulation.
Power. Drugs has no literal power, but power is equated
• DEPRESSION- ex. alcohol (an ex. of CNS
with the actions or effects of drugs. Describes the action
depressant it decreases the act. of the CNS or the
of the drugs or as we called the mechanisms of action or
simply known as MOA. brain leads to drowsiness, decrease
concentration, and affects balance or equilibrium
also decreases memory and learning function.
• IRRITTATION- ex. laxatives or cathartics (popular
ex. is bisacodyl (Dulcolax) a stimulant cathartic
promoting the peristaltic movement primarily by
irritating the wall GIT causes an increase in
motility and evacuation.
• ADDITION- multivitamins + minerals are
replenisher as they replace essential or
endogenous chemicals inside our body.

From this diagram the action of the drug is not solely a

pharmacodynamic event the intensity and quality of the
effects are influence by the physico-chemical properties
of the drug molecules and the pharmacokinetic
properties, somehow these properties dictate the
availability of the drug molecule in the site of action, how
much and how fast the drug gets in to the sites PRIMARY is intended/desirable or beneficial.
corresponds to the intensity and quality of action or SECONDARY is unintended that leads to undesirable
effect. effect or harmful (side effects or adverse drug effects).
 PHARMACOLOGY 1 (PRPM147)

Structural nonspecific- ex. the actions of antacids work B. ION CHANNELS- drugs can act as a blocker to
by structural nonspecific mechanism they alter the pH avoid block permeation going inside the cell or
of the stomach by neutralizing the hydrochloric acid. modulator that can increase or decreased the
Also, some antidotes such as activated charcoal works opening probability.
by absorbing the toxins. C. ENZYMES- drugs can also targets specific enzymes
Structural specific- which is most of the action. or inhibits the function of many enzymes and
prodrug which is inactive but upon interaction
with enzyme or through metabolism it becomes
active.
D. TRANSPORTERS- which they can facilitate the
entry of certain molecules going inside the cell or
they can inhibit these transporters by blocking
now the transport of molecules going now inside
the cell and these transporters can also be
blocked by drug by acting as a pseudo or false
substrate.

After interacting with the targets, a cascade of events

follow.

For a drug to produce a specific effect the drug must

interact first the specific molecule (molecular mechanism)
then followed by transduction (cellular mechanism) which
includes signals or targeting the channels, and this leads to
a tissue for an organ effect that primarily alters the system
functions.

Lock – receptor/substrate and it is specific or particular into

a key.

Key- drug or as we called the ligands or the natural ligands

(hormones and neurotransmitter). Which they can readily
attach to certain receptors which is represented by a lock.
Mabilis silang mag lock because they have the affinity
(ability of a molecule ligand of a drug to bind with the
receptor).

If we say a klik sound when they bind or the receptor and

ligands attachment it is the intrinsic activity which is the
ADDITIONAL NOTES efficacy of the drug. Upon binding with the receptor, the
A. RECEPTORS can either be agonists (it activates the drug elicit cellular response.
receptor that leads to different transduction
mechanism or a response is elicited) or
antagonists (primarily blocks the receptors so
that the agonists cannot bind).
 PHARMACOLOGY 1 (PRPM147)

GRAPH

1. X is the efficacy
2. Y is the dose
• Affinity bind into the receptor
• Intrinsic activity being able to elicit a cellular
response.

Agonist mimics the natural ligands such as the hormones

and neurotransmitter, in short agonist can also bind with
receptors or they have affinity which also has a klik
sound which also have a cellular response this is having
an intrinsic a certain level of intrinsic activity.
Antagonist can also bind with receptor and exhibit
affinity, however the key which represent the natural
ligands cannot bind because of that if there is a present
antagonist an agonist cannot bind and will have no
efficacy or intrinsic activity.

In short if a full agonist is present then you administer a

partial antagonist that partial exhibit as a zero intrinsic
activity in the present of the full antagonist by blocking the
receptor of the full agonist so never combined the two
drugs.

ADDITIONAL NOTES
ADDITIONAL NOTES
Agonist
Receptors are determinance of quantitative relations
1. Full Agonist 100 percent between concentration and the pharmacologic response.
2. Partial Agonist less than 100 percent less than
Majority of the most important receptors are regulatory
maximal response which is less than 1.
proteins components of chemical signaling mechanisms
3. Inverse Agonist they are the opposite of the full
which provides targets or important drugs hence selectivity
agonist had an opposite pharmacological
of the drug action.
response less than 0 percent.
Receptors are the key determinance of therapeutic and
Antagonist
toxic effects of drugs in patients.
Primarily zero is the intrinsic activity.
 PHARMACOLOGY 1 (PRPM147)

• Methotrexate an immunosuppressants agent and

an anticancer drug.
• Digoxin is a drug for congested heart failure.
• Colchicine blocks the receptor tubulin or micro
tubulin.

Also known ass ionotropic because they mediate the

opening or permeation of the certain ions and generate two
action potentials.

1. EPSP facilitates the influx or allowing the entry of

NA and CA inside the cell, and they carry a positive
charge and inside the cell it is excessively positive
if the numbering potential is excessively positive
that is called depolarization. (DEPOLARIZED).
2. IPSP opens the Cl and K channels and the entry of
those into the cell can lift the changes into the
membrane potentials as we all know Cl carries
negative charge and an excessive negative charge
inside the cell the membrane become
hyperpolarized. And for the K will leads to the
reflux of K outside of the cell means the positive
ADDITIONAL NOTES
charge are on the outside of the cell and sa loob
1. Ligand-gated ion channels – a receptor is linked
nagging excessively negative and become
or is coupled with an ion channel.
hyperpolarized also.
2. G protein-coupled receptors – they are coupled
with g proteins. Note for the sequence in the numbering.
3. Kinase-linked receptors – an enzyme linked
receptor primarily the enzyme called kinase
(thyroxin kinase linked)
4. Nuclear receptors – (intracellular receptor)
because the receptor is found in the nucleus.

123 are found within the cell membrane hence called as

transmembrane and they are hydrophilic and for the 4 it
should sufficiently be lipophilic to enter the cell for the drug
to interact within the cellular receptors.
 PHARMACOLOGY 1 (PRPM147)

GDP nag undergo ng phosphorylation into alpha GTP (which

is the active from of the G-protein) and now it will unbind
itself from the G-protein which goes to the cytoplasm to
look for certain effectors (usually enzymes). Ex. when an
enzyme is activated by alpha GTP they would facilitate the
production of secondary messenger (responsible for the
triggering the cellular response) while the first messenger is
the drug found with the receptor. The alpha GTP is
hydrolyzed into alpha GDP (which is inactive form) it will
Ligand gated – nakadepende yung opening or closing pag
attach itself again to the G-protein until another ligand bind
may nag bind na gamot. There is a binding with a ligand and
into the receptor uulit na naman sa alpha GDP to alpha GTP.
produces an opening and allowing the entry of ions and for
some drugs if there is a primarily inhibitor upon binding to
a receptor can lead to closure to an ion channel and
permeation is block.

Voltage gated – there is no binding and there are only

changes in the membrane potential. And after activation
closed na naman sila unless there is another nerve impulse.

1. Gq is activated to be alpha GDP it activates an

effector called phospholipase c and leads to
second messenger and these is collectively
known as phosphoinositides.
They make up the largest receptor family because of the • IP3 known as 1,4,5-triphosphate
receptor polypeptide chain snakes (serpentine) across the • DAG known as diacylglycerol
plasma membrane seven times (seven-transmembrane).
At the activation of the Gq protein activates
They generate action potential because of the opening and the effector phospholipase c.
closing of ion channel (type 1) and for the (type 2) it is
2. Gs (s for STUMULATES) the effector is adenylyl
unique it needs second messenger to elicit its cellular
cyclase
responses.
• cAMP or known as cyclic AMP which
leads to an increase of cyclic AMP
3. Gi (I for INHIBIT) the effector is adenylyl cyclase
it has the opposite effect of the Gs.
Without adenylyl cyclase there will no
conversion of ATP going to cyclic AMP that’s why
the activation of Gi is associated to low levels of
cyclic AMP

When a drug particularly binds with the receptor there is an

activation of G-protein which includes the (alpha, beta, and
gamma subunits) but the beta and gamma anchors the G-
proteins inside the cell membrane and the alpha subunit is
primarily linked to substance called GDP. When a drug Particularly the type 2 receptors
primarily binds with type 2 receptors binding of the drug to
the receptor phosphorylates alpha GDP to become GTP.
Bakit nagbind yung gamot sa type 2 receptor? Yung alpha
 PHARMACOLOGY 1 (PRPM147)

The activates receptor phosphorylate the tyrosine residues

on itself and other proteins. (ex. insulin).
The biological actions of cAMP is dependent upon
stimulation of protein kinase A

Particularly water soluble and diffuses into cytoplasm that

trigger the release of Ca by binding the ligand calcium Upon binding of ligands in type 3 receptors there is a
channel in the limiting membranes of internal storage phosphorylation of the tyrosine kinase residue by a ATP
vesicle (it facilitates the entry or release of calcium. which phosphorylate as in 1 why? Kahit isa lang ang
Elevated cycloplasmic calcium conc. Results to IP3 magundergo ng phosphorylation other tyrosine kinase
promoted opening of these channels (calcium known as residue which becomes phosphorylation. In one tyrosine
calmodulin) which regulates other activities of enzymes residue others also will become phosphorylated. And when
includes the calcium dependent protein kinases. the tyrosine residue become phosphorylated, they can now
activate different proteins which leads to cellular response.

Confined into membrane wherein it activates phospholipid

and calcium sensitive protein kinase c.
Ligand should be sufficiently lipid soluble or lipophilic.
For cAMP it is protein kinase a
Targets are the gene transcription factors in the nucleus.

Unlike cAMP which is sibuquitus and versatile carrier of

many messages

Relaxation of vascular smooth muscle leads to vasodilation

(lower the blood pressure).
Again it is lipid soluble so it can enter the cell, when the
ligand hydrophobic or lipophilic ligand enters the cell it can
 PHARMACOLOGY 1 (PRPM147)

now interact with the intracellular receptor or the nuclear

receptors. Binding of such intracellular receptor will lead
to changes in the genes transcription process (targets) and
also in the nucleus causing effect such as primarily
occurring as the longest for hours, days, or even months
and years.

noncompetitive

Bind to a receptor with low affinities that posses zero

intrinsic activity.

• Blocking the drugs ability to bind or

blocking the activity to activate

• Dose (usually known as ED50) opposite of

potency (dose is irreversibly proportional).
• Antagonist is said to be reversible, can we
overcome the reversible antagonist YES by
increasing the conc. Dose ni agonist.

• Chemical antagonist that for

neutralization/ acids – blocking the HCI
and we have protamine it neutralizes
the effects of heparin. Poison
associated with Cu should be treated
with penicillamine is a chemical
antagonist. It works by chelating
copper to promote excretion.
• Physiologic antagonists/functionally
opposite those of the agonists.
Ex. epinephrine (a functional
antagonists and histamine ex. we have
the ) and we have the histamine
( causing bronchi constriction and
 PHARMACOLOGY 1 (PRPM147)

Individually already are resistant to several

microorganisms.

Irreversible bind covalently to be non-competitive by that

reducing the number blockers available to the agonist
(kahit taasan mo ang dose wlang mangayari).
s-aureus can avail antibiotic by secreting an enzyme
Downward kasi kahit taasan mo walang nangyayari. called the beta lactamase, amoxicillin has beta lactam
ring and noy it will be destroyed will lead to
inactivation of amoxicillin. But when added we have
the

The principle of graded those respond curve as the conc.

Of the drug

• Addition example was alaxan (combination of

ibuprofen and paracetamol but both are pain
reliever.
• BZD and antihistamines both may cause CNS
depression which causes drowsiness or sedation.
• Kahit bigay mo lang yung isa if you increased the
dose of the drug alone it would have the same
effect with the combination of the two drugs at
low doses.
• Synergism ex is Bactrim (a combination of
trimethoprim and sulfamethoxazole).
 PHARMACOLOGY 1 (PRPM147)

Tolerance usually when you take a drug continuously

caffeine example.

Tachyphylaxis ex. opioid analgesic

Has a therapeutic index (TD50 over ED50).

Cannot be accommodated to adverse effect is the

idiosynocratic

Ex. allopurinol-can cause steven johnson syndrome cause

by erythema multi formic known as life threatening.

Placebo mind over matter.

Lethal for nanay. Basta may sakit ako siya na aagawa ko

para laro,

Warfarin, digoxin and padating