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Pharmacology
Pharmacology :the science which study of the biochemical
&physiological effects &source of drug &discovering & how
uses
Pharmacokinetics : the effects of the tissue on drugs which deal
with absorption distribution metabolism &excretion
Pharmacodynamics :the effects of the drugs on tissue
(biochemical & physiological effects )
& action on body
Mode of action :response of body to action
Mechanism of action : effect of drug on the cell
Drug : any substance which effect on living processes
Uses of drug :
1_for treatment
2_for diagnosis
3_for multi vitamin
4_conterceptive
Drug sources:
1_plants
a _ alkaloids like atropine ,caffeine , nicotine
b_ glycosides like digoxin , streptomycin
c_ gums like acacia d_ oils like castor oil
2_ bacterial & molds as Pancillin , tetracyclines
3_animals as hormones (insulin) &anticoagulants as heparin
4_minerals as electrolytes (Na, K, Cl ) & Iron & Iodine
5_laboratories (synthetic) as barbiturate , sulfonamides&
asprin
Drug _receptor interaction
*Receptor : protein molecule embedded in the cell membrane
or cytoplasm of the cell
* Ligand : molecule which binds (attaches) to a receptor & may
be protein , hormone , drug , toxin, & neurotransmitter .
Types of drugs _ receptors bonds :
1_Weak bond
a _ H bond
b _ Electrostatic bond} reversible association
c _ vaderval bond } reversible association
2_ Strong bond as covalent bond } irreversible
The action of drugs :
*the drug induce its effect after binding with specific
receptor (protein molecule in the cell )
* the number & rate of distribution of receptor depend on
its type .
The protein target of the drug :
1_Receptor : receptor binding drugs leading to alteration
in biochemical and or biophysical activity of a cell
eg * Receptor for histamine is called histamine receptor
eg * Receptor for Ach is called muscurinic \ nicotine
receptor
2_enzymes : drugs may bind with enzymes
eg* Inhibition of dihydrofolate reductase enzyme by
trimethoprim
eg* Inhibition of Ach esterase enzyme by neostigmine
3_ Ion channels : drugs act in two ways
a _ channels blocker : ( prevent passage of ion ) as local
anesthetic by preventing Na⁺ & ca⁺⁺ blocker by diltiazem
b _ channels modulator : by increase or decrease the entrance
of ion
4 _ Structural protein
eg: Tubulin is the receptor for colchicines in gout treatment .
Types of receptor :
1_ Ion channel receptors (Iono tropic Receptor ):
*the activity of these channels is regulated by the binding
of aligand to the channel
*Responsible for these regulation of the flow of ions a
cross cell membrane
* response to these receptors is very rapid & duration of
few milli second
eg: Ach _ nicotinic receptor stimulation by ach
eg: GABA receptor stimulate by Benzodiazepam
2_ G _ protein _ coupled receptor ( metabotropic
receptor ) :
*consist of G _ protein coupled receptor
* G _ protein having 3 subunit α_β_γ
* Binding ligand to extracellular region of receptor ,
which activate G_ protein , so that GTP replaced
GDP on α_ subunit
* β&γ interaet with other ion channel
* these effectors change the concentration of 2_
messenger which are responsible for further action
in the cell
* activation of adenyl cyclase by α _ GTP sub unit
production of c_ AMP (2_massenger)
* C_AMP regulate protein phosphorylation or case
Ca⁺² release or other than cellular effect
* Time scale is tens of seconds
* eg: Nep , dopamine , serotonin & Ach muscurinic
receptor
3_ Enzyme _ linked receptors :
*Binding of ligand to an extracellular domin , activate
or inhibits this cystolic enzyme activity
* Upon binding , the conformational changes in the
receptor
* kinase enzyme convert from in active to active form
* Binding ligand lead to kinase activity causes
autophosphory lation of receptor → target molecule
phosphorylate → cellular signals
* time scale is minutes
* eg : Insulin
4_ Intracellular receptor :
*this type of receptor differ from others due to
intracellular receptor
*ligand must be diffuse into the cell to interact with
receptor
*ligand must be lipid soluble to move across cell
membrane
*the activated ligand _ receptor complex migrate to
nucleus
*complex typically dimerize
*time scale is hours
*eg : Glucocorticoids
Drug _ receptor interaction
Agonist : a drug that bind to a receptor of a cell &
triggers a maximal response by the cell
*An a gonist mimics the action of naturally
occurring substance
*eg : Ach + nicotinic receptor induce
conformational changes in the receptors
associated ion channel
Partial agonist : molecule bind to receptors &
induce sub maximal response even when in
adequent amount of endogenous ligand are
present
*Partial agonist act as antagonist in presence
of full agonist
*eg: aripiprazole , buprenorphine
Antagonists : it’s a molecule or drug that
inhibit the action of anagonist but has no
effect in the absence of the agonist
Type of antagonism :
1_ receptor antagonist (pharmacologic
antagonist )
a _ competitive A : Drug which block directly
the binding site of agonist & divided into :
Reveres able : eg Adrenaline agonist &
propranolol antagonist
Irreversible : The drug still bind to receptor
even the drug concentration is completed
eg: Phenoxybenzamine (antagonist ) at α
receptor
b _ Non competitive A : the drug not bind to
the receptor but interfere with chemical
events & stop the action of a gonist
*eg: Diltiazem block calcium ion channel
2_ Non receptore antagonists :
a _ chemical A : it inactive the agonist by
modification it so result in active complex
*Protamine is bind to heparin ( anticoagulant )
& prevent heparin activity by producing inert
compound
b _ physiologic A : The drug will produce the
opposite function of other drug
*Histamine produce dilation of blood vessels
Adrenaline : Vaso constriction of blood vessels
C _ Kinetic A :it happened antagonized the
agonist in absorption or distribution or
metabolism or excretion
*eg: Diuretic increase the elimination of asprin
eg: Charcoal (activated ) decrease absorption
Potency : the concentration ( amount of drug )
which induce 50% of its maximal response
*potent drug as morphine which give larger
response at low concentration while the lower
potent drug like acetylsalicylic acid give small
response at low concentration
*Potency depend on Affinity & Efficacy
Efficacy : is the maximal therapeutic response
produce by the drug
*furosemide eliminate much salt & water than
chlorothiazide
Furosemide is greater efficacy than
chlorothiazide
Drug interaction :
*Additive effect : the summation of effects
which greater than separately effect
eg: Paracetamol + codine . (2+2)= 4
*Potentiation : the effect after combination is
more than the summation of their effect.
(2+2)=6
*eg:Probancid retards the excretion of
pencillin .
* So pencillin persists longer when taken with
it .
* Synergistic effect : the effect after
combination is more greater than the
summation of their effect (2+2) = 10
Eg: phenobarbiton + Ethanol .
*Antgonism : There is minimal or no effect
result in the combination of their effect .
(2+2)=0 or 1