Pharmacodynamic presentation for pharmacy

Note of pharmacodynamic

1. Pharmacodynamics
Pharmacodynamics includes the
experimental study of :
Mechanism of drug action.
Pharmacological effects.

2. Pharmacodynamic: (pharmacon: drug, dynamis: power)
It is study of effect of drug. Also called as What the drugs does to
body. It include study of drugs, their mechanism of action,
pharmacological action and adverse effects.
Principles of drug action
Drug generally does not impart any new function to the any system.
It simply changes the pace (rate) of ongoing activity. The basic
type of drug action are:-
-Stimulation: Enhancement of the level of activity of specialized
cells. Eg adrenaline stimulate heart resulting in increase heart
rate, force of contraction. Pilocarpine increase salivary glands
-Depression: Some decrease act by decreasing the activity of
specialized cells.barbiturate/benzodiazepine depress CNS
Acetylcholine depress activity of heart whereas stimulate
intestinal smooth muscle.

3. Cont..
-Irritation:Usually Nonselective, often noxious effect occur when
applied to epithelial cells connective tissue less specialized
cells. Mild irritant usually stimulate the action of cells. Eg bitter
substances increase salivary and gastric secretion. Strong irritant
may cause inflammation and morpholigcal damage
-Replacement: When there is deficiency of endogenous
substances, they can repcle by drugs. This refers the use of
natural metabolites, hormones, or their congeners in deficiency
states. Eg. Insulin in DM, thyroxine in hypothyroidism.
-Cytotoxic action: It is treatment infectious disease ,parasites or
cancer cells, with drug that are selective or non selectively toxic
for infecting organism or neoplasm(cancer cells) . Desirable is
selective action without significantly affecting the host cells

4. Mechanism of drug action:
Fundamental mechanism of drug action
1) Non receptor Mediated
i.Physical action
A physical property of the drugs is responsible for its action: eg
-Mass of the drug- Bulk laxative(Isapgol). Protective (Dimethicone)
-Adsorptive property- Activated charcoal adsorb toxin so used in
poisoning. kaolin
-Osmotic activity- 20%mannitol in cerebral oedema & acute congestive
glaucoma, magnesium sulfate
-Demulcent: cough syrup /lozenges produce soothing effect in
pharyngitis by coating inflamed mucosa
-Radiactivity- radioisotopes emit ray and destroy tissues. Eg 131I in
-Radioopacity- contrast media (Urografin, barium sulfate)
ii.Chemical action:
The drug reacts extracellularly according to simple chemical equations: ex
-Antacids neutralizes gastric Hcl.
-Acidifying(NH
4
cl) and alkalinizing(NaHCO
3
) agents react wither
buffers in plasma and alter pH of urine.

5. iii.Through enzymes:
Almost all biological reactions are carried out under catalytic
influence of enzymes; hence enzymes are a very important target of
drug action. Drugs can either increase or decrease the rate of
enzymatically mediated reaction. The action may be stimulatory or
inhibitory.
iv.2) Through receptors:
A large number of drugs act through specific macromolecular
components of the cell which regulate critical functions like
enzymatic activity, permeability, structural features. These
macromolecules or the sites on them which bind and interact with the
drug are called receptors.
v.Antimetabolites:
These drugs are similar to that of the nutrients used by
microorganism for multiplication. The cells absorb drugs in place of
nutrients so cannot multiply.

6. vi.Action on cell membranes:
Certain drugs interfere with the movement of the ions
through the cell membrane which prevent the function of
certain nerves and muscles.
vi.Cytotoxic effects:
Certain drugs are used to kill bacteria or malignant cells
without damaging the normal cells of the patients.
vii.Replacement of deficiencies:
These drugs are used to replace the deficiencies of some vital
substances which are necessary for the body function.

7. Dosing Regimen
dose, frequency, route
Concentrations
Plasma, urine, tissue…,
Parent and metabolites
EFFECTS
Rx, Toxic
Effect Site
Concentrations
source: A. Atkinsonsource: A. Atkinson

8. Mechanism of Action
A drug may produce its effect through:
• Receptor mediated action.
•Non-receptor mediated action.

9. General classification of drugs
•Agonist = stimulant.
•Partial agonist.
•Antagonist = blocker.
•Agonist: a drug has affinity, high efficacy and rapid rate of
association and dissociation with its receptor e.g. adrenaline,
morphine and histamine.
•Partial agonist: a drug has affinity, weak efficacy and moderate
association and dissociation. It produces an effect < the full
agonist when it has saturated the receptors. It acts as antagonist
in the presence of full agonist e.g. nalorphine, ergotamine,
succinylcholine and oxprenolol.
•Antagonist: a ligand having affinity, but no efficacy and slowly
associated and dissociated from the receptor.

10. Receptor-Related Diseases
•Myasthenia gravis: due to down-regulation of nicotinic
cholinergic receptors at the motor end plate of the
skeletal muscles.
•Insulin-resistant diabetes mellitus: may be due to
internalization & down-regulation of insulin receptors.
•Testicular feminization: due to resistance of the
receptors to androgen.
•Parkinsonism: in later stages of the disease the
striatum dopamine receptors are down-regulated

11. Non-Receptor Mediated Mechanisms
Drugs act on enzymes:
•Nitric oxide (NO) penetrates the cell membrane stimulating
cytoplasmic guanylyl cyclase enzyme leading to increase of
intracellular cGMP.
• Digitalis inhibits Na+/ K+ ATPase enzyme.
Drugs Act on Plasma Membrane:
•Polymixins and amphotricin B increase the permeability of
bacterial plasma membrane.
Drugs Act on Subcellular Structures:
•Erythromycin and chloramphenicol inhibit protein synthesis in
bacteria by binding to 50 S ribosomal subunit. Tetracyclines and
aminoglycosides bind 30 S ribosomal subunit.

12. Drugs Act by Chemical Action:
•Antacids neutralize gastric acid secretion.
•Protamine (alkaline & +ve charge) antagonizes
heparin (acid & -ve charge).
Drugs Act by Physical Means:
•Osmosis e.g. mannitol.
•Lubricant e.g. liquid paraffin.
•Adsorbent e.g. kaolin and charcoal.
•Demulcent e.g. bismuth salt and olive oil.

13. Chelation:
•Chelation is mainly employed in the treatment of heavy
metal poisoning. A chelating agent holds the toxic metal ion
to form a drug-metal complex, which is non-toxic, water-
soluble and easily excreted in urine e.g.:
•EDTA chelates calcium, lead and digitalis.
•Dimercaprol (BAL) chelates mercury and copper.
•Penicillamine chelates copper & used in treatment of
Wilson’s disease.
•Deferoxamine chelates iron in cases of iron toxicity.

14. Factors Modifying Drug Action
•The individual variation to drug response may be due to:
•Differences in body weight: the adult dose is calculated to
produce specific effect in population between ages 18-65 and
weighing about 70 kg, so very thin or obese individuals have to
receive special doses to give the same response.
•Individual dose= BW (kg)/70 X average adult dose
•Age: the immature liver or kidney of the very young may delay
drug metabolism and excretion. On the other hand delayed
distribution, metabolism and excretion are common in elderly
because of disease condition or normal deterioration of body
system.
–Individual dose= [Age/(Age+12)] X average adult dose (Young’s
formula)
–Individual dose= [Age/20] X average adult dose (Dilling’s formula)

15. Calculation of dose for
children:
•Clark's formula for
infants (<1 year):
•Young's formula:

•Dilling's formula:
12

yearsinAge
yearsinAge
xdoseAdultdoseChild
20
yearsinAge
xdoseAdultdoseChild
150
PoundsinWeight
XdoseAdultdoseInfant

16. Sex: males need higher doses than females owing to the higher
bulky muscles and androgen which is an enzyme inducer.
Drugs should be administered cautiously during pregnancy
and lactation.
Route of administration:
•MgSO4 orally on empty stomach
 (4g.) cholagogue
(15g.) saline purgative.
•i.v inhibits the CNS and used in eclampsia seizures.
•retention enema dehydration and used in cerebral edema
and eclampsia.

17. Disease states: long duration of action or toxic effect of
a drug may be related to liver or kidney disease and
long period of time for absorption and distribution
related to heart disease.
Immune factors: a drug may stimulate the immune
system causing urticaria or shock. From now on this
patient should not received this drug or its related
preparations e.g. penicillin and cephalosporins.
.

18. Psychological factors:
•the hopes, fears and expectation of the individual
often affect the drug action.
•Patients may even improve with placebo (tablet or
capsule containing sucrose or lactose).
•This may be due to release of endogenous
substances like endorphins and enkephalins in the
brain and other body parts