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1. Mechanism of drug action
(Pharmacokinetic and
Pharmacodynamic)
Ravish Yadav

2. Pharmacokinetic & pharmacodynamics drug
interactions.
Pharmacokinetic drug interaction is either
from absorption,distribution,metabolism &
elimination area.
Pharmacodyanamic is at receptor site or
another system

3. Homergic effect:
when two drug produce the same effect.
Hetergic:
when only one drug produce alter effect.
Altered effect may be additive,supra-additive
or synergistic responses.

4. Pharmacodynamics effect mechanisms:
1) Drugs having different pharmacological
effects or antagonists.
2) Drugs having similar effects or agonist.
3) Alteration of electrolyte levels.
4) Interaction at receptor site.

5. Pharmacokinetic:
Absorption:
1) Change of PH.
2) Complexation or adsorption.
3) Gastric motility changes.
4) Inhibition of GIT enzymes
5) Effects of surfactants.

6. Distribution:
1) Displacement of protein binding sites.
2) Hypoalbuminemia.
Metabolism:
1) Stimulation of metabolism
2) Inhibition of metabolism.

7. Excretion:
1) Alteration of urinary Ph
2) Intereference with urinary elimination.

8. Pharmacokinetic interactions:
1) Alteration of GI absorption:
Less or more absorption of drug change the effect of
timing.
a) Alteration of PH:
Some drugs are weak acids or bases. Noni-onised
drugs are easily absorbed while ionized drugs are
less soluble. Quaternary ammonium compound are
remain ionized throughout stomach presence less
absorbance like neostigmine.
Phenobarbital-antacids: phenobarbital is acidic
drug. Its absorption was delayed due to use of
antacid.

9. Pseudo-ephedrine-antacids: both are basic
in nature so aluminium hydroxide increases
the absorption of pseudo-ephedrine.
Aspirin-antacids: aspirin is weak acid &
absorbed from upper region of the GIT. If it
produces side effects it is used with
antacids.

10. Bisacodyl-antacids:
Laxative bisacodyl are enteric coated
because the drug is extremely irritating in
stomach. It should not be given with
antacid because it can dis-integrate the
tablet. It can lead to vomiting.

11. 2) Complexation & adsorption:
Tetracycline-metals:doxycycline & minocycline are
better absorbed with milk also. But aluminium
hydroxide gel can decrease the absorption of
these tetracycline. tetracycline capsules contain
citric acid,glucosamine & potassium
metaphophate increases the absorption in
presence of ions also.

12. Cholestyramine-colestipol: they bind to bile
acids & prevent their re-absorption. They also
bind with the drugs which are present in GIT.
Cholestyramine can interfere with absorption of
thyroid hormone. It also decrease the plasma
level of warfarin.
Decrease in fat soluble vitamins like vit-k.

13. Anti-diarrhoeal mixtures & antacids:
Anti-diarrhoeal decrease the absorption of drugs
like lincomycin,promazine,tetracycline,digoxin.
Lincomycin can cause diarrhea. To avoid it kaolin-
pectin combination is given as an anti-
diarrheal,but it can reduce the absorption of
lincomycin. Adsorption of digoxin is also reduced
by kaolin-pectin preparation.

14. Magnesium trisilicate decreases the absorption of
chlorpromazine,phenothiazine,.
Antacid: decrease the absorption of isoniazid.

15. Food: the presence of food in GIT will adversely
affect absorption of anti-infective agents.
Food enhances the absorption of nitrofurantoin &
hydrochlothiazide.
Bioavailability of propranolol & metaprolol increases
with food.
Food decreases their hepatic clearance.

16. Spironolactone active metabolite activity is
increase due to presence of food. Due to
food increases the activity of cholic acids
which increases the absorption active
metabolite.

17. Alteration of motility/rate of gastric emptying:
a) Cathartics: cathartic increases the GI
motility results in decrease in activity of drugs.
b) Anti-cholinergics: they decrease GIT motility
increases the absorption of drugs. Propantheline
increases the absorption of riboflavin &
hydrochlothiazid.
c) Acetaminophen-propantheline:
propantheline increases the absorption of
acetaminophen.

18. d) Effect of surfactants: surfactant can
influence the rate and /or the extent of
absorption of certain drugs, they can interact
with biological membranes & modify
membrane permeability .
Mineral oil-dioctyl sodium sulfosuccinate:
Dioctyl sodium sulfosuccinate is faecal
softener . it should not be used with mineral
oil . It can lead to toxicity.

19. Inhibition of GI enzymes:
a) Folic acid –phenytoin:
Folic acid is present in dietary food. It is
present in the form of polyglutametes. It is
converted to monoglutamate by action of
an intestinal conjugase enzyme.
Folic acid deficiency anemias are caused in
patients receiving phenytoin. Phenytoin
decreases the release of intestinal
enzymes.

20. b) Vitamins-oral contraceptives: use of oral
contraceptives may result in deficiency of folic
acid,cyanocobalamine,pyridoxine & ascorbic acid.
Oral contraceptives may interfere with
deconjugation of polyglutamate forms of folic acid
results in folic acid deficiency.

21. 6) Malabsorption states:
Drugs like
neomycin,laxatives,colchicine,cholestyramine &
aminosalicylic acid cause malabsorption problems
that result in decreased absorption of vitamins &
nutrients form the GIT.

22. Alteration of distribution:
1) Displacement from protein binding site:
Competitive displacement.
Unbound drug is metabolized & excreted from the
body.
Binding of drug to albumin.
Highly plasma protein bound drug is more than
90%

23. Warfarin-phenylbutazone:
both bound to albumin. Phenylbutazone has
greater affinity for albumin results
displacement of warfarin from binding sites
lead to risk of hemorrhage.
Bilirubin-sulphonamides: sulphonamides
displace bilirubin from binding site. It lead to
jaundice.

24. Methotrexate-sulphonamides:
sulphonamide & salicylates displace
methotrexate from binding sites lead to
toxicity of methotrexate.
Hypoalbuninemia: decrease the
concentration of protein increase the
free drug concentration lead to less
action of drugs.
When serum albumin concentration is
less than 2.5gm/100ml frequency of
prednisone side effects is almost
doubled.

25. Protein-binding sites & disease states:
due to poor renal function decrease binding
of drugs to plasma proteins like phenytoin.
Acidic drugs bound to lesser extent in
presence of renal failure.
Example: warfarin,barbiturates,salicylates.

26. 2) Alteration of metabolism:
1) Stimulation of metabolism:
enzyme induction:
a) Meprobamate & glutethimide: these
agents developed tolerance because they
have ability to stimulate their own
metabolism

27. b) Warfarin-phenobarbital:
phenobarbital increase the metabolism of warfarin.
There is a risk of thrombus formation. To
compensate this anticoagulant dose is increased.
Benzodiapine such as chlodiazepoxide & flurazepam
are not likely to interact with anticoagulant therapy
so they can be use.

28. c) Phenytoin-phenobarbital:
phenobarbital increases the metabolism
of phenytoin
d) Digoxin-phenobarbital:
phenytoin increases the metabolism of digoxin.
Plasma concentration of digoxin fall down upto
50%. Phenybutazone also affects the same.

29. e) Oral contraceptives:
rifampicin & barbiturates when
administered concurrently reduction in
blood levels of contraceptives will occur.
increased metabolism of steroid
hormones such as estrogen &
progesterone lead to withdrawal
bleeding or undesired pregnancy.

30. f) Glucocorticoids:
glucocorticoids get metabolite due to
phenobarbital. Phenytoin also increases
the rate of metabolism of prednisolone &
dexamethasone. Barbiturates cause
increased bronchospasm & pulmonary
function deterioration in asthmatic
patients having glucocorticoid therapy.

31. g) Vitamin-D-Phenytoin & Phenobarbital:
vitamin-D metabolism is also done by phenytoin.
Reduce serum calcium levels are found
inpatients on long term anti-convulsant
therapy,leads to vitamin D deficiency. It lead to
seizure control more difficult .

32. h) Environmental chemicals:
such as DDT,Chlorinated organic
pesticides & polycyclic hydrocarbons can
increase activity of hepatic microsomal
enzymes. They decrease the therapeutic
effect of warfarin. But phenytoin &
phenobarbital decrease the levels of
DDT..

33. i) SMOKING:
polycyclic hydrocarbons like 3,4- benzpyrene
present in cigarette smoke tend to increase the
microsomal enzyme activity. Decrease in activity
like chlorpromazine,chlordiazepoxide,diazepam,
theophylline,propoxyphene. Caffeine clearance is
more in heavy smokers. Charcoal broiled beaf &
smoked tandoori dishes also contain 3-4-
benzpyrene derivative lead to increase
metabolism of phenacetin.
Risk is more in women who are taking oral
contraceptives & smoke.

34. j) Alcohol: increased rate of metabolism of
drugs like tolbutamide,warfarin, & phenytoin in
chronic alcoholic.
k) Levodopa-pyridoxin:

35. Inhibition of metabolism:
1) Alcohol-disulfiram: disulfiram inhibits the
activity aldehyde dehydrogenase inhibiting
oxidation of acetaldehyde which is an oxidation
product of alcohol. It lead to effects of disulfiram
like
flushing,palpitation,hyperventilation,decrease
blood pressure & dyspnea. This interaction is
useful in alcohol abusers.

36. 2) Mercaptopurine & azathioprine- allopurinol:
allopurinol inhibits the enzyme xanthine oxidase &
reduces production of uric acid, that’s why used in
gout. Xanthine oxidase is involved in metabolism of
drugs like mercaptopurine & azathioprine which are
toxic anticancer drugs .

37. 3) Phenytoin-isoniazid:
isoniazid inhibits the metabolism of
phenytoin results in toxic effects of
phenytoin. Its in slow acetylators.
4) MAO-Inhibitors: MOA inhibitors
enhance the effect of drugs like barbiturates
& narcotics by inhibiting hepatic enzyme
systems involved in their metabolism.

38. ALTERATION OF EXCRETION:
1) Alteration of urinary PH:
A) Methanamine-Acidifying agents:
Methanamine is converted to formaldehyde
which is the active antibacterial agent. For this
conversion urinary ph should be 5.5 or less.
Acidifying agent such as mandelic acid &
hippuric acid are used with methanamine to
decrease the urinary ph.

39. B) Sulphonamide-methanamine:
acidic urinary ph required for methanamine
activity causes precipitation of sulphonamides
& development of crystalluria.
C) Salicylates-acidifying & alkaliniing agents:
low concentration of salicylates when urine is
alkaline & twice high when urine ph is acidic.

40. D) Anti-infective agents:
When urinary ph is acidic the activity of
tetracyclines,nitrofurantoin & methenamine
is quite good.
When ph is basic then aminoglycosides like
streptomycin & kanamycin are more active.
Erythromycin is also more active in basic ph.

41. 2) Interference with urinary excretion:
a) Penicillin-probenecid: probenecid
increases serum levels & prolongs activity of
penicillin derivatives by blocking their tubular
excretion. Used in gonorrhea.
b) Salicylates-furesemide: competition
between these two drugs for renal excretory
sites & patient may experience salicylate toxicity
at low doses.

42. c) Digoxin-quinidine: quinidine
increases serum levels of diqoxin. It is due
to reduction in the clearance of glycoside
induced by quinidine.

43. Pharmacodyanamic interactions:
1) Drugs having opposing
pharmacological effects:
2) Drugs having similar pharmacological
effects:
a) Alcohol-sedatives
b) Anti-psychotic drugs-anti-parkinsonism
drugs & antidepressants

44. c) Aminoglycoside antibiotics-diuretics:
The aminoglycosides like
gentamycin,streptomycin,neomycin & amikacin
have a potential to cause ototoxicity including
deafness. Ototoxicity develops rapidly when
diuretic like furosemide taken concurrently by the
intravenous route to patients on gentamycin or
amikacin therapy. A rapid rise in serum levels of
aminoglycoside lead to ototoxicity

45. 3) Alteration of electrolyte levels:
a) Digitalis glycosides-diuretics:
Thiazide diuretics like athacrynic
acid,furosemide & metazolone cause excessive
loss of potassium. Potassium depletion or
hypokalemia results in arrhythmias when
digitalis preparatios are combined with these
diuretics. The patients are advised to take
potassium rich food like bananas & oranges or
fruit juices. Potassium supplements &
potassium sparing diuretics like spironolactone
may be prescribed. Diuretic therapy also causes
hypomagnesemia,when magnesium is depleted
digitalis toxicity enhances.

46. b) Digitalis glycosides-calcium:
Increase in the level of calcium
enhances the sensitivity of the heart
to digitalis. Decrease in the response
to digoxin is attributed to
hypocalcemia.

47. c) Lithium carbonate-calcium:
Sodium depletion is known to enhance
lithium toxicity. The sodium depletion
caused by diuretics reduces the renal
clearance & increases the activity of
lithium.

48. d) Weight control pills:
Weight control pills contain like digitalis,thyroid a
diuretic a laxative a barbiturate, & amphetamine
as anorexic. They produce severe side effects in
patients. It also increases the loss of potassium
which increases the sensitivity of the heart to
digitalis & leads to digitalis toxicity even at lower
doses. Amphetamine reduces the appetite. There
is a loss of ions due to presence of diuretic &
laxative.

49. 4) Interaction involving the adrenergic system:
a) MAO-inhibitors & sympathomimetic agents:
MAO inhibitors increase the levels of
norepinephrine. MAO inhibitors like
pargyline,phenelzine & tranylcypromine when used
along with sympathomimetic amines such as
amphetamine severe problems like
headache,hypertension & cardiac arrhythmias
developed.

50. b) MAO inhibitors-Tyramine:
Certain foods have high content of pressor amine
tyramine & serious reactions.
c) MAO inhibitors-Tricyclic antidepressants:
Concurrent use of MAO inhibitors & tricyclic
antidepressant like amitryptilline,imipramine or
desipramine can cause serious atropine like
effects.tremors,convulsions,hyperthermia &
vascular collapse are the result of this combination.

51. d) Gaunethidine-tricyclic antidepressants:
TCA inhibit uptake of guanethidine in to the
neuron terminals thereby preventing the
absorption. The result is decrease in the effect
of guanthedine.
e) Gaunethedine-antipsychotic agents:
Chlorpromazine & haloperidol reverse the anti-
hypertensive effect of gaunethedine.

52. 5) Alteration of receptor site interactions:
a) Warfarin-dextrothyroxine:
Dextrothyroxine increases the activity
of warfarin. It increases the affinity of
drug at receptor site.
b) Warfarin-anabolic steroids:
Methandrostenolone & oxymethodone
increases the warfarin activity by
increasing the affinity for the receptor.

53. 6) Alteration of GI flora:
a) Anticoagulant-antibiotics:
7) Anti-biotic combinations:
Antagonism between chloramphenicol or
tetracycline is administered with penicillin.
a) Enhanced antibiotic action: synergism
Use of ampicillin & penicillin along with
aminoglycoside antibiotics such as
streptomycin or kanamycin for treatment of
enteroccocal endocarditis.

54. b) For treatment of mixed infections:
c) Treatment of severe infection:
d) Prevention of emergence of resistant
organisms
e) Broader range of activity.
f) Penicillin-tetracycline: combination is
beneficial.
g) Penicillin-chloramphenicol & streptomycin:
Used to treat bacterial meningitis.

55. b) Gentamycin-carbenicillin:
Used to treat pseudomonas infections.