drug interaction

COLLECTION OF DRUG-DRUG INTERACTION PHARMACOLOGY

BOOK 2

CNS

BUSPIRONE m/s-331

1.Metabolic enzyme inhibitors (Erythocine,ketoconazole,Diltiazem) will increase Buspirone plasma concentration.

2.Monoamine oxidase inhibitors precipitate serotonin syndrome with Buspirone.

TCA m/s-337

1.With MAOI:Atropine like toxicity and convulsions.
2.TCA antagonize Guanethine and Clonidine. WHY?


MAOIs m/s-339

drug-drug:

1.Potentiation of symphatomimetics (including cold remedies & nasal decongestants.
2.Toxic synergism with tricyclic antidepressant.
3.Reversal of reserpine action resulting in hypertension and excitement.
4.By INHIBITION of drug-metabolizing enzyme, they potentiate the action
of many drug.ex:Barbiturates,Opiates and Sulphonylureas.

drug-food:

1.Hypertensive crisis (CHEESE REACTION) occur in patients receiving MAOI after eating tyramine-rich food stuffs.ex:aged cheese,pickled herrings and broad beans.
2.This serious rection is treated by Phentolamine (5 mg I.V) and B-adrenoceptor blockers.



Antipsychotic drug.

(ex:Phenothiazines group) m/s-345

1.They potentiate the central depressant effect of some drug. ex:aspirin,morphine,sedatives,hypnotics,alcohol and General anaesthetics.
2.They potentiate the anticholinergic effect of some drugs.ex:TCA
3.They potentiate the hypotensive effect of antihypertensives.
4.They antagonize the effect of dopamine agonists and levodopa.


Levodopa. m/s-374

1.Non selective MAOIs:Lead to hypertensive crisis (CHEESE REACTION) due to accumulation of active dopamine and conversion into norepinephrine.
2.Pyridoxine (Vit. B6) enhances peripheral decarboxylation into dopamine.ex: antagonism of L-DOPA
3.Dopaminergic antagonist (phenothiazines and butyrophenones) abolish its effects.
4.Reserpine which depletes dopamine stores is also antagonistic.
5.Synergism: by anticholinergics and selegiline.
6.Its metabolites interfere with some laboratory test of pheochromocytoma.
7.FOODS: amino acid compete with L-DOPA for active transport in intestine.


MAO-B INHIBITORS (Selegiline). m/s-376

1.with Meperidine : respiratory depression,coma and hypotension.




ENDOCRINE.

Drug interaction with oral hypoglycemic : m/s-419

1.Drug which exaggerate the hypoglycemic effect:
a)Beta-blockers
b)Salicylates
c)Microsomal enzyme inhibitors (Dicumarol,chloramphenicol,cimetidine)

2.Drug which antagonize the hypoglycemic effect :
a)Beta agonist.(beta 2 increase hepatic glycogenolysis)
b)Diazoxide (activate K+ ATPase channel)
c)Thiazide and Frusemide (decrease insuline release and block peripheral utilization of glucose)
d)Anti-insuline hormones.ex: Thyroxin,steroids,contraceptive pills,glucagon,adrenaline,GROWTH hormone (they increase glycogenolysis and gluconeogenesis)



GLUCOCORTICOIDS. m/s-431

1.With NSAIDs: Increase the incidence peptic ulcer and delay its healing.
2.With insulin: it has anti-insulin effect (hyperglycemia)
3.With anti-coagulant drugs: it decrease their effect.
4.With DM.


VITAMIN D m/s-451

1.Phenytoin and Phenobarbitone (antiepileptic drug) stimulate hepatic micro somal enzymes leading to increase Vit.D metabolism, so epileptic patients on long term therapy may develope osteomalacia (adult) or rickets (children).
2.Cholestyramine and mineral oil decrease its absorption.
3.Corticosteroids decrease both Vit.D mediated intestinal calcium absorption and bone collagen synthesis.
4.Thiazide increase the hypercalcaemic effects of Vit.D.



CHEMOTERAPHY

SULFONAMIDE,TRIMETOPHRIM,QUINOLONES. m/s-513

-Through displacement from binding sites on plasma proteins of oral hypoglycemic drugs,oral anticoagulants (warfarin) ,methotrexate.


PENICILLIN m/s-526

1.Penicillins with bacteriostatic drug (tetracycline,chloromphenicol,erythromycin):since penicillin act by inhibiting cell wall synthesis,but drugs which decreases protein synthesis,interfere with the action of penicillin.

2.All antipseudomonal penicillins impair the anti bacterial action of gentamycin when the 2 drugs are mixed together in vitro.this inactivation is not likely to occur in vivo in patients with normal renal funtion, but the possibility exist in patiens with severe renal impairment.


AMINOGLYCOSIDES. m/s-533

1.With antibiotics:
-with cephalosporins nephrotoxicity increases.
-Anti-pseudomanal penicillins if combined together in same syringe because penicillins are acidic and aminoglyciside are alkaline.

2.Skeletal muscle relaxtants:
-Aminoglycosides increase the effect of non depolarizing NMB agents(see ANS).It could be reversed by neostigmine and calcium gluconate.
-Aminoglycosides should be administered with great caution during surgery or in the post-operative period.

3.Anticoagulants:
-With oral anticoagulants: oral aminoglycoside impair vitamin K production by intestinal bacteria potentiating the effect of anticoagulants.
-Heparin precipitate aminoglycosides (avoid their mixing in the same
syringe)

4.Diuretics and antihistamines :
-Diuretics.example:ethacrynic acid,frusemide,mannitol and antihistamines potentiate ototoxicity of aminoglycosides.



MACROLIDES. m/s-536

1.Combination of the therapeutic dose of erytromycin with penicillin antagonizes the bactericidal effect of penicillin.
2.Erytromycin decrease P450 enzymes,thus increase serum concentration of theophylline,oral anticoagulants,cyclosporins and digoxin.


TETRACYCLINES: m/s:541

1.Avoid simultaneous ingestion of dairy products (milk&cheese),antacids,laxatives or iron containing products with tetracycline because chelating action of tetracycline.
2.Avoid Doxycycline in alcoholic patients because ethanol causes induction of hepatic enzymes leading to decrease serum level of antibiotics.
3.With oral anti-coagulants,tetracycline decrease vitamin K synthesis in intestinal lumen leading to potentiation of anti-coagulants effects.


CHLORAMPHENICOL: m/s-543

-Chloramphenicol inhibits the activity of the liver microsomal enzymes and thus enhances the activity of drugs,such as dicoumarol,diphenylhydantoin and tolbutamide which are normally degraded by these enzymes.


Book 1

ANS

Adrenergic Neuron Blokers

CLONIDINE m/s:103

1.Tricyclic Antidepressant may block the antihypertensive effect of clonidine.
2.Beta-blockers may aggravate the hypertensive crises following sudden clonidine withrawal.
3.CNS depressants may cause excessive drowsiness with clonidine.


RENAL

Loop Diuretics
Frusemide,bumetanide,torsemide,ethacrynic acid and ethacrynic acid uricosuric congeners. m/s:179

1.The diuretic - induced K+ deficiency increases the sensitivity of myocardium to digitalis.
2.Concurrent glucocorticoid treatment produces additive decrease in serum potassium level.
3.Furosemide and Ethacrynic acid have high plasma protein binding capacity that may compete with other drugs such as Warfarin an Clofibrate for plasma protein binding sites.
4.Ethacrynic potentiates ototoxicity of aminoglycosides.
5.Furosemide potentiates nephrotoxicity of cephalosporins.
6.Non-steroidal anti-inflammatory drugs which are potent inhibitors of prostaglandin synthesis,reduce the natriuretic and diuretic effects of furosemide because these effects may be mediated through furosemide induced increase in synthesis of PGE2 and PGI2.
7.Organic acids such as probenicid and indomethacin which are secreted by the active organic acid secretory system in the PCT could inhibit tubular secretion of loop diuretics competitively and thus prevent them to reach their site of action and reduce their diuretic activity.



CVS

CCBs m/s-202

1.Verapamil with digitalis or with beta-blockers may cause A-V block due to additional effect on conducting system (nifedifine would be the drug of choice if B-blockers are used with CCBs).
2.CCBs and direct vasodilators may cause profound hypotension.


CENTRALLY ACTING ANTI-HYPERTENSIVES

CLONIDINE m/s-212

1.Tricyclic antidepressant (TCA) may block the antihypertensive effect of clonidine as TCA prevent neuronal reuptake of released norepinephrine leading to concentration of norepinephrine at adrenergic receptors.
2.Beta-blockers may aggravate the hypertensive crises following sudden clonidine withrawal.
3.CNS depressant may cause excessive drowsiness with clonidine.


GIT

H2 Receptor antagonist.
CIMETIDINE (enzyme inhibition) m/s-260

-Cimetidine inhibits cytochromr oxidase P-450,so decrease metabolism and increase effect of many drugs as: B-blockers,Ca2+ Channel blockers,warfarin.
-So,adjusment of the dose of these drugs during administration and during stoppage of cimetidine therapy should be considered.
-Cimetidine or Ranitidine decrease glucoronation of Acetaminophen (Paracetamol) thus may increase its effects.


Treatment of Bleeding Peptic Ulcer.

METOCLOPRAMIDE(Primperan) m/s-268

1.Metoclopramide must not be given concurrently with other Dopamine antagonists because they precipitate acute dystonic reactions (muscle contraction ) due to blockade of D2 receptor (which could be treated by stopping the drug and giving I.V atropine or its substitude which has antagonistic cholinomimetic action).
2.Corticosteroids have sinergitic effect in enhancing anti-emetic activity of Metoclopramide.

p/s:
kawan-kawan,menurut Dr Hisham DRUG INTERACTION ni penting untuk BOOK 2.sebab dalam tu ada banyak.dalam BOOK 1,xde sangat.
so,sama2x kita tekan seket untuk BOOK 2.

-untuk lihat lagi jelas,kawan-kawan boleh rujuk buku teks.no.muka surat sudah disediakan.

credit to fattah hamzah


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