DRUG INTERACTIONS

IN LABOR

A PRACTICAL VIEW

DRUG INTERACTIONS

IN LABOR

A PRACTICAL VIEWDr.Mohamed El SherbinyMD Obstetrics & Gynecology

Senior Consultant Damietta General Hospital

Damietta Egypt

DEFINITION :

Drug interaction means modification of the effect of a drug by concurrent administration of other drugs.

DEFINITION :

Drug interaction means modification of the effect of a drug by concurrent administration of other drugs.

Basic principles:

Adverse interaction includes:

1-Loss of drug action

2-Unexpected increase in drug action

3-toxicity

Adverse interaction includes:

1-Loss of drug action

2-Unexpected increase in drug action

3-toxicity

Beneficial interaction:e.g..

*Pethidine+ Metochlopromide(Plasil) *Naloxone+Morphia.

Beneficial interaction:e.g..

*Pethidine+ Metochlopromide(Plasil) *Naloxone+Morphia.

ADVERSE &BENEFICIAL INTERACTIONS

I-PHARMACOKINETICS:

Everything that happens to the drug in the body

I-PHARMACOKINETICS:

Everything that happens to the drug in the body

Mechanisms Of Interactions:

II-PHARMACODYNAMIC

* Everything the drug does to the body

II-PHARMACODYNAMIC

* Everything the drug does to the body

N.B Interaction outside the body (Incompatibility )e.g. ketamine is incompatible with barbiturate & diazepam

N.B Interaction outside the body (Incompatibility )e.g. ketamine is incompatible with barbiturate & diazepam

I-PHARMACOKINETIC

* Absorption * Distribution * Metabolism * Excretion

* Absorption: may be interfered with e.g.Al(OH)3 In most antacid adsorb digoxinAdrenaline to local anesthesia prolong effect

What happens to drugs in the body?

* Distribution: affected byCompetition for plasma protein

binding E.g:Indomethacine displaces

Warfarine . Free

Warfarine --> anticoagulant effect

NaHC3 pH of renal tubules

absorption

of Aspirin & Phenobarbital (weakly

acidic) . their excretion

their Effects.

* Excretion : drug clearance affected by

another drug e.g

* Metabolism

•Induction of liver micosomal Enzyme

CYTOCHROME P450(7-10 days) e.g.

Rifampicin, Phenobarbiton, Carbamaziben (Tegretol)Phenytoin:

They increase the metabolism and decrease activity of other drugs e.g.Theophyllin, & Valproic acid

Interfered with through liver enzymes:Interfered with through liver enzymes:

Inhibitor of liver enzymes(a rapid effect)

e.g. Cemitidin,Erthromycin decrease the metabolism andincrease activity of other drugs eg.Theophyllin,Anticoagulant

* Metabolism Cont..

2-PHARMACODYNAMICSynergism1-Addition 2+2=4 e.g. B Blockers +Thiazide

2-Potentiation 2+2=5 Trimethoprin+sulfmethexasol

Antagonism(Opposing)B-Blockers Propanolol(Inderal) prevent the bronchodilator effect

of Sulbitamol (Ventolin) or Terbutalin (Bricanyl)

Indomethacine inhibits biosynthesis of Vasodilator natruretic

prostaglandins -->inhibit diuretic effect of Lasix and Thiazide

I -DRUGS USED IN ORDINARY LABOR & C S.

I -DRUGS USED IN ORDINARY LABOR & C S.

II- -DRUGS USED IN LABOR WITH OBSTETRIC

DISORDERS.

II- -DRUGS USED IN LABOR WITH OBSTETRIC

DISORDERS.

III- DRUGS USED IN COMMON MEDICAL

DISORDERS.

III- DRUGS USED IN COMMON MEDICAL

DISORDERS.

TOPICS

Analgesic &Anesthetics

Antacids , H2 antagonist & antiemetisc

Antibiotics

Ecbolic (Oxytocics)

Intravenous additives

I -DRUGS USED IN ORDINARY LABOR & C S.

I -DRUGS USED IN ORDINARY LABOR & C S.

Opioids

Benzodiazepins:Diazepam(Valium)

&Midazolam(Dormicum)

Ketamine(ketalar or Kalypsol)

Analgesic &Anesthetics Analgesic &Anesthetics

Analgesic &Anesthetics (cont.) Analgesic &Anesthetics (cont.)

No2,Hydrocarbon inhalation anesthesia

Fluthane ,Triline,Muscle relaxant.Conduction Anesthetics

No2,Hydrocarbon inhalation anesthesia

Fluthane ,Triline,Muscle relaxant.Conduction Anesthetics

CNS depression producing drugscommonly used during labor

e.g. Anesthetics, Opioid,Magnesium sulfate,Anticonvulsant, MetoclopromideBenszodiazepine,Promothiazine

Skeletal muscle relaxant ,Barbiturate ,Beta adrenergic blockers, Antihistaminic,

Antidepressants

Usually they potentiate each other Usually they potentiate each other

AtropineAtropine

Atropine has these effects:

*Ketamin(Ketalar) : Delirium*Metoclopramide: Antagonize effect on GI motility

*Opioid : Constipation &urinary retention.

*Thiopental: Vagal effect

*Neostigmine : Muscrinic action of Acetyle cholin

Used for :* preanesthetic medication * fetal Bradycaredia

Other CNS depressants: Maternal and fetal CNC& Respiratory depression& hypotensione.

Anticholinergic: Sever constipation &Paralytic ileus

Opioid Morphine,pethidine,Butorphanol,

Nalbuphine ,fentanyl &,tramadolInteractions

Naloxon(Narcan)

• Reverses the analgesic and respiratory effect of opioids •Withdrawal symptoms in dependents

• Large dose may be required to reverse Butorphanol(Stadol)

Mono amine oxidas (MAO) Inhibitors

Antidepressant(Parnate) Sever fatal reaction :

(Excitation,sweating,sever hypertension)

Metoclopramide: Analgesia & Emetic effect.

But Promethazine (Sparin): Analgesia.

Oxytocine &Prostglandines : Potentiaton.

Ranitidine &Metoclopramide should given to oppose the delayed gastric effect of pethidine

Pethidine

Butorphanol(Stadol)It is (k)agonist& mixed (µ)agonist and antagonist

-2mg is comparable with 80mg pethidine

-2mg has respiratory depression of 10mg morphine

but greater doses has no further depression(ceiling)

Antagonizes narcotic effect of PethidineAntagonizes narcotic effect of Pethidine

Effect is altered by :Cimetidine,Erythromycine &Thiophylline( Hepatic)

Nalbuphine (NUBIN)

* It is a (µ) partial antagonist and( k) agonist*10mg = 10mg Morphine or 50 mg Pethidine*Higher dysphoria &fetal R. depression (So not popular)*Ceiling effect with dose > 30mg

Interaction:Concurrent .or following (µ) Analgesia & Respiratory depression

Tramadol (Tramal) (50mg)

Weak µ agonist less respiratory depression for the fetus50mg Tramal = 40mg PethidineMay antagonize antiepilepticsCarbamazepine (Tegretol) : decreases effect of tramadol

(Systemic ,Spinal & Epidural) 100 times as potent as morphine. 50 ug = 50mg pethidine More maternal nausea and vomiting, Similar neonatal side effect and More naloxon need for antagonist compared to pethidine

FentanylFentanyl

*Addition of Chloroprocaine(Nesacaine) . . . . +Fentanyl:(Epidural)Unexplained increase of post operative pain

KETAMINE (KETALAR OR kLAPYSOL) 50mg/ml

- Obstetric analgesia0.3mg/kg& anesthesia1mg/kg or to supplement No 2

- It stimulate CVS ---> hypertension,tachycardia.&increase C.output

- this effect is opposed by Bezodiazepine or Volatile anesthesia

Incompatible with barbiturate & diazepam

Interactions:Thyroid hormone:Hypertension &TachycardiaCNS depression producing drugs: Hypotension&R.depression Halogonated inhalation :Delayed recovery

Thiopental or diazepam : Dreams and illusion of ketamine

May produce myocardial depression with Labetalol(Trandate):

Antianxiety ( minor tranquilizers)

Benzodiazepines

Antianxiety ( minor tranquilizers)

BenzodiazepinesMidazolam (Dormicum)Diazepam Valium

- Antacids delay effect of oral Diazepam- Cimitidine & Erthromycin inhibit metabolism : Increase effect

With CNS depression drugs: Potentiate each others

Fentanyl or Thiopental Dose for induction

Should be limited to Status epilepticus&AnexityWas used for ECLAMPTIC fits

ThiopentalThiopental

CNS depression producing agents:

CNS & respiratory depression,

Hypotension ,and prolong anesthesiaHypotensive agents &diuretics:

Additive hypotension.

Used to induce sleep If used as anesthesia-:---> Marked neonatal depression

Rapid or high dose Ketemine(ketalar): : Risk of hypotension& respiratory depressionMgSO4 : CNS depressant& anaesthetic effects

NO2NO2CNS depression

Producing medication:

Anesthetic requirement Hypotension Respiratory depressionMethyledopa(Aldomet):

Decrease anesthetic requirement

HALOTHANE (FLUOTHANE)HALOTHANE (FLUOTHANE)

LABETALOL:Profound hypotension

Catecholamines (Dopamin,adrenaline ,Noradrenaline ),

Ephedrin or Cocaine : Risk of ventricular arrhythmia.

Ritodrin(Yutopar): Potentiate Arrhythmia &Hypotension

Nitrous Oxide Concurrent use : Requirement of the other

Ketamine ----->Prolonged recovery

OXYTOCICS : Decrease uterine respond

SUCCINYL-CHOLINEMgSO4, Aminoglycosides ,or Ranitidine(zantac)Potentiate muscle relaxant effect

Muscle relaxant

Digitalis toxicity (arrhythmia): due to shift of intracellular KDigitalis toxicity (arrhythmia): due to shift of intracellular K

Ketamine or Clindamycine :Prolongs apnea Ketamine or Clindamycine :Prolongs apnea

•B adrenergic blockers :Prolong the effect of Flaxidil& Pavulon

•Calcium salt: Reverses the blocking effect

•Opioids: Additive central respiratory depression

Nondepolarizing Neuromuscular Blockers

Nondepolarizing Neuromuscular Blockers

Gallamine(Flaxidil),Atracurium(Tracrium), Pancuronium(Pavulon)

N.B.. Atracurium(Tracrium) Has insignificant placental transfer and rapid reverse.

N.B.. Atracurium(Tracrium) Has insignificant placental transfer and rapid reverse.

•MgSO4 or Halothane : :Enhances blockade

Conduction (Regional)Anesthetics

Local Infiltration:

Before and after episiotomy or Emergency CS in absence of anesthetic support

0.5% Lidocaine(Zylocaine) or Chloroprocaine(Nesacaine)

(Increased effect by:Adrenaline,Beta blocker,Cemitidene, Diazipam,Ketamine and opioids,

Adrenaline will prolong the effect of Lidocaine. or Chloroprocaine

Pudendal Block:(before Forceps or Vacuum delivery) 1% Lidocaine. or Chloroprocaine.

Conduction (Regional)Anesthetics [Contin.]

Paracervical block:1% Lidocaine. or Chloroprocaine at 3&9 O’clock

Patient under heparin may have troublesome hematoma

Fetal bradycardia is common:No longer recommended

Spinal(Subarachonoid) block:

Tetracaine(Pontocaine), Bupivacine(Marcaine) (duration :90:150m. minutes) Lidocaine(60:90 minutes). or Chloroprocaine

The addition of 0.2 mg of Morphine improves pain control during & after delivery

Compared with IV. Analgesia: Epidural block hasSame degree of analgesia: Longer labor Chorioamnionitis, Forceps,and CS.

Epidural Analgesia:For Vaginal delivery &CS.

Morphia ,Pethidin,or Fentanyl + smaller dose of Bupivacine (Marcaine)Rapid onset, Good pain relief Shivering Tachyphlaxis of prolonged administrationBut higher pruritis (less with stadol) and U.retention*

0.5mg Ketamine+ 0.25% Bupivacaine (Marcaine ):prolongs the duration of Caudal block with reduction of the dose.

Epidural Analgesia:

-Uterine displacement+Hydration with balanced salt solution--.>Decrease incidence of hypotension after Spinal or Epidural block-Hydration with rapid infusion of 25 g Glucose:Can lead to fetal acidosis ,Hypoglycemia,&Hyperbilirubinemia.

Paradoxically:Hypertension associated with methergin is more common with spinal or epidural block.

*Addition of Chloroprocaine(Nesacaine) +Fentanyl:Unexplained increase of post operative pain*Addition of Lignocaine( Xylocaine) to. Bupivacaine can precipitate toxicity

Epidural analgesia ( Contin.)

ANTACIDS

Gastric alkalinization: The absorption & bioavailability of:

Some antimascarinics,Phenothiazine,Propranolol,Atenolol,DigoxineIndomethacine.Prednisone , Phenytoin, &Ranitidine(Zantac)

With Misoprostol (Cytotec ) &-PE2- :Diarrhea

Used in labor for prophylaxis with analgesia or anesthesia before CS will neutralize gastric contents in 90%.

Inhibits Cytochrom450&448

* Increased level of :Phenobarbiton.,Diazepam, ,Phenytoin,Tricyclic antidepressent Theophylline, ,&Lidocaine)B Blocker,C chanel Blockers* Decrease level of Metronidazol.

Ranitidine (Zantac)

Weak enzyme inhibitor = Less interaction than Cimetidine

H2 receptor Antagonist Cimetidine(Tagamet) & Ranitidine (Zantac) H2 receptor Antagonist Cimetidine(Tagamet) & Ranitidine (Zantac)

Ondansetron (Zofran)

Phenothiazines:Promazine (Sparine) Chloropromazine(Largactil )

Benzamide:Metochlopramide(Primperan,Plasil)

ANTIEMETICS

MMetochlopramide (Primperan,Plasil)

Used with opioid analgesia and preanaesthetic medication to reduce gastric volume and increase the tone of L.esophageal sphincter

Opioids :Primperan antagonize the emetic effect Gastric volume & Potentiats analgesic effect.

With CNS depressant drugs:Potentiate each others

Decreases absorption of Digoxine ---> Decreases its effect

Decreases effectiveness of AldometProlongation of action of Succinylcholine

Anticholinergics :lessen GIT motility effects of primperan

CYTOCHROME P450 Inducers(Rifampicin,Phenobarbiton,Carbamazepine (Tegretol)

&Phenytoin,) : Decrease activity of (Zofran)

Liver Enzymes Inhibitors(Cemitidin,Erthromycin )

: Increase activity of Zofran

Ondansetron (Zofran) Used in resistant postoperative vomiting

Phenothiazines:Promazine (Sparine) Chloropromazine(Largactil)

They should be limited to Psychotic patients or for sever nausea or vomiting

CNS depressants : Potentiate each others

-Potentiate orthostatic hypotension with Thiaside-Lower seizure threshold: Decrease effect of anticonvulsant & increase their toxicity--Inhibit effect of Adrenaline-Potantiate effects of Anticholinergics:

Potentiates respiratory depression of pethidine and decreases analgesic effect

,

ANTIBIOTICS

*AMPICILLIN : Potentiate Prednisolone,Digoxin,Thyophillin,&Ergot

*PEN ICILLINS or CEPHALOSPORENS )

:Mixing with aminoglycosides = Mutual inactivation

* PIPERACILLIN(Piprel)&Carbincellin(Pyopen) : Potentiate thrombolytic effect of Heparin & Aspirin*CEPHALOSPORINES Nephrotoxicity with Gentamycin or tobramycin(Nebcin)Cephoperazon(Cefobid): Nephrotoxicity with aminoglycosides and potentiate anticoagulant effect of thrombolytics

ERYTHROMYCIN :(It is A hepatic enzyme inhibitor)--> Potantiat effects of Digoxin, vasospasm of Ergot Theophylline,&Potantiat effects of Some antiepeleptics As :(Phyntoin(Epanutin),Carbamazepine(Tegratol),&Valproic acid(Depakene)

ANTIBIOTICS (Cont.)

METRONIDAZOL (FLAGYL)Potentiated by Phenbarbitone and phenytoinOpposed by Cemitidine

AMINOGLCOSYDES

1-Mutual inactivation with Penicillins or Cephalosporins

2-Indomethacine --> Nephrotoxicity in premature neonates

3- Potentiate ototoxicity of Vancomycin

( combination for endocarditis and resistant staph) :dose monitor

ANTIBIOTICS (Cont.)

4-Potentiate neuromuscular blocking agent

OXYTOCIN

IV oxytocin with General Anesthesia.; Sever hypotensione

With Hydrocarbon inhalation anesthesia:(Cyclopropan, Halothen,Enfluran &Isoflurin):Hypotension & Maternal Sinus BradycardiaHalothane,Enfluran Decrease oxytocic effect

Caudal block with vasoconstritcorsPotentiate the effect of prophylactic Vasoprerssors ---> severe hypertension even rupture of cerbral blood vessels

Excessive Saline :Water intoxication Maternal &Fetal convulsionsExcessive 5% dextrose ?? Neonatal hyperbilirubenemia

Pg E2 & Pg E1 : Additive effect

Non S. Anti inflammatory: Opposing

OXYTOCIN

METHERGIN* With general anesthetic:Potentiate vasoconstriction

*Halothane >1% : Opposes oxytocic effect -->Postpartum hemorrhage

*Sympathomimetics:

Hypertension & Headaches (additive)

*Paradoxically Hypertension with: Spinal and Epidural anesthesia B blockers

PROSTAGLANDINSPROSTAGLANDINS

Prostaglandin E1(Misoprostol=Cytotic) The same as in Pg E 2 PgE 1 + Mag. Antacid --> Diarrhea

ProstaglandinF2a May potentiate effect of vasopressorsMgSO4 : the effect of Pf 2 markedly

PgE2 PgE1 &P f 2 with methergin : of Bp.

All Prostaglandins are potentiated with concomitant oxytocin. Combination my be used therapeutically

INTRAVENOUS ADDITIVESINTRAVENOUS ADDITIVES

Guidelines:*Drugs should only be added when constant plasma concentrations are needed .

*In general one drug compatible should be added

*Drugs should not be added to blood products, substitutes, manitol or sodium bicarbonate

*Label : Name, drug and date.

Continuos or intermittent drug infusion?

Continuos or intermittent drug infusion?

Intermittent infusion :It is used if the drug is unstable

or incompatible over infusion period .

In 50: 200cmm over 30 - 60 minutes

Continuous in dextrose 5 % or saline

Calcium gluconate - Digoxine Naloxone - Magansium sulfate

Diazepam (Valium) or insulin in ( glass container)

Oxytocin in Dextrose: ?Hyperbilirubinemia

Methyl dopa (Aldomet)

Continuous in dextrose 5 %

Terbutaline (Bricanyl) - Ritordine (Yutopar)

Pg E 2

Intermittent in dextrose 5 % or saline

PenicillinsAztronate (Azactam)-Gentamycin -Tubramycin

Labetalol(Trandate) - Ranitidine(Zantac)

Ceftrixone (Cefobid) Not with calcium - Ceftazidime (Fortum)

Continuos or intermittent infusion

Cephradine (Velosef)

Cimetidine(Tagamet)

Metocolpramide(Primperan)

Atropine sulfate - Prostigmine - Adrenaline - Noradrenaline

II-LABOR & OBSTETRIC

DISORDERS

II-LABOR & OBSTETRIC

DISORDERS

PRETERM LABOR & PROM

PREECLAMPSIA & ECLAMPSIA

PRETERM LABOR & PROMPRETERM LABOR & PROM

*Clucocorticoids*Phenobarbital*Vitamin K1(Konakion)*Antibiotics

*Clucocorticoids*Phenobarbital*Vitamin K1(Konakion)*Antibiotics

*TOCOLYTICS1-Beta Adreneregic Agents2- Magnesium Sulfate3-Calcium Channel Blockers4- Antiprostaglandines

Ritodrine(yutopar) - Terbutaline (Bricanyl) Salbutamol(Ventolin) Ritodrine is the most effective tocolytic (Selective B2 agonist ) Pulse+ BP Rennin & Hyperglycemia

B adrenergics

--G.Anesth., Pethidine,or MgSO4:Arrhythmia& hypotension

-Atropine :Increase B.P.

-B Blockers :Decrease tocolytic effect.

-Asthmatic patients under B.Adrenergics:Tachyphlaxis(drug resistance)

-Diabetic patients : Insulin Antagonist( insulin requirement)

Ritodrine (yutopar)Interactions

Corticosteroids or MgSO4 : Pulmonary edema

Nifedipine (Adalat, Epilat)•Inhibits the influx of Ca ions into

. myometrial cells

•Excellent for hypertensives .

•Can be used for: • Diabetics,• M.valve prolapse

• Mild arrhythmia.

Calcium channel Blockers

*Neuromuscular blockade with MgSO4 (live threatining)

*Severe hypotension with:

Barbiuturat, B Blockers and with Fenanyl

Anesthesia

Calcium channel Blockers

Nifedipine (Adalat, Epilat) Cont.

*Low dose of both Nifidipen& B adrenergics (Epilate+Yutopar):

better uterine relaxation and fewer side effect

Calcium Gluconate or Chloride

*May antagonize the effect of calcium channel blockers

*Precipitate sever arrhythmia for patient taking digitalis

*Opposes the neuromuscular depression of magnesium sulfate

Nonsteroidal Anti inflammatory drugs(NSADs)

Nonsteroidal Anti inflammatory drugs(NSADs)

Indomethacin(Indocid) - Diclofenac(Voltaren,Olfen),Ibuprofen(Brufen) the safest during pregnancyNaproxin(Naprosyn),&Piroxicam(Felden) The last 3 can be used during lactation .

Indication: Antiinflammatory,Tocolysis.

Interactions :Increase effect of Digoxin,Aminoglycosides&antiepileptics Decreased effect by:Prostaglandins,Diuretics&B blockers

The effect of Oxytoctics especially Prostaglandins(PP.Hg)

Magnesium Sulfate(used when there is contraindication to Ritodrine

ActionAnticonvulsant Peripheral effect decreases Acetyl Choline at myoneural junction or direct effect at the muscle Central ? CNS depression

Tocolytic: Altering calcium uptake(Little effect if cervix>2cm)

Has Antiarrhythmic and coronary protector(Suitable for heart abnormalities )But with cautions of over load in valvular diseases.

Has Antiarrhythmic and coronary protector(Suitable for heart abnormalities )But with cautions of over load in valvular diseases.

Incompatibilities Calcium, Bicarbonates Clindamycine, Hydrocortisone & Salicylates

Infusion in Dextrose (Preeclampsia)& Saline (Tocolytics)

Magnesium Sulfate

Corticosteroids or yutopar : Pulmonary edema

InteractionsCalcium gluconate: AntagonistCNS depressant drugs : PotentiationDigitalis: Heart blockNifedipine: Potentiate Hypotension &neuro muscular block

Beta Adreneregics: Pulmonary edemaCorticosteroid : Pulmonary edemaPF2 (Enzaprost):Oppose its effect in postpartum hemorrhage

Neuromuscular blockers: Potentiation & delay recovery.

Magnesium Sulfate

2 Cardiac arrest at CS for preterm labor:First:Mgso4+ Thiopental +Supine hypocavel2 nd : Mgso4 + Methergin

Magnesium Sulfate

Interactions : Case reports. Interactions : Case reports.

Patient under corticosteroid

Obstetric disorders Preterm Labor Antiphospholipid and HELLP syndromes

Associated disorders

Allergic ( eg. Asthma) Hematologic disease ITP, Collagen disease (eg. SLE), Shock states, Arthritis

Ephedrine--> Increase metabolic clearance->less effect

Hepatic enzyme inducing agents(e.g..phenytoin,Baribturates,Carbamazepine,&Rifampicin--> Increase clearance->less effectDigitalis ---> Arrhythmia (due to hypokalemia)

CORTICOSTEROIDSCORTICOSTEROIDS

Nondepolarizing neuromuscular bloking agent--> Enhancing (due to hypokalemia) BUT Pancuronium(Pavulon) is inhibited (unknown)

Insulin-->More insulin dose

NSAIDS ( e.g. endomethacine): Potentiation of antirhumatic effect &GIT ulceration

Ritodrine (Yutopar)or MgSO4---> Pulmonary edema

BarbiturateBarbiturate

Enhance metabolism ( effect) of :Corticosteroids,Digitalis& ,Metronidazol

Digoxin,Phenothiazines,Tricyclic antidepressant

Enhance metabolism ( effect) of :Corticosteroids,Digitalis& ,Metronidazol

Digoxin,Phenothiazines,Tricyclic antidepressant

Hypotension with Calcium Channel BlockersHypotension with Calcium Channel Blockers

Induce microsomal enzymes leading to: Induce microsomal enzymes leading to:

Anticonvulsive : Mg SO4

PREECLAMPSIA & ECLAMPSIA

Antihypertensive drugs

Hydralzine (Aprisoline)

Labetalol (Beta & Alpha blockers)(Trandate)

Calcium Channel blockers(Adalat)

Drugs decreasing cardiac outputB.blockors: Nonselective : Propranolol(Inderal)B1 selective-No bronchospasm :Atenolol(Tenormin)Prazosin : blocking(Minipress)->in Resistant cases

Antihypertensive drugs used in chronic hypertension

Centrally acting Methyldopa(Aldomet)

Diuretics Thiazids in intravascular volume expansion

HYDRALZINE(Aprisoline)

*Drug of choice for acute control of sever pregnancy induced hypertension

*May be used with Methyldopa or B blocker for chronic hypertension.

*NSAID(eg Indomethacine):Reduce antihypertensive effect

*Additive hypotensive effect with : Aldomet

Labetalol(Trandate)Labetalol(Trandate)

A combined Alpha & Beta adrenergic blocker for control of severe pregnancy induced hypertensionIt may be used with thiazide for chronic hypertension.

Additive hypotensive effect and Bradycardia with (Reserpine)

Tremor with Tricyclic antidepressant.

Cimetidine decreases the effect of trandate.

A combined Alpha & Beta adrenergic blocker for control of severe pregnancy induced hypertensionIt may be used with thiazide for chronic hypertension.

Additive hypotensive effect and Bradycardia with (Reserpine)

Tremor with Tricyclic antidepressant.

Cimetidine decreases the effect of trandate.

Methyldopa (Aldomet)Methyldopa (Aldomet)

*Drug of choice for essential hypertension

*Additive hypotensive effect with: Hydralzine ,Beta adrenergic blockers&General anesthetics.

*Reduced hypotensive effect with:Tricyclic Antidepressent,Barbiturate&Sympathomymetics

NSAIDs(eg Indomethacine):Reduce its antihypertensive effect.

Ephedrine is less effective when used with aldometMOA inhibitoers: (Parnate) Hyperexcitability and sever hypertension .

Propnanolol(Inderal)Propnanolol(Inderal)

. Effect by:Cimetidine,Largactil&Hydralzin(Enzymeinheritors), Effect by:Phenytin,&barbirurates Effect of: Theophylline&Xylocaine

. Effect by:Cimetidine,Largactil&Hydralzin(Enzymeinheritors), Effect by:Phenytin,&barbirurates Effect of: Theophylline&Xylocaine

Additive Toxicity: Methergin: Sever Hypertension Requirement of InsulinNifedipen:Myocardial depression

Additive Toxicity: Methergin: Sever Hypertension Requirement of InsulinNifedipen:Myocardial depression

Heparin

Aspirin

Antidepressent

Insulin

Adrenaline

Antihestaminics

Theophyllines

Heparin

Aspirin

Antidepressent

Insulin

Adrenaline

Antihestaminics

Theophyllines

III- DRUGS USED IN

COMMON MEDICAL DISORDERS.

HEPARINHEPARIN

Potentiated by Platelet aggregation inhibitors as: Dextran, NSIDs, CarbencillinAspirin,Cephoperozon”Cefobid”&, Valproic acid“Depakene”

ASPIRINASPIRIN

*Decreased effect by Corticosteroid( metabolism).

* Requirement of Vit.K * Requirement of Heparin*Platelet aggregation inhibitors as: Dextran,, Carbencillin,Cephoperozon”Cefobid”&, Valproic acid“Depakene”

They potentiate bleeding tendency* Effec of NSIDs

*Decreased effect by Corticosteroid( metabolism).

* Requirement of Vit.K * Requirement of Heparin*Platelet aggregation inhibitors as: Dextran,, Carbencillin,Cephoperozon”Cefobid”&, Valproic acid“Depakene”

They potentiate bleeding tendency* Effec of NSIDs

*Low dose Aspirin is used for prophlaxis against DVT , Antiphosplipid syndrome,prevention of Pre eclampsia

Tricyclics

Impiramine(Tofranil) - Amitriptyline(Tryptazol)

*Potentiate the action of:CNS depressant D.Anticholinergics, Antihistamines,oral anticoagulant,Antithyroids&Phenothiazine

Tricyclics

Impiramine(Tofranil) - Amitriptyline(Tryptazol)

*Potentiate the action of:CNS depressant D.Anticholinergics, Antihistamines,oral anticoagulant,Antithyroids&Phenothiazine

AntidepressantsAntidepressants

Monoamine Oxidase inhibitors (MAO)

*Tranylcypromine(Parnate)Hypertensive crises with Pethidine or aldomet , metabolism of B Adrenergi

INSULININSULIN

*Hyperglycemic agents: Corticosteroid,ACTH,Diuretics,Epinephrine,&Thyroid hormone: ( Decrease the dose)

*Hypoglycemic agents : NSAIDs,B.blockers &Labetalol:(Increase the dose)

*Hyperglycemic agents: Corticosteroid,ACTH,Diuretics,Epinephrine,&Thyroid hormone: ( Decrease the dose)

*Hypoglycemic agents : NSAIDs,B.blockers &Labetalol:(Increase the dose)

*Increases toxicity of Antidepressent

*Beta Blockers: the pressor and bronchodilator effect

*Hydralazine : Reduced Pressor effect of adrenaline* Prolongs the effect of Local anesthetic agents

*Increases toxicity of Antidepressent

*Beta Blockers: the pressor and bronchodilator effect

*Hydralazine : Reduced Pressor effect of adrenaline* Prolongs the effect of Local anesthetic agents

AdrenalineAdrenaline

AntihistaminicsAntihistaminics

Ca channel blockers or Phenothiazine: Increase Risk of arrhythmia with Astemizol(Hismanal)but not with Loratidine (Claritine)

*Chlorophenramine,Dimethenedine(Fenistil):

Pheneramin (Avil) Celimestin(Tavegyl),

Nonsedative selective H1 antagonist Astemizol (Hismanal) & Loratidine (Claritine)

Potentiate anticholinergics & CNS depressants

Effect By:-

1-Liver enzymes inducers as:

Rifampicin,Barbiturates,Carbamazepin(Tegratol)

Phenytoin(Epanutin)

2-Antagonism: Diazepam&Metoclopramide

Effect By:

1-Liver enzymes inhibitors asCemitidine,Corticosteroid,Ertromycine,Proplanolol

2-Additive:Ephedrine ,Ketamine&Halothen.

Effect By:

1-Liver enzymes inhibitors asCemitidine,Corticosteroid,Ertromycine,Proplanolol

2-Additive:Ephedrine ,Ketamine&Halothen.

THEOPHYLLINE

Thank You

Thank You