1. ACUTE SELF-POISONINGS BY VERAPAMIL
B.Pavlovski, J.Pavlovska, T. Panovska, C.Bozinovska, N.Popovski, N. Becarovski, L.Meloska, Z. Pereska
Clinic of Toxicology and Urgent Internal Medicine and Institute of Cardiology. Clinical Center. Skopje. R. Macedonia

2. CALCIUM ANTAGONISTS:
VERAPAMIL (PROTECTIVE NAME), ISOPTIN. LECOPTIN,VERAPAMILUM, VERANORM),
NIFEDIPIN
DILTIAZEM
AMLODIPIN
NICARDIPIN
NITRENDIPIN

3. PHARMACODYNAMIC PROPERTIES
VERAPAMIL IS A PHENYLALKYLAMINE DERIVATIVE WHICH ANTAGONISES CALCIUM INFLUX THROUGH THE SLOW CHANNELS OF VASCULAR SMOOTH MUSCLE AND CARDIAC CELL MEMBRANES.
BY REDUCING INTRACELLULAR FREE CALCIUM CONCENTRATIONS, VERAPAMIL CAUSES CORONARY AND PERIPHERAL VASODILATATION AND DEPRESS MYOCARDIAL CONTRACTILITY AND ELECTRICAL ACTIVITY IN THE ATRIOVENTRICULAR AND SINOATRIAL NODES

4. PHARMACOKINETIC PROPERTIES ON CALCIUM ANTAGONISTS
Bioavailability p.binding.p T/2 renal elimination
VERAPAMIL hours %
DILTIAZEM
NIFEDIPIN
AMLODIPIN
EFFECT AFTER min.
PHARMACOLOGICAL RESPONSE ON DEPURATION
TECHNICS

5. CLINICAL PHARMACOLOGY ON CALCIUM ANTAGONISTS------TOXICOLOGICAL VIEW PHARMACODYNAMIC MECHANISM AND CONSEQUENCES ON MYOCARDIUM, CONDUCTION SYSTEM AND BLOOD VESSELS
DECREASE: 1.CONTRACTILITY
2. AV-CONDUCTION
3. TONUS OF BLOOD VESSELS
BRADYCARDIA, BLOCKS, HYPOTENSION, HYPOXIA, SHOCK, DYSMETABOLIC CHANGE
PHARMACOLOGICAL RESPONSE:
INCREASE: 1. CONTRACTILITY

6. THE AIM OF THIS STUDY WAS TO EVALUATE THE THERAPEUTIC APPROACH BY VERAPAMIL POISONINGS, ALONE AND COMBINED WITH THE OTHER DRUGS

7. MATERIAL AND METHOD:
We have observed thirty eight patients acutely intoxicated by Verapamil of both sexes,(29 women and 9 men). The mean age of this group was years.
Other drugs also were ingested by twenty five patients.
(Antibiotics, Benzodiazepines, Vitamins and Beta-Blockers in one case. The dose ingested ranged between 10 t0 40 tablets(800mgr to 3,2gr).All patients have treated in the Inensive
Care Unit

8. THERAPEUTIC PROCEDURES:
Drug removal by gastric lavage and administration of charcoal was the mainstay of the therapy in the firsts hours since ingestion.AV-blocks, I- II- grades, have treated with Atropin and Orciprenalin.The treatment of cardiogenic shock included artificial ventilation, several vasopresors, Dopamin, inotropic agents, plazma expanders and temporary pacemacer at one case(intoxicated by Verapamil and Atenolol). Calcium Gluconatum as antidote was given to every patients.
Othervise, vigorous fluid resuscitation, cardiac pacing and control of acid-base status and electrolytes measurements provided the basic of the therapy.

9. CLINICAL PICTURES:
GASTRIC SYNDROME
CARDIOVASCULARE SYNDROME
CEREBRAL SYNDROME
DISMETABOLIC SYNDROME
CARDIAC DYSRHYTHMIAS:
LOW GRADE- SINUS BRADICARDIAS
MILD GRADE- HYPOTENSION, AV- BLOCKS I AND II- GRADES
HARD GRADE- BRADYARHYTHMIAS, SHOCK

10. TIME AFTER ARRIVAL BP HR
Ecg h
120/8o /7o 90/ o/ /7o
o o
NSR AVB AVB AVB AVB I

11. TIME AFTER ADMISSION(h)
3, , , , ,o
6,o ,o , ,o ,0
Three hours after a,patients were hypokalemic and hyperglycemic. N K
Gly

12. ALL PATIENTS DEVELOPED CARDIAC CONDUCTION ABNORMALITIES AND BECOME HYPOTENSIVE. BLOOD PRESSURE WAS ON AVERAGE < 90/60 mmHg. HEART RATE ON AVERAGE < 50+-5,
PROLONGED PQ INTERVAL HAD 22 PATIENTS, AV- BLOCKS II- GRADES HAD 13 PATIENTS AND TOTAL AV-BLOCKS HAD 3 PATIENTS.

13. RESULTS AND CONCLUSIONS:
IN DESPITE OF INTENSIVE THERAPY , SEVERAL VASOPRESSORS, INOTROPIC AGENTS, NOOTROPIC DRUGS, Calcium Gluconatum, Glucagon, implantations of cardiac pacemacer, one patient died of hypotension and cardiac conduction total AV-block, 24 hours after overdose.The other patients recovered without deficit and were discharged from the Intensive Care Unit three days later.