pharma sheet # 38 - Shatha Al-s3odi

بسم الله الرحمن الرحيم
Pharma sheet no. 38.
Main subjects of this lecture:
• Digoxin; interactions ,adverse effects,…
• Spironolactone; mechanism of action, interaction with other drugs,….
• Arrhythmia .
• Hyperlipidemia(cholestremia).

Digoxin :
# the main drug that has interactions with dentistry .
 The best oral inotropic agent exist.
 Ginen by i.v. ;has a rapid onset of action.
 Disadvantage : intoxication is frequently precipitated by depletion of serum k+ due to diuretic therapy.
# potassium\k+ plays a major role within digoxin mechanism of action ; Y3ni,if k+ level changed the patient will be susceptible to arrhythmia, & that interferes with digoxin action (as it's used) for treatment of heart problems .
So, k+ should be always controlled (prevent occurrence of Hypokalemia).
** Lethal injection ; contains k+ (in high conc.) & thiopental.
If we give a patient high concentration of k+ , he will develops arrhythmia and cardiac arrest.
When the patient is susceptible to hypokalemia???
 when he take drugs that cause it & they are:
1. Thiazide.
2. Furosamide
Both(diuretics) causes hypokalemia , but ACE inhibitors causes hyperkalemia.
Patients taking ACE inhibitors are more susceptible to cardiac arrhythmia[bcoz of hyperkalemia] \they don’t interfere with digoxin, but in general; thiazide & furosamide patients have more incidence to develop arrhythmia (due to their interactions with digoxin ).
Digoxin ; adverse effects:
• Anorexia,
• Nausea & vomiting,
• Diarrhea
• Vision change (it’s aland mark for digoxin), in this case the patient will see yellow or red dots, epseciallly yellow dots.
Ex. When old patient[mainly above 65yrs] cones to ur clinic & you prescribe to him one of the Digital Digoxin Interaction drugs (erythromycin or tetracycline ) as prophylactic, he develop vision changes (yellow dots) => that give you a hint ,that this patient is taking digoxin ,even if he doesn't tell you.
 if patient with heart failure(valve stenosis or infection leads to Endocarditis) comes to ur clinic and you have to prescribe an antibiotic for him (the most common one is Penecillin),& unfortunately the patient may have sensitivity toward it , you give instead of that Macrolide {erythromycin or tetracycline}.
That's why you should be very very careful when giving such drugs.
Imp. Note: Macrolides causes digoxin toxicity.
Digoxin interactions :
Quinidine, Varapamil, Amiodarone => can cause digoxin intoxication , by competing with digoxin on it's binding sites.
But mainly dentists will not prescribe these drugs, bcoz they are of more concerne about macrolides.
Benzodiazepines(diazepam , itraconazole) & NSAIDs (Ibuprofen, Indomethacin)=> Itraconazole ; very imp drug for dental practice. Given mostly to old & young patient (have weak immunity) who suffers from candidiasis[thrush]. Considered as Drug of choice in that case.
Diazepam may increase digoxin level.
Remember : NSAIDs will elevate blood pressure –doesn't interfer with digoxin directly – rather than that; it will make deactivation for the antihypertensive agents causing hypertension & that worsen the heart failure.
The solution is to use Acetaminophine always instead of any other previous drug , esp. with eldrly & young patients.
Spironolactone
Drug of choice for patients who have interactions between digoxin & the other 2 types of diuretics(thiazides & furosamide).
Note: the main side effect of diuretics is Electrolyte disturbances, the most common one is potassium(k+).
Spironolactone ;
considered as k+ sparing diuretic , one of the drugs that reserve k+ levels in the body.
very imp drug in life.
Acts on collecting duct(i.e. in the last collective duct in the nephron reabsorption of Na+ & k+ occur).
So, in case of toxicity by [thiazides & furosamide] with digoxin….. we give the patient spironolactone .
Interaction of spironolactone:
Have interaction with endocrine system[causes endocrine abnormalities],,, considered as direct antagonist of aldosterone causes deactivation for the receptors that aldosterone should bind to.
Main side effect :
CNS effect ,confusion.
Endocrine disturbances.
Gastric disturbances, like peptic ulcer.
The last group of drugs for treating heart failure, β-adrenergic agonist ;
1. Amrinone : new drug ,doesn't have interactions with dentistry.
Used in short term therapy ,when patients are not responding (in case of heart failure drugs included digoxin).

Arrhythmia:
very critical when you deal with it .
Now, hypertension patient ;you will see him every day ,so recommendations should be always in your mind . Patients with blood pressure above 80/110 don't deal with them , bcoz they are susceptible to develop Hypertensive attack & also you can't give them vasopressor(vasoconstrictor) with lidocaine (local anesthesia).
In case of angina you have to take a really good history from the patient (i.e. prepare nitroglycerine in case of sudden attack ), you may test him by asking him to go up the stairs.
Heart failure,,, the patient is also susceptible to develop sudden attack, he may have hypoventilation, pulmonary edema (remember that ; these manifestations you might make them by leaving the patient lying on his back for long period. )
Arrhythmia is defined as ; either the HEART IS BEATINNG TOO SLOWLY [Bradycardia], OR the HEART BEATING TOO RAPIDLY[Tachycardia].
But in general , arrhythmia is known tachycardia, from the slides[Simple dysfunction cause abnormalities in impulse formation & conduction in the myocardium].
Arrhythmia occurs in different sites,
Atrium(atrial fibrillation ) ; more easy or somehow safe.
Ventricle(ventricular arrhythmia ); dangerous , the patient would reach death level ,bcoz the main pump in the body is the left ventricle. The most common & complex problem we face is Superventricular Tachycardia.
In normal situation the masseges are from:
1. SA node.
2. AV node.
3. Perkinji fibers.
The main causes of arrhythmia :
Either SA node send a lot of msgs to AV node.
SA node msgs doesn't reach to AV node.
Responding to impulses originating from sites other than the SA node. [Abnormal Automaticity].
Abnormalities in impulse conduction [Re-entry]
Automaticity ; the cardiac cell can produce action potential by itself , y3ni without receiving msgs from any where , this idea is related very well with atrial fibrillation… what happened is any delay in conducting the impulses , the respond by producing it's own action potential ,but after a while the SA node will produce an action potential . So, that will result in 2 sources of action potential.
Re-entry ; normally, impulse conduction from the pacemaker centers , divided then move regular way .
If there is any error in the conducting circle ,the result is called REENTRY .
Explanation; in the way (of impulse conducting) there is disable cells , which doesn't conduct impulses properly …stopping the pulse circle leading to reentry from the same direction Making arrhythmia.









Arrhythmia & Drugs
 Most of the arrhythmic drugs suppress automaticity by blocking either sodium or calcium channels to reduce the ratio of these ions to potassium.
 Thus result in a reduction in the depolarization or diastolic & raises the threshold of discharge to a less negative voltage .
 These drugs prevent reentry by slowing conduction or increasing the refractory period.
Anti-arrhythmic drugs classified into 4 groups, class I, II, III ,IV. There's another classification, class 1a, 1b, 1c, & 2, 3, 4.
Class I : Membrane Stabilizing agents & fast Na+ channel blockers Quinidine, Procainamide, Disopyramide, Lidocaine.
Class II : β-adrenergic blocking agents e.g. propranolol.
Class III : drugs prolong repolarization in phase 3 Amiodarone, Defetilide, Adinosine.
Class IV : calcium channel blockers Varapamil & Diltiazim.
Class I : 1) Quinidine
One of the most old drugs. Depends on joining with Na+ channels , inhibition Na+ & Ca++ entry… So, slower rapid depolarization.
The End result , is Prolonging the refractory period ((Elongation of QT interval)) , by that we give the chance for normal entry to take place .
Removing Reentry.
Decreases the impulses that are coming from sources other than SA node[reduces automaticity].
When taking it over long period of time , causes problems bcoz of the anti-cholinergic effect …. Causes reduces salivation production & secretion [Xerostomia] which will lead to candiditis with periodontal disease .
2) Disopyramide : xerostomia
3)Procainamide : very common use, taken orally , makes taste disorders.
4)Lidocaine : Metallic taste ,
The only one that doesn't make QT interval elongation, have anti-arrhythmic effect on heart.
Not used orally , only by injections (only in hospitals), given in high doses in order to decrease arrhythmia .
## Also phynetoin [antiepiliptic] can be used, but not very much.
All of them cause QT interval elongation( except Lidocaine).
Don't give them with Erythromycin, Moxafluxacin, anti-depressant drugs… bcoz they all cause QT interval elongation . So, the idea is to prevent the duplication of that effect.
Class II : β-blockers (propranolol)
Depresses automaticity & decrease heart rate & cotractability.
Useful in treating tachycardia .
Class III: QT interval elongation drugs ; prolonging QT interval for repolarization activity & interfere with k+ more than Na+[and that's the main difference btwn class I&III]
Amiodarone : blocks Na+, k+, Ca++ but mainly k+, increase QT interval & refractory period… Makes abnormal salivation and taste.
Defetilide : the same as amiodarone except that it doesn't have interferences with dentistry.
Adinosine: don't make QT interval elongation . mainly used in hospitals.
Nowadays, it's the drug of choice for treating Acute Super ventricular Tachycardia.
Class IV: calcium channel blockers.(varapamil & diltiazim)
Acts on heart rate , negative inotropic activity . They slow conduction & prolonging the refractory periods.
Don't give these 2 drugs together ,bcoz they both cause –ve inotropic effect ,Varapamil is stronger than diltiazim, you can give diltiazim with β-blockers but NEVER give it with varapamil.
Dental Implication
 Drugs that in group 1 & 3 prolong QT interval which trigger Torsades de point , which is lethal ventricular tachycardia / in normal cases of taking these drugs torsade de point don't occur , but it will occur bcoz of wrong or sever taking of them .
 If patient is taking quinidine, never give him antibiotics [erythromycin or moxifloxacin -drug used for respiratory infections - ] bcoz these drugs together cause QT interval elongation.
 About Epinephrine , anti-cholinergic drugs and any other drug that has excitatory influences on the heart should be used with caution in patients who present with a history of any cardiac arrhythmia.
 Recommendations about epinephrine use are not clear ,but you should be cautious.
If you have to give them vasopressor (epinephrine),it shouldn't exceed the dose 1:100,000.
Group 2 & 4: doesn't any effect on QT interval.
 Amiodarone: (orally), inhibits lidocaine metabolism which increases lidocaine toxicity has occurred during surgical procesures using this anesthetic.
It would be wise to reduce maximum doses of any amide local anesthetic(lidocaine/infiltration injection) to half those normally permitted when treating patients with amiodarone .
Articaine, would appear safer alternative (for patients who take amiodarone) due to rapid hydrolysis of its ester side chain. It prolong the paresthetic effect .
By that we had finished the main subjects of heart problems….. and we are going to talk about , new subject which is :
Hyperlipidemia
Also called hypercholetremia or hypertriglyceremia …
Its defined as high cholesterol levels in the body. We should control choles. Levels , bcoz any increase will lead to CVDs & Ischemic diseases , which is the most common causes of death in the world & of cours in Jordan also(particularly; ischemic diseases).
Life_style problem ; why we develop ischemic diseases , atherosclerosis , or hypercholetremia??????
Ans: Bcoz there is something what we call , Risk Factor.
That means ; some patients are more susceptible to develop the previous disease more than others , bcoz of the presence of risk factor (which is a genetic factor).
»» If someone have genetic factor with bad life style he will develop that diseases 100% , risk factor with good life style will not develop diseases … en sha2 allah.
Risk factor with controlled drug treatment is a good solution .
But , put in mind that ischemic diseases would occur even without the existence of risk factor .
The solution is :
1) don't eat foods containing a lot of fat.
2) Do exercises.
3) If we have to do smthng else, we can give drugs called STATINS.
Statins exist in almost all jordainian homes although its very expensive, include : lipostate, lapetore, atropistatin, simvistatin.
Mechanism of action , works on HMG-CoA reductase enzyme, this enzyme is responsible for cholesterol synthesis in the body. 1 gm is produced and 0.4 gm is burned/consumed daily , excess of cholesterol used in building up mechanisms in the body such as DNA .
120 mg/dl the normal level of cholesterol in the body.(you have to memorize this no.)
1] The main idea from all that , we want to decrease cholesterol production , by making inhibition for the rate limiting step… which is HMG-CoA enzyme.
These drugs are , Simvistatin , Pravastatin.
2] another idea , give drugs that binds to lipids in the GI tract, we could call it inhibition for lipid absorption from the GI tract. Such drug is Ezitimibe [the most newly one].
3] Bile acid sequestrants ; absorb bile acids , so by that when we remove bile acids from the body we are removing lipids.
4] Fibrates: inhibition of lipolysis in the body , by that decreasing triglycerides from going into the blood .
5] Vitamin B3 (ayasi /nyasin ) reduce triglycerides with totally cholesterol level.
Increase billiary secretion of cholesterol but not bile acids, not widely used.
## patients taking statins are susceptible to develop Myopathy (mascular pain ) esp. knee and thigh areas … very common .
Tetracycline preparations will be poorly absorped in patients taking bile acid sequestrants.
Fenofibrates : makes dry mouth & tooth disorders .
»» Sorry for any mistakes…..
Done by: Shatha Al-s3odi 