Pharma sheet # 34 - Leen Kutachi

Hypertension
Last lecture we started with hypertension and we said that there are two type of agents B-Blockers and diuretics so any person is diagnosed with newly hypertensive patient prescribe him thiazide (which is always the first line therapy) and sometimes we may prescribe B-Blockers as the first line therapy but almost always thiazide is the 1st line therapy (so B-blocker Comes in the 2nd choice. why ?bcs they have less activity so less hemosasis).

last lecture we finished B-Blockers
Stage 1 hypertension we give them thiazide
Stage 2 combination (in addition to thiazide or B-Blockers if the patient use to take it + (any of these three agent)
ACEI , Angiotensin II-receptor antagonist ,Ca –channel blockers or alpha1 blockers.
Alpha1 has a relation with men 50% of men over 55 have prostate hyperplasia this hyperplasia is combined with hypertension so we give 1 agent for two things at the same time, so in women these alpha 1 drugs prazosin , doxazosin are rarely used but in men it is wide spread bcs less side effect as it’s one drug for 2 things
Slide 19
Important note:
All antihypertensive agent ( except ca channel blockers) are affected by NSAIDS (aspirin, diclofenac , bruffen … )
So any of these NSAIDS is opposing the action of antihypertensive drugs except calcium channel blockers actually there is an effect but very little So you can see in the table the lead to decrease antihypertensive effect.
Actually that happens in chronic use of NSAIDS so after 5-7 days the effect will appear
Remember that Indomethasine (imp not written in the slide) is the most potent NSAIDS so it’s effect on antihypertensive agent is the most.
So if we give diuretics plus bruffen or indomethasine,indomethasine has higher ability to reduce the effect of the diuretics than bruffen.
And the least one is low dose aspirin (not high dose) and sulindac which is like diclogesic but it has lower activity towards the prostaglandins
When you give the patient NSAIDS it inhibits prostaglandin – mediated vasodilation and promote salt and water retention remember chronic use of NSAIDS cause renal failure and that is the reason bcz it affects the blood supply towards the kidney
So prostaglandin makes vasodilation and when you inhibit the prostaglandin ( by using the NSAIDS) you Increase the pressure bcs of the increase in the water and salts.

Q) Why normal people (without hypertension ) are not affected by the NSAIDS ?
Actually their pressure increase too .but it is not manifested ( 5-10!)
The doc. Read the first paragraph of slide 21
So although the drug we give doesn’t increase the pressure of the patient but when the patient is taking antihypertensive drug the effect appears(his pressure increases)
So there is difference between synergisim (with antagonist) and additive activity
Dr. read : elderly patients and those with heart failure may be more sensitive to the effects of NSAIDS on their antihypertensive or diuretics therapy so the reverse activity will be higher than normal people .
Back to the table slide 19
Diuretics with barbiturates makes orthostatic hypotention (NOT HYPERTENTION) bcs barbiturates makes depression to the activity of CNS
Important note;β-blockers inhibit metabolism of amides in local anesthesia (amides are lidocaine ,atracaine ,……………)
This might not manifested but when you give large amount of local anesthetic this makes arrhythmias ,hypotention bcs of building up of amides this has relation of cyp450 ( reduction of metabolism of amides)
β – blockers ( the non selective )with bronchodilator might decrease response of the bronchodilator this will affect beta 2 blocking so asthma patient might have manifestation but that is not imp in our work bcs we neither prescribe B-blockers nor a bronchodilator
table 20
diuretics make dry mouth and lichenoid reactioin more with furosemide than thiazide
β - blockers gives little lichenoid reaction but important in dry mouth and makes some taste changes but less than ACE INHIBITORS which makes aloss in taste ( most imp)
ACE Inhibitors
Very widely used almost all patients above 60 years take ACEI bcs it is the drug of choice in heart failure, very nice agent to patient suffering from diabetes + hypertention ( a lot in Jordan) so it is found alot in our life.
This group is the (………pril) : Enalapril (most used) ,Lisinopril, Captopril (which is the oldest and the prototype ),Ramipril (the newest.
ACEI its inhibit the conversion of angiotensin I to angiotensin II Which has two effects
1. Vasoconstriction so vasodilation occurs with ACEI
2. Aldosterone selection so –ve with ACEI
so by this you make inhibition to vasoconstriction and inhibition to sodium and water retention

3.and ACEI causes bradykinin building up

imp : Bradykinin the most potent vasodilator in the body so ACEI doesn’t work only on angiotensin cascade.

But also makes building up for bradykinin ( so reduce hypertension) vasodilation.
Bradykinin building up has bad effect although it has a good effect bcs { in 10% or more it makes
1. Dry cough so patient who take ACEI have dry cough(V.IMP) }
2. Angioedema is an allergic rxn which makes swelling in the area around the neck affect the breathing.

ACEI dental related side effects (IMP)
1. Glossitis (inflammation of the tongue)
2. Loss of taste
3. Oral ulceration (stevess Johnson syndrome)and it related to enalapril and captopril
4. Lichenoid rxn And xerostomia
5. Angioedema
6. First dose syncope bcs ACEI reduce sympathetic output.
(b-blockers (atenolol)is easy to deal with bcs less first dose syncope incidence)
Angiotensin II receptors antagonists
Ends with (sartan) losartan ,cadesartan widely used
They have the same side effects as ACEI except the effect of bradykinin so the incidence of dry cough angioedema is reduced. (low incidence )
(glossitis ,first dose syncope are reduced too bcs not very strong vasodilation)

Note:NSAIDS reverse the activity of ACEI and ARB (angiotensinII receptor blockers)

Here the Dr. was relating to a table but its not found in our H .OUT 20??
In systemic antifungal (not local) drugs if you give the patient anticandida and it didn’t heal we give the patient systemic antifungal ( either orally or injection)
Such as flucanazole ,etracanazole they increase the level of of losartan so increase antihypertension activity bcs they inhibit losartan metabolisim.

Sedative like valium( you are giving the patient some sort of hypotention but not noticed one ) so when the patient takes antihypertension drugs its effect is increased


Calcium channel blockers
We use it If the previous agent didn’t work
3 types : (scientific name not included)
1. Varapamil nonselective
2. Deltiazem nonselecive
3. Nifedipine selective no activity toward the heart
MOA:they all make vasodilation
(imp)L-type calcium channels are found in the heart so it makes vasodilation and negative inotropic activity ,only 1+2(nonselective)make that.

Dr.read paragraph 2 slide 31

Varapamil
Related to dentestry(a)
-gives –ve inotropic activity,so don’t gie these patients B-blockers bcs it makes –ve inotropic activit so transient heart failure occurs bcs it blocks the movement from SA node to AV node (both drugs)
But varapamil is taken by patient who has arrhythmia (so varapamil means arrhythmia patients)
Bcs it is the only drug from CCB prescribed for arrhythmias (hypertension+arrhythmia) if hypertension alone this drug is not prescribed.


Diltiazem
Called Adalat
Same idea, but the effect on heart is less than varapamil and it can be used with B-blockers although it has –ve inotropic activity but bcs it is less extensive

The third class of these drugs is (dihydropydidines) (the dr. said not to memorize the chemical names) and they include:
-Nifedipine(1st generation)
-Amelodipine(not amlodipine),felodipine,isradipine,narcridine, nisoldipine(2nd generation)

-No –ve inotropic activity
-no activity towards the heart
-main activity towards the vessels
-drugs used in hypertension without arrhythmias

*CCB are prescribed after the usage of diuretics, b-blockers and it is not right to prescribe them at first.

Nifedipine(the most CCB) in gingival hyperplasia(side effect) that we saw in phenytoin too.
Amolodipine might cause that too but rarely and the others don’t cause.
SO,it is said that CCB cause gingival hyperplasia (all of them) but the most is nifedipine (the cheapest) and the least is the 2nd generation ,but they all do.
(that what exactly the doc. Said but it seems contradict to the point before??)

Other ide effects:
-xerostomia
-orthostatic hypotension
-dizziness
-fatigue is related with patients that takes CCB for the first time for the first 2 months.
-constibation
-light headedness

*CCB is not affected by NSADS ,but in drugs leaflet it is written that it is affected .actually v.v.little effect thy only write that to protect the company.

*varapamil and diltiazem make CYP3A4 inhibtion
(dr. read last para. Slide 48 and ti is only related to diltiazem and varapamil ,remember that midazolam (syrup) prescribed to children and children usually don’t have heart problems.


*Clarithromycin,Erthromycin (macrolides)interact with verapamil and diltiazem causing cardiac toxicity related to prolonged QTintervals (bradycardia)
So it cause bradycardia and atrioventricular blocks
*Tricyclic antidepressants are related to QT intervals too. So don’t prescribe them erythromycin .

Back to the table:
1.CCB (eg. Paramile)with benzodiazepine increase sedation activity bcs of the metabolism of metazolam and triazolam .

2.CCB with asprine by increasing antihypertensive effect of CCB related with varapamil ,diltiazem more than nifedipine and amilodipine.

3.CCB with NSAIDS decrease antihypertensive agent but as we said his is a neglectable effect.

CCB is for calcium channels blockers


DONE BY:Leen Kutachi
Date of lec:mon,20/12

# 34