Pharma sheet # 33 - Zaina Ayman

Antihypertensive Drugs
From now till the end of this semester, we are going to talk about a new group of drugs: Cardiovascular drugs.
Cardiovascular medications are used as a means to control or to prevent certain forms of heart disease. Many people with advanced heart disease may take several of these drugs. This means that we have to be aware of any drug-drug interactions.
Cardiovascular diseases are very common in our society as well as the world. The incidence of hypertension in the US –for people over 50 years of age- is around 50%. The incidence of people –over 55 years- to develop hypertension is 90%, which is a very high percentage! These statistics are of great importance; they show that there's a high possibility for us to be dealing with a patient whose hypertensive and he's not aware of it!
Being in a dental clinic –for some people- is a stressful situation, and being in such situation could trigger a response which would unmask a hidden hypertension or angina. One major reason for this is the increase of adrenaline level in the blood that leads to increase the in the blood pressure.
Antihypertensive agents are used for the treatment of hypertension. It's a very large category, around 8 groups. They are all drugs B because we don’t prescribe any of them but with Atenolol as an exception since we prescribe it sometimes.
Hypertension is divided to:
A. Sustained systemic blood pressure [of greater than 140mmHg]
B. Sustained diastolic blood pressure [of greater than 90 mmHg].
Memorize these numbers because you should not deal with a patient whose blood pressure is more than 180/110 mmHg [cutoff point = red line]. Never do any sort of dental procedure for such patients; because you are dealing with the idea of heart arrest, arrhythmias.
Always take your patients history! That’s the only way you would know about his hypertension [Ask him about his medications]. Remember that you are dealing with people from different backgrounds and knowledge levels so it's better if you know these drugs very well. Notice signs on your patient, if he told you that he suffers from recurrent headaches, suspect hypertension!
We have different stages of hypertension: [Pre-hypertension, Stage1 & Stage2]
• Less than 120/80 or 115/80 mmHg = normal
• 140/90 = Pre-hypertension
• Once the diastolic increases over 90 = the patient is hypertensive = stage1
• Once the diastolic reaches 100 = stage2. Also called: uncontrolled hypertension.
In our community out of every 100 hypertensive patient, only 30 of them is stage1= controlled hypertension and the rest are uncontrolled hypertensive patients. Why? Because most hypertensive patients are 60+ years old and they don’t have any sort of compliance! They take the drug one day then miss it the next 2 days! Hypertension is known as the silent killer , as it shows little or no symptoms, and that's why patients underestimate this illness .

Advise: take your patients vital signs! Your patient might not know that he has hypertension OR he knows but he's not taking his medications the way they should be taken! It's a common problem with people. You as a dentist should be prepared for whatever situations.
The dr. read slide 4 =)
A little physiology ;)
1. Sympathetic and parasympathetic systems are what control blood pressure [how much you lose or reserve water]. Their baroreceptors are found on the heart, some vessels and coronary arteries. This is also called moment to moment control.
2. Another way to control blood pressure is the kidneys [long term control] = Angiotensin- Aldosteron- Renin system.
By manipulating 1 or 2 we can change the pressure[decrease or increase it].
The good thing about sym and parasym systems is that they're for emergencies. For instance, a patient has hypotension; I give him epinephrine or dopamine as vasopressor. Notice that I don’t give him a drug that causes Na retention or water retention! Why? Because these drugs need a lot of time to affect the pressure!!!
Moment to Moment Control Drugs.
As we all know Angiotensinogen is converted to anginotensin by the action of Renin.
• At the level of Anginotensin
A drug called Aliskiren prevents anginotensin from becoming angeotensin1 by inhibiting the Renin.
• At the level of Angiotensin1
A group of drugs targets angiotensin1 since Angiotensin Converting Enzyme converts it to angiotensin2 [as we all know angiotensin2 is the most potent vasopressor/ vasoconstrictor in the body] and by blocking this mechanism we can achieve vasodilatation that lowers the blood pressure. Medications to be used are ACEis [like Captopril, Anapril, Ramipril..].. this group of drugs act by inhibiting the Angiotensin Converting Enzyme.
Notice: ACEis [-pril group]
• At the level of angiotensin2 [-tan group]
In order for the Angiotensin2 to function, it has to bind to a receptor called the angiotensin receptors. Angiotensin2 receptor antagonists [ Losartan and eprosartan] work by antagonizing the activation of angiotensin receptors.

Diuretics [-zide group]
A diuretic is any drug that elevates the rate of urination and this way it increases the excretion of water from the body thus lowering the volume of the plasma = lowers the blood pressure.
Most famous diuretic is Thiazide.
Beta blockers. [-lols group]
Although they are more of a sympathatic / parasympathatic regulation mechanism, they also affect renin functions [inhibition of renin].
They affect the beta receptors on the heart as we all know.
Alpha Agonists
Such as Methyldopa, Clonidine and Cocaine. These drugs are centrally acting medications, meaning that they lower blood pressure by stimulating alpha-receptors in the brain which open peripheral arteries easing blood flow.
Alpha Antagonists
Work at the level of sympathatic system which is responsible for contraction of the vessels walls. We use Alpha blocking agents [-sin group] like Doxazosin, Prazosin and Terazosin. Another advantage of alpha blockers is that they may be useful for some men with symptoms of prostate diseases like prostate hyperplasia.
At the level of peripheral sympathatic nerve terminals, we interfere with the production of adrenaline and nor-adrenaline by drugs like Reserpine which causes depletion of nor-adrenaline in the neurons of the blood vessels thus controlling heart rate, force of cardiac contraction and peripheral resistance
The last group is vasodilators that act directly on the smooth muscle of arteries to relax their walls so blood can move more easily through them. Drugs like Hydralazine & Sodium nitroprusside.
They've got nothing to do with alpha or beta receptors. They just act on the nitrogen oxide which affects the production of ATP and dilatation of the vessels.
Newly diagnosed patients' first line therapy is diuretics and beta blockers. These patients are usually stage1 or primary hypertensive patients.
Patients on diuretics only as well as patients on beta blockers only [monotherapy] are –kind of- safe patients to deal with; these patients are usually in stage1 and their blood pressure is controlled. If the patient in on more than one drug it means he's in stage2.
As a rule… each antihypertensive drug on its own lowers the blood pressure by 10 to 15%. So if the blood pressure was 140 n we wanted to lower it till 120-125 we'd give him a monotherapy. If the blood pressure was 160, its not enough to lower it only 15%, he'd be still in stage1! We have to reduce it below stage1! That’s when a combination therapy is needed.
Diuretics are currently recommended as the first line therapy for hypertension unless there are convincing reasons to chose another agent. Advantage: low dose is safe and effective in preventing stroke, MI and congestive heart failure. The most important drugs are Thiazide and Chlorathiazide. Concerning the disadvantages, Thiazide –just like all antihypertensive drugs- cause orthostatic hypotension, they just differ in the severity. Thiazide causes a very mild orthostatic hypotension comparing to alpha1 blockers which cause pooling of the blood [first dose syncope], and that’s its advantage over the rest of drugs. It still does cause a little bit though!!
It also causes xerostomia -just like all antihypertensive drugs- but again they differ in the level of severity. Patients who are under a combined therapy for hypertension and angina [diuretics and beta blockers] for example suffer from severe thirst because of xerostomia.
All antihypertensive drugs cause fatigue since they affect the sympathatic system in a direct or indirect way!
Diuretics' Hyperuricemia results from drug-drug interaction at the level of elimination. Uric acid of our body competes with diuretics on the same site of elimination. Usually diuretics win and uric acid stays in the body causing Gouts disease. Patients complain of a swollen toe or a painful joint as a result of the accumulation of uric acid in that joint.

Loop diuretics.
The only case these drugs are prescribed is if the patient has hypertension PLUS renal failure [Furosemides].
Thiazide doesn’t work with patients with renal failure, so we use loop diuretics. Whenever you see a patient whose being treated with loop diuretics [which means he has renal failure] automatically you would have to change the dose of whatever drug you're giving him [ usually you lower the dose, coz almost all our drugs are excreted through the kidneys] OR pick a drug that’s excreted in the bile.
Adverse effects:
• IRREVERSIBLE ototoxicity when used with Aminoglycosides like Gentamicin. Gentamicin is widely used coz it's the only one effective on gram –ve bacteria.
Never give gentamicin for more than one week coz it causes renal failure!
• Lichenoid drug reactions are skin eruptions [allergic reactions] that occur after ingestion, contact, or inhalation of certain chemicals, with the most common inducers being Beta blockers, Thiazide diuretics and Furosemide [loop diuretics]. Most affected areas are the lower lip and the lower limbs. This happens with almost 80% of patients.
Revision:
Diuretics.. 2 types :
1- Thiazides: A type for all patients except renal failure patients..
• Cause a mild orthostatic hypotension with elderly.
2- Furosemides: A very potent drug.
• Causes severe orthostatic hypotension! Why? Because it manipulates sodium to control water retention and blood pressure.
• Used for renal failure patients.
• If a patient is scheduled for a long treatment, tell him to postpone his diuretic pill till after the procedure since it causes more frequent urination.
• Never prescribe this drug with Gentamicin.
Beta blockers
• Block beta receptors on the heart and reduce the cardiac output [negative inotropic conotropic activity]
• 2 types: selective and nonselective.

Adverse effects:
• Never give it for asthmatic patients , certain types of heart failure patients.
• Never give nonselective beta blockers with epinephrine = hypertension episode.
• Orthostatic hypotension, xerostomia, drowsiness = all associated with beta blockers
• Sudden drug withdrawal may cause rebound hypertension as a result of up regulation of beta blockers. Explanation: when a patients' beta receptors are blocked by Atenolol, his body reacts by increasing the number of receptors and increase in the receptors affinity to the drug. Once the patient stops the drug, and you give him epinephrine [vasopressor] beseer fe hojom 3ala el receptors min el drug o beser 3endo hypertensive episodes and increase in heart rate.
48.56 seconds =) The End.. Sorry for any un-intentional mistakes and as usual corrections are welcomed!
Done By: Zaina Ayman.
Sunday 19th/dec/2010.

# 33