Pharmacology – Exam 5
For notes on Hematology and Osteoporosis Drugs from DDS2005 click here.
Three main reasons for therapeutically intervening in the hemostatic mechanism:
1> to inhibit blood coagulation (use of anticoagulants)
2> to stimulate lysis of a thrombus (us
3> e
of thrombolytics, or fibrinolytic)
à
in certain surgical procedures (hip joint replacement, coronary bypass) in
which whole blood comes into contact with foreign materials, a thrombus may be
formed
4> to inhibit platelet function (use of antiplatelets)
Hematology Definitions
|
Anticoagulant |
Any agent that prevents, suppresses, delays or nullifies the activation of the blood coagulation cascade |
|
Antiplatelet |
Any agent that acts selectively on the platelet to inhibit platelet aggregation and formation of a platelet thrombus (white-thrombus) |
|
Antithrombotic |
Any agent that prevents formation of an intravascular thrombus |
|
Thrombus |
Aggregation of blood factors (mostly platelets and fibrin) with entrapment of cellular elements causing vascular obstruction |
|
Embolism |
Sudden blocking of an artery by a blood clot of foreign material which arrives to its site of lodgment by blood flow |
|
Hemostatic Agent |
An agent that arrests the flow of blood; either through physiological properties such as vasoconstriction and coagulation or by mechanical means (pressure packs, sutures) |
|
Hemorrhage |
Escape of blood from a blood vessel Petechiae à very small Purpura à up to 1 cm Ecchymoses à larger Types of
Hemorrhage: Major à intracranial or overt bleeding Associated with > 5g /dL decrease in blood Hb concentration Minor à associated with 3-5g /dL decrease in Hb concentration Oozing à less serious Associated with < 2g /dL decrease in Hb concentration Considered insignificant |
|
Hematoma |
Accumulation of blood within tissue |
|
Fibrinolytic |
Induces fibrinolysis by enzyme action Involves dissolution or inactivation of fibrinogen in the blood |
|
Type of Drug |
Example (Brand Name) |
Notes |
|
Common Anticoagulants (Tx of arterial
thrombosis, atrial fibrillation, cardiomyopathy, cerebral emboli, hip surgery, vascular
prosthesis, heart valve disease, venous thromboembolism) |
Warfarin (Coumadin) |
Administered |
|
Heparin (generics) |
Administered IV or SC |
|
|
Low Molecular Weight Heparin (Laminox) |
|
|
|
Bishydroxycoumarin (Dicoumarol) |
Administered |
|
|
Factor Xa inhibitors |
|
|
|
Thrombolytics (acute myocardial infarction, deep vein thrombosis, pulmonary
embolism) |
Tissue Plasminogen Activator (Activase) |
Also known as TPA Administered IV |
|
Streptokinase (Streptase) |
Administered IV or IC |
|
|
Warfarin Antidotes |
Vitamin K (Menadione) |
Administered IV or Action is on the liver |
|
Phenytonadione (Aquamephyton or Mephyton) |
||
|
Heparin Antidotes |
Promatine Sulfate (generics) |
Administered IV (very slowly) |
|
Local Hemostatics |
Epinephrine (Adrenalin) |
|
|
Absorbable gelatin foam packs (Gelfoam) |
|
|
|
Oxidized cellulose (Oxycel) |
|
|
|
Oxidized regenerated cellulose (Nu-Knit) |
|
|
|
Collagen hemostat (Avitene, Collacote, Collatape, Collaplug) |
|
|
|
Thrombin (sterile) |
|
|
|
Astringents |
Aluminum Chloride (Hemodent), aluminum sulfate (Gelcord), ferric sulfate (Hemodent-S) |
|
|
Antifibrinolytics |
Aminocaproic acid (Amacar) |
For emergency use Usually after blood transfusion Not routine in dental surgery |
|
Tranexamic acid |
Mouth rinse |
Alternative targets for anticoagulant therapy within the common pathway of the clotting cascade include:
Concurrent platelet aggregation and clot formation
Damage to vessels exposes collagen
Exposed collagen initiates platelet aggregation
Exposed collagen activates factor XII (Hageman factor)
Factor XII activates a series of factors leading to the activation of Thrombin
Platelet aggregation also upregulates the activation of Thrombin through the release of PF3 (platelet phospholipid)
Thrombin upregulates platelet aggregation
Thrombin also initiates the formation of a fibrin meshwork
Platelet aggregation is inhibited at normal endothelial (vessel) surface by prostacyclin
Platelet aggregation is activated by exposed collagen
The aggregation process is continued through positive feedback loops
|
ADP |
Released by platelets Enhances ability to stick to forming aggregation |
Therapeutically blocked by Plavix class of drugs |
|
Thromboxane A2 |
Released by platelets Enhances ability to stick to forming aggregation Enhances release of ADP |
Action is blocked by aspirin |
Actions of Thrombin
1. conversion of fibrinogen to fibrin
2. activation of Factor XIII (stabilizes fibrin meshwork)
3. enhances its own activation from prothrombin
4. enhances platelet aggregation
Role of Hageman Factor (factor XII)
1. through a cascade activates the formation of a clot
2. through a different cascade activates plasmin (which slowly brings about the dissolution of the clot)
Therapeutic role of TPA or Tissue Plasminogen Activators (also known as clot busters)
à these enhance the activation of plasmin, thus helping to break down clots
à intended for unwanted clots, but TPA is non-selective
à can be very dangerous, causing excess bleeding
Therapeutic overview of platelet aggregation inhibition
|
Aspirin |
Cerebrovascular accident, stroke After coronary artery by-pass surgery Restenosis after angioplasty or thrombolysis Myocardial infarction Transient ischemic attack |
|
Dipyridamole Ticlopidine Clopidogrel (Plavix) |
Cerebrovascular accident, stroke |
Topical Hemostatic Adjuncts Used To Manage Bleeding
|
Type |
Brand Name |
|
Absorbable Gelatin |
Gelfoam |
|
Oxidized Cellulose |
Surgicel |
|
Microfibrillar Bovine Collagen |
Avitene |
|
Topical Thrombin Preparations |
|
|
Antifibrinolytics |
Amicar |
Astringents Used to Manage Bleeding
|
Type |
Brand Name |
|
Ferric Sulfate (used in clinic) |
Astringedent Hemodent-S |
|
Aluminum Chloride |
Hemodent |
|
Aluminum Potassium Sulfate |
|
|
Aluminum Sulfate |
Gel-Cord |
Vasoconstrictors Used to Manage Bleeding à Epinephrine (Adrenalin)
Local Methods to
Prevent or Control Bleeding
*cold water rinse
*local pressure (by biting on gauze or tea bags)
*site packing (using hemostatic agents listed above)
*additional suturing
*electrocautery
*topical thrombin powder
*new research shows that potato starch (applied directly to wound) reduces bleeding time by up to five minutes
*tranexamic acid mouth rinse, 5% (antifibrinolytic)
*amino caproic acid mouth rinse, 5% (antifibrinolytic)
à for mouth rinses, hold 10 mL liquid in mouth 30 min prior to surgery for 2 min, then repeat q2h (every two hours) for 6-10 doses. May be continued prn.
Avoid Additional Bleeding Risks for 24 Hours
*hot liquids
*mouth washes
*hard foods
*NSAIDS and antiplatelet agents
Ibuprofen has a transient effect on COX-1
Aspirin irreversibly inhibits COX-1
Cardiovascular Safety
of Dental Hemostatic Agents
*Epi-impregnated pellets (Racellet) and 20% ferric sulfate (Viscostat) showed adequate bleeding control with no change in BP or pulse rate from pre-op values
*Racellet showed better hemostasis
Hemostatic Pellets
|
Brand Name |
Type |
Notes |
|
Epidri |
Cotton pellets w/ epinephrine |
1.9 mg epi/pellet for local hemostasis activated by tissue moisture |
|
Racellet |
Cotton pellets w/ reduced epinephrine |
1.15 mg OR 0.55 mg /pellet local hemostasis control light bleeding and seepage along gingival margins |
|
Rastringent |
Cotton pellets w/ aluminum sulfate |
Local hemostasis |
Fibrin-Thrombin Adhesives
*Most common adhesive method in use today
*uses body’s natural glue
*usually two solutions are mixed
*similar to final stage clotting (activation of fibrin mesh by thrombin)
*generally collected from pooled plasma of donors
*autologous donation is preferred as it eliminates viral contamination
*adhesive strength is not as high
*may generate antibodies or thrombin inhibitors
Reduction in Vascular Events in Conjunction with Antiplatelet Therapy Following a Myocardial Infarction
|
Vascular Event |
Short-Term Therapy |
Long-Term Therapy |
|
Nonfatal reinfarction |
~50% |
~31% |
|
Nonfatal stroke |
~46% |
~40% |
|
Death from vascular disease |
~23% |
~15% |
|
Any vascular incident |
~28% |
~25% |
Rationale for Antiplatelet Therapy
1. Prevents platelet activation
2. Decreases platelet aggregation
3. Inhibits thromboxane A2 synthesis
4. Prevents release of other platelet products that promote atherogenesis
1 and 2 refer to prevention of a thrombus formation
3 is accomplished directly by aspirin
Use of Aspirin in primary prevention is recommended for
(1) men over 40
(2) postmenopausal women
(3) pts. with risk factors such as diabetes, HTN, smoking, or family history of CVD
Antiplatelet Drugs
|
Drug |
Action |
Notes |
|
Low Dose Aspirin 81-325 mg/day Ecotrin, Bayer |
Irreversible inhibition of COX-1 |
*Taken orally *Contraindicated in pts with ASA or other NSAID hypersensitivity *No á in benefit w/ higher dose *â GI bleeding w/ lower dose *Celebrex, Vextra, Vioxx affect COX-2 w/ no affect on COX-1 or platelets *It takes approximately 8 days for blood thromboxane levels to return to normal after ingestion of aspirin *Chewing aspirin hastens the antiplatelet effect |
|
Ticlopidine Ticlid |
Blocks APD induced aggregation and platelet release reactions (blocks ADP receptor on platelet) |
*Taken orally *Originally to â risk of thrombotic stroke * Irreversible effect for life of platelet *á risk of agranulocytosis (0/8%) *Banned in |
|
Clopidogrel Plavix |
Inhibits binding of ADP to platelet membrane receptor |
*Chemically related to ticlopidine *Irreversible effect *Used in preventing stroke, MI, and peripheral vascular thrombosis *Associated with a lower risk of agranulocytosis |
|
Dipyridamole |
Platelet PDE inhibitor |
*á intracellular cAMP *â platelet aggregation *Approved in combination w/ low dose ASA à Aggrenox *25 mg aspirin combined with 200 mg dipyridamole |
|
Tirofiban Aggrastat |
Non-peptide agonist of GP IIb/IIIa platelet receptor (this receptor is involved in binding of fibrinogen
causing platelet aggregation) |
*Platelet aggregation inhibition is reversible upon stopping drug *Indicated in unstable angina and acute coronary syndromes * I.V. only |
Halfprin
Should low-dose aspirin therapy be stopped prior to oral surgery? à No
¨ Patients stopping therapy 7 days prior averaged a bleeding time of 1.8 minutes
¨ Patients remaining on therapy averaged a bleeding time of 3.1 minutes
¨ Although the time difference is nearly 2X, both averages are well within the normal range
¨ No problem with uncontrolled bleeding was observed, and normal hemostasis procedures were sufficient for both types of patients
Low-dose Aspirin Interaction with Ibuprofen
Plavix
¨ Known as Clopidogrel
¨ Inhibits ADP-induced platelet aggregation
¨ Acts directly to inhibit ADP binding to its receptor
¨ This action prevents subsequent activation of the GPIIb/IIIa complex
¨ Therapeutic value in inhibiting platelets reduces the number of cardiovascular events (because platelets participate in the initiation and/or evolution of these events)
¨ Similar to aspirin in efficacy, with â risk of agranulocytosis (compared to Ticlid)
Ticlopidine (Ticlid)
GP IIb/IIIa Receptor Blockers
¨ Given only by injection (I.V. only)
¨ Used to prevent platelet thrombotic events during percutaneous coronary intervention (angioplasty, stents, etc.)
¨ Act to block the receptor on the platelet surface (which is the common final pathway of aggregation and thrombi formation)
¨ Reversibly bind to platelets with short half-lives
¨ Usually combined with aspirin and anticoagulants
¨ Very effective in acute situations
¨ Examples include à Abciximab (ReoPro), Eptifbatide (Integrelin), Tirofiban (Aggrastat)
Dental Aspects of
Managing Patients on Antiplatelet Drugs
1>
Is the patient taking aspirin (ASA)?
If soà
what is the dose? Frequency? Was it Rx? Evidence of bleeding problems?
2> Is
the patient taking Plavix or Aggrenox?
If soà
why was it Rx? ASA also? Taken regularly? Evidence of bleeding problems?
3> Unless the pts Hx indicates they are medically compromised, there is no need to get a medical consult prior to dental procedures
4> In
the case of a medical consult where the M.D. indicates the pt should stop
antiplatelet use
Have the M.D. advise the pt and take responsibility (document this in pt chart)
5> Normal hemostatic agents may be used to control local procedure induced bleeding/oozing
6> Avoid prescribing NSAIDs (Coxibs are OK) since the NSAIDs may accentuate the effects of the antiplatelet agent
7> Pts
may be taking ASA for non-cardiovascular reasons (arthritis, migraines, etc.)
the dose is typically many times higher than the antiplatelet regimen
these pts will show the same increase in bleeding times as with low-dose ASA
Hematological
Drugs III
Heparin
Warfarin (and other coumadin derivatives)
¨ May be taken orally
¨
Block the reduction of vitamin K to its active
form
thus inhibits the synthesis of
liver factors II, VII, IX, and X
¨ Vitamin K aids in the conversion of certain glutamate residues to GLA residues in the liver
¨
Certain Vitamin K dependant proteins begin to
disappear
Prothrombin takes 2-3 days to
disappear
¨ Takes at least 2 days to take effect and then lasts about 2-10 days
¨ 99% bound to albumin
¨ Anti-warfarin therapy includes administering inactive vitamin K (Menadione) which is then activated in the liver, or infusion of fresh plasma
¨ Has a lower therapeutic index in elderly pts, those with a Hx of GI bleeding, and those with poor nutritional status
When treating with Heparin/Warfarin/Coumadin the target INR is in the range of 2.0 to 3.0
à the target INR range is 3.0 to 3.5 when anticardiolipin antibody is present
Four Determinants of the INR response to
Warning Signs and Symptoms of Bleeding Associated with Warfarin Therapy
|
Epistaxis |
Prolonged or extensive nose bleeding |
|
GI Bleeding |
Dark or black stools (melena) Abdominal pain or vomiting “coffee grounds” (hematemesis) |
|
Gingival Bleeding |
Prolonged oozing from gums |
|
Hematoma |
Soft tissue swelling and bruising |
|
Hematuria |
Dark brown (tea-colored) or bloody urine |
|
Hemoptysis |
Coughing blood (often from posterior epistaxis) |
|
Hemorrhoidal Bleeding |
Bright red rectal bleeding (hematochezia) |
|
Intraarticular Bleeding |
Acute joint pain and swelling |
|
Intracranial Bleeding |
Symptoms of acute stroke |
|
Menorrhagia |
Prolonged, excessive vaginal bleeding |
|
Hemorrhagic Ovarian Cyst |
Sudden severe abdominal pain, usually at mid-cycle |
|
Subconjunctival Bleeding |
Bloody red eye without pain or loss of vision |
|
Retroperitoneal Bleeding |
Severe flank pain from internal bleeding |
Warfarin Safety
Questions
1. When was your last INR determination, and what was the value?
2. What is the color, shape and strength of tablets? Has the dose changed?
3. Are you eating poorly? Have there been any changes in your diet?
4. Have you started/stopped any other meds or herbal remedies?
5. Have you been acutely sick or noticed a change in any chronic illness?
6. Have you developed any bleeding or changes in the color of your stools or urine?
7. Are you planning to have any surgery, dental surgery or other invasive procedures? Have you had any injury or hard fall?
Warfarin Drug Interactions (by class)
**Warfarin alone or in combination with ASA
àsuperior to ASA alone in reducing the incidence of composite events after an acute MI
àBUT, was associated with a high risk of bleeding
**If a patient is taking Warfarin (anticoagulant therapy) should they concurrently use an NSAID?
Studies show a 13 fold increase in the risk of GI bleeding in pts taking both
Therefore, DO NOT take NSAIDs while on anticoagulant therapy
**Warfarin interacts with the following drugs to cause an increase in PT
Amiodarone, Cimetidine
Ciprofloxacin,
Erythromycin, Fluconazole, Ketoconazole,
Trimethoprim/Sulfa
Isoniazid, Levostatin, Metronidazole
**Warfarin interacts with the following drugs to cause a decrease in PT
Phenobarbital, Rifampin
**Should warfarin be discontinued or dose reduced before dental procedures involving anticipated bleeding?
|
Benefits to Dentist |
Decreased bleeding during procedure Less post-operative bleeding |
|
Risks to Patient |
Increased risk of thrombus formation with catastrophic results à stroke, MI, pulmonary embolism, death |
|
|
Risk of localized bleeding is increased in pts on warfarin Dentist should obtain a medical consult |
In regard to the above question, an article in JADA (November 2003) states the following:
¨ Scientific literature does not support routine discontinuation of oral anticoagulant therapy for dental patients
¨ Dental therapy for pts w/ medical conditions requiring anticoagulant therapy must provide for potential excess bleeding
¨ However, routine discontinuation of these drugs prior to dental care can place these pts at unnecessary medical risk
¨ INR must be evaluated before invasive dental procedures are performed
¨ Any reduction/discontinuation of anticoagulant therapy must be in collaboration with the pts physician (medical consult)
Ischemic and Hemorrhagic Stroke Incidence Related to INR
à At LOW INR, the incidence of Ischemic Stroke increases
à At HIGH INR, the incidence of Hemorrhagic Stroke increases
Considerations for
Dental Patients Taking Warfarin
¨ Ascertain the pts INR (the value should be current; <1 week)
¨ Carefully describe expected dental procedures on medical consult to ensure accuracy of consult
¨ Never tell the patient to discontinue their warfarin. If indicated, have the pts physician determine INR, instruct pt, and assume responsibility
¨ Use appropriate hemostatic agents to control prolonged or excessive local bleeding for pts currently on warfarin
¨ Many pts are taking antiplatelet drugs (ASA) in conjunction with warfarin. Again, do not tell the pt to discontinue aspirin
¨ Do not initiate drug therapy for pts on warfarin unless there is certainty of no interaction
Notes on INR
|
Prothrombin Time (PT) |
A laboratory diagnostic screening test for: * identifying acquired or inherited deficiencies of the activities of fibrinogen, prothrombin, and factors V, VII, and X involved in blood coagulation *monitoring oral anticoagulant therapy |
|
Thromboplastin |
A source of tissue factor * Typically derived from brain, lung, placenta * Responsiveness of thromboplastin varies * â responsive thromboplastin yields a smaller increase in PT as compared to more responsive thromboplastin * Standards for thromboplastin are managed by the WHO |
|
International Sensitivity Index (ISI) |
* Measure of responsiveness to a given thromboplastin compared to the WHO standard * The lower the ISI, the more responsive the thromboplastin * Typical values in
* Scandanavian ISI values are around 1.0 to 1.1 (nearly identical to the WHO standard) |
|
Prothrombin Time Ratio |
* The first step in correcting for thromboplastin variability * The pts PT is compared to a mean reference PT * A typical mean
reference PT is around 11 seconds (may range from |
|
International Normalized Ratio (INR) |
* A derived value determined by using the PT ratio and the ISI according to the equation INR = [PT ratio]ISI * Allows comparison of PT values worldwide * A normal, healthy individual will have an INR = 1.0 * Increase in INR relates to an increase in bleeding (i.e., decrease in coagulation) * Most anticoagulation therapy has a target INR of 2.0 to 3.0 * Intense therapy may target INR at 3.0 to 4.5 |
Summary of INR Values
Major Drugs
|
Class |
Target |
Mechanism |
Result |
Examples |
|
b-adrenergic antagonists (beta-blockers) generally avoided in pts with asthma, reactive
airway disease, or 2nd or 3rd degree heart block |
Heart |
â force and rate of cardiac contraction |
â cardiac output |
b1
and/or b2 Propanolol Nadolol Pindolol Timolol Labetolol Carteolol Penbutalol b1
selective Atenolol Metoprolol Acebutolol betaxolol |
|
Kidney |
â blood volume |
â cardiac output |
||
|
Brain |
â sympathetic outflow |
â cardiac output â total peripheral resistance |
||
|
a-adrenergic agonists (centrally acting sympatholytics) |
Brain |
â sympathetic outflow |
â cardiac output â total peripheral resistance (act at basal motor center in brain stem w/ á negative effects) |
Clonidine (patch) Guanabenz Methyldopa Guanfacine |
|
Sympathetic nerve ending blockers (norepi depleters) |
|
|
|
Guanethidine Guanadrel (Reserpine is obsolete) |
|
Peripheral a-adrenergic receptor antagonists |
Heart |
â force and rate of cardiac contraction |
â cardiac output |
Prazosin Terazosin Doxazosin |
|
Smooth muscle |
Relax vascular smooth musle |
â total peripheral resistance |
||
|
Induces vasodilation May result in orthostatic hypotension |
||||
|
Direct vasodilators |
Smooth muscle |
Relax vascular smooth musle |
â total peripheral resistance |
Hydralazine Minoxidil (hair growth) |
|
Pts may have intense reflex tachycardia May be on a b-blocker to prevent this |
||||
|
ACE inhibitors Prevent conversion of angiotensin I to angiotensin
II Contraindicated in pregnant women or those likely to
become pregnant Should not be used in pts w/ history of angioedema |
Kidney |
â blood volume |
â cardiac output |
Captopril Enalapril Lisinopril |
|
Smooth muscle |
Relax vascular smooth musle |
â total peripheral resistance |
||
|
Angiotensin receptor
antagonist |
* Block the angiotensin receptors on blood vessels * Many pts do not respond to this class * Contraindicated in pregnant women or those likely to become pregnant |
Losartan |
||
|
Diruetics |
Kidney |
â blood volume |
â cardiac output |
Benazepril Fosinopril Quinapril Ramipril |
|
Synergistic with other agents Enhances Na excretion and H2O loss â plasma volume |
||||
|
Thiazide class â BP, â stroke, â MI tendency to á blood sugar, thus not indicated for diabetics (ACEI is a better choice here as it provides some protection for the kidneys) |
||||
Metropolol is the most commonly prescribed cardioselective beta-blocker
Hypertension (HTN)
Risk of CVD Associated with HTN
¨
Approx. 50 million people in the
¨ BP relationship to CVD risk is continuous
¨ Each increment of 20/10 mmHg in BP doubles the risk of CVD
¨ Prehypertension (>120/80) signals the need for á education to reduce BP
Benefits of Lowering BP
¨ â Stroke incidence by 35-40%
¨ â Myocardial Infarction incidence by 20-25%
¨ â Heart Failure incidence by 50%
Classification of HTN and Management
|
Classification |
Systolic |
Diastolic |
Lifestyle Modification |
Therapeutic Management |
|
|
<120 and < 80 |
Encourage |
None indicated |
|
|
Prehypertension |
120-139 or 80-89 |
Yes |
None indicated |
|
|
Stage 1 |
140-159 or 90-99 |
Yes |
Thyazide-type diuretics for most Maybe ACE inhibitor, Angiotensin Receptor Blocker (ARB), beta-blocker, Ca-channel blocker, or combo |
|
|
Stage 2 |
≥ 160 or ≥ 100 |
Yes |
Two drug combo for most (usually thiazide-type diuretic and one of the others listed above) |
|
*NOTE à if the pt has compelling indications (e.g., Heart failure, post-MI, high coronary disease risk, diabetes, chronic kidney disease, or recurrent stroke prevention) other antihypertensive drugs may be considered, and then the use of those listed above as needed. In these cases ACE inhibitors are the most common class of antihypertensives that are prescribed.
Measuring BP
¨
Different measurements will be recorded for the same
person depending on position (standing, sitting, lying)
à
if measured while standing the BP will read lower
¨
Orthostatic, or Postural, Hypotension is a
decrease in standing BP >10 mmHg
à
associated with dizziness/fainting
à
more frequent in pts with diabetes, those taking diuretics, those on
ventilators, or on certain psychotropic drugs
à
BP should be measured in an upright position
à
Avoid volume depletion and excessively rapid dose titration of drugs
¨
Two readings, 5 minutes apart and sitting is
common method
à
if elevated, measurement on the other arm is indicated
¨
An increase in BP is sometimes associated with
phobia/anxiety à
“white coat” HTN
à
Normally a 10-20% decrease in BP while sleeping for the anxious pt
à
if this drop is not observed, it may indicate increased risk for CVD
¨
Pt should self-monitor
à
provides information on response to therapy, and evaluation of “white coat” HTN
Identifiable Causes of HTN
¨ Sleep Apnea
¨
Drug induced or related causes
à
pseudoephedrine (a decongestant) is a powerful sympathomimetic and causes á BP
¨ Chronic kidney disease
¨ Primary aldosteronism
¨ Renovascular disease
¨ Chronic steroid therapy and Cushing’s syndrome
¨
Pheochromocytoma
à
a tumor of the adrenal medulla
à
causes á
blood levels of epinephrine
¨
Coarctation of the
aorta
à
constriction of the aorta that can cause á BP in upper
extremities and â
BP in lower extremities as well as á strain on the heart
¨ Thyroid or parathyroid disease
Lifestyle Modifications
|
Modification |
Approx. BP Reduction, mmHg |
|
Weight Reduction |
5-20 per 10 kg weight loss |
|
Low-cal, Low-lipid diet |
8-14 |
|
â dietary Na |
2-8 |
|
Physical activity |
4-9 |
|
Moderate alcohol consumption |
2-4 |
Diuretics
¨
The most common are the benzothiadiazides (or thiazides)
à
pt will be taking hydrochlorothiazide
à
hydrochlorothiazide is short acting with a long record of benefit; #1 choice
¨
Others include Amiloride,
Bumetanide, Chlorthalidone,
Furosemide, Indapamide, Metolazone, Spirolactone, and Triameterene
à
chlorthalidone (thiazide
class) is the #2 choice, and is longer acting
à
furosemide (loop
diuretic), or Lasix
has a very quick onset of action and an increased risk of hypokalemia
(excess K+ loss) with chronic use
¨
Avoid concurrent use of NSAIDs
à
can inhibit the diuretic and antihypertensive effect, particularly thiazides
and loop diuretics
Therapeutic Overview
|
Goal |
To á excretion of salt and water to treat several diseases and conditions |
|
Thiazide Diuretics Hydrochlorothiazide |
* Action is on the distal convoluted tubule * Promote Na+/H2O loss * Also have associated K+ loss * Tx of HTN, mild CHF * Also for renal calculi, nephrogenic diabetes insipidus, chronic renal failure (as an adjunct to loop diuretics), and osteoporosis * All have sulfa moiety à pts with sulfa allergy should not use thiazides * Tendency to á blood sugar, thus not indicated for diabetics * Other metabolic disturbances include á uric acid levels * Should be used cautiously in gout or a history of significant hyponatremia |
|
Furosemide (Lasix) |
* Acts on thick ascending limb of Loop of Henle * Associated K+ loss * Tx of HTN (in pts w/ impaired renal fnc) and moderate to severe CHF * Also for acute pulmonary edema, chronic or acute renal failure, nephrotic syndrome, hyperkalemia, chemical intoxication (to á urine flow) |
|
K-Sparing Diuretics Spironolactone Triameterene (Dyazide) |
* Acts on distal tubule and cortical collecting tubule * Used in conjunction with thiazide and loop diuretics to counter K+ loss Spironolactone affects aldosterone receptor Triameterene (Dyazide) contains hydrochlorothiazide and is the #1 prescribed combination product * Tx for chronic liver failure, CHF when hypokalemia is a problem * Can cause hyperkalemia |
|
Carbonic Anhydrase Inhibitors |
* Acts on proximal tubule * Tx of cystinuria, glaucoma, periodic paralysis that affects muscle membrane fnc, acute mountain sickness (to counteract respiratory alkalosis), metabolic alkalosis |
|
Osmotic Diuretics |
* Tx of acute/incipient renal failure, â intraocular or intracranial pressure (preoperatively) |
Thiazides show no therapeutic advantage in doses > 25 mg
Diuretic induced xerostomia is probably not a very prominent problem (<1%)
Examples of Combination Anti-hypertensive Products
|
Brand Name |
Components |
|
Dyazide |
Triameterine (K-sparing) + hydrochlorothiazide(thiazide) |
|
Aldactazide |
Spironolactone(K-sparing) + hydrochlorothiazide(thiazide) |
|
Vasoretic |
Enalapril(ACE inhibitor) + hydrochlorothiazide(thiazide) |
|
Capozide |
Captopril(ACE inhibitor) + hydrochlorothiazide(thiazide) |
|
Inderide |
Propranolol(non-selective b-blocker) + hydrochlorothiazide(thiazide) |
|
Hyzaar |
Losartan(Angiotensin receptor antagonist) + hydrochlorothiazide(thiazide) |
|
Tenoretic |
Atenolol(b1 selective blocker) + chlorthalidone(thiazide) |
|
Minizide |
Prazosin(peripheral a-adrenergic antagonist) + polythiazide(thiazide) |
Calcium Channel
Blockers (CCB)
¨ Channels regulate Ca2+ flow into vessel
¨ CCB’s block flow of Ca2+ which inhibits excitability/contraction
¨ #1à Amlodipine (Norvasc), #2à Diltiazem (Cardizem), #3à Nifedipine (Procardia)
¨ Others include Isradapine (DynaCirc), Nicardapine (Cardene), Nisoldipine (Sular), Varapamil (Calan)
¨ Use of nifedipine is associated with gingival hyperplasia
Dental Aspects of Diuretic and/or Antihypertensive Drugs
|
Condition |
Problem Drug(s) |
|
Gingival Hyperplasia |
Nifedipine or other dihydropyridines |
|
Dry cough |
ACE inhibitors |
|
Dry mouth |
Diuretics (continual thirst) Sympatholytics (clonidine) à severe xerostomia |
|
Dizziness |
Direct and indirect vasodilators (prazosin, minoxidil) |
|
Orthostatic hypotension |
Most agents and is dose dependant |
|
Hypokalemia |
Thiazide and loop diuretics |
|
Hyperkalemia |
K-sparing agents ACE inhibitors |
|
Loss of Efficacy |
Interaction with NSAIDs |
|
Taste disturbances (dysguesia, aguesia) |
ACE inhibitors |
|
Metallic taste |
ACE inhibitors (captopril) |
|
Ototoxicity (hearing loss) |
High doses of loop diuretics |
Conditions requiring rapid BP â
- malignant hypertension
- pheochromocytoma
- hypertensive encephalopathy
- refractory hypertension of pregnancy
- acute left ventricular failure
- aortic distension
- coronary insufficiency
- intracranial hemorrhage
Preparations for treating hypothyroidism
¨ Levothyroxine (T4) à preferred and used most universally
¨ Triiodithyronine (T3)
¨ Liotrix à a combination of T4 and T3)
¨ Desiccated thyroid or thyroid extract
Thyroid Hormone Therapy
|
Appropriate Uses and Indications |
Unproven Uses |
|
Symptoms associated with hypothyroidism |
Fatigue syndromes |
|
Myxedema |
Obesity in euthyroid (normal state) patients |
|
Iodine-rich medication induced hypothyroidism iodine turns off cascade resulting in â T3 and T4 |
Premenstrual syndrome |
|
Nontoxic colloid goiters |
Severe systemic illness in euthyroid patients |
|
Hashimoto’s thyroiditis (goiter) |
Alopecia (loss of hair) |
|
Hypercholesterolemia |
Nontoxic nodular goiters in the elderly |
|
Menorrhagia in hypothyroid patients |
|
Dental Aspects of Thyroid Therapy
Thyroid Storm
|
Cardinal Features |
Other Manifestations |
Uncommon Features |
|
Fever Tachycardia Change in mental
status |
Tremulousness Profuse sweating Nausea and vomiting Diarrhea Jaundice |
Complete heart
block Coma Stroke Apathy Liver cell failure |
|
Treatment à propanolol is usually given first (peripherally blocks b response) Other meds include propythiouracil
(direct action on thyroid) and iodine
(direct action on thyroid) as well as others |
||
Manifestations of Thyroid Overdose
|
Chest pain |
Irritability, nervousness |
|
Diarrhea |
Leg cramps |
|
Tachycardia |
á sensitivity to heat |
|
Cardiac arrhythmias |
Shortness of breath |
|
Hand tremors |
Sweating |
|
Headache |
Insomnia |
|
Fever |
Excessive weight loss |
Thyroid hormone excess à potentiates the action of catecholamines
Thyroid hormone deficiency à reduces sensitivity to the action of catecholamines
Drug Interactions with Thyroid Hormones
|
Sympathomimetics |
Concurrent use may á effects of thyroid preparation Thyroid preparations enhance effects of sympathomimetics Thyroid hormones á risk of coronary insufficiency Only concerned if excess circulating T3/T4 * If pt is euthyroid, then there is no likely enhancement of epinephrine’s action |
|
Anticoagulants warfarin |
* á of thyroid dose may require â in warfarin dose due to risk of á INR and PT * pts on both meds should have INR checked regularly |
|
Tricyclic antidepressants |
Induces severe xerostomia (á caries risk) á risk of cardiovascular toxicity á risk of thyroid toxicity arrhythmias and CNS stimulation are most common |
|
Hepatic Enzyme Inducers Phenytoin,
barbiturates |
á metabolic degredation of T4 |