NEET MDS Lessons
Pharmacology
PHARMACOLOGY OF VASOCONSTRICTORS
All local anesthetics currently used in dentistry today produce some degree of vasodilatation. This
characteristic results in the increased vascularity of the injected site and results in a shorter duration of local
anesthetic action due enhanced uptake of the local anesthetic into the bloodstream.
- Using a “chemical tourniquet” to prolong the effect of local anesthetics
- The vasoconstrictive action of epinephrine reduces uptake of local anesthetic resulting in a significant increase in the duration of local anesthetic action.
- the addition of vasoconstrictors in local anesthetic solutions will:
1. Prolong the effect of the local anesthetic
2. Increase the depth of anesthesia
3. Reduces the plasma concentration of the local anesthetic
4. Reduces the incidence of systemic toxicity
5. Reduces bleeding at surgical site
Local anesthetics containing epinephrine produce:
1. Localized
VASOCONSTRICTION MEDIATED BY ALPHA RECEPTOR ACTIVATION
i. Hemostasis at surgical site
ii. Ischemia of localized tissue
2. Systemic
HEART
i. Increased heart rate (β1)
ii. Increased force and rate of contraction (β 1)
iii. Increased cardiac output
iv. Increases oxygen demand
v. Dilation of coronary arteries
vi. Decreases threshold for arrhythmias
LUNGS
i. Bronchodilation (β2 )
SKELETAL MUSCLE
i. Predominately vasodilation (fight or flight response) (β 2 )
CNS
i. Minimal direct effect due to difficulty in crossing the blood-brain barrier. Most effects on the CNS are manifestations of the vasoconstrictor on other organs such as the heart.
Concentrations of vasoconstrictors
1. Epinephrine The most commonly used epinephrine dilution in dentistry today is 1:100000. However it appears that a 1:200000 concentration is comparable in effect to the 1:100000 concentration.
2. Levonordefrin Levonordefrin is a synthetic compound very similar in structure to epinephrine. It is the only alternate choice of vasoconstrictor to epinephrine. It is prepared as a 1:20000 (0.05mg/ml)(50 mcg/ml) concentration with 2 % mepivacaine.
Cardiovascular considerations
The plasma concentration of epinephrine in a patient at rest is 39 pg/ml.1 The injection of 1 cartridge of lidocaine 1:100000 epinephrine intraorally results in a doubling of the plasma concentration of epinephrine.
The administration of 15 mcg of epinephrine increased heart rate an average of 25 beats/min with some individuals experiencing an increase of 70 beats/min.
Clinical considerations
It is well documented that reduced amounts of epinephrine should be administered to patients with:
HEART DISEASE (ANGINA HISTORYOF MI)
POORLY CONTROLLED HIGH BLOOD PRESSURE
It is generally accepted that the dose of epinephrine should be limited to 0.04 mg (40 mcg) for patients that have these medical diagnoses
RENIN-ANGIOTENSIN SYSTEM INHIBITORS
The actions of Angiotensin II include an increase in blood pressure and a stimulation of the secretion of aldosterone (a hormone from the adrenal cortex) that promotes sodium retention. By preventing the formation of angiotensin II, blood pressure will be reduced. This is the strategy for development of inhibitors. Useful inhibitors of the renin-angiotensin system are the Angiotensin Converting Enzyme Inhibitors
First line treatment for: Hypertension , Congestive heart failure [CHF]
ACE-Inhibitor’s MOA (Angiotensin Converting Enzyme Inhibitors)
Renin-Angiotensin Aldosterone System:
. Renin & Angiotensin = vasoconstrictor
. constricts blood vessels & increases BP
. increases SVR or afterload
. ACE Inhibitors blocks these effects decreasing SVR & afterload
. Aldosterone = secreted from adrenal glands
. cause sodium & water reabsorption
. increase blood volume
. increase preload
. ACE I blocks this and decreases preload
Types
Class I: captopril
Class II (prodrug) : e.g., ramipril, enalapril, perindopril
Class III ( water soluble) : lisinopril.
Mechanism of Action
Inhibition of circulating and tissue angiotensin- converting enzyme.
Increased formation of bradykinin and vasodilatory prostaglandins.
Decreased secretion of aldosterone; help sodium excretion.
Advantages
- Reduction of cardiovascular morbidity and mortality in patients with atherosclerotic vascular disease, diabetes, and heart failure.
- Favorable metabolic profile.
- Improvement in glucose tolerance and insulin resistance.
- Renal glomerular protection effect especially in diabetes mellitus.
- Do not adversely affect quality of life.
Indications
- Diabetes mellitus, particularly with nephropathy.
- Congestive heart failure.
- Following myocardial infraction.
Side Effects
- Cough (10 - 30%): a dry irritant cough with tickling sensation in the throat.
- Skin rash (6%).
- Postural hypotension in salt depleted or blood volume depleted patients.
- Angioedema (0.2%) : life threatening.
- Renal failure: rare, high risk with bilateral renal artery stenosis.
- Hyperkalaemia
- Teratogenicity.
Considerations
- Contraindications include bilateral renal artery stenosis, pregnancy, known allergy, and hyperkalaemia.
- High serum creatinine (> 3 mg/dl) is an indication for careful monitoring of renal function, and potassium. Benefits can still be obtained in spite of renal insufficiency.
- A slight stable increase in serum creatinine after the introduction of ACE inhibitors does not limit use.
- ACE-I are more effective when combined with diuretics and moderate salt restriction.
ACE inhibitors drugs
Captopril 50-150 mg
Enalapril 2.5-40 mg
Lisinopril 10-40 mg
Ramipril 2.5-20 mg
Perindopril 2-8 mg
Angiotensin Receptor Blocker
Losartan 25-100 mg
Candesartan 4-32 mg
Telmisartan 20-80 mg
Mechanism of action
They act by blocking type I angiotensin II receptors generally, producing more blockade of the renin -angiotensin - aldosterone axis.
Advantages
• Similar metabolic profile to that of ACE-I.
• Renal protection.
• They do not produce cough.
Indications
Patients with a compelling indication for ACE-I and who can not tolerate them because of cough or allergic reactions.
Ciclopirox:Ciclopirox is a synthetic antifungal agent for topical dermatologic use.
Ethosuximide (Zarontin): use in absence seizures (may exacerbate tonic-clonic seizures)
Mechanism: ↓ T-type Ca currents in thalamic neurons, inhibits bursts of APs, ↓ synchronous neuronal firing
i. Thalamo-cortical reverberating circuits: during absence type seizures, have reverberating circuits between cerebral cortex and thalamus at 3 Hz maintained by T-type Ca channels (since blocking these channels blocks the reverberating circuit)
Side effects: quite non-toxic; common= N/V and anorexia; less common = headache, sedation, photophobia
Biguanides
metformin
Mechanism
↓ gluconeogenesis
appears to inhibit complex 1 of respiratory chain
↑ insulin sensitivity
↑ glycolysis
↓ serum glucose levels
↓ postprandial glucose levels
Clinical use
first-line therapy in type II DM
Toxicity
no hypoglycemia
no weight gain
lactic acidosis is most serious side effect
contraindicated in renal failure
Osmotic diuretics
An osmotic diuretic is a type of diuretic that inhibits reabsorption of water and sodium. They are pharmacologically inert substances that are given intravenously. They increase the osmolarity of blood and renal filtrate.
Mechanism(s) of Action
1. Reduce tissue fluid (edema)
2. Reflex cardiovascular effect by osmotic retention of fluid within vascular space which increases blood volume (contraindicated with Congestive heart failure)
3. Diuretic effect
o Makes H2O reabsorption far more difficult for tubular segments insufficient Na & H2O capacity in distal segments
o Increased intramedullary blood flow (washout)
o Incomplete sodium recapture (asc. loop). this is indirect inhibition of Na reabsorption (Na stays in tubule because water stays)
o Net diuretic effect:
Tubular concentration of sodium decreases
Total amount of sodium lost amount increases
GFR unchanged or slightly increased
Toxicity
Circulatory overload, dilutional hyponatremia, Hyperkalemia, edema, skin necrosis
Agents
Mannitol
NATURAL ANTICOAGULANTS:
1. PGI-2.
2. Antithrombin.
3. Protein-C.
4. TFPI.
5. Heparin.
6. Fibrinolytic system.