pharmacology of vasoconstrictors Flashcards
What are vasoconstrictors?
Substances that cause contraction of smooth muscle in the vasculature, increasing vascular tone.
How do vasoconstrictors affect arteries and arterioles?
They cause contraction, increasing blood pressure by raising vascular resistance.
How do vasoconstrictors affect venules and veins?
They cause contraction, increasing blood pressure by decreasing the space available for blood storage.
What is one use of vasoconstrictors in dentistry related to local anesthesia?
They are co-formulated with local anesthetics (LAs) to provide local anesthesia.
How are vasoconstrictors used in oral surgery?
They help control bleeding (hemostatic effect)
How do vasoconstrictors assist in emergency situations?
They are used to treat acute anaphylaxis.
What is the action of vasoconstrictors with local anesthetics?
They act as agonists at α1 adrenergic receptors.
What is the effect of vasoconstrictors on vascular smooth muscle?
They cause contraction of vascular arteriolar smooth muscle.
What is the response of vasoconstrictors on blood flow at the site of local anesthetic injection?
They reduce blood flow to the site of injection.
How do vasoconstrictors affect the absorption of local anesthetics?
They slow the rate of absorption into systemic circulation, limiting side effects.
How do vasoconstrictors enhance the effectiveness of local anesthetics?
They prolong the duration of the anesthetic at the injection site.
What are the two vasoconstrictors co-formulated with local anesthetics?
Epinephrine
Levonordefrin (only combined with mepivacaine)
How do epinephrine and levonordefrin differ in potency and concentration?
Levonordefrin is less potent than epinephrine.
Higher concentrations of levonordefrin (e.g., 1:20,000) are used compared to epinephrine (e.g., 1:50,000 or 1:100,000) to achieve a similar effect.
What is a common side effect of local anesthetics, and how does it affect their duration?
vasodilating activity, which enhances their absorption into the blood.
This results in a shorter duration of anesthesia if used without a vasoconstrictor.
What is Epinephrine (Epi)?
Structural Class: Catecholamine.
Source: Endogenous hormone released from the adrenal medulla (inner part of the adrenal gland) in response to sympathetic nervous system (SNS) activation.
What happens when the SNS is activated (e.g., fight or flight response)?
Epinephrine is released into the blood, enhancing:
Cardiac output.
Blood flow to muscles.
What does “catecholamine” mean?
Catechol: two OH groups on adjacent carbons of a ring.
Amine: Refers to a nitrogen-containing group.
What are the key effects of a short-term stress response?
Heart rate increases
Metabolic rate increases
Blood pressure increases
Bronchioles dilate
Liver converts glycogen to glucose and releases glucose to the blood
Blood flow changes, reducing digestive system activity and urine output
What are the key effects of a long-term stress response?
Kidneys retain sodium and water
Blood volume, blood pressure blood glucose increases
Proteins and fats are converted to glucose or broken down for energy
Immune system is suppressed
What are the receptors for catecholamines called?
Adrenergic receptors.
Why are they called adrenergic receptors?
They are the receptors for adrenaline (epinephrine).
What is norepinephrine (NE)?
A catecholamine similar in activity to epinephrine.
Released by neurons instead of the adrenal medulla.
How does epinephrine affect the heart?
Sinoatrial node and Ectopic pacemakers: Accelerates via β1, β2
Contractility: increases via β1, β
How does epinephrine affect blood vessels?
Skin, Mucosa, Splanchnic Vessels: Causes contraction via α receptors.
Skeletal Muscle Vessels: Relaxes via β2 receptors, Contracts via α receptors.
How does epinephrine affect bronchiolar smooth muscle?
Relaxes bronchioles via β receptors.
Severe Reactions:
Palpitations
Tachycardia
Chest pain
Increased systolic blood pressure
Arrhythmias (e.g., ventricular fibrillation)
Cardiac arrest
Mild Reactions:
Restlessness
Headache
Tremors
Dizziness
Pallor
What group in epinephrine’s structure makes it prone to oxidation?
The catechol group.
What happens to epinephrine in the presence of oxygen at basic pH?
It is easily oxidized.
What is the appearance of oxidized epinephrine?
It turns brown.
Is oxidized epinephrine pharmacologically active?
No, it is inactive.
What substances are added to LA vials with epinephrine to prevent oxidation?
Sodium metabisulfite (0.5 mg/mL) and hydrogen chloride.
What is the purpose of sodium metabisulfite in LA cartridges?
It acts as an antioxidant to prevent oxidation of epinephrine.
What role does hydrogen chloride play in LA vials with epinephrine?
It serves as a stabilizer to increase the shelf life of the cartridges.
Why might bisulfites in LA vials cause allergic reactions?
They can trigger hypersensitive reactions, especially in asthmatics.
What is the route of administration for epinephrine in local anesthesia?
Injection with LA in dilute solutions
How is epinephrine used for hemostasis?
It is applied topically in concentrations of 1:50,000 to 1:1000 to stop bleeding.
What is the route and dose of epinephrine for systemic effects, such as anaphylaxis?
Administered via subcutaneous (s.c.) or intramuscular (i.m.) injection using an EpiPen
What percentage of anaphylaxis reactions involve skin symptoms, and what are the common symptoms?
80–90% of reactions involve the skin, with symptoms including:
* Hives (urticaria)
* Itching (pruritus)
* Flushing
* Pruritus and swelling of lips, tongue, uvula, or palate
What percentage of anaphylaxis reactions involve the airway, and what are the symptoms?
70% of reactions involve the airway, with symptoms including:
* Larynx: pruritus, throat tightness, dysphonia, and hoarseness
* Lungs: dyspnea, chest tightness, wheezing, or bronchospasm
What central nervous system symptoms are associated with anaphylaxis, and how common are they?
10–15% of reactions involve CNS symptoms, including:
* Uneasiness
* Throbbing headache
* Dizziness
* Confusion
* Tunnel vision
How is the cardiovascular system affected during anaphylaxis, and what percentage of reactions involve these symptoms?
10–45% of reactions involve cardiovascular symptoms, including:
* Chest pain
* Hypotension
* Tachycardia
T or F: epinephrines alpha and beta, receptors adrenergic effects prevent and relieve, life-threatening symptoms of anaphylaxis and most organ systems
True
Why is epinephrine not useful after oral administration?
It has poor oral bioavailability due to the high levels of metabolizing enzymes in the intestine and liver.
What is the half-life (T1/2) of epinephrine in plasma?
2-5 minutes
How long does it take for the effects of epinephrine to dissipate after injection into the blood?
10-25 min
Why does epinephrine have a short half-life?
due to rapid metabolism by the enzymes MAO and COMT.
Which enzymes are responsible for the metabolism of epinephrine?
catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).
What is the result of the metabolism of epinephrine by COMT and MAO?
formation of inactive metabolites.
What are some contraindications to the use of vasoconstrictors or local anesthetics?
Recent myocardial infarction (<1 month or symptomatic)
High-risk arrhythmia
Uncontrolled or severe hypertension
Unstable angina
Patients taking digoxin
Uncontrolled diabetes mellitus
Uncontrolled hyperthyroidism
Moderate to severe asthma (avoid sulfite-containing LA)
Documented allergy to anesthetic or vasoconstrictor
Pheochromocytoma (catecholamine-producing tumors)
Patients taking non-selective beta blockers (due to risk of excessive vasoconstriction)
Why should non-selective beta blockers be avoided in patients using vasoconstrictors?
block B2-mediated vasodilation, leading to excessive alpha1-mediated vasoconstriction, which can cause severe complications.
What is the maximum safe dose of epinephrine for a cardiac patient?
0.04 mg, which is one fifth of the normal maximum adult dose (0.2 mg).
How do tricyclic antidepressants (TCAs) like amitriptyline and imipramine interact with epinephrine?
elevate serotonin and norepinephrine, and levonordefrin may have a greater interaction with TCAs than epinephrine due to its specificity for vasoconstriction.
How do non-selective beta adrenergic receptor antagonists (blockers) affect epinephrine?
cause excessive vasoconstriction due to unopposed alpha receptor activation by epinephrine.
What is the effect of α1 antagonists and phenothiazine antipsychotics on epinephrine?
can cause serious vasodilation due to unopposed beta receptor activation.
Why do many drugs have drug-drug interactions with epinephrine?
They enhance the activity of catecholamines in the body by either decreasing metabolism (e.g., COMT inhibitors and MAO inhibitors) or decreasing reuptake by neurons (e.g., tricyclics, cocaine, amphetamines).
How do MAO, COMT tricyclics, cocaine, and amphetamines inhibitors interact with epinephrine?
decrease the metabolism of catecholamines, increasing epinephrine’s effects.
