Griseofulvin

• Griseofulvin is an antifungal drug. It is used both in animals and in humans, to treat ringworm infections of the skin and nails. It is derived from the mold Penicillium griseofulvum.
• It is administered orally.

Stages of anesthesia

Stage I

Analgesia

Still conscious but drowsy

Stage II

Excitement stage

Loss of consciousness, however, irregular ventilation may be present which affects absorption of inhalation agents.

Reflexes may be exaggerated.

This is a very dangerous stage

Stage III

Surgical anesthesia

Loss of spontaneous movement

Regular, shallow respiration

Relaxation of muscles

Stage IV

Medullary paralysis

Death

Selective serotonin reuptake inhibitors (SSRIs)

e.g. fluoxetine, paroxetine, citalopram, and sertraline
- Most commonly used antidepressant category
- Less likely to cause anticholinergic side effects
- Relatively safest antidepressant group in overdose
- Selectively inhibits reuptake of serotonin(5-HT)

Mode of Action;
- Well absorbed when given orally
- Plasma half-lives of 18-24 h allowing once daily dosagedaily dosage
- Metabolised through CYP450 system and most SSRIs inhibit some CYP isoforms
- Therapeutic effect is delayed for 2-4 weeks

ADVERSE DRUG REACTIONS

- Insomnia, increased anxiety, irritability
- Decreased libido
- Erectile dysfunction, anorgasmia, and ejaculatory delay
- Bleeding disorders
- Withdrawal syndrome

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

Sympatholytics (Antiadrenergic Agents)

PHENOXYBENZAMINE
It is a potent alpha-adrenergic blocking agent 

It effectively prevents the responses mediated by alpha receptors and diastolic blood pressure tends to decrease.
It interferes with the reflex adjustment of blood pressure and produces postural hypotension. 
It increases the cardiac output and decreases the total peripheral resistance.

It is used in the management of pheochromocytoma and also to treat peripheral vasospastic conditions e.g. Raynaud’s disease and shock syndrome.

Phentolamine, another alpha blocker is exclusively used for the diagnosis of pheochromocytoma and for the prevention of abrupt rise in blood pressure during surgical removal of adrenal medulla tumors.

ERGOT ALKALOIDS

 Ergotamine is an  important alkaloid that possesses both vasoconstrictor and alpha-receptor blocking activity. Both ergotamine and dihydroergotamine are used in the treatment of migraine.

METHYSERGIDE

It is a 5-hydroxytryptamine antagonist ). It is effective in preventing an attack of migraine. 

SUMATRIPTAN

It is a potent selective 5-HT 1D  receptor agonist used in the treatment of migraine.

PRAZOSIN
It is an piperazinyl quinazoline effective in the management of hypertension. It is highly selective for α1  receptors. It also reduces the venous return and cardiac output. It is used in essential hypertension, benign prostatic hypertrophy and in Raynaud’s syndrome.
Prazosin lowers blood pressure in human beings by relaxing both veins and resistance vessels but it dilates arterioles more than veins.

TERAZOSIN
It is similar to prazosin but has higher bioavailability and longer plasma t½

DOXAZOSIN
It is another potent and selective α1 adrenoceptor antagonist and quinazoline derivative.
It’s antihypertensive effect is produced by a reduction in smooth muscle tone of peripheral vascular beds.

TAMSULOSIN
It is uroselective α1A  blocker and has been found effective in improving BPH symptoms.

Other drugs used for erectile dysfunction

Sildenafil: It is orally active selective inhibitor of phosphodiesterase type 5 useful in treatment of erectile dysfunction.

CLASSICATION OF ANTICOAGULANT DRUGS

1. Direct Acting Anticoagulants

a) Calcium Chelators (sodium citrate, EDTA)

b) Heparin

2. Indirect Acting Anticoagulant Drugs

a) Warfarin