NEET MDS Lessons
Pharmacology
Antidepressant Drugs
Drug treatment of depression is based on increasing serotonin (5-HT) or NE (or both) at synapses in selective tracts in the brain. This can be accomplished by different mechanisms.
Treatment takes several weeks to reach full clinical efficacy.
1. Tricyclic antidepressants (TCAs)
a. Amitriptyline
b. Desipramine
c. Doxepin
d. Imipramine
e. Protriptyline
2. Selective serotonin reuptake inhibitors (SSRIs)
a. Fluoxetine
b. Paroxetine
c. Sertraline
d. Fluvoxamine
e. Citalopram
3. Monoamine oxidase inhibitors (MAOIs)
a. Tranylcypromine
b. Phenelzine
4. Miscellaneous antidepressants
a. Bupropion
b. Maprotiline
c. Mirtazapine
d. Trazodone
e. St. John’s Wort
Antimania Drugs
These drugs are used to treat manic-depressive illness.
1. Lithium
2. Carbamazepine
3. Valproic acid
SYMPATHOMIMETICS
β2 -agonists are invariably used in the symptomatic treatment of asthma.
Epinephrine and ephedrine are structurally related to the catecholamine norepinephrine, a neurotransmitter of the adrenergic nervous system
Some of the important β 2 agonists like salmeterol, terbutaline and salbutamol are invariably used as bronchodilators both oral as well as
aerosol inhalants
SALBUTAMOL
It is highly selective β2 -adrenergic stimulant h-aving a prominent bronchodilator action.
It has poor cardiac action compared to isoprenaline.
TERBUTALINE
It is highly selective β2 agonist similar to salbutamol, useful by oral as well as inhalational route.
SALMETEROL
Salmeterol is long-acting analogue of salbutamol
BAMBUTEROL
It is a latest selective adrenergic β2 agonist with long plasma half life and given once daily in a dose of 10-20 mg orally.
METHYLXANTHINES (THEOPHYLLINE AND ITS DERIVATIVES)
THEOPHYLLINE
Theophylline has two distinct action:
smooth muscle relaxation (i.e. bronchodilatation) and suppression of the response of the airways to stimuli (i.e. non-bronchodilator prophylactic effects).
ANTICHOLINERGICS
Anticholinergics, like atropine and its derivative ipratropium bromide block cholinergic pathways that cause airway constriction.
MAST CELL STABILIZERS
SODIUM CROMOGLYCATE
It inhibits degranulation of mast cells by trigger stimuli.
It also inhibits the release of various asthma provoking mediators e.g. histamine, leukotrienes, platelet activating factor (PAF) and interleukins (IL’s) from mast cell
KETOTIFEN
It is a cromolyn analogue. It is an antihistaminic (H1 antagonist) and probably inhibits airway inflammation induced by platelet activating factor (PAF) in primate.
It is not a bronchodilator. It is used in asthma and symptomatic relief in atopic dermatitis, rhinitis, conjunctivitis and urticaria.
LEUKOTRIENE PATHWAY INHIBITORS
MONTELUKAST
It is a cysteinyl leukotriene receptor antagonist indicated for the management of persistent asthma.
Routes of Drug Administration
Intravenous
- No barriers to absorption since drug is put directly into the blood.
- There is a very rapid onset for drugs administered intravenously. This can be advantagous in emergency situations, but can also be very dangerous.
- This route offers a great deal of control in respect to drug levels in the blood.
- Irritant drugs can be administer by the IV route without risking tissue injury.
- IV drug administration is expensive, inconvenient and more difficult than administration by other routes.
- Other disadvantages include the risk of fluid overload, infection, and embolism. Some drug formulations are completely unsafe for use intravenously.
Intramuscular:
- Only the capillary wall separates the drug from the blood, so there is not a significant barrier to the drug's absorption.
- The rate of absorption varies with the drug's solubility and the blood flow at the site of injection.
- The IM route is uncomfortable and inconvenient for the patient, and if administered improperly, can lead to tissue or nerve damage.
Subcutaneous
Same characteristics as the IM route.
Oral
- Two barriers to cross: epithelial cells and capillary wall. To cross the epithelium, drugs have to pass through the cells.
- Highly variable drug absorption influenced by many factors: pH, drug solubility and stability, food intake, other drugs, etc.
- Easy, convenient, and inexpensive. Safer than parenteral injection, so that oral administration is generally the preferred route.
- Some drugs would be inactivated by this route
- Inappropriate route for some patients.
- May have some GI discomfort, nausea and vomiting.
- Types of oral meds = tablets, enteric-coated, sustained-release, etc.
- Topical, Inhalational agents, Suppositories
Drugs Used in Diabetes
Goals of diabetes treatment
lower serum glucose to physiologic range
keep insulin levels in physiologic range
eliminate insulin resistance
best initial step in management: weight loss, contractile-based exercise weight loss is more important for insulin sensitivity than is a low-carb diet
Modalities of diabetes treatment
Type I DM
insulin
low-sugar diet
Type II DM
exercise
diet
insulin
6 classes of drugs
Insulin
Sulfonylureas - Glyburide
Meglitinides - Nateglinide
Biguanides Metformin
Glitazones (thiazolidinediones) Pioglitazone
α-glucosidase inhibitors Acarbose
GLP-1 mimetics (incretin mimetics) Exenatide
Amylin analog Pramlintide
Patient positioning
The most common medical emergency encountered in the dental office setting is syncope. So patients in the supine or semi-supine position to improve venous return and cerebral blood flow provided that the position is tolerated by the patient and is appropriate for their medical condition.
Non-barbiturate sedatives
1- Chloral hydrate is trichlorinated derivative of acetaldehyde that is converted to trichlorethanol in the body. It induces sleep in about 30 minutes and last up to 6 hr. it is irritant to GIT and produce unpleasant taste sensation.
2- Ramelteon melatonin receptors are thought to be involved in maintaining circadian rhythms underlying the sleep-wake cycle. Ramelteon is an agonist at MT1 and MT2 melatonin receptors , useful in patients with chronic insomnia with no rebound insomnia and
withdrawal symptoms
3- Ethanol (alcohol) it has antianxiety sedative effects but its toxic potential out ways its benefits.
Ethanol is a CNS depressant producing sedation and hypnosis with increasing dose.
Absorption of alcohol taken orally is rapid, it is highly lipid soluble, presence of food delayed its absorption, maximal blood concentration depend on total dose, sex, strength of the solution, the time over which it is taken, the presence of food and speed of metabolism.
Alcohol in the systemic circulation is oxidized in the liver principally 90% by alcohol dehydrogenase to acetaldehyde and then by acetaldehyde dehydrogenase to products that enter the citric cycle.
Alcohol metabolism by alcohol dehydrogenase follows first order kinetics in the smallest doses. Once the blood concentration exceeds about 10 mg/100 ml, the enzymatic processes are saturated and elimination rate no longer increases with increasing
concentration but become steady at 10-15 ml/ 1 hr. in occasional drinkers.
Thus alcohol is subject to dose dependant kinetics i.e. saturation or zero order kinetics.
Actions
- Ethanol acts on CNS in a manner similar to volatile anesthetic.
- It also enhances GABA so stimulating flux of chloride ions through ion channels.
- Other possible mode of action involve inhibition of Ca-channels and inhibition of excitatory NMDA receptors.
- Ethanol has non selective CNS depressant activity.
- It causes cutaneous vasodilatation, tachycardia and myocardial depression
Seizure classification:
based on degree of CNS involvement, involves simple ( Jacksonian; sensory or motor cortex) or complex symptoms (involves temporal lobe)
1. Generalized (whole brain involved):
a. Tonic-clonic:
Grand Mal; ~30% incidence; unconsiousness, tonic contractions (sustained contraction of muscle groups) followed by clonic contractions (alternating contraction/relaxation); happens for ~ 2-3 minutes and people don’t breathe during this time
Drugs: phenytoin, carbamazepine, Phenobarbital, lamotrigine, valproic acid
Status epilepticus: continuous seizures; use diazepam (short duration) or diazepam + phenytoin
b. Absence:
Petit Mal; common in children; frequent, brief lapses of consciousness with or without clonic motor activity; see spike and wave EEg at 3 Hz (probably relates to thalamocorticoreverburating circuit)
Drugs: ethosuximide, lamotrigine, valproic acid
c. Myoclonic: uncommon; isolated clinic jerks associated with bursts of EEG spikes;
Drugs: lamotrigine, valproic acid
d. Atonic/akinetic: drop seizures; uncommon; sudden, brief loss of postural muscle tone
Drugs: valproic acid and lamotrigine
2. Partial: focal
a. Simple: Jacksonian; remain conscious; involves motor or sensory seizures (hot, cold, tingling common)
Drugs: carbamazepine, phenytoin, Phenobarbital, lamotrigine, valproic acid, gabapentin
b. Complex: temporal lobe or psychomotor; produced by abnormal electrical activity in temporal lobe (involves emotional functions)
Symptoms: abnormal psychic, cognitive, and behavioral function; seizures consist of confused/altered behavior with impaired consciousness (may be confused with psychoses like schizophrenia or dementia)
Drugs: carbamazepine, phenytoin, laotrigine, valproic acid, gabapentin
Generalizations: most seizures can’t be cured but can be controlled by regular administration of anticonvulsants (many types require treatment for years to decades); drug treatment can effectively control seizures in ~ 80% of patients