NEET MDS Lessons
Pharmacology
Class I Sodium Channel Blockers
• Block movement of sodium into cells of the cardiac conducting system
• Results in a stabilizing effect and decreased formation and conduction of electrical impulses
• Have a local anesthetic effect
• Are declining in use due to proarrhythmic effects and increased mortality rates
• Na channel blockers - Class 1 drugs are divided into 3 subgroups
• 1A. 1B, 1C based on subtle differences in their mechanism of action.
• Blockade of these channels will prevent depolarization.
• Spread of action potential across myocardium will slow and areas of pacemaker activity is suppressed.
Class IA Sodium Channel Blockers
• Treatment of: symptomatic premature ventricular contractions, supraventricular tachycardia, and ventricular tachycardia, prevention of ventricular fibrillation
– Quinidine (Cardioquin, Quinaglute)
– Procainamide (Pronestyl, Procanbid)
– Disopyramide (Norpace)
• Quinidine – prototype
• Low therapeutic index
• High incidence of adverse effects
Class IB Sodium Channel Blockers
• Treatment of: symptomatic premature ventricular contractions and ventricular tachycardia, prevention of ventricular fibrillation
– Lidocaine (Xylocaine)
– Mexiletine (Mexitil)
– Tocainide (Tonocard)
– Phenytoin (Dilantin)
Side Effects: Lidocaine
• Drowsiness • Paresthesias • Muscle twitching • Convulsions • Changes in mental status (disorientation, confusion) • Hypersensitivity reactions (edema, uticaria, anaphylaxis)
Side Effects: Phenytoin (Dilantin)
• Gingival hyperplasia
• Nystagmus
• Ataxia, slurring of speech
• Tremors
• Drowsiness
• Confusion
• Lidocaine – prototype
• Must be given by injection
• Used as a local anesthetic
• Drug of choice for treating serious ventricular arrhythmias associated with acute myocardial infarction, cardiac surgery, cardiac catheterization and electrical conversion
Class IC Sodium Channel Blockers
• Treatment of: life-threatening ventricular tachycardia or fibrillation and supraventricular tachycardia unresponsive to other drugs
– Flecainide
– Propafenone
Adverse Effects
• CNS - dizziness, drowsiness, fatigue, twitching, mouth numbness, slurred speech vision changes, and tremors that can progress to convulsions.
• GI - changes in taste, nausea, and vomiting. CV - arrhythmias including heart blocks, hypotension, vasodilation, and potential for cardiac arrest.
• Other Rash, hypersensitivity reactions loss of hair and potential bone marrow depression.
Drug-Drug Interactions
• Increased risk for arrhythmias if combined with other drugs that are know to cause arrhythmias- digoxin and beta blockers
• Increased risk of bleeding if combined with oral anticoagulants.
Drug Food Interactions
• Quinidine needs an acidic urine for excretion. Increased levels lead to toxicity
• Avoid foods that alkalinize the urine- citrus juices, vegetables, antacid, milk products
Other sedatives: carisoprodol, cyclobenzaprine, and methocarbamol are used for muscle relaxation.
Baclofen
1. Used in spasticity states to relax skeletal muscle.
2. Occasionally used in trigeminal neuralgia.
Antihistamines (first-generation H1 receptor blockers)
1. Used for sedation (e.g., diphenhydramine).
Ethyl alcohol
Buspirone
1. Short half-life (2–4 hours).
2. Relieves anxiety.
3. Does not act as an anticonvulsant.
4. Is not a good muscle relaxant.
5. Minimum abuse potential.
OXYMETAZOLINE
It is a directly acting sympathomimetic amine used in symptomatic relief in nasal congestion which increases mucosal secretion.
It is used:
- As a nasal decongestant in allergic rhinitis, with or without the addition of antazoline or sodium chromoglycate.
- As an ocular decongestant in allergic conjunctivitis.
Compounds like naphazoline and xylometazoline are relatively selective α2 agonists, which on topical application produce local vasoconstriction.
Characteristics of Opioid Receptors
mu1
Agonists : morphine phenylpiperidines
Actions: analgesia bradycardia sedation
mu2
Agonists : morphine phenylpiperidines
Actions: respiratory depression euphoria physical dependence
delta
Actions: analgesia-weak, respiratory depression
kappa
Agonists: ketocyclazocine dynorphin nalbuphine butorphanol
Actions: analgesia-weak respiratory depression sedation
Sigma
Agonists: pentazocine
Action: dysphoria -delerium hallucinations tachycardia hypertension
epsilon:
Agonists: endorphin
Actions: stress response acupuncture
DIAGNOSIS
Affective disorders:
I. unipolar depression – depression alone
bipolar affective disorder – alternating II. bipolar affective disorder – alternating depression and mania
Diagnosis is based on
At least five of the following for 2 weeks
I. Depressed mood most of the day
II. Markedly diminished interest or pleasureII. Markedly diminished interest or pleasure
III. Significant weight loss or weight
IV. Insomnia or hypersomnia
V. Psychomotor agitation or retardation
VI. Fatigue or loss of energy
VII. Feelings of worthlessness or excessive guilt
VIII. Diminished ability to think or concentrate,
IX. Recurrent thoughts of death
Underlying biological basis for depression is a deficiency of the monoamine neurotransmitters norepinephrine and/or serotonin in the brain.
Neuron Basic Structure (How brain cells communicate)
• Synapse:A junction between the terminal button of an axon and the membrane of another neuron
• Terminal button(orbouton):The bud at the end of a branch of an axon; forms synapses with another neuron; sends information to that neuron.
• Neurotransmitter:A chemical that is released by a terminal button; has an excitatory or inhibitory effect on another neuron.
Different types of Synapses
1-Axo-denrdritic
2-Axo-axonal
3-Axo-somatic
Chemical transmission in the CNS
The CNS controls the main functions of the body through the action endogenous chemical substances known as “neurotransmitters”.
These neurotransmitters are stored in and secreted by neurons to “transmit”information to the postsynaptic sites producing either excitatoryor inhibitory responses.
Most centrally acting drugs exert their actions at the synaptic junctions by either affecting neurotransmitter synthesis, release, uptake, or by exerting direct agonistor antagonistaction on postsynaptic sites.