NEET MDS Lessons
Pharmacology
Structure of the CNS
The CNS is a highly complex tissue that controls all of the body activities and serves as a processing center that links the body to the outside world.
It is an assembly of interrelated “parts”and “systems”that regulate their own and each other’s activity.
1-Brain
2-Spinal cord
The brain is formed of 3 main parts:
I. The forebrain
• cerebrum
• thalamus
• hypothalamus
II. The midbrain
III. The hindbrain
• cerebellum
• pons
• medulla oblongata
Different Parts of the Different Parts of the CNS & their functions CNS & their functions
The cerebrum(cerebral hemispheres):
It constitutes the largest division of the brain.
The outer layer of the cerebrum is known as the “cerebral cortex”.
The cerebral cortex is divided into different functional areas:
1.Motorareas(voluntary movements)
2.Sensoryareas(sensation)
3.Associationareas(higher mental activities as consciousness, memory, and behavior).
Deep in the cerebral hemispheres are located the “basal ganglia” which include the “corpus striatum”& “substantianigra”.
The basal gangliaplay an important role in the control of “motor”activities
The thalamus:
It functions as a sensory integrating center for well-being and malaise.
It receives the sensory impulses from all parts of the body and relays them to specific areas of the cerebral cortex.
The hypothalamus:
It serves as a control center for the entire autonomic nervous system.
It regulates blood pressure, body temperature, water balance, metabolism, and secretions of the anterior pituitary gland.
The mid-brain:
It serves as a “bridge”area which connects the cerebrum to the cerebellum and pons.
It is concerned with “motor coordination”.
The cerebellum:
It plays an important role in maintaining the appropriate bodyposture& equilibrium.
The pons:
It bridges the cerebellum to the medulla oblongata.
The “locus ceruleus”is one of the important areas of the pons.
The medulla oblongata:
It serves as an organ of conduction for the passage of impulses between the brain and spinal cord.
It contains important centers:
• cardioinhibitory
• vasomotor
• respiratory
• vomiting(chemoreceptor trigger zone, CTZ).
The spinal cord:
It is a cylindrical mass of nerve cells that extends from the end of the medulla oblongata to the lower lumbar vertebrae.
Impulses flow from and to the brain through descending and ascending tracts of the spinal cord.
Methicillin
Methicillin is an antibiotic related to penicillin and other beta-lactam containing antibiotics. It is often used to treat infections caused by bacteria carrying an antibiotic resistance, e.g., staphylococci. As methicillin is deactivated by gastric acid, it has to be administered by injection.
Uses Methicillin serves a purpose in the laboratory to determine antibiotic sensitivity in microbiological culture.
On the basis of Receptors, drugs can be divided into four groups,
a. agonists
b. antagonists
c. agonist-antagonists
d. partial agonists
a. Agonist
morphine fentanyl pethidine
Action : activation of all receptor subclasses, though, with different affinities
b. Antagonist
Naloxone , Naltrexone
Action : Devoid of activity at all receptor classes
c. Partial Agonist: (Mixed Narcotic Agonists/Antagonists)
Pentazocine, Nalbuphine, Butorphanol , Buprenorphine
Action: activity at one or more, but not all receptor types
With regard to partial agonists, receptor theory states that drugs have two independent properties at receptor sites,
a. affinity
The ability, or avidity to bind to the receptor
Proportional to the association rate constant, Ka
b. efficacy
or, intrinsic activity, and is the ability of the D-R complex to initiate a pharmacological effect
Drugs that produce a less than maximal response and, therefore, have a low intrinsic activity are called partial agonists.
These drugs display certain pharmacological features,
a. the slope of the dose-response curve is less than that of a full agonist
b. the dose response curve exhibits a ceiling with the maximal response below that obtainable by a full agonist
c. partial agonists are able to antagonise the effects of large doses of full agonists
Gabapentin (Neurontin): newer; for generalized tonic-clonic seizures and partial seizures (partial and complex)
Mechanism: unknown but know doesn’t mimic GABA inhibition or block Ca currents
Side effects: dizziness, ataxia, fatigue; drug well-tolerated and no significant drug interactions
Antiarrhythmic Drugs
Cardiac Arrhythmias
Can originate in any part of the conduction system or from atrial or ventricular muscle.
Result from
– Disturbances in electrical impulse formation (automaticity)
– Conduction (conductivity)
– Both
MECHANISMS OF ARRHYTHMIA
ARRHYTHMIA – absence of rhythm
DYSRRHYTHMIA – abnormal rhythm
ARRHYTHMIAS result from:
1. Disturbance in Impulse Formation
2. Disturbance in Impulse Conduction
- Block results from severely depressed conduction
- Re-entry or circus movement / daughter impulse
Types of Arrhythmias
• Sinus arrhythmias
– Usually significant only
– if they are severe or prolonged
• Atrial arrhythmias
– Most significant in the presence of underlying heart disease
– Serious: atrial fibrillation can lead to the formation of clots in the heart
• Nodal arrhythmias
– May involve tachycardia and increased workload of the heart or bradycardia from heart block
• Ventricular arrhythmias
– Include premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation
|
Class |
Action |
Drugs |
|
I |
Sodium Channel Blockade |
|
|
IA |
Prolong repolarization |
Quinidine, procainamide, disopyramide |
|
IB |
Shorten repolarization |
Lidocaine, mexiletine, tocainide, phenytoin |
|
IC |
Little effect on repolarization |
Encainide, flecainide, propafenone |
|
II |
Beta-Adrenergic Blockade |
Propanolol, esmolol, acebutolol, l-sotalol |
|
III |
Prolong Repolarization (Potassium Channel Blockade; Other) |
Ibutilide, dofetilide, sotalol (d,l), amiodarone, bretylium |
|
IV |
Calcium Channel Blockade |
Verapamil, diltiazem, bepridil |
|
Miscellaneous |
Miscellaneous Actions |
Adenosine, digitalis, magnesium |
Indications
• To convert atrial fibrillation (AF) or flutter to normal sinus rhythm (NSR)
• To maintain NSR after conversion from AF or flutter
• When the ventricular rate is so fast or irregular that cardiac output is impaired
– Decreased cardiac output leads to symptoms of decreased systemic, cerebral, and coronary circulation
• When dangerous arrhythmias occur and may be fatal if not quickly terminated
– For example: ventricular tachycardia may cause cardiac arrest
Mechanism of Action
• Reduce automaticity (spontaneous depolarization of myocardial cells, including ectopic pacemakers)
• Slow conduction of electrical impulses through the heart
• Prolong the refractory period of myocardial cells (so they are less likely to be prematurely activated by adjacent cells
Benzodiazepines (BZ):
newer; depress CNS, selective anxiolytic effect (no sedative effect); are not general anesthetics (but does produce sedation, stupor) or analgesics
BZ effects:
1. Central: BZs bind GABAA receptors in limbic system (amygdala, septum, hippocampus; involved in emotions) and enhance inhibition of neurons in limbic system (this may produce anxiolytic effects of BZs)
a. GABA receptor: pentameric (α, β, δ, γ subunits)
i. Binding sites: GABA (↑ conductance (G) of Cl-, hyperpolarization, inhibition), barbiturate (↑ GABA effect), benzodiazepine (↑ GABA effect), picrotoxin (block Cl channel)
b. GABA agonists: GABA (binds GABA → Cl influx; have ↑ frequency of Cl channel opening; BZs alone- without GABA don’t affect Cl channel function)
c. Antagonists: bicuculline (competitively blocks GABA binding; ↓ inhibition,→ convulsions; no clinical use), picrotoxin (non-competitively blocks GABA actions, Cl channel → ↓ inhibition → convulsions)
2. Other agents at BZ receptor:
a. Agonists: zolpidem (acts at BZ receptor to produce pharmacological actions)
b. Inverse agonists: β-carbolines (produce opposite effects at BZ binding site-- ↓ Cl conductance; no therapeutic uses since → anxiety, irritability, agitation, delirium, convulsions)
3. Antagonists: flumazenil (block agonists and inverse agonists, have no biological effects themselves; can precipitate withdrawal in dependent people)
Metabolism: many BZs have very long action (since metabolism is slow); drugs have active metabolites
2 major reactions: demethylation and hydroxylation (both very slow reactions)
Fast reaction: glucuronidation and urinary excretion
Plasma half life: long (for treating anxiety, withdrawal, muscle relaxants), intermediate (insomnia, anxiety), short (insomnia), ultra-short (<2hrs; pre-anesthetic medication)
Acute toxicity: very high therapeutic index and OD usually not life threatening (rarely see coma or death)
Treatment: support respiration, BP, gastric lavage, give antagonist (e.g., glumazenil; quickly reverses BD-induced respiratory depression)
Tolerance: types include pharmacodynamic (down-regulation of CNS response due to presence of drug; this is probably the mechanism by which tolerance develops), cross-tolerance (with other BZ and CNS depressants like EtOH and BARBS), acquisition of tolerance (tolerance develops fastest in anticonvulsant > sedation >> muscle relaxant > antianxiety; means people can take BZs for long time for antianxiety without → tolerance)
Physical dependence: low abuse potential (no buz) but physical/psychological dependence may occur; physical dependence present when withdrawal symptoms occur (mild = anxiety, insomnia, irritability, bad dreams, tremors, anorexia; severe = agitation, depression, panic, paranoia, muscle twitches, convulsions)
Drug interactions: minimally induce liver enzymes so few interactions; see additive CNS depressant effects (can be severe and → coma and death if BZs taken with other CNS depressants like ethanol)
Fifth Generation:
These are extended spectrum antibiotics.
Ceftaroline, Ceftobiprole