NEET MDS Lessons
Pharmacology
Sedative-Hypnotic Drugs
Sedative drug is the drug that reduce anxiety (anxiolytic) and produce sedation and referred to as minor tranquillisers.
Hypnotic drug is the drug that induce sleep
Effects: make you sleepy; general CNS depressants
Uses: sedative-hypnotic (insomnia ), anxiolytic (anxiety, panic, obsessive compulsive, phobias), muscle relaxant (spasticity, dystonias), anticonvulsant (absence, status epilepticus, generalized seizures—rapid tolerance develops), others (pre-operative medication and endoscopic procedures, withdrawal from chronic use of ethanol or other CNS depressants)
1- For panic disorder alprazolam is effective.
2- muscle disorder: (reduction of muscle tone and coordination) diazepam is useful in treatment of skeletal muscle spasm e.g. muscle strain and spasticity of degenerative muscle diseases.
3-epilepsy: by increasing seizure threshold.
Clonazepam is useful in chronic treatment of epilepsy while diazepam is drug of choice in status epilepticus.
4-sleep disorder: Three BDZs are effective hypnotic agents; long acting flurazepam, intermediate acting temazepam and short
acting triazolam. They decrease the time taken to get to sleep They increase the total duration of sleep
5-control of alcohol withdrawals symptoms include diazepam, chlordiazepoxide, clorazepate and oxazepam.
6-in anesthesia: as preanesthetic amnesic agent (also in cardioversion) and as a component of balanced anesthesia
Flurazepam significantly reduce both sleep induction time and numbers of awakenings and increase duration of sleep and little rebound insomnia. It may cause daytime sedation.
Temazepam useful in patients who experience frequent awakening, peak sedative effect occur 2-3 hr. after an oral dose.
Triazolam used to induce sleep in recurring insomnia and in individuals have difficulty in going to sleep, tolerance develop within few days and withdrawals result in rebound insomnia therefore the drug used intermittently.
Drugs and their actions
1. Benzodiazepines: enhance the effect of gamma aminobutyric acid (GABA) at GABA receptors on chloride channels. This increases chloride channel conductance in the brain (GABA A A receptors are ion channel receptors).
2. Barbiturates: enhance the effect of GABA on the chloride channel but also increase chloride channel conductance independently of GABA, especially at high doses
3. Zolpidem and zaleplon: work in a similar manner to benzodiazepines but do so only at the benzodiazepine (BZ1) receptor type. (Both BZ1and BZ2 are located on chloride channels.)
4. Chloral hydrate: probably similar action to barbiturates.
5. Buspirone: partial agonist at a specific serotonin receptor (5-HT1A).
6. Other sedatives (e.g., mephenesin, meprobamate, methocarbamol, carisoprodol, cyclobenzaprine):
mechanisms not well-described. Several mechanisms may be involved.
7. Baclofen: stimulates GABA linked to the G protein, Gi , resulting in an increase in K + conductance and a decrease in Ca2+ conductance. (Other drugs mentioned above do not bind to the GABA B receptor.)
8. Antihistamines (e.g., diphenhydramine): block H1 histamine receptors. Doing so in the CNS leads to sedation.
9. Ethyl alcohol: its several actions include a likely effect on the chloride channel.
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
Benzodiazepines
All metabolites are active sedatives except the final glucuronide product.
Elimination half-life varies a great deal from drug to drug.
?-Hydroxylation is a rapid route of metabolism that is unique to triazolam,
midazolam, and alprazolam.
This accounts for the very rapid metabolism and short sedative actions of these
drugs.
Pharmacological effects of benzodiazepines
- Antianxiety.
- Sedation.
- Anticonvulsant (including drug-induced convulsions).
- Amnesia, especially drugs like triazolam.
- Relax skeletal muscle (act on CNS polysynaptic pathways).
Indications
- IV sedation, (e.g., midazolam, diazepam, lorazepam).
- Antianxiety.
- Sleep induction.
- Anticonvulsant (e.g., diazepam, clonazepam).
- Panic disorders.
- Muscle relaxation.
Adverse effects
- Ataxia, confusion.
- Excessive sedation.
- Amnesia (not a desired effect with daytime sedation).
- Altered sleep patterns (increase stage 2 and decrease stage 4 sleep).
Excretion
Routes of drug excretion
The most important route of drug elimination from the body is via the kidney
Renal Drug Excretion
- Glomerular Filtration
- Passive Tubular Reabsorption: drugs that are lipid soluble undergo passive reabsorption from the tubule back into the blood.
- Active Tubular Secretion
Factors that Modify Renal Drug Excretion
- pH Dependent Ionization: manipulating urinary pH to promote the ionization of a drug can decrease passive reabsorption and hasten excretion.
- Competition for Active Tubular Transport
- Age: Infants have a limited capscity to excrete drugs.
Nonrenal Routes of Drug Excretion
Breast Milk
Bile, Lungs, Sweat and Saliva
The kidney is the major organ of excretion. The lungs become very important for volatile substances or volatile metabolites.
Drugs which are eliminated by the kidney are eliminated by:
a) Filtration - no drug is reabsorbed or secreted.
b) Filtration and some of the drug is reabsorbed.
c) Filtration and some secretion.
d) Secretion
By use of the technique of clearance studies, one can determine the process by which the kidney handles the drug.
Renal plasma clearance = U x V ml/min U / Cp = conc. of drug in urine
Cp = conc. of drug in plasma
V = urine flow in ml/min
Renal clearance ratio = renal plasma clearance of drug (ml/min) / GFR (ml/min)
Total Body Clearance = renal + non-renal
First Generation Cephalosporins
Prototype Drugs are CEFAZOLIN (for IV use) and CEPHALEXIN (oral use).
1. Staph. aureus - excellent activity against b-lactamase-producing strains
Not effective against methicillin-resistant Staph. aureus & epidermidis
2. Streptococci - excellent activity versus Streptococcus sp.
Not effective against penicillin-resistant Strep. pneumoniae
3. Other Gm + bacteria - excellent activity except for Enterococcus sp.
4. Moderate activity against gram negative bacteria.
Caution: resistance may occur in all cases.
Susceptible organisms include:
E. coli
Proteus mirabilis
Indole + Proteus sp. (many strains resistant)
Haemophilus influenzae (some strains resistant)
Neisseria sp. (some gonococci resistant)
Uses
1. Upper respiratory tract infections due to Staph. and Strep.
2. Lower respiratory tract infections due to susceptible bacteria e.g. Strep.pneumoniae in penicillin-allergic patient (previous rash)
3. Uncomplicated urinary tract infections (Cephalexin)
4. Surgical prophylaxis for orthopedic and cardiovascular operations (cefazolin preferred because of longer half-life)
5. Staphylococcal infections of skin and skin structure
Fluconazole: an antifungal used orally, intravenously or vaginally to treat yeast and fungal infections. Side-effects of systemic administration include hepatotoxicity (liver damage).
- For vaginal candidiasis (vaginal thrush), a once-only oral dose is often sufficient.
Methods of general anesthesia
CIRCLE SYSTEM
*HIGH-FLOW
FRESH GAS FLOW > 3 l/min.
*LOW-FLOW
FGF ok. 1l/min.
*MINIMAL-FLOW
FGF ok. 0,5 l/min.