NEET MDS Lessons
Pharmacology
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)
CHOLINERGIC DRUGS
Produce actions similar to Acetylcholine (Ach)
Cholinergic Agonists
1 Acetylcholine 2 Methacholine 3. Carbachol 4 Bethnechol
Alkaloids
1.Muscarine 2 Pilocarpine 3. Arecoline
MECHANISM OF ACTION
I Heart- hyperpolarizes the SA node and decreases the rate of diastolic depolarisation. thus the frequcncy of impulse generation is decreased. bradycardia.
2 Blood vessels- vasodilatation
3. Smooth muscles - increased contraction. increased tone. increased peristalsis.
4. Glands- increased sweating. increased lacrimation.
5 Eye- contraction of the circular muscle of iris (miosis).
Nicotinic action
Autonomic ganglia - stimu1ation of sympathetic and parasympathetic system.
Skeletalmuscles - contraction of fibres.
CNS..No effect as it does not penetrate the blood-brain barrier.
Toxic effects
Flushing. sweating.salivation. cramps. belching. involuntary mictuirition. defaccation.
Contraindication
1.. Anginapectoris- decreases the coronary flow.
2 Pepticulcer - increases the gastric secretion
3 Asthma- bronchoconstriction
4 Hyperthyroidisim
Cholinomimetic Alkaloids
Pilocarpine
Prominent muscarinic actions. causes marked sweating. salivation. Increase of secretions. small doses cause fall in BP but higher doses increase in BP. Applied to the eye cause miosis. fall in intraocular tension
Uses
I. .Open angle glaucoma
2. To counteract mydriasis
Anticholinesterase
They inhibit the enzyme cholinestrase and prolong the action of Ach
Reversible
Physostigamine, Ncostigamine, Pyridostigamine, Ambenonium, Edrophonium, Demecarium
Irreverible
Dyflos. Echothiphate.
Pharmacological Actions
I Ganglia - persistent depolarisation of ganglionic nicotinic receptors.
2 CVS - unprcdictable as Muscarinic-I receptor causes bradycardia but ganglionic stimulation
tachycardia.
3. Skeletal muscles - as Ach is not destroyed and rebinds to the same receptor or it diffuses on to the neighbouring receptors to cause repetitive firing. twitching and fasciculations.
Uses
I As miotic
a) Glaucoma : Acute congestive (narrow angle) glaucoma, Chronic simple (wide angle) glaucoma
b) Counter act atropine mydriasis.
2) Post operative paralytic ileus
3) Myasthenia gravis
4) Postoperativedecurarization
5) Cobra bite
6) Belladona poisoning
7) Other drug overdoses
Serotonin-norepinephrine reuptake inhibitors(SNRIs)
e.g. venlafaxine and duloxetine
- Inhibit the reuptake of both 5-HT and norepinephrine
- Has a more favourable adverse effect profile than TCAs
Norepinephrine reuptake inhibitor
e.g. bupropion, reboxetine
Monoamine receptor antagonists
e.g. mirtazapine, trazodone, mianserin
Warfarin (Coumadin):
- The most common oral anticoagulant.
- It is only active in vivo.
- Warfarin is almost completely bound to plasma proteins. -96% to 98% bound.
- Warfarin is metabolized by the liver and excreted in the urine.
- Coumarin anticoagulants pass the placental barrier and are secreted into the maternal milk.
- Newborn infants are more sensitive to oral anticoagulants than are adults because of lower vitamin K levels and lower rates of metabolism.
- Bleeding is the most common side effect and occurs most often from the mucous membranes of the gastrointestinal tract and the genitourinary tract.
Oral anticoagulants are contraindicated in:
• Conditions where active bleeding must be avoided, Vitamin K deficiency and severe
hepatic or renal disease, and where intensive salicylate therapy is required.
Phenoxymethylpenicillin (penicillin V) Phenoxymethylpenicillin, commonly known as penicillin V, is the orally-active form of penicillin. It is less active than benzylpenicillin
Indications:
infections caused by Streptococcus pyogenes, tonsillitis, pharyngitis, skin infections, prophylaxis of rheumatic fever, moderate-to-severe gingivitis (with metronidazole)
Ciclopirox:Ciclopirox is a synthetic antifungal agent for topical dermatologic use.
EPHEDRINE
It act indirectly and directly on α and β receptors. It increases blood pressure both by peripheral vasoconstriction and by increasing the cardiac output. Ephedrine also relaxes the bronchial smooth muscles.
Ephedrine stimulates CNS and produces restlessness, insomnia, anxiety and tremors.
Ephedrine produces mydriasis on local as well as systemic administration.
Ephedrine is useful for the treatment of chronic and moderate type of bronchial asthma, used as nasal decongestant and as a mydriatic without cycloplegia. It is also useful in preventing ventricular asystole in Stokes Adams syndrome.