Pharmacology Flashcards
Components of pain
Affective Cognitive Discriminative Arousal Motor
Pain transmission horns
Non-noxious stimuli (dynamic allodynia) through A beta - Laminae 3 4 5 deep horns
Nociceptive mechanical and thermoceptive stimuli (polymodal, static allodynia) through A delta - Laminae 1 2o 5 superficial horns and some deep
Nociceptive mechanical, thermoceptive, and chemical stimuli (polymodal) through C - Laminae 1 2o superficial horns
Wide dynamic range horn
Horn 5
Serotonin excitatory and inhibitory receptors
5-HT1 = inhibitory
5-HT3 = excitatory
AMPA
More selective to sodium entry than calcium and the antagonist is CNQX (cyan quaxaline)
NMDA
repeated depolarisation is needed as well as two ligands (glu + gly), and the antagonists are ketamine (also used to treat depression) and memantine but neither are used any more clinically due to serious side-effects such as hallucinations and motor effects
There are presynaptic receptors but less studies on them, all we know is that the repeated depolarisation mechanism for releasing magnesium is not important for them
SP and NK-1
SP: co-released with NKA, CGRP, and glutamate
IP3: GPCR, postsynaptic, increases release of calcium from intracellular stores by generating IP3, antagonists have failed, involved in mood, stress, anxiety, and pain
Descending controls transmitter systems
Opioidergic, noradrenergic, and serotonergic
Morphine microinjection provides analgesia in which section?
PAG
What drugs cause schizophrenic attacks and susceptible patients?
LSD and phencyclidine
What receptor causes the psychedelic effects of LSD?
5HT2A
Which receptors does LSD not affect?
5HT3 5HT4
How does the immune system promote addiction?
TLR4
Tinazidine Contraindications
Should not be taken with fluvoxamine (antidepressant) or ciprofloxacin (antibiotic) either. If it is taken in high doses for a long time, it causes withdrawal effects.
Local Anaesthetic Nerve Fibre Order Of Action
L.As block in the following order: small myelinated axons (Ad), then unmyelinated axons (C- fibres), then large myelinated axons (Ab) & motor axons.
What does PABA inhibit?
Sulphonamide
Drug-induced PD
Drugs that reduce the amount of dopamine in the
brain (e.g. reserpine).
Drugs that block dopamine receptors (e.g.
antipsychotics such as chlorpromazine).
Which anti-epileptic drugs are highly bound to plasma proteins?
phenytoin & valproic acid
What is the status of activity of antiepileptic drug metabolites?
they are active and also cleared through hepatic pathways, some of the older anti-epileptics are hepatic microsomal enzyme potentiators
Valproate special use
In adolescents where grand & petit mal co-exist since it is effective against both (unlike most antiepileptics)
Which drug is the first choice in absence seizures?
Ethosuximide (T subtype inhibited as it is the one responsible for absence seizures)
Tiagabine and vigabatrin MOA
Tiagabine GAT1 inhibited reuptake
Vigabatrin GABA-T inhibited transaminase inactivation
Uses of vigabatrin
Adjunct therapy in refractory complex partial seizures
West’s syndrome (infantile spasms)
Which BZD is also an anti-depressant?
Alprazolam
What is midazolam also used for?
Anaesthesia
Which hypnotic reduces REM sleep the least?
Zolpidem (and BZDs relatively less), GH release is unaffected, SW reduced
BZD duration of action
Diazepam: long acting for anxiolysis
Flurazepam: long acting for hypnosis
Temazepam: intermediate acting for hypnosis
Triazolam - short acting
Which BZD has an active metabolite?
Nordazepam -> N-desmethyldiazepam (60 hour half-life)
What is special about buspirone?
Takes long time to work (cannot be given for acute attack) and can be withdrawn abruptly and safely
3Zs side effects
Zolpidem & zaleplon: nightmares, agitation, headache, G.I upset, dizziness
Zopiclone: taste alteration, impairment of driving skills, palpitations (following withdrawal from drug after prolonged use)
Zolpidem & zopiclone: anterograde amnesia
(more so than zaleplon)
Which hypnotic causes endocrine changes and what are they?
Ramelteon, increase in prolactin and decrease in testosterone
What is the danger in using tacrine?
Tacrine causes hepatotoxicity (liver damage/failure) too. Thus, it is required simultaneous monitoring for hepatotoxicity, recently not used much.
Which AChE and BuChE inhibitor affects the heart?
Galantamine (also nAChRs enhancer)
Do not forget that memantine can also cause hypertension is a side-effect
Which drug, if given in gradual doses, does not show as much side-effects?
Rivastigmine
Which drug is given in gradual doses to avoid toxicity?
Carabamezepine
Other Treatments For AD
Levetiracetam: An anticonvulsant with a novel mechanism of action (which is not clear), anti-inflammatory processes in the brain, may slowdown the AD progression.
Caprylidene (Caprylic triglyceride): A formulation of coconut oil, which release ketones, provide alternative energy source to glucose. It might be useful in mild to moderate AD to improve memory and cognitive function, but it does not reverse neuronal degeneration.
Curcumin (Extract of turmeric): It has both the anti-inflammatory and anti-oxidant properties that can suppress the formation of NFTS and Aβ deposit.
Latrepirdine (Dimebon): It is a weak inhibitor of AChE, BuChE, and NMDA receptors.
Methylthioninium chloride compound (MTC): It is a tau kinase inhibitor that reduce the formation of NFTs.
Partition Co-efficient
(P = [organic]/[aqueous]).
Examples of pharmacological approaches to bypassing the blood brain barrier
Chemical delivery system (lipidisation): enhanced delivery of ganciclovir to the bran by covalently attaching with 1-methyl-1,4-dihydronicotinate to a hydroxymethyl group.
Prodrug: Valacyclovir is a prodrug of acyclovir. In oral administration it rapidly gets converted to acyclovir.
Polymeric micelles: Pluronic P85 micelles loaded with a neuroleptic drug is targeted to the brain by conjugating micelles with neurospecific antibodies as targeting moieties.
Nanoparticles (ApoE-albumin): hexapeptide dalargin
Why are CGRP antagonists not used?
Hepatotoxic
