Drugs Flashcards
Triptans (Sumatriptan etc)
Used to treat migraines
They are selective 5HT1B/5HT1D agonists
5HT1B receptors are on smooth muscle and voasconstriction
5HT1D lies on trigeminal nerve terminals and blocks release of vasoactive peptides from trigeminal nerves
What drugs are used in the prophylaxis of migraine?
B-blockers (bisoprolol, propanolol etc)
Antiepileptic drugs (gabapentin, pregabalin etc)
Antidepressants (Amitriptyline etc)
Calcium channel blockers (Nifidipine etc)
Tissue plasminogen activator (tPA)
Used to treat ischaemic stroke only
Disperses thrombus and restores blood flow
Must be administered in 3 hours for maximum effect
Stroke prophylaxis
Antihypertensives
Statins (reduces risk of thrombus formation but also contraindicated in haemorrhagic stroke)
Antiplatelets (Aspirin, clopidogrel)
Anticoahulants (Warfarin)
Compression stockings
Orlistat
Only centrally acting licensed drug in the UK for obesity
Acts as a lipase inhibitor and prevents the breakdown of dietary fats to fatty acids as well as decreasing the absorption of fats by 30%
Side effects of orlistat
Oily stools, abdominal cramps, flatus with discharge
Anti epileptics (VGSC blockers)
Phenytoin, Carbamazepine, Lamotrigine, Sodium Valproate
Keeps the VGSC in an inactivated state allowing it to produce 1 AP but not many successive AP’s
Anti-epileptics (VGCC blockers)
Ethosuxamide, Gabapentin, phenytoin
Allows for AP causes by VGSC but does not allow it to be propagated by VGCC’s
Levetiracetam
Anti epileptic that directly reduces vesicle fusion hence there is less Glu release therefore less neuronal excitation
Vigabatrin
Anti-epileptic that increase GABA synthesis causing more inhibition of neurones
Tigabine
Anti-epileptic that reduces the reuptake of GABA allowing for inhibition of neurones
How do benzodiazepines and barbituates help with epilepsy?
They increase the effectiveness of GABAa receptors which are Cl- channels which will prolong channel open time
Felbamate
Anti-epileptic that blocks NMDAr’s thereby reducing AP’s
However very hepatotoxic
Topiramate
Anti-epileptic that blocks AMPA/Kainate receptors thereby reducing AP’s
Retigabine
Anti-epileptic that activates K+ channels and makes the neurone less excitable both pre/post synaptically
Lesigamane
Anti-epileptic that blocks low threshold Na currents which decreases the propagation of AP’s
L-DOPA
Aimed at replacing the lost DA in Parkinson’s
L-DOPA is converted to DA by DOPA decarboxylase thereby causing increased DA synthesis
Carbidopa/bensarzide
Co-administered with L-DOPA to as a peripheral DA blocker to reduce the peripheral side effects of L-DOPA
Selegiline
MAO inhibitor to reduce degradation of DA
Baclofen
Used for antispasticity
Targets and reduces motor output in the spinal cord
Z-drugs (Zopiclone, zolpidem, zolepton)
Non-benzo’s which bind to GABAa receptors
Has a short duration of action
Less likely than benzo’s to cause rebound insomnia
Can cause dependence
Typical antipyschotics (1st gen)
Eg Chlorpromazine, Haloperidol
High affinity D2 antagonists
Effective against the +ve symptoms of Schizophrenia via D2 blockade in the mesolimbic pathway
Around 80% block required for antipsychotic effects to occur
Extrapyramidal side effects of 1st gen antipsychotics
Acute dystonias (Parkinson like)
Tardive dystonias (Huntingtons like)
Galctorrhea caused by increased prolactin release due to D2 block in TI pathway
Decreased pleasure due to inhibition of mesolimbic pathway
Non dopamine related side effects of typical antipsychotics
Antipsychotics are also antagonists at other GPCR’s
Can cause sedation (H1)
Hypotension (alpha adrenergic receptors)
Blurred vision, dry mouth, constipation (Muscarinic)
Sexual dysfunction (muscariinic, adrenergic and dopaminergic)
Atypical antipsychotics (2nd gen)
Eg Clozapine, Olanzipine, Rispiredone, aripiprazole
Low affinity D2 block so causes partial block of D2 but also of 5HT2 recepetors
5HT2 blockade reduces inhibition of DA neurons in mesocortical pathway and nigrostriatal pathway as they don’t appear elsewhere
This reduces treats the -ve symptoms and also reduces the motor side effects seen with typical antipsychotics
Side effects associated with atypical antipsychotics
Weight gain and diabetes
Agranulo cytosis/leukopenia (rare and occurs moreoften with clozapine)
Why is clozapine different to other atypicals?
The only antipsychotic shown to be clinically more effective than the others
However has serious side effects of agranulo cytosis/leucopenia and other blood dyscrasis
Only given if more than 2 other antipsychotics have been tried and were ineffective
Cholinesterase inhibitors
Eg Donepazil, rivastigmine, galantamine
Used in treatment for alzheimers (Does not slow progression)
ACH is important in memory formation so these act to reduce ACh breakdown in synapses thereby enhancing levels of ACh
Memantine
Non-competive NMDA receptor blocker
Is neuroprotective in some way or form and can cause slight cognitive improvement
Irreversible MOAi
Eg Phenezine, Tranyleypromine, iproniazid
Used in treatment of depression
Irreversibly inhibits MAO which inactivates DA/NA/5HT
Problematic as consumption of cheese can result in gut MAO not metabolising tyramine due to block resulting in sympathomimetic side effects
Moclobemide
Used in depression treatment
Safer to use than irreversible inhibitors as high concentrations of tyramine can overcome the block in the gut
Therefore there is much less chance of the cheese reaction occurring
Long acting hypnotics
Flurazepam/Dalmane/Diazepam (2-keto metabolised in liver)
Long duration of action owed to active metabolites
Can result in a ‘hangover’ effect due to long duration of action
Short acting hypnotics
Restoril/Tempazepam/Triazolam/Halcion (3-OH converted to glucaronide radicals)
Shorter half life and duration of action than 2- keto benzo’s
Little to no hangover effect
Rophynol is part of this class and is known as the date rape drug
Herbal hypnotics
Valerian root
The active ingredients are suggested to bind to 5HT, GABA and adenosine receptors
Benzodiazepines
Diazepam,
Binds to allosteric sites on GABAa receptors (CL- channels) increasing their activity
Binds between alpha/gamma subunits
TCA’s
Tricyclic antidepressants eg imipramine, amitriptyline
Blocks the uptake of monoamines with preference for 5HT/NA over DA
Competitive and non selective
Blockade of histamine and ACh recpetors contributes to side effects
Major metabolites are also active
Major side effects of MAOi’s
Hypotension
Atropine like effects
Hepatocellular jaundice
Major side effects of TCA’s
Sedation Atropine like effects Postural hypotension Mania and convulsions Dysrhythmia and heart block
SSRI’s
Citalopram, Fluoxetine, Sertraline
Much more selective for 5HT receptors and so have less S/E from NA enhancement
Much safer in overdose as well
Mirtazipine
Blocks alpha2 adrenceptors/5HT2C receptors causing enhanced NA/5HT release
Trazodone
Blocks 5HT2A/2C and 5HT reuptake
Mianserin
Blocks multiple 5HT receptors as well as alpha 1/2 adrenoceptors
Agomelatine
Blocks melatonin receptors
Useful in depression that causes sleep disturbance
Lithium
Reduces both mania and depressive phases
Possibly permeates through Na+ but doesn’t leave causing depolarisation of excitabel cells
Also inhibits IP3
>1.5mmol is toxic
Lithium side effects
Polyuria/Polydipsia (too much drinking/urinating) Weight gain Aggravation of skin disorders Tremors and muscle twitching GI symptoms Drowsiness Hyper-reflexia, Coma Huntington/Parkison like symptoms
