Mechanisms Flashcards
Opioids
3 opioid receptors : mu , delta , kappa Natural endogenous opioids are : Enkephalins Dynorohins Endorphins
Endorphins act on u
Closing of voltage gated Ca channels and open K channels allowing efflux of K ions.
Opioids Adverse effects
Nausea Vomiting Anti tussive Respiratory depression Immune Suppression Constipation Flushing (meperidine morphine) Itching Urinary retention Dependence
Buprenorphine
Partial agonist of u rec
Antagonist of k and d rec
Produces partial effect thus less risk of abuse
Naloxone
Opioid antagonist
Morphine antidote
Anesthesia stages
- Induction
- Excitement
- Surgical Anesthesia
- Medullary paralysis
1st group Anesthesia
Etomidate
Propofol
Barbiturates
Unconsciousness more then analgesia
Act on GABA a
Hyperpolarization of resting potential . Open Cl channels, suppress neuronal excitability .
Used in Induction phase.
1st group Anesthesia Adverse effects
Etomidate
Renal suppression
Transient Skeletal muscle movements (myoclonus)
Propofol
Respiratory depression
Hypotension
Barbiturates
Bronchospasm
Respiratory depression
2nd group Anesthesia mech
Ketamine (IV)
Nitrous Oxide
Xenon
Cyclopropane
No effect on GABA
More Analgesia than unconsciousness
Ketamin
Act on N-methyl D aspartate rec NMDA
Inhibits NDMA receptors. Inhibit glutamate excitatory action
Xenon
Cyclopropane
Selectively inhibit NMDA
2 pore domain K channels . Efflux of K ions
2nd group adverse effects
Ketamine: Htn tachy Hypersalivation Hallucinations Delrium
Nitrous oxide , cyclopropane
Dizziness nausea vomit
Xenon: none
3rd group
Halothane Enflurane Isoflurane Sevoflurane Desflurane
Act on all
GABA a, NMDA & 2 pore domain K channels and many other
3rd group side effects
Dose dependant hypotension
Low cardiac output
Arrhythmia hepatotoxicity (halothane)
Renal toxicity ( Sevoflurane)
Dexmedotomidine
Unique Anesthetic
Presynaptic a2 adrenergic rec
Brady
Hypotension
Local anesthetics mechanism
Bind to a site on voltage gated Na Channels prevention of Na Influx .
Local anesthetics adverse effects
Systemic effects: Blurry vision Light headedness Seizure Cardiac arrhythmia
Alzheimer’s drugs mechanisms
Anti cholinesterases
Rivastigmine ( both Acetyl and butyl cholinesterase)
Donapezil
Galantamine
Tacrine
Inhibit cholinesterase enzyme and promotes prolonged action of Ach
NMDA rec antagonist
Memantine
Abnormal B -amyloid accumulation may cause high levels of glutamate by inhibiting it’s uptake and triggering more release from glial cells.
Memantine binds to NMDA receptors and block excitatory action of glutamate by blocking Ca influx
Side effects Alzheimer’s
Anti cholinesterase
SLUD
Brady
Weight loss
Memantine
Insomnia
Diarrhea
Headache
Parkinson’s mechanism
Parkinson’s develops when neurons connecting substantia Niagra to striatum degenerate
Dopaminergic neurons originate in substantia niagra
Low dopamine causes more GABA & more Ach
Increase inhibition in thalamus and reduced excitatory input to motor cortex
Parkinson’s drugs mechanisms
Pre BBB crossing
Tyrosine –th–> L-Dopa –AADC–> DOPAMINE
DOPAMINE released
Broken by MAO-B and COMPT
Levodopa (precursor of Dopamine) (BBB crossing)
Carbidopa (inhibits Dopamine Decarboxylase)
Entacapone (inhibits COMPT)
Parkinson’s drugs mechanisms
Post BBB
Selegeline
Rasagiline
Inhibit MAO-B
Tolcapone: inhibits COMT
Parkinson’s drug mechanism
Anti Muscarinic Agents
Benztropine
Biperidine
Procyclidine
Trihexphenidyl
Parkinson’s drugs
Dopamine mimics
Bromocriptin Ropinorole Pramipexole Rotigotine Apomorphine
Stimulate dopamine receptors to produce similar effects as dopamine
Amantadine Parkinson’s
Facilitates pre synaptic dopamine release
Blocks Glutamate NMDA rec
Parkinson’s drug Adverse effects
Levo carbi Nausea loss of appetite Hypotension Mental disturbance Discolored urine
Selegeline rasagiline Nausea Insomnia Dyskinesia Hallucinations
Entacapone tolcapone
Diarrhea (tolcapone severe)
Hepatotoxic (tolca)
Discolored urine
Dopamine mimics Nausea Hypo Daytime sleepiness Mental disturbance Bromocriptin (cardiac and pulmonary fibrosis)
Anticholinergic
Dry mouth
Constipation
Blurred vision
Seizures classification
Focal seizure (one hemisphere) May or may not be unconscious
Generalize
Both hemisphere
Always unconscious
Why seizures happen?
Too much Glutamate can cause abnormal influx of Na ions (AMPA rec) & Ca ions (NMDA rec) . GABA a opens Cl channels and influx of Cl ions can neutralize it. But if Little or no GABA. Seizures.
Epilepsy drugs mechanisms
Na Channel blockers
Carbamazepine Oxcarbazepine Lamotrigine Phenytoin Topiramate Valproic Acid Zonisamide
Epilepsy drugs
Ca channel blockers
High voltage activated Ca channel blockers
Lamotrigine
Topiramate
T-type Ca ch blocker
Valproic Acid
Zonisamide
Epilepsy drugs
Ca ch subunit
Gabapentin
Pregabalin
Act on HVA Ca ch subunit alpha2 delta1
Levetriacetam
Felbamate
Epilepsy
Binds to SV2A protein in walls of glutamate containing vesicles. Glutamate release impaired
Felbamate: blocks NMDA rec
Anti epilepsy
Barbiturates
Benzodiazepines
Act on GABA rec
Prolongs opening of Cl channels
Inhibitory action
Antiepleptics drugs
GABA
Tigabine (GAT1 inhibitor)
Inhibits GABA transporter and blocks GABA reuptake
Vigabatrin
Inhibits GABA aminotransferase (GABA-T) which catabolizes GABA. Thus GABA conc is increased.
Antiepleptics
Side effects
All
Sedation
Dizziness
Carbamazepine oxcarbazepine
Hyponatremia
Vigabatrin lamotrigine
Visual disturbances
phenytoin
Double vision
Gingival hyperplasia
Hirsutism
Zonisamide topiramate
Cognitive disturbance
Wt loss (topiramate)
Valproic Acid
Wt gain
pregabalin gabapentin
peripheral edema
Hepatotoxic
Felbamate
Rare aplastic anemia
Dopamine hypothesis
Mesolimbic pathway (⬆️ Dopamine) (hallucinations)
Mesocortical pathway (⬇️ Dopamine) (social withdrawal, no motivation)
Nigrostriatal pathway . ⬆️ Dopamine hyperkinetic movement dyskinesia ⬇️ Dopamine dystonia Parkinson
Tubero infundibular pathway.
Dopamine here inhibits prolactin
Antipsychotics
1st generation
D2 blockers in all 4 pathways
So mesocortical dopamine ⬇️⬇️⬇️ social withdrawal, no energy, sad
Nigrostriatal Dopamine ⬇️⬇️⬇️ tremors, muscles rigidity
Tuberoinfundibular Dopamine ⬇️⬇️⬇️ gynecomastia, galactorrhea, sexual dysfunction
Antipsychotics
1st generation
Typicals
High potency Haloperidol Flupenazine Prochlorperazine Trifluoperazine
Low potency
Chlorpromazine
Bind to other receptors a B adrenergic and Histamine receptors causing more side effects
Antipsychotics
2nd generation
Atypicals
D2 blockers and 5HT2A serotonin receptors
Reduced side effects
Aripiprazole Clozapine Lurasidine Olanzapine Quetiapine Risperidone ziprasidone
2nd generation antipsychotics side effects
5HT2A blockers Clozapine, Olanzapine
Hyperglycemia
Hyperlipidemia
H1 blockers Clozapine Quetiapine:
Sleepiness
Wt gain
a1 blockers Clozapine Risperidone
Orthostatic Hypotension
Risperidone extrapyridimal side effects. Hyperprolactinemia
Clozapine Agranulocytosis
Benzodiazepines
Mechanisms:
Act between gamma and alpha subunits of GABA a receptors and increase GABA binding to the receptors. Cl channels frequency increases and Cl influx happens
Adverse effects Dizziness Drowsiness ⬇️Motor coordination ⬇️ Alertness
Barbiturates
Mechanisms
Bind to GABA a receptors between a and b subunits. They keep the Cl channels open for long period of time. In high doses they become GABA mimics as well.
Side effects Dizziness Lightheaded Respiratory depression Narrow therapeutic index Overdose coma death
Non benzodiazepines hypnotics
Selectively bind to a1 subunit in GABA A receptors
a1 subunit GABA A receptors are involved in sleep
While a2 & a3 subunit receptors are involved in anxiety control.
Thus these hypnotics only induce sleep not anxiolytics
Side effects Memory loss Day time sedation Cognitive impairment ⬇️Motor function
Zolpidem
Zalpelon
Eszopiclone
