Disease and drugs Flashcards
Give an example of a drug that effects transmitter biosynthesis
L-DOPA replacement therapy- increases dopamine production in Parkinson’s disease
Give some examples of drugs that effect action potential propagation
Phenytoin and carbamazepine
Selectively blocks inactivated Na channels used in epilepsy
Give examples of drugs that effect transmitter release
Phenytoin, ethosuximide
Ca channel blockers
Anticonvulsant activity
Used in epilepsy
Give examples of drugs with antagonist receptor mediated effects
D2 receptor- haloperidol- antipsychotic, metaclopramide and chlorpromazine- antiemetics
mAChR- benztroprine- anti parkinsonian
5-HT(3)- ondansetron- antiemetic
Give examples of drugs with agonist receptor mediated effects
Bromocriptine- D1 receptor- anti parkinsonian
Morphine- opiod (u receptor)- analgesic
Buspirone- 5-HT(1A)- anxiolytic
Give examples of allosteric modulators of receptors
GABA-A receptors Benzodiazepines- diazepam Barbiturates- phenobarbitone Sedatives/hypnotics/anxiolytic anticonvulsant Anaesthetics
Give examples of drugs that interfere with signal termination via re-uptake inhibition
Tri-cyclic antidepressants- amitriptyline- block NA, 5-HT reuptake
Selective 5-HT re-uptake inhibitors- fluoxetine (Prozac)
GABA uptake (GAT1) blocker- tiagabine- anticonvulsant
Dopamine unotaje inhibitor- nomifensine- anti parkinsonian (antidepressant)
Give examples of drugs that interfere with signal termination by degradative enzyme inhinbition
Monoamine oxidase inhibitors (MAOI)- phenelzine- antidepressant
Selective MAO-B inhibitor- selegiline- anti parkinsonian
GABA transaminase inhibitor- vigabatrin- anticonvulsant
Give an example of a drug that interfere with signal termination by autoreceptor-mediated feedback inhibition
Mainserin- antidepressant
Summarise the drug approach to treating depression
Autoreceptor antagonism, degenerative enzyme inhibition, reuptake inhibition
Summarise the drug approach to treating Parkinson’s disease
Replacement therapy, through precursors Direct antagonism Re-uptake inhibition Degradative enzyme inhibition Muscarinic receptor antagonist
Summarise thew drug approach to treating epilepsy
Na channel blocker- decrease AP propagation
Ca channel blocker- decrease transmitter release
Allosteric modulation
Reuptake inhibition
Degradative enzyme inhibition
Summarise the drug approach to treating Alzheimer’s disease
Replace the loss of ACh with the precursor
ACh agonists
Not successful
Degradative enzyme inhibition- donepezil, rivastigime, galantamine
List some CNS injurues
Spinal chord injury
Traumatic brain injury
Stroke
Brain cancer
Describe the CNS response to injury
BBB compromised- lesion cavity expands as inflammatory cells interact with reactive glial cells
Astrocytes seal off BBB too retained. Tissue integrity and limit inflammation
Scarring is associated with inhibitory molecules and deposition of ECM
CNS is non permissive to regeneration amd dystrophic neurones develop which are characteristic of abortive regeneration- severed axons and axonal sprouting, highly active structures that are stalled without functional growth
Astrocytes deposits scar amd upregulate CSPG- potent inhibitory molecules
Transected neurones die and become unmyelinated leaving debris and the oligodendrocytes express inhinbiutroy molecules before and after
Micro glia area activated by injury amd become phagocytic
Compare the PNS and CNS for regeneration
Schwann cells in the PNS are permissive for growth- align and growth cones reach distal segments and reinnervate peripheral targets
They produce growth promoting factors
Oligodendrocytes in the CNS do not form a guiding path for sprouting axons and express inhibitory molecules
Astreocytea deposit scar tissue amd release inhibitory molecules (proteoglycans)
Myelin debris not cleared and express inhibitory molecules- Nogo, MAG and Omgp
Describe strategies for CNS repair
Trophic support
Inhibit inhibitory molecules- antibodies to Nogo, digestion of CSPG, Rho inhibitors, Nogo siRNA and survival neuroprotection caspases knockdown (siRNA)
Endogenous stem cells- olfactory bulb, subgranular zone in the hippocampus
Cell therapy- replace dead cells and create a favbourabke environment, bridge any cysts and cavitities using autologous cells
Describe therapeutics in CNS injury
Combinatorial approaches has shown some functional recovery
