Lecture 7 - pharmacological development of. drugs used to treat neurological disorders

Question 1

what does an ideal AED do?

Answer 1

completely suppress seizures whilst showing minimal sedation or other undesirable CNS toxicity. it would have rapid onset of auto following parenteral injection for control of status epileptics. t should have long duration of effect following oral administration for prevention of recurrent seizures.

Question 2

describe the acid phenobarbital

Answer 2

phenobarbital is a weak acid with a pKA of 7.3. has 3 hydrogen bond acceptors and 2 hydrogen bond donors. it does not have a choir centre

phenobarbital binds to and activates the GABAa receptor, by mimicking the inhibitory action of GABA in the brain

Question 3

where does valoprate act?

Answer 3

potency correlated with the molecular shape descriptors suggests valproate and related not acting at the receptor site. the suggested mechanism of action is membrane disruption.

Question 4

describe gabapentin properties as an antiepileptic drug.

Answer 4

water soluble amino acid originally designed as a GABA mimetic capable of penetrating the CNS

RAISES BRAIN GABA LEVELS IN PATIENTS with epilepsy

binds to calcium channels

also used for treating spasticity arising in MS

Question 5

describe lamotrigine properties as an antiepileptic drug.

Answer 5

produces a blockade of sedum channel repetitive firing

valproate significantly increases the half life of lamotrigine by inhibiting the N-glucuronidation process which produces lamotrigine major metabolite

Question 6

describe topiramate properties as an antiepileptic drug.

Answer 6

induces CYP3A4 and inhibits CYP2C19 which results in increased plasma phenytoin levels in co administered

children 4-17 can have 50% increase in clearance compared than adult

Question 7

what is Parkinson’s disease?

Answer 7

Parkinson disease is a brain disorder that leads o skiing stiffness and difficulty with walking, balance and coordination.

Question 8

what is the treatment for Parkinson disease?

Answer 8

the mainstay of PD tretments aim to replace dopamine deficiency in striatum

this can be accomplished by:
augmentation of the synthesis of the brain Dopamine, stimulation of Dopamine release from presynaptic sites, direct stimulation of dopamine receptors, decreasing reuptake at presynaptic sites, decreasing metabolism of dopamine or its precursor, or a combination of above

Question 9

what drugs is used for Parkinson treatment

Answer 9

dopiame itself is unable to cross the BBB, but the dopamine precursor levodopa can. To reduce the side effects of levodopa, it is used in combination treatment with benserazide, to Give co-beneldopa.

co-careldopa can also be used which is a combination of levodopa with carbidopa

Question 10

what are the physicochemical properties of levodopa?

Answer 10

L-dopa is decarboxylated to generate dopamine. dopamine is too polar and does not cross the BBB. L-dopa is transported into the brain by L-amino acid transporter .

Question 11

how is L-DOPA peripheral decarboxylation competitively inhibited?

Answer 11

by coadminsitration of carbidopa or benserazide

Question 12

descrie carbidopa and benserazide meolceules

Answer 12

polar molecules, inhibitors of extra cerebral decarboxylase inhibitors, prevent decarboxylation of L-DOPA to DA before reaching the brain, therefore requires 2.5-3.0 fold lower dose of L-DOPA

Question 13

describe gastro resistant tablets and their advantages