GABA System, Sedative-Hypnotic & Anxiolytic Drugs - 28 Flashcards
How many types of GABAa subunits have been identified?
18
How can you gain region or effect specificity when targeting the GABAa receptor?
By targeting specific GABAa receptor sub-types (subunit combos)
What are GABAa receptor subtype selective drugs called?
Z-Drugs
Z-Drugs are structurally similar to the barbiturates and benzodiazepines. They bind to the same site as benzos. (Statement 1/Statement 2)
S1 - F : S2 - T
What are the Z-drugs known as?
Sedative Hypnotics
How do Z-drugs relate to BDZs?
Less day-after psychomotor depression : less amnesia effects : more selective for GABAa Alpha-1-subunit
What general effects do Z-drugs have?
Shorten sleep latency, prolongs sleep time : (Less likely to change sleep patterns)
What is an example of a Z-Drug? Its half-life? Something interesting about it?
Zolpidem (Ambien) : 2.5hrs : Women metabolize it more slowly
How are Z-Drugs metabolized?
By P450s
What effect would barbituates in your system have on your metabolization of Zolpidem?
It would make the Zolpidem less effective (metabolize faster)
Safety and Adverse effects of Z-drugs:
Wakeful behavior/amnesia : Low tolerance when used as directed : Few withdrawal reactions (some with long term use) : NO TOLERANCE TO THERAPEUTIC EFFECTS
What are “centrally acting muscle relaxants”?
Drugs that diminish output of nerve impulses to voluntary muscles
What are examples of centrally acting muscle relaxants?
Diazepam, Mephenesin, Baclofen (GABAb agonist)
What is Baclofen used for?
Trigeminal Neuralgia, MS and spinal cord injury
Why do epilepsy and seizures happen?
Excessive excitability of neurons in the CNS
The term “seizure” refers to:
A general term referring to all types of epileptic events
The term “convulsion” refers to:
Abnormal motor phenomenon
All __________ can be called ____________, but not all _____________ can be called ________________.
Convulsions : seizures : seizures : convulsions
If a seizure stays in one part of the brain, it is called a _______________
Partial seizure
If a seizure spreads to a larger area of the brain, it is called a ________________.
Generalized seizure
What is the difference between seizures and epilepsy?
Seizures can be symptoms of an underlying condition due to genetics, trauma, infection, tumor, autoimmune disorders, or pharmacology. :
Epilepsy is a disease defined by recurrent seizures and accompanying increases in electrical neural activity.
How many people are effected by epilepsy?
50 million people worldwide (30% without good control)
Partial seizures can be ______________ or _________________.
Simple or complex
Simple partial seizures:
Effect 1 part of the brain : have a specific disturbance (motor, sensory, speech) : consciousness unimpaired
Complex partial seizures:
Effect more than one area of the brain : can induce dreamy/blank/vacant state with automated movements : impairment of consciousness
Generalized seizures can be _______________ or __________________.
Convulsive or nonconvulsive
What are the 2 phases of a convulsive seizure?
Tonic (flexed) and Clonic (relaxed)
What may happen during a convulsive seizure?
Contraction of respiratory muscles (little/no breathing)
What is an example of a non-convulsive seizure?
Petit Mal : sudden/brief cessation in activity
Basic First aid for Seizures:
Cushion head, turn on side, look for ID, loosen neckwear, offer help when it ends
Diagnosis and AED selection:
Specific antiepileptic drugs for specific seizure disorders : make physiological/neurological assessments over time : EEG Essential
What are the primary mechanisms of action for anticonvulsive drugs?
Promote GABA activity : Keep Na channels inactivated : Keep Ca channels inactivated
What were the negative effects that made Phenobarbital not great as the first anticonvulsant?
Induces its own metabolism : tolerance develops to anti-convulsive effects : highly sedating
When is phenobarbital used today?
Rarely, for partial and general seizures : mostly in children
What drugs are used to stop status epilepticus?
Diazepam and lorazepam
Why are benzos not used as mainstay anticonvulsive therapy?
They cause cerebellar toxicity
Examples of anticonvulsive drugs that target Na channels:
Phenytoin & Carbamazepine
Examples of anticonvulsive drugs that target Ca channels:
Ethosuximide
Examples of anticonvulsive drugs that target both Na and Ca channels:
Valproic Acid
Action potentials rely on activation of ____________________
Voltage gated Na, K, and Ca channels
T/F voltage gated channels go from closed to open depending on the membrane potential.
F - the go from Closed - Open - Inactive - Closed - Open ………
How does Phenytoin work? How is it used? Positive/negative characteristic?
Binds “inactive” Na channels and slows recovery : used as mainstay treatment for partial/generalized seizures : Relatively non-sedating/narrow therapeutic window - metabolism saturates (cant break down as expected)
Side effects of Phenytoin:
Cerebellar toxicity : Gingival hyperplasia : many drug-drug interaction
How do Carbamazepines work? How are they used? Negatives to it?
Delays Na channel recovery : used for partial complex seizures : cerebellar toxicity - induces P450 - metabolized by P450s
How do ethosuximides work? What are they used for? Pros/Cons?
Inactivated Ca channels : absence seizures : NO CEREBELLAR TOXICITY - GI distress, headache, dizziness
How does Valproic acid work? When is it used?
Inactivated Na AND Ca channels and inhibits GABA metabolism : for partial, general, and absence seizures
Side effects of Valproic Acid
Thrombocytopenia, inhibition of P450
What is thrombocytopenia?
Deficiency of platelets in the blood (slow blood clotting and bleeding into tissues/bruising)
Why is it bad to inhibit P450s?
Causes hyperammonemic metabolic disturbance (build up of ammonia) causing hepatotoxicity (liver toxicity)
What are the newest anticonvulsant drugs?
Lamotrigine and Gabapentin
How does Gabapentin work? What is it used for?
Increases GABA : partial seizures : dizziness/drowsiness
How does Lamotrigine work?
Prolongs sodium channel inactivation and blocks glutamate release :
What are some “other uses” for antiepileptic drugs?
Used to treat Mania and Neuropathic pain (trigeminal neuralgia)
What are the common toxicities of antiepileptic drugs?
Cerebellar toxicity: ataxia/nystagmus, sedation, drug interactions (induce/inhibit P450s)
What are some negative effects that antiepileptic drugs may have on a fetus? Why would someone still take them?
Valproic acid has high risk of spina bifida/neural tube defects, oral facial clefts : risk from uncontrolled seizures is greater than risk from AED
What things can you do for a woman taking AEDs while pregnant?
Use lowest effective dose : use only 1 AED : Supplement folic acid : Supplement Vit K
T/F AED are CNS depressants
TRUE
What are some examples of drugs that will effect metabolism of other drugs through P450 interactions?
Phenytoin, carbamazepine, valproic acid, oral contraceptives
What are some dental related side effects of AEDs?:
Increased incidence of infection : xerostomia : gingival hypertophy :delayed healing : bleeding gums : postop bleeding
When does autism become apparent?
In the first 3 years
Autism affects the development of _________________________.
Social and communication skills
How prevalent is autism today?
1 in 68 - 4:1 male:female
What are some examples of comorbid conditions to autism?
Anxiety disorder, ADHD, sensory integration dysfunction, immune disorders, neuroinflammation
T/F Children with autism will stop progressing indefinitely
F - early intervention is key
Does autism influence life expectancy?
NO - but there is a higher incidence of accidental death
What is Asperger syndrome? Characteristics?
High functioning autism : normal language development, socially inappropriate, hyper/hyposensitive to sensory input
Symptoms of Autism:
Lack of pretend play : impaired social interactions : impaired verbal/nonverbal communication : sensitive to change : trouble remaining still : tantrums
What are some common medications prescribed for autism?
Risperidone, methylphenidate, SSRIs
What are some examples of damaging oral habits displayed by some with autism?
Bruxism, Self-injurious behavior (picking at gingiva), eating/chewing gravel, pens…
What are good approaches when treating autistic patients?
Work with the family, adjust expectations, reduce distractions, be sensitive to sound, maintain routine, praise good behavior, may need to sedate.
