Trans 047 Pharma Doc Torres Flashcards
• Old sedatives • Category D drugs in pregnancy
barbiturates
contraindications to barbiturates?
Contraindications: Porphyria
most common AE of barbiturates is
porphyria
an attack of porphyria may manifest as?
an attack, manifested by severe abdominal pain, nausea, vomiting, psychiatric disorders, and neurologic abnormalities.
DOC for Febrile Epilepsy?
barbiturates
only barbiturates available in the PH. long acting?
PHENOBARBITAL
short acting barbiturates?
pentobarbital
intermediate acting barbiturate?
secobarbital
Evidence of human fetal risk has been documented, but the benefits to the mother may be acceptable despite the risk to the fetus. Drugs in this class may be used in pregnancy if the benefits to the mother outweigh the risk to the fetus (i.e. a life threatening situation or a serious disease for which safer medication cannot be used or are not efficacious). Examples of medications in this class are phenytoin, valproic acid and phenobarbital.
what category of drug?
Category D
Studies in animals have revealed adverse effects on the fetus and there are no controlled studies in women, or studies in women and animals are not available. Drugs from this class can be given to pregnant women if the benefit to the mother outweighs the risk to the fetus. Examples of medications in this class are diltiazem and spironolactone.
what category
category C
Bind selectively to a subgroup of GABA-A receptors, acting like benzodiazepines to enhance membrane hyperpolarization
what drug?
benzodiazepine GABA A
which benzodiazepine GABA A:
• No active metabolites • Available in 5-10 mg per ta
Zolpidem
which benzodiazepine GABA A:
• Inhibit aldehyde dehydrogenase • 5-20 mg per capsule
Zaleplon
which benzodiazepine GABA A:
• Minor active metabolite
• Available in 1-3 mg per tablet
Most potent
Eszopiclone
- Anxiolytics – treatment for anxiety
* Category B drugs in pregnancy
5-HT-1A AGONISTS
a serotonin receptor subtype located in presynaptic and postsynaptic membranes.
5-HT-1A
Either animal‐reproduction studies have not demonstrated a fetal risk but there are no controlled studies in pregnant women, or animal studies have demonstrated risk to the fetus that was not confirmed in controlled studies in pregnant women in the first trimester and there is no evidence of a risk in later trimesters. Medications in this class are generally considered safe. Examples of medications in this class are acetaminophen and amoxicillin
what category?
Category B
which 5HT1A?
Most commonly used and the only one available in the Ph
• 5-10 mg per tablet BID/TID
relieves anxiety without causing marked sedative, hypnotic, or euphoric effects.
Buspirone
Before, it was an herbal plant, now it is approved as a hypnotic Activates MT1 and MT2 receptors in suprachiasmatic nuclei in the CN. Promotes rapid onset of sleep with minimal rebound insomnia or withdrawal symptoms
M1-M2 Agonist (melatonin)
• DOC for Insomnia and Jetlag • 8 mg per tablet • Category C drugs in pregnancy
Ramelteon (M1-M2 Agonist)
Most commonly used sedative
Most potent but non-addicting • Toxic dose – 100 mg
BENZODIAZEPINE GABA-Cl (Chloride)
MOA benzodiazepine GABA cl
MOA: Bind to specific GABA-A receptor subunits at central nervous system (CNS) neuronal synapses facilitating GABA-mediated chloride ion channel opening frequency. Also enhance membrane hyperpolarization
antidote for BENZODIAZEPINE GABA-Cl (Chloride)
FLUMAZENIL (BDZ-Antagonist)
approved for use in reversing the CNS depressant effects of benzodiazepine overdose and to hasten recovery following use of these drugs in anesthetic and diagnostic procedures. MOA: Antagonist at benzodiazepine binding sites on the GABA-A receptor
FLUMAZENIL (BDZ-Antagonist)
BENZODIAZEPINE GABA-Cl (Chloride) has Additive depressant effects with:
Additive depressant effects with: Alcohol, Anti-H1 (anti-histamine), Anti-HPN When added to alcohol, it causes more depression that’s why additive effect
BENZODIAZEPINE GABA-Cl (Chloride) that is
active?;
very active?
CHLORDIAZEPOXIDE
DIAZEPAM
BENZODIAZEPINE GABA-Cl (Chloride) that is
• Long half-life
FLURAZEPAM
BENZODIAZEPINE GABA-Cl (Chloride) that is
Rapid-acting; most rapid ?;
slow acting? ;
Short-acting; shortest
Commonly used in the elderly
alprazolam
temazepam
Triazolam
BENZODIAZEPINE GABA-Cl (Chloride) that are pro drug?
CLORAZEPATE
OXAZEPAM
LORAZEPAM
NITRAZEPAM
peptides found in specific hypothalamic neurons that are involved in the control of wakefulness and that are silent during sleep.
increase in the day and decrease at night.
Loss of this neurons is associated with narcolepsy, a disorder characterized by daytime sleepiness and cataplexy. Animal studies show that orexin receptor antagonists have sleep-enabling effects.
OREXIN A and B
Blocks binding of orexins, neuropeptides that promote wakefulness, thus, promoting sleep onset and duration.
Newer hypnotic drugs
• AE: Somnolence
Orexin Antagonist
Example of Orexin Antagonist
SUVOREXANT / Almorexant
Old drug but still used today • Cyclic ureides • Blocks Na, K, and Ca channels • GABA potentiators (inhibitory) • AE (oral): gingival hyperplasia
PHENYTOIN ORAL / FOSPHENYTOIN IV
a sodium channel-blocking antiseizure drug that acts in a similar fashion to carbamazepine and other agents in the class.
is effective in preventing focal onset seizures and also tonic-clonic seizures, whether they are focal-to-bilateral tonic-clonic (secondarily generalized) or occurring in the setting of an idiopathic generalized epilepsy syndrome.
PHENYTOIN ORAL / FOSPHENYTOIN IV
Tricyclic anti-depressant
• AE: bone marrow depression, aplastic anemia
is one of the most widely used antiseizure drugs despite its limited range of activity as a treatment for focal (partial onset) and focal-to-bilateral tonic-clonic seizures. It was initially marketed for the treatment of trigeminal neuralgia, for which it is highly effective; it is usually the drug of first choice for this condition.
a mood stabilizer used to treat bipolar disorder.
Carbamazepine
- Cyclic ureides
* For febrile epilepsy/convulsion
PHENOBARBITAL
This is a new drug. The next couple of drugs are also new • For infantile spasms
VIGABATRIN
- Blocks the voltage-gated Na and Ca channels
- Also inhibits the neurotransmitter Glutamate
- Used in Lennox-Gastaut Syndrome
- AE: Life-threatening dermatitis in children
LAMOTRIGINE
- NMDA and GABA-A blocker
- Used in Lennox-Gastaut Syndrome
- AEs: Aplastic anemia, hepatitis
- Not commonly used
Felbamate
- Used for Diabetic Neuropathy and for pain in herpetic neuralgia and for neurologic pain
- Aka “Gabapentinoids”
GABAPENTIN / Pregabalin
bind avidly to α2δ, a protein that serves as an auxiliary subunit of voltage-gated calcium channels but may also have other functions.
which drug?
GABAPENTIN / Pregabalin
• Blocks glutamate, GABA and Calcium channels • Also inhibits the synaptic vesicle glycoprotein 2A (SV2A) SV2A is prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release
binds selectively to SV2A, a ubiquitous synaptic vesicle integral membrane protein, which may function as a positive effector of synaptic vesicle exocytosis. Binding to SV2A in the vesicle reduces the release of the excitatory neurotransmitter glutamate during trains of high-frequency activity.
Levetiracetam
• Not commonly used
AEs: blue-colored vision and retinal detachment
Tiagabine / Retigabine
• They undergo phosphorylation • Blocks Na and Ca channels, GABA and Glutamate
likely acts through several cellular targets, which may account for its broad-spectrum activity in epilepsy and migraine.
Possible sites of action relevant to its clinical activities are (1) voltage-gated sodium channels; (2) GABA-A receptor subtypes; and (3) AMPA or kainate receptors. • Also used in Lennox-Gastaut Syndrome
• Used for migraine and absence infantile spams • AEs: Myopia and glaucoma
• Teratogenic for pregnant women – causes Hypospadia
TOPIRAMATE
• Blocks voltage-gated Na and Ca channels • Used for myoclonias and cognitive impairment
Zonisamide
• Amino acid related • Blocks voltage-gated Na channel • Does not bind to Benzodiazepine Nuclear Factor (BDNF)
Lacosamide
• Commonly used in the US for myoclonic epilepsy in children known as Dravet’s Syndrome (discovered in 2007) • 10 mg/kg/day
Stiripentol
(severe myoclonic epilepsy of infancy) is a rare genetic epileptic encephalopathy characterized by diverse generalized and focal seizure types, including myoclonic seizures, tonic-clonic seizures, absence seizures, atonic seizures, and one-sided hemi-convulsive and focal seizures.
Dravet’s Syndrome
• Trample-derivative • Blocks GABA and Na channels • Used for Lennox-Gastaut Syndrome for children 4 years and above
Rufinamide
Banned already because it produces euphoria, SLE1, and SJS2, severe ang adverse effects kaya na-ban
Dati ito ang DOC for petit mal
• Cyclic ureides – Ca/K Blocks calcium and potassium
ETHOSUXIMIDE
is a first-line broad-spectrum antiseizure drug that is thought to offer protection against many seizure types. In addition, it is used as a mood stabilizer in bipolar disorder and as prophylactic treatment for migraine.
VALPROIC ACID/VALPROATE Na
• Block NMDA/GABA/Na – effective in all types of epilepsy
Used in grand mal, petit mal, & myoclonic epilepsy
• AE: Hepatotoxic – to prevent hepatotoxicity you have to use a fat burner which is L-Carnithine
• Teratogenic: causes spina bifida, cardiovascular abnormalities, orofacial abnormalities, digital abnormalities
Pinaka-prominent is spina bifida (board question)
DOC ngayon for petit-mal
VALPROIC ACID/VALPROATE Na
• IV push 20-30mg STAT
DOC for status epilepticus (emergency epilepsy)
Overdose: 100mg
DIAZEPAM
How many times can you use diazepam IV? 3 injections lang. Every 15 minutes.
given intravenously is a first-line treatment for status epilepticus. It is also used in a rectal gel formulation for the treatment of acute repetitive seizures (seizure clusters). The drug is occasionally given orally on a long-term basis, although it is not considered very effective in this application, because of the development of tolerance.
DIAZEPAM
More commonly used in the treatment of status epilepticus because it has a more prolonged duration of action after bolus intravenous injection.
LORAZEPAM
• IV • Freely soluble • Used as an alternate drug Water-soluble prodrug of phenytoin that may have a lower incidence of purple glove syndrome. This phosphate ester compound is rapidly converted to phenytoin in the plasma and is used for intravenous administration and treatment of status epilepticus.
FOSPHENYTOIN
DRUG FOR MYOCLONIC/INFANTILE SPASMS
Clonazepam
Nitrazepam
Stiripentol
Carbonic anhydrase inhibitor
Acetazolamide
rarely used for chronic therapy because tolerance develops rapidly, with return of seizures usually within a few weeks. The drug is often used in the intermittent treatment of menstrual seizure exacerbations in women. The usual dosage is approximately 10 mg/kg/d to a maximum of 1000 mg/d.
Acetazolamide
- 4:1 • Sinemet/Parcopa • 1 hour before meals
- Enter the brain via (L-A.A.Tr)
They are not the DOC because Levodopa is usually broken down in the periphery that’s why it is combined with Carbidopa to prevent the peripheral conversion of Levodopa to Dopamine
levodopa/carbidopa
Contraindication of levodopa/carbidopa
• CI: Malignant Melanoma, Angle Closure Glaucoma, Peptic Ulcer Disease, and Psychosis
acting directly on postsynaptic dopamine receptors may have a beneficial effect in addition to that of levodopa. Unlike levodopa, they do not require enzymatic conversion to an active metabolite, act directly on the postsynaptic dopamine receptors, have no potentially toxic metabolites, and do not compete with other substances for active transport into the blood and across the blood-brain barrier.
Dopamine Agonist
DOC for PD?
DOC: Dopamine agonists (Ergot & Non-ergot)
Ergot DopamineAgonist
BROMOCRIPTINE ; PERGOLIDE; Cabergoline
Ergot dopamine agonist that is a
D2 Agonist:
Directly stimulates both D1 and D2?
Bromocriptine
Pergolide
what are the adverse effect of ergot alkaloids
Erythromelalgia
Marked reddening of the skin
Also produce ergotism (St. Anthony’s Fire) characterized by mental retardation, peripheral vasospasm
Abortifacient
Non ergot dopamine agonists? (3)
Pramipexole Ropirinole, Quinagolide
D3!
it has preferential affinity for the D3 family of receptors. It is effective as monotherapy for mild parkinsonism and is also helpful in patients with advanced disease, permitting the dose of levodopa to be reduced and smoothing out response fluctuations.
Pramipexole
a relatively pure D2 receptor agonist that is effective as monotherapy in patients with mild disease and as a means of smoothing the response to levodopa in patients with more advanced disease and response fluctuations ▪ D2
Ropirinole
Contraindications of Non ergot
Psychosis, Myocardial Infarction, Peptic Ulcer Disease, Peripheral Vascular Disease
Adverse effects of Dopamine Agonist?
ADR of Dopamine Agonists: Mental Impulse (gambling, shopping, excessive eating, bulimia nervosa, hypersexuality) Due to the accumulation of dopamine in the brain
Monoamine oxidase A metabolizes ___________; monoamine oxidase B metabolizes _________
norepinephrine, serotonin, and dopamine
dopamine selectively.
A selective irreversible inhibitor of monoamine oxidase B at normal doses (at higher doses it inhibits monoamine oxidase A as well), retards the breakdown of dopamine.
Selegiline
Another monoamine oxidase B inhibitor, is more potent than selegiline in preventing MPTP-induced parkinsonism and is being used for early treatment in patients with mild symptoms.
DOC for excessive dopamine accumulation.
Rasagiline
Very effective combination lalo na if L-DOPA + C-DOPA is not effective anymore for PD?
L-DOPA,+ C-DOPA + ENTACAPONE (STALEVO)
o Subcutaneous
o Off-periods o Rescue drug – 10mg
o Before the attack of parkinsonism you can use apomorphine
o Drug-induced nausea
Produce nausea and vomiting during off periods
Apomorphine
o Anti-adenosine (A2a) Antiviral drug; it is not anymore used o ADR: Livedo reticularis They block your NMDA also
may potentiate dopaminergic function by influencing the synthesis, release, or reuptake of dopamine. It has been reported to antagonize the effects of adenosine at adenosine A2A receptors, which may inhibit D2 receptor function.
Amantadine
These agents may improve the tremor and rigidity of parkinsonism but have little effect on bradykinesia. Anti-muscarinic to prevent the abnormal movement and tremor of parkinsonism
Anti M1
Examples of Anti M1
o BENZTROPINE o BIPERIDEN o TRIHEXYPHENIDYL
Treatment for tremors?
• Propranolol/Metoprolol • Topiramate/Alprazolam/Gabapentin
Treatment for huntignton’s
• abnormal dancing movement due to abnormality in chromosome 4 • Reserpine/Tetrabenazine – Cerebral dopamine depletion • Haloperidol/Fluphenazine/Olanzapine – Dopamine Blockers
Treatment for Hemiballismus
• Botulinum toxin alpha/ Botulinum toxin type A (BoNT-A), subcutaneous (SC) a new drug for Hemiballismus
treatment for Tics (Gilles De La Tourette’s)
• Uncontrolled movement of the head, body, and extremities
• BoNT-A SC
• Haloperidol/Pimozide/Aripiprazole – D2 Blockers
• Clonidine – A2 agonist
• Clonazepam/Carbamazepine
You can use whichever is available
treatment for Dyskinesia and Dystonia?
• Benztropine IV (for abnormal motor movements)
Diphenhydramine IV (anti-allergy)
• Diazepam IV Again, whichever is available.
RESTLESS LEG SYNDROME/SLEEP DISORDER • discomfort in the legs and arms (Pregnant, uremic, a sign of diabetic neuropathy)
treatment?
Ropirinole/pramipexole/Gabapentin/Clonazepam
• Due to excess copper in the brain, tissues; affects the pancreas and the eyes Characteristic symptom: Kaiser-Fleischer ring
Wilson’s Disease
DOC for wilson’s disease
DOC: D-penicillamine
