2 - Pharmacology

Question 0

What are the tx options for migraine?

Answer 0

1) OTC: NSAIDS, acetominophen
2) Abortive:
- Sumatriptan: 5-HT(1) agonist on cranial blood vessels, terminals of trigeminal sensory branches, and in brain stem on secondary neurons from trigeminal sensory branches
- > CONTRA for IHD, HPTN, CV disease, and MAO inhibited
- Ergot Alkyloids (ergotamine, dihydroergotamine): “messy drugs;” act on adrenergic, Serotonergic and dopaminergic receptors; cause vasoconstriction of system and coronary and uterine smooth muscle contraction
3) Prophylactic: mechanism unknown
- propranalol (B-blocker), topiramate (anti-seizure), amitryptyline(TCA), verapamil (Ca blocker), ibuprofen, botulinum toxin

Question 1

What are the medications of choice for treatment of ADHD?

Answer 1

1) methyphenidate (Ritalin)
2) dextroamphetamine (Adderall)
3) cylet -> third line due to hepatotoxicity
4) clonidine/tenex -> tx in combination with 1 or 2
5) wellbutrin -> non-SSRI antidepressent acting on dopamine; good for uncertain dx
6) imiprimine/desipramine -> Tri-Cyclic that USED to be primary medication, but is found to cause sudden death

Question 2

What is the Dopamine Hypothesis of Schizophrenia?

Answer 2

• the Dopamine Hypothesis states that Schizophrenia is due to an excess of Dopamine in the brain
• this is founded primarily on the beneficial effects of D2 Antagonists to ameliorate the symptoms of schizophrenia and the ability to induce psychosis w/ Dopamine agonists

Question 3

What are the major side effects of neuroleptics?

Answer 3

Non-Neurological:

1) Orthostatic Hypotension: antagonists to a1 receptors on vessels prevents sympathetic stimulation to maintain BP
2) Altered Sexual Functions: antagonists to a1 cause decreased libido and difficulty ejaculating
3) Increased Prolactin Secretion: dopamine usually has an inhibitory effect on the prolactin-secreting cells of the pituitary gland; can present as Galactorrhea/Amenorrhea in women and Gynecomastia in men.
4) Weight Gain: more pronouced in atypicals
5) Sedation
6) Seizures: lower seizure threshold
7) Anticholinergic effects: nasal congestion, dry mouth, blurred vision, constipation, urinary retention (autonomics)
8) Phototoxicity: easily burned
9) Leukopenia (dyscrasias): rare by serious; usually presents easily controlled w/ lower dose or Anticholinergic (Benztropine; Trihexphenidyl)
2) Dystonias: uncoordinated, bizarre,jerking movements -> controlled w/ anticholinergic (Benztropine) or antihistime (diphenhydramine)
3) Akathisias: restlessness/agitation -> controlled with Benztropin
4) Tardive Dyskinesia: coordinated, rhythmic, abnormal, involuntary sucking, chewing, licking and pursing -> no tx

Question 4

Where are the following neurotransmitters “released” from in the CNS:

1) NE
2) 5HT
3) DA

Answer 4

1) NE: Locus Coeruleus -> tegmentum of mid Pons
2) 5HT: Raphe Nuclei -> multiple nuclei throughout the brainstem
3) DA: Substantia Nigra, pars compacta -> upper midbrain; Ventral Tegmental Area -> upper midbrain

Question 5

What is the mechanism of addiction?

Answer 5

1) pleasure is thought to be caused by elevation of DA in the N. Accumbens
2) this DA acts on D2 receptors to inhibit GABA neurons that project to Ventral Pallidum and the Medial Thalamus
3) the N. Accumbens also receives input from the PRC, amygdala and Hippocapus (all via Glu/excitatory)
4) neuronal inputs that INHIBIT the GABA neurons of N. Accumbens are REWARDING; those that STIMULATE the GABA are DISAGREEABLE

Question 6

How do the following drugs cause addictive impulses:

1) amphetamine
2) cocaine
3) opiates
4) alcohol

Answer 6

1) amphetamine: increases DA from VTA to GABA of N. Accumbens -> more inhibition -> rewarding; long term use leads to increase in cAMP in cell, depletion of DA, and desensitization of D2 receptors -> tolerance/withdrawal
2) cocaine: blocks monoamine reuptake; increase DA in N. Accumbens and follows similar to above
3) opiates: binds to mu receptors on enkephalin neurons -> this inhibits the GABA neurons both in the VTA and N. Accumbens leading to increased DA and more direct inhibition of GABA -> euphoria and addiction
4) alcohol: blocks NMDA receptors and potentiates GABAa receptors, leading to more inhibition -> addiction