Synaptic Transmission Drugs (8-18-15)

Question 1

Metyrosine

Answer 1

Indication: HTN
*MOA: Competitive inhibition of tyrosine hydroxylase

(binds but cannot be transformed to DOPA -> decreases production of dopamine -> reduces NE production)

Question 2

Reserpine

Answer 2

Indication: HTN
*MOA: Inhibits VMAT uptake of monoamines

(-> depletion of NE, DA and serotonin; CAN cross BBB and block uptake in CNS neurons which can contribute to depression -> now used at LOW doses & combined w/ other anti-HTN drugs)

Question 3

Bretylium

Answer 3

Indication: Ventricular arrhythmia
*MOA: Inhibits AP generation & Ca2+ dependent synaptic vesicle fusion

(inhibits excitability of nerve terminal membrane & Ca2+ dependent fusion of synaptic vesicle with PM -> reduces NT release; has SPECIFIC effects on adrenergic neurotransmission)

Question 4

Cocaine

Answer 4

Indication: Analgesia in surgery
*MOA: Blocks monoamine re-uptake

(Blocks NE, dopamine & serotonin re-uptake; one of the first anesthetics/analgesics in surgery; not used much clinically anymore)

Question 5

Amphetamine or Ephedrine

Answer 5

Indication: Narcolepsy, ADHD
*MOA: Reverse monoamine reuptake transporters

(-> release endogenous NT back out to synaptic cleft; Ca2+ independent)

Question 6

Naloxone, Naltrexone

Answer 6

Indication: Opioid overdose or dependence
*MOA: Non-peptide blockers of opioid receptors in CNS

(Naloxone - small lipophilic molecule widely used to reverse opioid OD; naltrexone has a LONGER duration of action and is used in the tx of opiate addiction & alcoholism)

Question 7

SSRIs

Answer 7

Indication: Depression, anxiety
*MOA: Selective inhibition of serotonin reuptake transporter

(MUST be able to cross BBB; can have significant side-effects, particularly in cardiovascular system)

Question 8

ACE Inhibitors (ex: lisinopril)

Answer 8

Indication: HTN

*MOA: Inhibits peptide cleavage of angiotensin I to angiotensin II

Question 9

Phenylephrine

Answer 9

Indication: HYPOtension during surgery
*MOA: Direct agonist of adrenergic receptor

(Resistant to degradation by COMT and thus has a longer 1/2 life)

Question 10

MAO inhibitors

Answer 10

Indication: Depression
*MOA: Blockade of cytoplasmic metabolism of monoamines

(-> increases catecholamines in the cytoplasm; NE accumulates in cytoplasm -> transporter protein reverses direction -> NE into synapse; dietary sources of of certain amino acids can produce ADVERSE effects when combined with MAO inhibitors)

Question 11

L-DOPA

Answer 11

Indication: Parkinson’s Disease
*MOA: Precursor of dopamine, stimulates dopamine production

(bc dopaminergic neurons are damaged in PD)

Question 12

Carbidopa

Answer 12

Indication: Parkinson’s Disease
*MOA: Blocks L-DOPA conversion to dopamine, does NOT cross BBB–so protects peripheral adrenergic neurons from producing too much dopamine & NE

(REDUCES PERIPHERAL SIDE-EFFECTS OF L-DOPA IN PD PTS)

Question 13

Tyramine

Answer 13

Indication: N/A (ingested in diet/not therapeutic)
*MOA: Competes with NE for transport into synaptic vesicle

(CAN CAUSE HTN CRISIS WHEN COMBINED WITH MAO INHIBITORS–bc excess NE in the periphery -> excessive vasoconstriction)