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Pharmacology FINAL (2nd sem) > A: 34-38 > Flashcards

A: 34-38 Flashcards

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1
Q

Drugs used in Parkinsons

A
  • Levodopa/Carbidopa- precursor of dopamine
  • Selegeline- MAO-B inhib.
  • Entacapone- COMT inhib. entaCapon for Comt
  • Ropinirole-
    • Dopamine-2 agonist. same ROLE as dopamine
  • Pramipexole-
    • Dopamin 3 agonist
  • Amantadine -
    • Anti-viral
    • M-block
    • enhance dopaminergic transmission ( increase synthesis/release, decrease reuptake)
  • Procyclidine- Ach blocker
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2
Q

Why give Ach blockade in Parkinsons?

A

When physiologic Dopamine decreases –> excessive excitation of cholinergic neurons ( Ach release)

Ach and Dopamine are out of balance in parkinsons

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3
Q

Levodopa/Carbidopa-

MOA ,duration

A

precursor of dopamine

Carbidopa:

  • Dopamine DeCarboxylase inhibitor (periphery)
  • does NOT enter CNS

L-DOPA:

  • prolonged plasma T1/2
  • lower doses of L-dopa is effective
  • fewer peripheral SE

*oral COMT & MAO-B Inhibitors allow smaller doses & prolong action.

  • responsiveness gradually decreases with time
  • DOA= 6-8hrs
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4
Q

Levodopa/Carbidopa-

indication

A

Primary drug used in Parkinsons

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5
Q

Levodopa/Carbidopa-

SE

A
  • GI upset:
  • dyskinesia (on-off phenomenon)
  • behavioral effects:
    • anxiety .
    • hallucination,
    • depression,
    • confusion ,
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6
Q

Dopamine agonists

A
  • Pramipexole
    • D3-agonist
    • IND:
      • monoth. in early parkinsons disease
      • adjunct with L-DOPA in advanced disease
    • oral
    • renal elim
  • Ropinirole
    • D2 agonist
    • IND:
      • monoth. in early parkinsons disease
      • adjunct with L-DOPA in advanced disease
    • oral
    • Hepatic metab
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7
Q

Dopamine agonists side effects and drugs

A
  • pramipexole
  • ropinirole
  1. anorexia
  2. nausea
  3. constipation
  4. postural hypotension
  5. dyskinesia
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8
Q

MAO-I

A
  • selegiline
    • Inhibits MAO-B
    • IND:
      • monoth. in early parkinsons
      • adjunctive with L-DOPA /carbidopa in advanced disease
    • oral
    • long T1/2
    • hepatic metb. to form des-methyl-selegiline (neuroprotective) and amphetamine (psychosimulant)
    • hungarian development!!!!
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9
Q

MAO-I SE

A
  • Serotonin syndrome with
    • meperidine (opioid)
    • SSRI
    • TCA
  • dyskinesia
  • psychosis
  • hypotension
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10
Q

COMT inhibitors

drugs, ind, administration

A
  • Entacapone
    • Block L-DOPA metabolism in periphery (COMT-inhib)
    • IND:
      • parkinsons disease (prolongs L-dopa actions)
    • oral
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11
Q

COMT-I SE

A
  • entacapone, tolcapone
  • related to increased L-DOPA levels
  • sleep disorders
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12
Q

Amantidine MOA , admin, eliminatio

A
  • anti-viral medication
  • enhances dopaminergic neurotransmission by:
    • increasing synthesis/release
    • or decreases reuptake of dopamine.
  • Muscurinic-block
  • NMDA receptor antagonists with neuroprotective properties. (like memantine)

oral

renal elimination

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13
Q

Amantidine clinical use

A
  • Parkinsons disease (adjunct to levo-dopa/carbidopa)
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14
Q

Amantidine SE

A
  • livedo reticularis ( dermatological)
  • psychosis
  • GI disturbances
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15
Q

Procyclidine MOA,

A
  • Anti-muscurinic (Ach blocking agent)
    • decreases excitatory acitivity of cholinergic neurons
    • improves tremor and rigidity
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16
Q

Procyclidine, adminis, clinical use

A
  • oral
  1. parkinsons disease (not recommended as monotherapy in early disease)
  2. drug induced extra-pyramidal symptoms
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17
Q

Procyclidine SE

A
  • atropine like effects
    1. dry mouth
    2. urinary retension
    3. constiptaion
    4. hyperthermia
    5. sinus tachy
    6. mydriasis
    7. blurred vision
    8. toxicity: cardiotoxic, convulsions, coma
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18
Q

Procyclidine CI

A
  • glaucoma
  • prostatic hyperplasia
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19
Q

Alzheimer drugs

A

Rivastigmine- AchE inhib.
Memantine- NMDA-R blocker
אתה ממתין שסבתא תיזכר כי יש לה אלצהיימר

Piracetam- nootropic. Helps with cognitive functions
זו תרופה שהיא פיראטית

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20
Q

Rivastigmine

MOA, IND, Administration, SE

A
  • Ach-Esterase inhibitor (centrally acting)
  • oral
  • IND:
    • alzhiemers (1st line);
      (modest reduction in rate of congnitive function loss)
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21
Q

AchE inhibitor rivastigmine SE

A

SE:

​

  • bradycardia
  • diarhhea
  • nausea, vomit
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22
Q

Memantine MOA, IND, Administration

A
  • glutamate NMDA-R blocker
  • oral
  • alzhiemers disease
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23
Q

memantine se

A

SE:

  • Confusion
  • Agitation
  • Restlessness
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24
Q

Nootropic drug

A
  • Piracetam
    • interferes with neurotransmitter realease by binding to synaptic vesicle protein (SV2A) ( protein involved in vesicle docking, fusion
  • therapeutic potential as congitive enhancer in treatment of
    • schizophrenia
    • depression
    • ADHD
    • PARKINSONS
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25
Drugs for GI spasm and uterus
* **Butyl-scopolamine** * **Solifenacin, Oxybutinin** * **Papaverine** * **Drotaverine**
26
Butyl-scopolamine MOA, IND
* M-blocker non selective * quaternary amine * IND : * smooth m spasm * abdominal, menstural cramps * spasmodic activity in GI , GU tracts
27
Solifenacin, oxybutinin MOA, administration, doa
* competitive antagonist (inverse agonist at all M-r but modest selectivity for M3 * Oxybutynin: oral, transdermal, * solifencacin : Oral * Duration: 12–24 h
28
SOLIFENACIN, OXYBUTININ indicatio
ind: * hyperactive bladder syndrome * urinary urgency, incontinence
29
Papaverine and Drotaverine moa
PAPA help me! Drota! like when you curse * CCB * PDE-Inhibitor ( non selective) * opioid alkaloid derivative
30
papaverine, drotaverin Administration, IND
* oral, parenteral IND: * GI, GU spasms
31
Agents relaxing pregnant uterus
* **Atosiban**- * Oxytocin antag. לעכב לידה Ato for Atopic * I.V infusion * IND: Tocolysis for preterm labor * effective from gestational week 24 * **Terbutaline**- * SABA. (Beta-2 selective agonist) * IND: * Relaxation of pregnany uterus * Prompt onset for acute bronchospasm * Aerosol inhalation, parenteral, oral * **Mg-**sulfate * i.v * IND: * tocolytic agent * seizure prevention in preeclampsia/eclampsia * protective role on fetal brain * * **Ethanol** * **​tocolytic** * **I.V**
32
Atosiban- MOA, ADMINISTRATION
* Oxytocin antag. לעכב לידה Ato for Atopic * I.V infusion
33
atosiban ind , se when is it effective
* IND: Tocolysis for preterm labor * se: * Concern about rates of infant death * not FDA approved **effective from gestational week 24**
34
Terbutaline- MOA, admin route
SABA. (Beta-2 selective agonist) Aerosol inhalation, parenteral, oral
35
terbutaline ind
IND: * Relaxation of pregnany uterus * Prompt onset for acute bronchospasm
36
Mg-sulfate Administration, IND
* i.v * IND: * tocolytic agent * seizure prevention in preeclampsia/eclampsia * protective role on fetal brain
37
Mg-sulfate SE
SE: * maternal : * lethargy, * headache, * weakness, * pulmonary edema, * cardiac arrest * neonatal * hypotension, * respiratory depression
38
location of H1-receptor and prototypic antagonist
* **H1:** * Brain, Endothelium, Smooth muscles, (BES) * Gq coupled (IP3, DAG) IGE-mediated response : * **Prototypic antagonist:** **Diphenhydramine, loratidine** * . ## Footnote **QSII**
39
location of H2-r and antagonist
H2: * Brain, Heart, Mast cell, Stomach (BHMS) * Gs coupled (cAMP) * mediates gastric acid secretion by parietal cells * + cardiac stimulant effect * + negative Fb reduces histamine release from mast cells: Cimetidine QSII
40
H3- receptor location , mechanism, antagonist
H3: * ​CNS, Nerve endings (CN) - * Gi (decrease cAMP) mediates * presynaptic modulation of histaminergic neurotransmission in CNS, * increases apetite * in periphery its a presynaptic heteroR with modulatory effects on release of other transmitters ( adrenergic n transmission) : Clobenpropit (investigational) - No agonist or antagonist of H3 and H4 receptors are available for clinical use QSII
41
H4-r location, mechanism, antagonist
H4: * CD4-T cells, * Leukocytes (esp eosinophils), * mast cells- Gi involved in chemotactic response : Thioperamide - No agonist or antagonist of H3 and H4 receptors are available for clinical use QSII
42
Enhanced cervical dilation
Drotaverine
43
Tocolytic drug meaning
Designed to inhibit contractions of myometrial smooth muscle cells delay your delivery for a short time (up to 48 hours) if you begin labor too early in your pregnancy.
44
Agents contracting uterus
OME is a women * **Oxytocin:** * **​**oxytocin-r agonist * I.V , intranasal * ind: * induction and augmentation of labor * control of postpartum uterine hemmorage (high dose) * induction of lactation (intranasal) * SE: * fetal distress, placental abruption, uterine rupture * **Misoprostol**- * PGE1 analog. סיום הריון 60 יום * oral * causes abortion in combo with mifepristone (progesterone antagonist) * effective up to 60 days into pregnancy * **Ergotamine**- * induces vasoconstriction and uterine contraction * ergot alkaloid derivative * parenteral * ind: * control of postpartum bleeding * (DONT give before delivery of placenta) Misoprostol+Mifepristone
45
Oxytocin MOA , administration
​oxytocin-r agonist I.V , intranasal
46
oxytocin ind
ind: * induction and augmentation of labor * control of postpartum uterine hemmorage (high dose) * induction of lactation (intranasal)
47
oxytocin SE
SE: * fetal distress, * placental abruption, * uterine rupture
48
Misoprostol- MOA, ADMINS
PGE1 analog. סיום הריון 60 יום oral
49
Misprostol ind, till when is it effective
* causes abortion in combo with mifepristone (progesterone antagonist) effective up to 60 days into pregnancy
50
Ergotamine- MOA, doa
* Partial agonist at * 5-HT * Alpha r * esp in blood vessels, uterus * ergot alkaloid * 10-12hr
51
ergotamine effect on vessel and uterus
induces vasoconstriction and uterine contraction
52
ergotamine ind, administration CI
parenteral ind: * control of postpartum bleeding * migraine * cluster headache (DONT give before delivery of placenta)
53
ergotamine SE
* Nausea, vomiting, diarrhea, * severe vasospasm
54
drugs acting on Male reproductive
**Tamsulosin**- * competitive antagonist at alpha-1 . ( Alpha1-selective blockers ) * BPH : reduce urinary hesitancy and prevent urinary retention in men with benign prostatic hyperplasia. * relaxes muscle of prostate and neck of bladder * SE: orthostatic hypotensive response to the first dose, little reflex tachy Sildenafil- PDE-5 inhib. * erectile dys * pulmonary hypertension * SE: * priapism (prolonged erection) * severe hypotension in combo with nitrates * blue-tinted vision (via inhibiting PDE-6 in retina)
55
Antiemetics
Piiii DOM DAD blahhhs it make me vomit * *Dimehydrinat**- H1 blocker * *Ondansteron**- 5HT3 blocker * *Palonosteron "**5HT3 blocker * *Metoclopramide**- D2 blocker * *Droperidol** D2 blocker * *Aprepitant**- NK1 antagonist * *Dronabinol**- CB1 cannabinoid agonist. When you smoke weed you feel like yor dron and you want to eat bino shawarma
56
Serotonin receptors location and antagonist
* 5-HT 1D/1B : Brain (Gi) ----- * 5-HT2 : Brain, Smooth m, Platelets (Gq) : **ketanserin** * 5-HT3: Area postrema(CNS), Sensory nerves, Enteric nerves (ligand gated Na/K ch) : **Odansetron** * 5-HT4 : presynaptic nerve terminals in the ENS (Gs) : **Tegaserod (partial agonist)** iq- ligand gated - s
57
5-HT1D/1B receptor location, action
* brain * Gi , decreases cAMP * IQ - ligand gated Na/K - I (all serotonin receptors mnemonic )
58
5-HT2 location, receptor mechanism, antagonist
* Smooth muscle * platelets * brain. (BPS) * Gq; ↑ IP3, DAG Ketanserin
59
5-HT3 location action antagonist
* Area postrema (CNS), * sensory nerves * enteric nerves Ligand-gated Na+/K+ channel ondansetron
60
5-HT4 location action antagonist
* Presynaptic nerve terminals in the enteric nervous system Gs; ↑ cAMP Tegaserod
61
dimenhydrinate MOA, DOA
* H1 blockers, first generation (Diphenhydramine, **dimenhydrinate**) * MOA: * Competitive block of _peripheral_ & _CNS_ H1 receptors * + α-block + M-receptor block. * Anti-motion sickness effect * DOA: 6-8 hrs
62
dimenhydrinate IND, admin
IND: * motion sickness * Anti-emetic * used orally as OTC sleep aid; adm: Oral, parenteral
63
dimenhydrinate SE
SE: * Sedation * autonomic block * Rare CNS excitation
64
Ondansteron- Palonosteron MOA
* 5-HT3 Blocker : Ondansetron, Palonosteron * blocks _chemoreceptor trigger zone_ + _enteric nervous system_ 5-HT3 receptors
65
ondansteron, Palonosteron IND ,administration
IND: **Anti-emetic** * Chemotherapy, radiation induced vomiting * postoperative vomiting Oral, IV
66
ondansteron, Palonosteron DOA, SE
* Duration: 3–6 h SE: * QT prolongation, * possible arrhythmias, * May slow colonic transit
67
Metoclopramide- MOA
* **Prokinetic agents** * D2 receptor blocker ; * increases gastric emptying and intestinal motility (_area postrema_ is also of value in **preventing emesis** )
68
Prokinetic agents :
* Metoclopramide, (D2 receptor blocker) * domeperidone, ( like metroclopramide but less CNS effct * cholinomimmetics * (neostigmine): * for colonic pseudo-obstruction in hospitalized patients * Macrolides: * erythrornycin useful in diabetic gastroparesis but tolerance develops
69
Metoclopramid, IND , administra
IND: Anti-emetic * Gastric paresis (eg, in diabetes) * antiemetic (surgical anasthesia, chemotheraperutic drugs) * Oral and parenteral formulations
70
metoclopramid se
SE: * if chronic use can cause * Parkinsonian symptoms due to block of CNS D2 receptors * other extrapyramidal effects * Hyperprolactinemia.
71
Droperidol MOA
* potent D2 blocker * + alpha-1 blocker
72
droperidol ind, se
IND: 1. anti-pscyhotic 2. anti-emesis (CHEMO, RADIO, post operative) SE: prolong QT
73
Aprepitant- MOA
* neurokinin 1 (NK1) blocker * moa: Tachykinin NK1 receptor blocker
74
aprepitant ind
* IND: * ANTI-emetic for chemotherapy-induced nausea and vomiting
75
aprepitant se
SE: * fatigue, * dizziness, * diarrhea, * P450 interactions se: Asthenia, hiccups
76
APREPITANT administration, doa
oral Half-life: 9–13 h
77
Dronabinol MOA ind se
* CB1 cannabinoid agonist * Anti-emetic * for use in chemotherapy-induced nausea and vomiting, * SE: associated with CNS marijuana effects
78
Drugs used for IBS
* **5HT-3 blocker** : Alosetron * Severe diarrhea-predominant IBS in women * oral * SE: due to se restricted use! * Rare but serious constipation * ischemic colitis * bowel infarction * **Anticholinergics:** nonselective action on GI activity; associated with typical antimuscarinic toxicity * dicyclomine and hyoscyamine are used as antispasmodics to relieve abdominal pain but efficacy not convincing * **Chloride channel activator:** lubiprostone = laxative (activate type 2 Cl- ch in small intestine) * in constipation-predominant IBS in women
79
Laxative
* Irritants and stimulants **:** * **Sennoside** the colon is So Blocked! * **Bisacodyl-** * Bulk-forming laxative**:** * **Plant fiber**- lubrication * osmotic laxatives * **Mg-sulfate/oxide/citrate** * **Lactulose** * lubricant laxative**:** * **Paraffin oil**
80
Irritants and stimulants (laxative)
the colon is So Blocked! * Sennoside. * a natural complex of anthraquinone glycosides * its degradation product acts as irritant on colonic wall \> induces fluid secretion and colonic motility * oral, rectal * Bisacodyl * potent stimulant of colon, acts on nerves in colonic mucosa
81
bisacodyl SE
SE: * abdominal cramps * atonic colon (prolonged use) * damage to enteric protective coating
82
Bulk-forming laxative:
* Plant fiber- (methylcellulose) : * indigestable parts of fruits, vegetable * forms gel in colon\> water retension \> intestinal distension \> increased peristalsis * increase volume, stimulate evacuation
83
osmotic laxatives
* Mg-sulfate/oxide/citrate * osmotic agents (non-absorbable salt) increase water content in stool. * oral * IND: * Simple constipation * bowel prep for endoscopy (especially PEG solutions) * SE: Mg may be absorbed and cause toxicity in renal impairment * Lactulose * cannot be hydrolysed by intestinal enzymes * oral, degraded by colonic bacteria into lactic , formic, acetic acid * also used in hepatic encephalopathy (decreases ammonia)
84
lubricant laxative:
Paraffin oil * Acts by facilitating passage of hard stool (lubricant) * taken orally, in upright position to avoid aspiration and lipid pneumonia
85
Antidiarrheal
Eating DAL is good for you gut * **Diphenoxylate**, **Loperamide**- (oral) * opioid derivatives, P450 metabolism * activate u-opioid receptors in ENS (inhibits Ach release) * **Activated charcoal** * ​attract and expel ingested toxins from GI tract * oral * IND: non specific, non infecious diarrhea
86
Diphenoxylate, Loperamide MOA, indication, administration
* (oral) * opioid derivatives, P450 metabolism * MOA- activate u-opioid receptors in ENS (inhibits Ach release) * slows motility * negligible CNS effect ( diphenoxylate high doses can cause CNS opioid effects and toxicity) * IND: non-specific, non-infecious diarrhea se:Mild cramping but little/no CNS effect
87
Liver and biliary drugs
* *N-acetylcysteine**- Acetaminophen toxicity * *Sillimarine**- for alcohol liver injury **ursodeoxycholoc acid** This silly marine drunk too much!!
88
N-acetylcysteine MOA , characteristics, clinical use , se
* provides SH groups * oral, I.V , inhaled * T1/2 =5-6 hrs * P450 metabolism * IND: * acetaminophen toxicity (within 8-10 hrs of overdose) * mucolytic agent (used in COPD , CF) * SE: * nausea, vomit, * anaphylaxis-like allergic rxn
89
Sillimarine MOA, characteristic, clinical use, SE
* derived from fruit and seeds of silybum marianum * support liver function * oral * IND: * Protects against liver injury caused by * alcohol * acetaminophen * amanita mushroom * antidote to amanita phalloides mushroom poisoning
90
ursodeoxycholoc acid (Ursodiol) moa, characterictics
* Reduces cholesterol secretion into bile \> dissolve cholesterol gallstones * potential anti-inflammatory effect in GI * oral
91
ursodeoxycholoc acid (Ursodiol) Clinical use, SE
* IND: * Gallstones in patients refusing or not eligible for surgery * primary biliary cirhosis (PBC) SE: little/no toxicity , diarhhea
92
drugs used in peptic ulcer disease
* Antacids- * **MgO , Aluminum-hydroxide** * H2-R antag.- * **Famotidine**. peptic ulcer is in the FAMily TIDINE is for allery suffix * PPI- * (**es) Omeprazol** and P**antoprazol (**Panting!) * Mucosal protection- * **Sucralfate**. Sugar fate is into the stomach. protective gel like
93
Antacids- drugs, administration, clinical use, SE
* **MgO , Aluminum-hydroxide** * **​**oral * poorly absorbed from bowel * OTC for symptomatic relief of heartburn * Not as useful as PPI and H2-blocker in peptic diseases SE of MgO: diarhhea SE: Al2(OH)3 : constipation
94
H2-R antag.- drugs, administration routes, DOA
* **Famotidine,** cimetidine, nizatidine, ranitidine peptic ulcer is in the FAMily TIDINE is for allery suffix * oral, parenteral * DOA: 12-24 hrs * CYP450 metabolism, inhibitor of cyp450 enzymes * reduce nocturnal acid but less effective than PPIs against stimulated secretion * very safe, available over the counter (OTC). * Cimetidine, but not other H2 blockers, is a weak antiandrogenic agent and a potent P450 enzyme inhibiton
95
H2-R blocker drug and SE
* **famotidine**, cimetidine, nizatidine, ranitidine * SE: * GI distress * antiandronergic effects : gynecomastia, decreased libido ( cimetidine) * confusion, agitation (elderly) * milder drug interactions
96
famotidine indication
reduce nocturnal acid but less effective than PPIs against stimulated secretion very safe, available over the counter (OTC). Cimetidine, but not other H2 blockers, is a weak antiandrogenic agent and a potent P450 enzyme inhibiton ind: * GERD * PUD * H.pylori ass ulcers * NSAIDs induced ulcers * prophylaxis against stress-related mucosal injury * Zollinger elson syndrome
97
PPI- MOA, DOA , administration route full supressing effect achieved in how many days?
* **(es) Omeprazol** and **Pantoprazol** (Panting!) * Irreversible blockade of H+/K+ ATPase in active _gastric parietal cells_ * oral (on empty stomach) , I.V * Half-lives much shorter than duration of action (T1/2= 1-2 hrs) * full supressing effect achieved in 3-4 days
98
PPI- indication
IND: * Peptic ulcer, * GERD, * erosive gastritis
99
PPI SE
SE: Low toxicity: * diarrhea, * abdominal pain, * headache. * hypergastrinemia (Chronic treatment ) * decrease oral bioavalability of VITB12 and drugs which require acidic environment for GI absorption (digoxin, ketoconazole) * small increase in the risk of respiratory and enteric infections * reduction of stomach acid may reduce absorption of some drugs and increase that of others * eg: omeprazole inhibits CYP450 ; effects * warfarin * phenytoin * diazepam
100
Mucosal protective agent in PUD administration, MOA, SE
* **Sucralfate**. Sugar fate is into the stomach. protective gel like * oral, 4x daily * prodrug: requires acidic pH ( antaacid, ppi, H2blocker interefe) * MOA: polymerizes at site of tissue damage and protects against further damage * very insoluble with no systemic effects * SE: constipation
101
Sucralfate indication
IND: * improves healing after mucosal damage * prevent re-occurance
102
Drugs acting on smooth muscle - contraction
\*controlled by ANS, hormones. - through Ca +2 DIRECT - cAMP\>\>MLCK (P/dephosphorylation) **Contraction:** * **Neurotransmitter:** * **​Ach (M) :** Betanechol (urinary retension), pilocarpine (glaucoma, contract ciliary m\> increase aquous humor\> decrease IOP * **E/NE** = endogenous mediator , act by alpha-1 * **Autacoids=** endogenous molecules which don't fall into traditional autonomic groups. They DONT act on cholinoR nor adrenoR but have powerful pharmacologic effect on smooth m and other tissue. They are produced at site of action and act there as local mediator. Short acting compounds, with broad spectrum of biological activity; acts on smooth m * **Histamine (biogenic amine)** * **Serotonin (5-hydroxytryptamine) - biogenic amine** * **Eicosanoids= arachidonic acid derivative (PG, LT)** * **​PGE2 (natural dinoprost) -** used in gynecology + contraction for labour * **PGF2 (carboprost)** * **TXA2** * **LTD4, LTE4 :** important in bronchoconstriction * **Angiotensin , VIP, Kinins** * **Polypeptides :** * **​Oxytocin** * **Angiotensin II** * **Endothelin (ETR1 |----** Bosertan (ETR1 BLOCKER) **--\> pulmonary hypertension** * **ATP-derivatives**

Pharmacology FINAL (2nd sem) (37 decks)

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