Pharmacology 1 Flashcards
Zero Order Elimination Drugs(4)
“PEA” ( a pea is round- shaped like the “0”)
- Phenytoin
- Ethanol (causes hangover!!)
- Aspirin(at high or toxic concentrations)
- cisplatin
Constant amount of drug elimination per unit time
Weak acids(3) eliminated in urine How treat overdoses?
- Phenobarbital
- Methotrexate
- Aspirin
Trapped in basic environment.
Treat overdose w/ Bicarbonate
Weak bases(2) eliminated in urine How treat overdoses?
- amphetamines
- TCAs
Trapped in acidic environment
Treat overdose w/ Ammonium chloride
Notoriously slow Acetylators
Significance
Asians»White/Af. Am
increase drug concentration–> increase drug reactions
Drugs with lower Therapeutic Index(4)
Whats the formula for Therapeutic Index?
- Digoxin
- Lithium
- Theophylline
- Warfarin (monitor PT/INR)
TI= ToxD50/ED50
(in animal studies= LD50/ED50)
Diazepam is an agonist at GABA-R
What effect does Flumazenil have on the GABA receptor?
Competitive antagonist (resembles substrate)
- decrease potency, no change in efficacy
- can be overcome with increased concentration of agonist substrate
NE is an agonist at alpha-R
What effect does phenoxybenzamine have on the alpha-R?
Noncompetitive antagonist
- decrease efficacy
- can’t be overcome by increased agonist substrate concentration
Morphine is a full agonist at the u-R.
What effect does buprenorphine have on the u-R?
partial agonist
- acts at same site as full agonist but with lower efficacy
Sypathetic G-protein type: a1 a2 B1 B2 B3
a1- q a2-i B1-s B2-s B3-s
Parasympathetic G-protein type: M1 M2 M3 What type of receptor is nAch-R
M1-q
M2-i
M3-q
nAch-R: ligand-gated Na/K channel (Nn and Nm)
Dopamine G-protein type:
D1
D2
D1-s
D2-i
Histamine G-protein type:
H1
H2
H1-q
H2-s
Vasopressin G-protein type:
V1
V2
V1-q
V2-s
Mnemonic for G-proteins
“After QISSeS(kisses), you get a QIQ(kick) out of SIQ(sick) SQS (super qinky sex)”
Which receptors are Gs linked?
B1-3, D1, H2, V2
Which receptors are Gi linked?
M2, a2, D2
“MAD 2’s”
Which receptors are Gq linked?
H1, a1, V1, M1, M3
“HAVe 1 M&M”
Hemicholium (experimental rat drug):
MOA
inhib choline transporter
prevent choline uptake into cholinergic axon
Vesamicol(experimental rat drug):
MOA
inhib vAchT (prevent Ach transport into vesicle in cholinergic axon terminal)
Botulium:
MOA
inhib SNAP-25
prevent Ach vesicle fusion for NT release
Metyrosine:
MOA
inhib tyrosine hydroxylase
prevent tyrosine–>DOPA
Reserpine (anti-pysch):
MOA
Important adverse
Inhib VMAT (prevent Dopamine transport into Noradrenergic vesicle) * decrease BP b/c prevents NE storage-->loose a1 vasoconstriction
Bretylium & Guanethidine (never used):
MOA
inhib Noradrenergic vesicle fusion at synapse –> inhib NT release
Amphetamine & ephedrine:
MOA
increase fusion of vesicles at Noradrenergic synapse–> increase release of all Monoamines
- Amphetamines use NET to enter presynaptic terminal, and use the VMAT to enter vesicle. This displaces NE from vesicle. Once NE reaches threshold concentration w/in terminal–>reverse NET and NE is expelled into Synaptic Cleft contributing to increased NE observed
Cocaine & TCAs & Amphetamine:
MOA
inhib reuptake transporter & inhib DA transporter
–>many monoamine’s reuptake inhibited–> Feel great and jacked up
ACEi effect on adrenergic-R in axon
inhib AT-II binding to “Release-modulating receptors”
–>prevent release of monoamines
Precursor to Tyramine (enzyme for conversion)
Enzyme which degrades Tyramine
Foods which contain Tyramine
- Tyrosine–>tyramine via tyrosine decarboxylase
- degraded by MAO
- Cheese and Wine
Describe D-D Tyramine & MAOi interaction
- Excess tyramine enters presynaptic vesicles and displaces other NTs
- increase active presynaptic NTs
- increase NT diffusion in cleft
- increase sympathetic stimulation
- –>HYPERTENSIVE CRISIS
Buproprion: MOA Use (2) Adverse(4) Sexual effect?
-increase Ne/DA via unknown MOA
Uses: 1. depression 2. smoking cessation
- Tachycardia
- insomnia
- HA
- seizures in ANOREXICS
* NO SEXUAL SIDE EFFECTS
Describe the C. botulinum toxin: type of toxin MOA site of action Where do adults get toxin Where do babies get toxin Antidote
-heat-labile toxin (protease) cleaves SNARE
-Toxin inhib Ach release at NMJ–>Flaccid paralysis
-Adults= inject preformed toxin
-Babies= ingest Honey spores–>Floppy Baby
Tx: Anti-toxin
Can Dopamine cross BBB?
Can L-DOPA cross BBB?
No
Yes
Direct Cholinergic agonists:
Name (4)
- BethaneCHOL
- CarboCHOL
- MethaCHOLine
- Pilocarpine
Bethanechol: Action Effects Use (3) ACHE effect
“Bethany, call me to activate bowels and bladder”
- Post-op ileum
- neurogenic ileus (common in DM)
- urinary retention
- resistant to AchE
Carbachol:
Description
Use (1)
CARBon copy of AcetylCHOLine
1. open-angle glaucoma (constricts pupil and relieves IOP)
Methacholine:
MOA
Use (1)
Stimulates mAchR in airways when inhaled
1. Asthma challenge test (measure FEV1 and FVC)
Pilocarpine:
MOA
ACHE effect
Use(4)
- Contract CiliaryM. and pupillary Sphincter
- resistant to AchE
1. stim Sweat, tears, & saliva
2. Open angle glaucoma (ciliary m.)
3. Closed angle glaucoma (sphincter m.)
4. Sjogrens (xerostomia)
“you cry, drool, and sweat on your PILOw”
another term for anti cholinesterase
overall effect
- indirect agonists
- increase Ach
3 anticholinesterases used to treat Alzheimers
- Donepezil
- Galantamine
- Rivastigmine
Edrophonium:
Use
Half-life
Diagnosis Myesthenia Gravis historically
(now diagnosed by anti-ache Ab test)
very short acting
Neostigmine:
Use(3)
CNS penetration
- post-op/neurogenic ileum & urinary retention (like bethanachol
- Myasthenia gravis
- Reversal of NMJ blockade (post-op)
No CNS penetration (quaternary amine) “Neo CNS”
Physostigmine:
Use
CNS penetration
“PHYsostigmine ‘PHYxes’ atropine overdose
1. Anticholinergic toxicity
CNS penetration (tertiary amine)
Pyridostigmine:
Use
CNS penetration
Half-life
“PyRIDostiGMine gets RID of Myasthenia Gravis”
1. Myasthenia gravis (increase muscle strength)
No CNS penetration (quaternary amine)
Long-acting
2 drugs used to treat Myasthenia Gravis
- NEOstiGMine
- PyRIDostiGMine
(neither cross BBB)
2 Contra/Caution for all cholinomimetic agents (both direct and indirect agonists)
- COPD/Asthma exacerbation
2. Peptic Ulcers (in susceptible patients)
Symptoms of Cholinesterase inhibitor poisoning
Who is the typical patient on Boards? Typical cause?
Farmer with organophosphate poisoning like parathion "DUMBBELSS" Diarrhea/N Urination Miosis Bronchospasm Bradycardia Excitation of Sk.Muscle/CNS Lacrimation Sweat Salivation -->Respiratory failure if untreated
Antidote for cholinesterase inhibitor poisioning (2)
- atropine (competitive inhib)
2. pralidoxime (regenerates AchE if given early)
3 drugs which produce Mydriasis and Cycloplegia
- atropine
- homatropine
- tropicamide
Muscarinic antagonist to treat
Parkinson’s/ Acute dystonia
Benztropine
“park my Benz”
2 uses for Glycopyrrolate
“‘GI’copyR(resp)rolate”
parenteral: pre-op reduction of airway secretions
oral: drooling and peptic ulcers
No cross BBB
2 muscarinic antagonists to treat Irritable bowel Synd
- Hyoscyamine
2. Dicyclomine
2 muscarinic antagonists to treat COPD/Asthma
- Ipratropium
- tiotropium
“TIO PRAys to breath”
4 drugs to treat Overactive bladder/urge incontinence
” On the Darn Toilet, Sorry”
- Oxybutynin
- Trospium
- Darifenacin
- Tolterodine
- Solifenacin
Drug to treat motion sickness
Scopolamine
Atropine Effects: Eye Airway Stomach Gut Bladder
dilate/cycloplegia decrease secretions in airway decrease stomach acid secretions decrease GI motility decrease urgency in cystitis
Atropine:
Use
Adverse
Blocks DUMBBeLSS in cholinesterase inhib poisoning. DOES NOT BLOCK ‘E-EXCITATION OF SK.MUSCLE/CNS WHICH AR MEDIATED BY nACH-R
- Hot as a hare (M3)
- Dry as a bone (M3)
- Red as a beet (M3)
- Blind as a bat (M3)
- Mad as a hatter (M1 in CNS
Atropine:
CONTRA (3)
- Elderly (can cause Closed angle glaucoma via mydriasis)
- Men with BPH (urinary retention)
- infants (hyperthermia)
Effect of Jimson weed (Datura)
Chemicals causing effect (2)
Gardener’s pupil
MYDRIASIS due to plant alkaloids (ENLARGED FROM SPHINCTER PARALYSIS)
- scopolamine
- atropine
Albuterol/ Salmeterol:
Receptor target
Use
B2>B1 (COPD/Asthma)
Albuterol (SABA)
Slmeterol (LABA)
Dobutamine:
Receptor target
Use (2)
B1>B2, a
- HF (inotropic>chronotropic)
- cardiac stress testing
Dopamine:
Receptor target
Use (3)
Dose dependent actions
D1=D2>B>a
- unstable bradycardia
- HF
- shock
Low dose (Beta)-->inotropic and chronotropic effects High dose (alpha)-->vasoconstriction
Epinephrine:
Receptor target
Use(3)
Dose dependent actions
B2/B1>a (methyl group addition from Ne–>Epi)
- Anaphylaxis
- Asthma
- Open-angle glaucoma
High dose–>alpha effect predominate
Fenoldopam:
Receptor target
Use(4)
Potential adverse(2)
D1 (“FenolDOPAM”)
- post-op hypertension
- hyeprtensive crisis
- vasodiltor (coronary, peripheral, renal, and splanchnic)
- promote naturesis
Potentially cause hypotension and tachycardia
Isoproterenol:
Receptor target
Use
potential adverse
B1=B2
1. electrophysiologic eval of tachyarrhythmias
potentially can worsen ischemia
Midodrine:
Receptor target
Use(2)
potential adverse
a1
- autonomic insuff.
- postural hypotension
potentially exacerbate spine hypertension
Norepinephrine:
Receptor target
Use(2)
a1»a2>B1
- hypotension
- septic shock
Phenylephrine:
Receptor target
Use(3)
a1>a2
- hypotension (vasoconstriction)
- ocular procedures (mydriatic)
- rhinitis (decongestant)
Amphetamine:
MOA(3)
Use (3)
Indirect general agonist, reuptake inhib, release stored catecholamines
- Narcolepsy
- obesity
- ADHD
Cocaine:
MOA (2)
Use(1)
Indirect general agonist, reuptake inhib
- vasoconstrictor/ local anesthetic for Rhinoplasty
Cocaine:
What should never be given if cocaine intoxication is suspected?
Why?
BB
–>can lead to unopposed a1 activation–>extreme HTN
Ephedrine:
MOA(2)
Use (3)
indirect general agonist, releases stored catecholamines
- Nasal decongestion
- Urinary incontinence
- Hypotension
Which dopamine receptor is generally in PNS?
CNS?
**exceptions to this rule do exist
PNS–> D1 (perpheral, coronary, renal, splanchnic circulations for widespread vasodilation)
CNS–>D2
Low dose DA stimulates?
High dose DA stimulates?
low= D1 (vasodilation) high= a1(vasoconstriction)
Clonidine/ Guanfacine:
MOA
Use(3)
Adverse (5)
a2-agonist (Gi)
Use: 1. hypertensive urgency 2. ADHD 3. Tourette
Adverse:
- CNS depression
- Bradycardia
- Hypotension
- Resp depression
- Miosis
alpha-methyldopa:
MOA
Use (1)
Adverse (2)
a2-agonist (Gi)
Use: HTN in pregnancy
Adverse:
- Direct Coombs (autoimmune hemolytic anemia)
- SLE-like syndrome (check anti-histone) (“Lupus is SHIPP-E, but not included)
Effects of a2 stimulation
Sympatholytic:
- decrease SNS
- decrease insulin release
- decrease lipolysis
- decrease aqueous humor prod. in eye
- increase platelet aggregation
Nonselective a-blockers:
Name (2)
which is reversible vs. irreversible?
Shared adverse (2)
- Phenoxybenzamine- irreversible
- Phentolamine- reversible
“PhenTOLamine is TOLtally reversible” - Orthostatic Hypotension
- Reflex tachycardia (via baroreceptors)
Phenozybenzamine:
MOA
Use(1)
nonselective, irreversible a-blocker
- Pheochromocytoma (pre-op) to prevent Hypertensive crisis
* classic question on boards!!!
Phentolamine:
MOA
Use(1)
nonselective, reversible a-blocker
“PhenTOLamine is TOLtally reversible”
- Give to patient on MAOi’s who eats tyramine containing foods (prevent hypertensive crisis)
* classic question on boards!!!
Prazosin Terazosin Doxazosin Tamsulosin: MOA Use (3) Adverse(3)
a1 selective blockers (all end in ‘-osin’)
- BPH urinary symptoms
- PTSD (‘P’razosin)
- HTN (except tamsulosin
Adverse: 1. 1st dose orthostatic hypotension 2. Dizzy/HA
Mirtazapine:
MOA
Use (1) & How
Adverse (3)
a2 selective blocker
Treat Depression
(no (-)feedback–> increase 5-HT/NE/DA release)
- sedation
- increase cholesterol
- increase appetite
BBs:
Name (12)–>”-olol”
- Acebutolol (partial agonist)
- Atenolol
- Betaxolol
- Carvedilol
- Esmolol
- Labetalol
- Metoprolol
- Nadolol
- Nebivolol
- Pindolol (partial agonist)
- Propranolol
- Timolol
- A-M= B1 selective
- N-Z= B2 selective
- Nonselective a and B antagonists have modified suffixes: CarvedILOL & LabetALOL
BB effects on:
Angina Pectoralis
MI
HTN
Angina: decrease HR–>decrease O2 consumption
MI: decrease mortality
HTN: decrease CO & decrease Renin secretion via block of JGA cells (B1-R)
BB:
2 drugs to treat SVT:
MOA
(supraventricular tachycardia)
Class II antiarrhythmics:
- metoprolol
- Esmolol
decrease AV conduction velocity
BB:
3 drugs to treat Heart Failure
- Bisoprolol
- Carvediol
- Metoprolol
decrease mortalilty
BB:
1 drug to treat glaucoma
MOA
Timolol (‘Timmy can BBarely see’)
decrease secretion of aqueous humor (B2=ciliary process)
BB:
2 drugs for variceal bleeding
MOA(2)
- Nadolol
- Propranolol
decrease hepatic venous pressure gradient
decrease portal hypertension
BB:
Adverse(4)
- Erectile dysfunction (not really true though)
- CV- bradycardia, AV block, HF
- CNS- seizures, sedation, sleep alterations
- dyslipidemia (metoprolol
- asthma/COPD exacerbations (Never use nonselective BB in these pts)
BB:
2 Contraindications
Can diabetics use BB
- Cocaine use: risk of unopposed a-adrenergic agonist activity
- COPD/Asthma (nonselective BBs contra)
Despite theoretical concern of masking hypoglycemia in DM, benefits likely outweigh risks (NOT A CONTRA)
BB:
2 drugs which are partial agonists
- acebutolol(B1 selective antagonist) (partial agonist)
2. pindolol (B2 selective antagonist) (partial agonist)
BB–>Nebivolol:
MOA/Receptors involved
combines B1-block with B3-R stim –>increase NO release–>Sm. Muscle relaxes–> decrease TPR/Afterload
Importance of B1 selective blocking?
cardio selective
decrease HR/contractility/CO/MVO2
3 important varicies
2 BB drugs to treat vatical bleeding
- esophageal–> 30% chance of killing patient
- umbilical
- rectal
Tx: Propranolol, Nadolol
3 Ingested Seafood toxins
- tetrodotoxin
- ciguatoxin
- Histamine from scombroid poisoning
Tetrodotoxin: geographic / source Action Symp (4) Treatment
- Japan/ pufferfish
- highly potent, binds fast VGNa Channels in Cardiac/Nerve–>prevent depolarization
- N/D 2. Paresthesias 3 Dizzy 4. Weakness/Loss of Reflexes
Treat: supportive
Ciguatoxin: geographic source(3) Action Symp Treatment
- 20% foodborne toxin in USA
- barracuda, snapper, moray eel
- Opens Na+ channels–>depol in all memb
- Symp: mimic Cholinergic poisoning (N/V/D/abd. pain after fish)
Treat: supportive
Scamboid Poisoning: Source(4) Action Symp/ Misdiagnosis Treatment
- Spoiled dark-meat fish (tuna, mahi-mahi, mackerel, bonito)
- histadine–>histamine via Bacterial histidine decarboxylase
-symp mimic Anaphylaxis (misdiagnosed as fish allergy)
(burning of mouth, flushing, erythema, urticaria, itching–>broncospasms/angioedema/hypotension
Treat: 1. Anti-histamines 2. Albuterol/Epi if needed