Pharm DIT Flashcards
Parasympathetic Nerves
CN 3, 7, 9 ad 10
2nd and 3rd sacral spinal nerves
AChE block due to ?
Antidote?
organophosphate poisoning - see excess cholinergic effects
Atropine and pralidoxime
Location of ACh receptors - Nicotinic and muscarinic
Nn - parasympathetic pre-ganglia synapse
Nm - neuromuscular junction for somatic transmission
Muscarinic - parasympathetic post ganglia synapse
- Odd one of muscarinic receptor for sympathetic stimulation of sweat glands
Sympathetic length of preganglionic nerves vs parasympathetic
Sympathetic nerves are short pre ganglionic and long post ganglion - pretty much all turn on at once
parasympathetic ganglionic have longer preganglionic neurons -> more selectivity
Parasympathetic activation -> (9) GI Bladder Eye Lung Heart Lacrimal Salivary glands Uterus Penis/cliterus
GI - increased digestion -> more transit and increased recall sphincter tone Bladder - wall contraction and relaxed sphincter Eye - mitosis and ciliary contraction Heart - decreased HR and contractility Lung - bronchospasm Lacrimal gland - stimulates tears salivary gland - water secretion Uterus - contracts Penis - erects
Why choniergic excess not the same as parasympathetic activation?
organophosphate poisoning-
Have some nicotinic receptors at the neuromuscular junction that are activated and not parasympathetic
Also have sweat glands w/ muscarinic receptors that are sympathetic innervated
DUMBBELLS
Presentation of ptosis and diplopia that worsens throughout the day is?
Test w/?
Rx?
myasthenia Gravis
Edrophonium - tensilon test
Pyridostigmine
Thyectomy might be implicated in this disorder of general weakness
Myasthenia gravis
Direct Agonists - Cholimetric (4)
-chols
bethanechol - urinary retention or illeus
carbachol - glaucoma
Pilocarbine - salivattion stimulant
Methacholine - asthma test inducer
Old test for asthma
methacholine challenge - ACh agonist
Potent stimulator of sweat, tears and saliva
pilocarbine
Cholinergic agonist used to treat glaucoma
carbachol
Cholinergic used for urinary retention or postoperative ileus
Bethanechol
Indirect agonists (anticholinesterases) (6)
-stigmines
Neostigmine - reverses neuromuscular blockafe, myasthenia gravis (NO CNS)
pyridiotigmine - myasthenia gravis
edrophonium - short acting
physostigmine - Atropine overdose (CNS action)
Alzeheimer drugs - doneprezil, galantine, rivastigmine
Ecothiophate - open angle glycoma
Alzheimer drugs work by?
3?
indirectly increasing the ACh
Doneprezil
rivastigmine
galantamine
Side effects of atropine overdose?
muscarinic blockade
hot as a hare - hyperthermia
dry as a bone - decreased secretions
red as a beet - flushing
blind as a bat - cyclopegia (loss of accommodation w/ ciliary muscle)
mad as a hatter - delirium
bloated as a toad - illeus and constipation
Have a elderly patient that has acute onset of delirium look for?
Change in medications and addition of an anticholinergic
be wary of anti-muscarinics as well
Anticholinergic Drugs (4)
1st Gen H1 - diphenhydramine -doxylamine - chlorpherniramine Neuroleptics - thioridazine -chlopromazine - clozapine -olanzapine Tricyclic antidepressants Amantidine
Anticholinergics used in Rx of urge incontinence (4)
On The Darn Toliet
oxybutynin
tolteridine
Darifenacin/solifenacin
Trospium
Eye dilation short term (3)
Homatopine
tropicamide
Cyclopentolate
-act as antimuscarinic
Rx for tremors and rigidity seen w/ Parkinson’s meds
Benztropium
anti - muscarinic
Rx for motion sickness and decreases salivation
Scopolamine
Anti muscarinic Rx for COPD
Ipratropium
Tiotropium
Alpha 1 stim (5)
vascular smooth muscle contraction
pupillary dilator contraction -> mydriasis
intestinal and bladder sphincter contraction
increased peripheral resistance (reflex bradycardia)
increase BP
Alpha 2 stim (2)
inhibits NE release on presynaptic auto receptor
lowers insulin release acting on pancreatic Beta cells
Beta 1 stim (4)
increase HR
Increase contractility
increase in Renin
increase in lipolysis
Beta 2 stim (5)
bronchodialation vasodilatation (minimal) increase in HR (secondary) increase lipolysis decrease uterine tone - tocolysis
Rx for pheochromocytoma
alpha antagonist - nonselective
Phenoxybenzamine
HTN medication in pregnancy
STOP what drug?
alpha methydopa
Ace inhibitor
Selective Alpha1 a d blocker used in BPH
Tamsulosin
nonselective alpha blockers (2)
phenoxybenzamine - irreversible
phentolamine - reversible
Alpha 1 selective blocker ? (3)
USed for
HTN and urinary retention w/ BPH
- zosins
parazosin
terazosin
doxazosin - tamsulosin
alpha 1 and Beta 1 blockers (2)
used for
carvediol
labetelol
used for slowing the heart and lowering peripheral resistance
Partial beta agonists -> antagonist (2)
Useful for ?
acetebutolol
pindolol
useful for HTN w/ bradycardia, NOT for CAD
Nonselective Beta blockers(3)
Worry about using in who?
propranolol
nadolol
timolol
do not use in asthma/COPD or emphysema due to loss of beta 2 -> bronchospasm
Selective Beta 1 blockers(3)
esmolol
atenolol
metoprolol
betal blockers used in glaucoma
Opthalmic use
(beta 2 blocking of aqueous humor)
Nadolol
timolol
Beta blockers are primarily used for (6)
Angina pectoris (CAD) HTN aortic disection Anxiety SVT Gaucoma (timolol)
Maybe CHF(pulm edema worries), hyperthyroid symptoms, migrane prophylaxis
Worrisome Side effects of Beta blockers (3)
bradycardia and AV block -> CHF
masking of hypoglycemia in beta blockers
bronchospasm w/ nonselective beta blockers
3 enzymes used in the production epinephrine/NE
2 cofactors?
-Phenylalanine start
phenylalanine hydroxylase
-tyrosine(brought in w/ Na) tyrosine hydroxylase (blocked by metyrosine)
-LDOPA dopamine decarboxylase (w/B6
-NE-> Epi w/ Vitamin C
drug inhibiting the packaging of ACh
Vesamicol
Drug inhibiting the packaging of NE
reserpine
Natural stimulator for the release of ACh and NE from the presynaptic terminal
Ca 2+
Black widow spider toxin has what effect on nerve transmission
increases the release of ACh leading to spastic paralysis and cholinergic excess
What toxin causes flaccid paralysis at the cholinergic junction
Botulinism
Choline is brought into the cholinergic nerve by what mech?
What inhibits this?
Na cotransport brings in
Hemicholinium inhibits
Enzyme making ACh
choline acetyltransferase combining acetyl Co A and Choline
then packaged in vesicles
4 things that can happen to ACh in the synaptic cleft
bind to receptor
bind to autoreceptor - presynaptic regulating release
diffuse away
acted on by AChE which lyse into choline(recycled) and Acetyl coA
4 things that can happen to NE in the synaptic cleft
Act on Alpha 1, Beta 1 and 2 post synaptic neuron Act on Alpha 2 prenaptically Reuptake into presynaptic Metabolized - COMT -> methylation -MAOI - > oxidizes
Drugs blocking reuptake of NE in synaptic cleft (2)
TCAs and Cocaine
4 substances that induce the release of NE in the synaptic cleft
Ca - natural
Amphetamine
Tyramine
Ephedrine
2 drugs that block NE release
Guanethidine
betrylium - Ca channel blocker
angiontensin II effect on the presynaptic Noradrenergic neuron
leads to increase in NE release
Alpha2 and M2 on presynaptic noradrenergic neuron
decreases NE release
Gq uses what receptors
Qc HAVe 1 M&M
Gq uses H1 alpha1 Vasopressin 1 M1 M3
Gi uses what receptors
MAD 2s
M2
Alpha 2
D2
Gs uses what receptors
Leftovers from
Qc HAVe 1 M&M
MAD2s
Beta1 beta2 D1 V2 H2
Receptor Gq pathway
4 steps
other way to get this path?
phospholipase C
PIP2 from lipids spit to DAG and IP3
DAG -> Protein Kinase C
IP3 -> release Ca (smooth muscle contraction)
Tyrosine Kinase (does the Ras path too)
Receptor Gs pathway
2 steps
implicated in what disease?
adenylyl cyclase converts ATP ->cAMP
cAMP levels activate protein kinase A
implicated in Cholera
Receptor Gi pathway
2 Steps
implicated in what disease
BLOCKS adenylyl cyclase from converting ATP ->cAMP
low cAMP levels DO NOT activate protein kinase A
implicated in pertussIs
H1 vs H2 stimulation ->
3 vs 1 function
nasal and bronchial mucus secretions and contraction of bronchioles and puritus
vs
gastric acid secretion
V1 vs V2 stimulation
increased smooth muscle contrition (pressor in codes)
vs
increased reabsorption of H2O in the collecting tubules (2 for 2 kidneys)
M1 vs M2 vs M3
enteric nervous system
decreased HR and contractility (SA node)
increased gland secretion, gut peristalsis, bronchconstriction, bladder contraction, mitosis, ciliary muscle contraction (accommodation)
D1 vs D2
relaxes the renal vasculature
modulates brain NT
Km =
related to?
affected by?
amount of substrate needed for 1/2 Vmax
inversely related to affinity. higher affinity -> smaller Km
affected by competitive inhibition
Vmax
related to?
Affected by?
the maximum rate at which a reaction proceeds
directly relates to enzyme concentration
- affected by noncompetitive inhibiors
Linewaver burk plot
x- axis
Y axis
Slope
x axis = 1/-km
y axis = 1/vmax
slope =Km/Vmax
Role of Noncompetative inhibitor on
Vmax
Km
As seen on lineweaver
Vmax decreases - seen as a higher y intercept
Km does not change - seen at the same point
Role of competitive inhibitor on
V max
Km
As seen on lineweaver
V max does not change - hits the same y axis
Km increases ( need more substrate to get 1/2 Vmax)
-seen as a x intercept closer to zero
Adding an enzyme affects the line weaver plot how?
The 1/-Km (x axis does not change)
The y axis (1/Vmax) drops down closer to zero
Increasing the affinity of a drug affects the line weaver plot how?
The (1/Vmax, y axis, does not change) no added enzyme
The x axis( 1/-Km) shifts to the left,
Higher affinity means a smaller Km
-vs an x axis shift to the right (closer to 0) means more substrate is needed due to lesser affinity (same as giving a competitive inhibitor)
drug is infused how long to reach steady state?
4-5 half lives to 94% Concentration
How would you drop a dose by half if toxic levels seen in a patient?
Stop the infusion for one half life
Kidney trouble will affect which loading dose and maintenance dose how if renal cleared?
No change on loading dose
Decreases maintenance dose
efficacy of a drug is?
what can drop efficacy? (2)
the MAX EFFECT a drug can produce, related to Vmax. NEED to know max response of a drug to determine efficacy
noncompetitive antagonists and partial agonist
potency of a drug is?
what can drop the potency
the DOSE of a drug needed to achieve a given effect, inversely related to Km
competetative inhibitors can decrease potency - shift the curve to the right
Partial agonists can have variable effects on potency while always dropping the efficacy
Therapeutic Index =
LD50/ED50
Lethal dose for 50%/Effective dose for 50%
What is better when looking at therapeutic index - high or low value?
ex of poor therapeutic index drugs? (4)
High therapeutic index - more dose needed to kill than compared to needed to have therapeutic effect.
Warfarin, lithium, anti-seizure, digoxin
Phase 1 metabolism completes the following reactions (3)
to get what metabolites?
reduction
oxidation
hydrolysis
slightly polar, water soluble, slightly active(toxic or prodrug active)
Phase 2 metabolism completes the following reactions? (4)
to get what metabolites
Glucuronidation
acetylation
Sulfation
methylation
Inactive, VERY polar metabolites -> renal excreteted
Geriatric patients lose this metabolism 1st?
Cyp 450 is characterized by this metabolism?
Phase 1 - reduction/oxidation/sulfation
Phase 1 again
Slow acetylators means what?
Phase II metabolism is impaired and going to see higher drug levels in patients w/ increased toxicity and side effects
2 enzymes in alcohol metabolism and drugs that inhibit them
limiting reagent in both?
alcohol dehydrogenase - fomepizole
acetaldehyde dehydrogenase -disulfiram
NAD which picks up the H -> NADH
Disulfram like reaction drugs?(4)
metronidazole
certain cephalosporins
procarbazine
1st gen sulfaureas (tobutamide)
11 drugs that induce Cyp 450
CRACK AMIGOS
Cimetidine Ritonavir = protease inhibitors Amiodarone Ciprofloxacin Ketoconazole
Acute Alcohol Macrolides Isoniazid Grapefruit Juice Omeprazole Sulfonamide
7 drugs that inhibit Cyp 450
Guiness, Coronas, and PBRS induces CHRONIC ALCOHOLISM
Griseofulvin Carbamazapine Phenytoin barbituates Rifampin St johns Wart Chronic Alcoholism
ASA overdose how do you clear it?
Acidic drugs you want to alkalinize the urine by given NaHCO3
HA -> H + A-
(shifts the formula to the L by taking away Hs) A- is an anion that gets trapped in the urine
Amphetamine overdose how do you clear it?
Basic drugs you want to acidify the urine by giving NH4Cl
BH+ <- H + B
(shifts the formula to the R by adding more H and trapping the polarized basic drug in the urine
