-
ACh Receptors: Na+/K+ channels
Nicotinic ACh receptors
-
ACh Receptors: G-protein-coupled receptors
Muscarinic ACh receptors
-
G protein linked 2nd messengers: a1
Q
NE and Epi
increase vascular smooth muscle contraction, pupillary, sphincters
-
G protein linked 2nd messengers: a2
I
NE and Epi
decrease sympathetic outflow
-
G protein linked 2nd messengers: B1
S
NE and Epi
increase heart rate, contractility, renin release
-
G protein linked 2nd messengers: B2
S
NE and Epi
vasodilation, bronchodilation, decreased uterine tone, increased HR and contractility
-
G protein linked 2nd messengers: M1
Q
ACh
CNS/ENS
-
G protein linked 2nd messengers: M2
I
ACh
Decrease heart rate and contractility of atria
-
G protein linked 2nd messengers: M3
Q
ACh
increased bronchoconstriction, bladder contraction
-
G protein linked 2nd messengers: D1
S
Dopamine
renal vascular relaxation
-
G protein linked 2nd messengers: D2
I
Dopamine
Brain NT release
-
G protein linked 2nd messengers: H1
Q
Histamine
increased nasal mucous production
-
G protein linked 2nd messengers: H2
S
Histamine
increase gastric acid
-
G protein linked 2nd messengers: V1
Q
ADH (vasopressin)
increase vascular smooth muscle contraction
-
G protein linked 2nd messengers: V2
S
Vasopressin (ADH)
increase water permeability and reabsorption in kidney collecting tubules
-
What are the symptoms of excess parasympathetic activity?
- Diarrhea
- Urination
- Miosis
- Bronchospasm
- Bradycardia
- Excitiation of CNS / Skeletal muscle
- Lacrimation
- Sweating
- Salivation
-
Name the cholinomimetic direct agonists and their primary use.
Bethanechol - ileus, urinary retention (Bethany call to relieve bowels and bladder)
Carbachol - glaucoma
Pilocarpine - stimulates tears, sweat, saliva
Methacholine - Dx asthma
-
Name the anticholinesterases (indirect agonists) and their primary use.
Neostigmine - ileus, urinary retention
PyRIDostigmine - myasthenia gravis (gets RID of MG)
Physostigmine - Glaucoma, atropine OD
Edrophonium - Dx MG
Echothiophate - glaucoma
Donepezil - alzheimers
Galantamine - alzheimers
Rivastigmine - alzheimers
-
How do you treat organophosphate poisoning?
Atropine + Praloxidime
-
Most common NMJ disorder. Autoantibodies to postsynaptic AChR.
Ptosis, Diplopia, Weakness worsen with muscle use
Myasthenia Gravis
-
Name the muscarinic antagonists (besides atropine) and their primary use
Benztropine - Parkinsons (Park my Benz)
Scopolamine - Motion Sickness
Ipratropium - Asthma / COPD
Oxybutynin, Glycopyrrolate, Tolterodine, Darifenacin, Solefenacin, Trospium - urinary retention
Methscopolamine - Peptic Ulcer
-
Describe the effects of Atropine
Blocks DUMBBELLS
increase dilation and cycloplegia, body temp
decrease secretions, motility and urgency in cystitis
-
What is the mnemonic for Atropine?
- Hot as a Hare
- Dry as a Bone
- Mad as a Hatter
- Red as a Beet
- Blind as a Bat
- Bloated as a Toad
-
When is atropine contraindicated?
- BPH
- Hyperthermia
- Glaucoma
- Delirium
- Ileus/Obstruction
-
What group of genes are responsible for skeletal development?
HOX genes
-
- 1 - Vesamicol
- 2 - Hemicholinium
- 3 - Acetyl Co A
- 4 - Ca2+
- 5 - Botulinim Toxin (flaccid paralysis)
- 6 - Black widow spider Toxin
- 7 - Choline Acetyltransferase
-
- 1 - tyrosine hydroxylase
- 2 - Metyrosine
- 3 - Reserpine
- 4 - Guanethidine (stops vesicle release)
- 5 - Amphetamines, Ephedrine, Tyramine (increases NE release)
- 6 - Cocaine, amphetamines, TCA's (prevent reuptake)
-
Describe Gq pathways
Phopholipase C -> PIP2 ->
a) IP3 -> increase Ca2+ intracellular -> Ca2+ binds calmodulin -> activate CaM kinase
b) DAG -> activate protein kinase C
-
Tyrosine kinase receptors are associated with what?
Growth factors
-
What enzymes are used in the catabolism of NE?
COMT - methylates
MAO - oxidizes
then excrete in urine
-
- 1 - dorsal root ganglion
- 2 - dorsal horn (sensory)
- 3 - lateral horn
- 4 - ventral horn (motor)
- 5 - ventral root
- 6 - white communicating rami (toward dot)
- 7 - grey communicating rami
- 8 - sympathetic ganglion
-
Name the sympathomimetic drugs, their primary receptor and their primary function.
Epinephrine - A1, A2, B1, B2 - anaphylaxis, glaucoma
Norepinephrine - A1, A2, B1 - Septic Shock - but reflex brady!
Isoproterenol - B1, B2 - AV block (reflex tachy)
Dopamine - A1, A2, B1, B2, D1 - Cardiogenic Shock
Dobutamine - B1 - Cardiogenic Shock
Phenylephrine - A1, A2 - nasal decongestion
Metaproterenol and Albuterol - B1 and B2 - asthma
Salmeterol - B1 and B2 - long term asthma
Terbutaline - B1 and B2 - reduce premature contractions
Ritodrine - B2 only - reduce premature contractions
-
Name the indirect sympathomimetics and their primary function.
Amphetamine - Narcolepsy, ADD, Obesity
Ephedrine and Tyramine- nasal decongestion, urinary incontinence
Cocaine - vasoconstriction
-
Name the sympathoplegics and their primary function.
Clonidine and a-methyldopa - a2 agonists - HTN with renal disease.
-
What drug do you give hypertensive pregnant women?
a-methydopa
-
Name the nonselective alpha blockers and their primary receptor and use.
Phenoxybenzamine - A1 and A2 - pheochromocytoma
Phentolamine - A1 and A2 - HTN crisis (MAO inhibitors eating tyramine foods)
-
Name the a1 blockers and their primary use.
Prazosin, Terazosin, Doxazosin - HTN, Urinary retention in BPH
-
This drug class has 1st dose hypotension
A1 blockers
-
Name the a2 blockers and their primary use.
Mirtazapine - depression for elderly (increases sleep and appetitie)
-

Describe what happens after alpha blockade with phentolamine (non selective alpha blocker):
 - B2 vasodilation is unopposed - reversal of blood pressure change
-

Describe what happens after alpha blockade with phentolamine (non selective alpha blocker):
 - No B effects means suppression, but not reversal
-
Name the B1 selective Beta Blockers
A BEAM
- Acebutolol
- Betaxolol
- Esmolol
- Atenolol
- Metoprolol
-
Name the effects of Beta Blockers and applications for use:
HTN - decrease cardiac output and renin secretion
Angina - decrease heart rate and contractility
MI - decrease mortality
SVT - decrease AV conduction (propranolol and esmolol)
CHF - ONLY CHRONIC
Glaucoma - decrease secretion of aqueous humor
-
What B blocker would you give for thyroid storm?
Propranolol
-
What are the common side effects of B Blockers?
- sedation
- impotence
- exacerbation of asthma
- bradycardia
- AV block
- increased blood glucose
-
What patients should be given B blockers with CAUTION?
- diabetics
- asthmatics
- CHF
- Cocaine users
-

What is Km? What is Vmax?
Km - the amount of substrate needed to get 1/2 Vmax.
A low Km means the enyzme loves the substrate. Just eating that shit up.
Vmax = maximum velocity (how fast is substrate bindind enzyme)
-

What is a noncompetitive inhibitor?
Doesn't bind active site - therefore, doesn't compete.
Noncompetitive inhibitors are in no hurry because they have no competition, so they bring Vmax and efficiency DOWN.
-
Competitive or Noncompetitive?
Resembles substrate
Binds active site
Increases Km
Decreases potency
Competitive Inhibitor
-
Name the 4 equations you need to know for pharmacokinetics.
1) Vd = amount of drug in body/ plasma drug concentration
2) Cl = 0.7 x Vd / T1/2
3) Ld = Cp x Vd
4) Md = Cp x Cl
-

What order elimination?
Zero order
-

What order elimination?
First order
-
Vmax or Km?
Potency
Km
amount of drug needed for a given effect
-
Vmax or Km?
Efficiency
Vmax - maximal effect a drug can produce
-

Describe what happens to Km
Right shift = less potent
Km increases
-

Describe what happens to Vmax
Down shift - Vmax decreases
less efficient
-

Describe what happens to Vmax and Km
Left shift and down shift - Km increases, Vmax decreases
Less efficient, more potent
-
Therapeutic Index: give formula and explain
Ld50/Ed50
lethal dose/ effective dose = therapeutic index
high index = safer
-
Name 4 drugs with low therapeutic index
- Warfarin
- Phenobarbital
- Lithium
- Digoxin
- Anti-seizure drugs too
-
What drug do you use to treat benzo overdose?
Flumenazil
-
What are 3 drugs that have zero order elimination?
-
Ionized species are trapped and eliminated easily. What do you treat a weak acid drug overdose with?
a base
Bicarb
-
Ionized species are trapped and eliminated easily. What do you treat a weak base drug overdose with?
an acid
Ammonium Chloride
-
Phase I metabolism describes what 3 processes?
- Hydrolysis
- Oxidation
- Reduction
"HOR" - Cytochrome P450 is Phase I
-
Phase II metabolism describes what three processes?
- Glucuronidation
- Acetylation
- Sulfation
"GAS" - Geratric patients lose Phase I and rely on this, they are Gassy.
-
Name the P450 Inducers:
MAGIC RACKS
- Macrolides (Erythromycin)
- Amiodarone
- Grapefruit
- Isoniazid
- Cimetidine
- Ritonavir
- Acute Alcohol
- Cipro
- Ketoconazole
- Sulfonamides
-
Name the P450 Inhibitors
Queen Barb Steals Phen Phen and Refuses Greasy Carbs
- Quinidine
- Barbiturates
- St John's Wart
- Phenytoin
- Rifampin
- Griseofulvin
- Carbamazepine
Chronic Alcohol Use
-
What is the general biproduct of a phase I metabolism? Phase II?
Phase I - polar water soluble metabolites
Phase II - very polar inactive metabolites
-
What overdose can be treated with bicarb? With ammonium chloride?
Bicarb - Aspirin OD
Ammonium Chloride - Amphetamine OD
-
Describe the steps in ethanol metabolism
ethanol -> alcohol dehydrogenase -> acetaldehyde -> acetaldehyde dehydrogenase -> acetate
-
What drug inhibits alcohol dehydrogenase? When would you use it?
Fomepizole
Antidote for methanol or ethylene glycol poisoning
-
What drug inhibits acetaldehyde dehydrogenase?
Disulfiram
discourage alcohol abuse
-
Drug suffix: ane
inhaled anesthetics
-
Drug suffix: azine
Phenothiazines
-
Drug suffix: ipramine
TCA's
-
Drug suffix: oxin
cardiac glycoside
-
Drug suffix: tidine
H2 blockers
-
Drug suffix: dronate
bisphosphonates
-
Drug suffix: mustine
nitrosureas
-
Drug suffix: caine
local anesthetics
-
Drug suffix: cycline
protein synthesis inhibitors (tetracyclines)
-
Drug suffix: phylline
methlyxanthines
-
Drug suffix: terol
B2 agonists
-
Drug suffix: triptyline
TCA's
-
-
Drug suffix: stigmine
indirect muscarinic agonist
-
Drug suffix: curonium
paralytic, non depolarizing NMJ blocker
-
Drug suffix: glitazone
TZD's (diabetes)
-
Drug suffix: dipine
CCB's (dihydropyridines)
-
Name the Sulfa Drugs
PSST FACTS!
- Probenecid
- Sulfasalazines
- Sulfonylureas
- Thiazides
- Furosemide
- Acetazolamide
- Celecoxib
- TMP-SMX
- Sumatriptan
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