3/15 pharm Flashcards
Clearance can be impaired w/defects in which systems?
cardiac, renal, hepatic.
Clearance
-equation:
Cl = (rate of elim of drug)/(plasma drug conc.) Cl = (Vd)*(Ke) Cl = (Q)*(Er)
Q = flow to that organ (ie. liver) Er = extraction ratio
Loading dose
-equation
Loading dose = (Cp)(Vd) / (F)
Cp = target plasma concentration at steady state F = bioavailability
Maintenance dose (MD) -equation
MD = (Cp)(Cl)(t) / F
t = dosage interval (time between doses), if not administered continuously.
*If continuous, leave t out. You will also know its IV so F = 1. B/c only IV is continuous.
In liver or renal disease, does maintenance dose inc. or dec.?
Dec.
-less being cleared, so less dose needed.
Which drugs follow zero-order elimination?
-mnemonic?
-Phenytoin, Ethanol, and Aspirin (at high or toxic concentrations).
-PEA. (A pea is round, shaped like the “0” in
“zero-order.”)
Capacity-limited elimination
-0 or 1st order?
0 order elim.
Flow-dependent elimination
-0 or 1st order?
1st order elim.
Phase I drug metabolism
P450 system
-Reduction, oxidation, hydrolysis.
Phase II drug metabolism
Conjugation (Glucuronidation, Acetylation, Sulfation)
Which is most common P450 enzyme?
CYP3A4 = most common
Name 3 drugs that might cause trouble in a slow acetylator.
-which would also have a bimodal pop. distribution.
- hydralazine, isoniazid, procainamade
* HIP: its not hip to be a slow acetylator.
What kind of antagonist is ketamine?
-ketamine (noncompetitive antagonist) on NMDA receptors.
Therapeutic index:
-equation:
TI = Toxic dose/Effective dose
*high therapeutic index is good b/c that means theres a big difference btwn toxic and effective doses.
Whats good, a high or low therapeutic index?
High.
-Safer drugs have higher TI values.
Is the therapeutic index the same as therapeutic window?
No, b/c the therapeutic window would never extend all the way until the toxic dose.
Some receptors that respond to autonomic neurotrasmitters/drugs receive NO nerve innervation (must get ligand through blood).
-can you name these uninnervated autonomic receptors?
- muscarinic receptors on endothelium of blood vessels
- adrenoreceptors on apocrine sweat glands
- alpha-2 and beta adrenoreceptors in blood vessels.
para/pre, sym/pre: all release what?
ACh
All ganglia have what type of receptor?
Nicotinic: ligand-gated ion channels.
Do all sym/post release NE?
NO
- adrenal medulla releases NE and epi.
- sym/post release ACh that innervate sweat glands & piloerector muscles. These = sympathetic cholinergic.
sympathetic cholinergic
sym/post that releases ACh
-innervate sweat glands & piloerector muscles.
All glands have what receptors on them?
muscarinic
-even sweat glands that have sym/post innervation: these sym/posts dump ACh, not NE (sympathetic cholinergic).
adrenal medulla & sweat glands = part of sym nervous system but are innervated by _______ fibers.
cholinergic
Nicotinic ACh receptors
-what type of receptor is it?
-ligand-gated Na/K channels.
which receptors are more sensitive to activation, alpha or beta?
beta
Epi: acting more on alpha1 or beta2?
- low dose =
- high dose =
- low dose - acts more on beta-2
- high dose - acts more on alpha-1
*remember, beta-receptors are more sensitive.
Ciliary muscle innervation:
- muscarinic
- its NOT dual innervated.
*if there is an effect on accomodation, its a muscarinic (agonist or antagonist) drug
Cycloplega = what is it, what can cause it?
paralysis of ciliary muscles = M-antagonist
Gs => inc. cAMP => PKA => phosphorylates MLC kinase.
-whats the result?
smooth muscle relaxation
-hence beta-2 (Gs) causing smooth muscle relaxation in lungs.
Hemicholinium
- mech:
- use:
- Prevents reuptake of choline so you have less in nerve terminal so you make less ACh and release less ACh.
- NO CLINICAL USE.
NMJ
-what kind of receptor?
nicotinic, ACh.
Reserpine
- inhibit vesicular monoamine transporter (VMAT); limit dopamine vesicle packaging and release.
- used in huntingtons.
guanethidine
- like botulinum but for NE.
* not clinically used
Where do you find AChE?
- AChE is only found in the synpatic cleft.
- Not everywhere you find a M or N receptor.
*that means AChE inhibitor can not vasodilate b/c endothelial cell M3 receptors are not innervated = no synaptic cleft.
Can AChE inhibitors vasodilate?
- AChE is only found in the synpatic cleft.
- Not everywhere you find a M or N receptor.
*that means AChE inhibitor can not vasodilate b/c endothelial cell M3 receptors are not innervated = no synaptic cleft.
M agonists
-give pattern of what type of lung disease?
-obstructive, like COPD.
What an effect you can see via cholinomimetic drugs that you dont see w/parasym. nerve stimulation?
sweating
-b/c sweat glands have sym innervation but release ACh at the sweat glands M3 receptor.
Is bethanechol resistant or sensitive to AChE?
- resistant to AChE.
- not the same exact structure as ACh so its not broken down by AChE!
Someone at movie and gets intense pain in their eyes.
-They’re in a dark room, their pupils dilate, the angle gets smaller, and this precipitates their glaucoma
Administer _______ to Cystic Fibrosis pt to get sweat so you can do sweat test
pilocarpine
Pilocarpine is resistant or sensitive to AChE?
resistant, just like bethanechol.
-not exactly the same structure as ACh so AChE doesn’t break it down.
myasthenic crisis
not enough ACh
cholinergic crisis
too much ACh
-can resemble myasthenic crisis
Which receptors do AChE inhibitors act at?
muscarinic & nicotinic
atropine OD
-which AChE inhibtor can you give?
- physostigmine bc atropine gets into CNS and so does physostigmine.
- physostigmine = a tertiary amine = not charged, lipid soluble.
Myasthenia Gravis
- how was it historically Dx?
- how is it Dx now?
-historically: edrophonium.
-Myasthenia now diagnosed by anti-AChR Ab (anti-
acetylcholine receptor antibody) test.
What to watch out for before giving cholinomimetic?
COPD, asthma, peptic ulcers.
parathion
organophosphate
-irreversible AChE inhibtor.
sarin
organophosphate
-irreversible AChE inhibtor.
*nerve gas
organophosphate poisoning
-Tx:
-atropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early).
why isn’t atropine enough for organophosphate poisoning tx?
Atropine is a muscarinic antagonist.
- it is NOT a nicotinic antagonist!
- Nicotinic toxicity is treated by regenerating active cholinesterase w/pralidoxime.
Which one gets desensitized, muscarinic or nicotinic?
nicotinic
- muscarinic does NOT get desensitized.
- succinylcholine acts on nicotinic.
Glycopyrrolate
- mech:
- use:
muscarinic antagonist
- Parenteral: preoperative use to reduce airway secretions.
- Oral: drooling, peptic ulcer.
Atropine
-uses:
Used to treat bradycardia & for ophthalmic applications.
ACh
-its excitation of skeletal muscle & CNS mediated via which receptor?
nicotinic
Jimson weed
-what effects?
- atropine poisoning if you consume Jimson weed.
- aka Belladonna alkaloids.
hexamethonium, mecamylamine
- what are they?
- use?
- nicotinic (ganglion) blockers
- They will be used in problems b/c they block baroreflex changes in heart rate.
- If you use these you WIPE OUT the ANS, b/c all ganglia use Nn receptors.
- just remember what the predominant tone on the system is at rest, and cancel out that tone.
What resting tone does our heart have?
PARA
Epi
-low dose effects:
- B/c beta receptors are more sensitive, you will get primarily a beta response with a low dose of epi.
- THIS IS KEY. At low dose acts like isoproterinol (nonselective beta agonist).
Epi
-medium dose
- alpha-1 gets involved.
- alpha-1 and beta-2 antagonize each other.
- so at medium dose epi looks like a beta-1 agonist. (like DOPUTAMINE, a selective beta-1 agonist)
Epi
-high dose
- alpha-1 will PREDOMINATE.
- You will vasoconstrict and get inc. BP.
- You will get tachy OR reflex brady. This looks just like NE.
*you can not distinguish NE and high dose EPI in cardiac parameters.
NE vs high dose epi.
-differences:
- If it bronchodilates, inc. lipolysis, inc. glycogenolysis, or inc. gluconeogenesis; then it MUST be EPI,
- beta-2 does these things and NE does NOT act on beta-2.
How do you unmask beta-2 action of epi?
- give an alpha-1 blocker.
- alpha 1 is opposing beta-2.
Can NE, under any circumstances, reduce BP?
NO
Can epi, under any circumstances, reduce BP?
Yes, but only at low dose where beta-2 is activated but alpha-1 is not.
Isoproterenol
-what does it do to pulse pressure?
nonselective beta-agonist.
- inc inotropy = inc systolic.
- inc vasodilation = dec diastolic
- inc. pulse pressure.
cardiac stress testing
-which drug is used?
dobutamine
terbutaline
- mech:
- use:
- beta-2 agonist
- reduce premature uterine contractions
beta agonist
-can they cause hypo or hyperkalemia?
hypokalemia
-inc activity of Na/K pump which brings K into cells.
name some mobile pool releasers
tyramine, amphetamine, ephedrine.
Ephedrine
- mech:
- use:
- releases stored catecholamines.
- Nasal decongestion, urinary incontinence, hypotension.
Cocaine intox
-should you give beta-blockers?
- No.
- you never want to risk having unopposed alpha-1 action by blocking beta-2.
- can get hypertensive crisis.
amphetamine & cocaine
-predominantly the inc. in which chemical leads to addiction?
dopamine
Clonidine
-uses
-ADHD, severe pain, and a variety of off-label indications (e.g., ethanol and opioid withdrawal).
Whats the only anti-HTN drug w/approved analgesic use?
clonidine
phentolamine vs phenoxybenzamine
-which one is irreversible?
phenoxybenzamine = irreversible
-both =nonselective alpha blockers
Give ________ to patients on MAO inhibitors who eat
tyramine-containing foods
phentolamine
Can tamulosin also be used for HTN like other alpha-1 blockers?
-No, tamulosin more specific for smooth muscle in urinary tract.
Mirtazapine
- mech:
- use:
- s/e:
- alpha-2 blocker
- depression
- inc appetite, inc serum cholesterol, sedation.
Beta-blocker OD
-tx:
glucagon
- beta-1 & beta-2 both = Gs, they inc. cAMP.
- glucagon also = Gs, so it inc. cAMP as well.
beta-blockers
-can you use in a diabetic?
-Despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweigh risks; not contraindicated
beat-blocker
-s/e:
- Impotence
- CV adverse effects
- CNS adverse effects (seizures, sedation, sleep alterations)
- dyslipidemia (metoprolol)
- asthmatics/COPDers (may cause exacerbation)
beta-1 selective blockers
-mnemonic?
A to M
non-selective beta-blockers
-mnemonic?
N to Z
pindolol
-why is it better to use in asthmatics?
- partial non-selective agonist.
- it will also have some sympathetic effects, like slightly bronchodilating for instance.
beta-blockers
-which ones are non-selective ALPHA & beta blockers?
- carvedilol, labetalol
* dont end w/”olol”.
Nebivolol
-what is unique about it?
Nebivolol combines cardiac-selective β1-adrenergic blockade with stimulation of β3-receptors, which activate nitric oxide synthase in the vasculature.
Which drugs can cause cutaneous flushing?
-mnemonic?
VANC
-Vancomycin, Adenosine, Niacin, Ca2+ channel
blockers.
Which drugs can cause Hyperglycemia?
-mnemonic?
Taking Pills Necessitates Having Blood Checked
- Tacrolimus
- Protease inhibitors
- Niacin
- HCTZ
- β-blockers
- Corticosteroids
Which drugs can cause hypothyroidism?
Lithium, amiodarone, sulfonamides
Which drugs can cause diarrhea?
-mnemonic?
Might Excite Colon On Accident
- Metformin
- Erythromycin
- Colchicine
- Orlistat
- Acarbose
Lanugo
- what is it?
- what disease is it seen in?
Fine body hair
-anorexia nervosa
Parotitis
-bulimia or anorexia?
Both
-there is binge/purge type of anorexia.
Does calcium bind troponin or tropomyosin?
-troponin C
Prominent U wave
-hypo or hyperkalemia?
hypokalemia
what happens to haptoglobin-Hb complex?
its hepatically cleared
Winged scapula
-common causes?
- mastectomy surgery & accidentally nick the long thoracic nerve.
- stab wounds.
clavicular fx
-where in clavicle?
middle 1/3
ACL & PCL
-connect which two bones?
tibia & femur
ACL & PCL
-which one more commonly injured?
ACL
ACL or PCL
-which one attaches to medial condyle of femur?
PCL
*anterior lateral surface of medial epicondyle of femur.
ACL or PCL
-which one attaches to the lateral condyle of femur?
ACL
*post. medial lateral femoral condyle.
Where on femur does PCL attach?
medial condyle of femur.
Where on femur does ACL attach?
lateral condyle of femur.
Septic arthritis
- usually due to what?
- how do u treat it?
gonococcus
-ceftriaxone
How does colchicine reduce acute inflammation of gouty arthritis?
inhibits neutrophil migration into inflamed areas.
Which vitamin D is created upon exposure to sun?
D3 = cholecalciferol
Major cause of morbidity in sarcoidodis?
pulm. fibrosis.
medial or lateral cruciate ligament attached to its corresponding meniscus?
MCL.
Ligation of sup. thyroid art:
-which nerve at risk?
-external branch of superior laryngeal n.
Ligation of inf. thyroid art:
-which nerve at risk?
-recurrent laryngeal n.
