Pharmacokinetics and Autonomic Drugs Flashcards
1
Q
what is bioavailability?
A
- bioavailability (F) = % of administered drug reaching systemic circulation unchanged
2
Q
when is bioavailability usually 100%?
A
F=100% for an IV dose
3
Q
why is bioavailability usually less than 100% for an oral drug?
A
due to incomplete absorption and first pass metabolism
4
Q
what is volume of distribution (Vd)?
A
- amount of drug in the body / [drug] in the plasma
5
Q
compartment and drug types when low volume of distribution
A
- compartment: blood
- drug types: large/charged molecules; plasma protein bound
6
Q
compartment and drug types when medium volume of distribution
A
- compartment: ECF
- drug type: small hydrophilic molecules
7
Q
compartment and drug types when high volume of distribution
A
- compartment: all tissues including fat
- drug type: small lipophilic mcs, especially if bound to tissue protein
8
Q
what is the equation for half life for a first order elimination?
A
t1/2=0.693 x Vd / CL
9
Q
what is clearance (CL)?
A
- volume of plasma cleared of drug per unit time
- may be impaired with defects in cardiac, hepatic, or renal function
- CL=(rate of elimination of drug / plasma drug concentration) = Vd x Ke
- Ke= elimination constant
10
Q
what is loading dose?
A
loading dose = Cp x Vd / F
Cp = target plasma concentration at steady state
11
Q
what is maintenance dose?
A
maintenance dose = Cp x CL x t / F
Cp = target plasma concentration at steady state
t = dosage interval (time b/w doses), if not administered continuously
12
Q
maintenance dose and loading dose in renal or liver disease
A
- maintenance dose decreases
- loading dose is usually unchanged
13
Q
what does the time to steady state depend on?
A
- half life
- independent of dose and dosing frequency
14
Q
what is the difference between zero order elimination and first order elimination?
A
- zero order–rate of elimination is constant regardless of Cp
- constant amount of drug eliminated per unit time
- Cp dec linearly with time
- first order–rate of elimination is directly proportional to drug concentration
- constant fraction of drug elminated per unit time
- Cp dec exponentially with time
- applies to most drugs
15
Q
which drugs are zero order?
A
-
PEA–a pea is round shaped like the “0” in zero order
- Phenytoin
- Ethanol
- Aspirin
16
Q
what are weak acid drugs?
where do they get trapped?
how do you treat overdose?
A
- phenobarbital, methotrexate, aspirin
- trapped in basic environments
- treat overdose with bicarbonate
17
Q
what are weak base drugs?
where do they get trapped?
how do you treat overdose?
A
- amphetamines
- trapped in acidic environments
- treat overdose with ammonium chloride
18
Q
what are phase 1 types of drug metabolism?
what enzyme do they require?
what do they yield?
what occurs in geriatric patients?
A
- reduction, oxidation, hydrolysis
- require cytochrome P 450
- yield slightly polar, water soluble metabolites
- geratric patients lose phase I first
19
Q
what are phase 2 type of drug metabolism?
what do they yield?
A
- conjugation–Methylation, Glucuronidation, Acetylation, Sulfation
- geriatric patients have More GAS (phase 2)
- yields very polar, inactive metabolites (renally excreted)
20
Q
what occurs in patients who are slow acetylators?
A
- have increased side effects from certain drugs b/c of decreased rate of metabolism
21
Q
effect of competitive antagonist on receptor binding
A
- shifts curve right (decreased potency)
- no change in efficacy
- can be overcome by increasing the concentration of agonist substrate
22
Q
effect of noncompetitive antagonist on receptor binding
A
- shift curve down (decrease efficacy)
- cannot be overcome by inc agonist substrate concentration
23
Q
effect of partial agonist (alone) on receptor binding
A
- acts at same site as full agonist, but with lower maximal effect (dec efficacy)
- potency is an independent variable
24
Q
what is the therapeutic index?
A
- measurement of drug safety
-
Therapeutic Index = TD50/ED50 = median toxic dose / median effective dose
- TITE
- safer drugs have higher TI values
- drugs with lower TI values frequently require monitoring
- therapeutic window–dosage range that can safely and effectively treat dz
25
alpha 1 receptor:
type of receptor
G protein class
major functions
* sympathetic
* q
* functions:
* inc vascular smooth muscle contraction
* inc pupillary dilator muscle contraction (mydriasis)
* inc intestinal and bladder sphincter muscle contraction
26
alpha 2 receptor:
type of receptor
G protein class
major functions
* sympathetic
* i
* functions:
* dec sympathetic (adrenergic) outflow
* decrease insulin release
* dec lipolysis
* inc platelet aggregation
* dec aqueous humor product
27
beta 1 receptor
type of receptor
G protein class
major functions
* sympathetic
* s
* functions:
* inc heart rate
* inc contractility
* inc renin release
* inc lipolysis
28
beta 2 receptor:
type of receptor
G protein class
major functions
* sympathetic
* s
* functions:
* vasodilation
* bronchodilation
* inc lipolysis
* inc insulin release
* dec uterine tone (tocolysis)
* ciliary muscle relaxation
* inc aqeuous humor production
29
beta 3 receptor:
type of receptor
G protein class
major functions
* sympathetic
* s
* functions:
* inc lipoysis
* inc thermogenesis in skeletal muscle
30
M1 receptor
type of receptor
G protein class
major functions
* parasympathetic
* q
* functions:
* CNS
* enteric nervous system
31
M2 receptor
type of receptor
G protein class
major functions
* parasympathetic
* i
* functions:
* dec heart rate
* dec contractility of atria
32
M3 receptor
type of receptor
G protein class
major functions
* parasympathetic
* q
* functions:
* inc exocrine gland secretions
* lacrimal, sweat, salivary, gastric acid
* inc gut peristalsis
* inc bladder contraction
* bronchoconstriction
* inc pupillary sphincter muscle contraction (miosis)
* ciliary muscle contraction (accommodation)
33
D1 receptor
type of receptor
G protein class
major functions
* dopamine
* s
* functions:
* relaxes vascular smooth muscle
34
D2 receptor:
type of receptor
G protein class
major functions
* dopamine
* i
* functions:
* modulate transmitter release, especially in brain
35
H1 receptor:
type of receptor
G protein class
major functions
* histamine
* q
* functions:
* inc nasal and bronchial mucus production
* inc vascular permeability
* contraction of bronchioles
* pruritus
* pain
36
H2 receptor:
type of receptor
G protein class
major functions
* histamine
* s
* functions:
* increase gastric secretion
37
V1 receptor:
type of receptor
G protein class
major functions
* vasopressin
* q
* functions:
* inc vascular smooth muscle contraction
38
V2 receptor:
type of receptor
G protein class
major functions
* vasopressin
* s
* functions:
* inc water permeability and reabsorption in collecting tubules of kidney
* "V2 is found in **2** kidneys"
39
how to remember G protein linked 2nd messengers
"After **qiss**e**s** (kisses), you get a **qiq** (kick) out of **siq** (sick) **sqs** (super kinky sex).
40
tyramine--mechanism
* normally degraded by monoamine oxidase (MAO)
* levels inc in patients taking MAO inhibitors who ingest tyramine rich foods (ie. cheese, wine)
* excess tyramine enters presynaptic vesicles and displaces other neurotransmitters (ie. NE) --\> inc active presynaptic neurotransmitters --\> inc diffusion of neurotransmitters into synaptic cleft --\> inc sympathetic stimulation
41
what does tyramine classically cause?
hypertensive crisis
42
name the 4 direct cholinomemetic agonists
* bethanechol
* carbachol
* methacholine
* pilocarpine
43
**bethanechol**--mechanism
* activates **b**owel and **b**ladder smooth muscle
* resistant to AChE
* "**Bethany call (bethanchol)** me to activate your **b**owels and **b**ladder."
44
bethanechol--use
* postoperative ileus
* neurogenic ileus
* urinary retention
45
**carbachol**--mechanism
* **carb**on copy of **a**cetyl**chol**ine
46
carbachol--use
* constricts pupil and relieves intraocular pressure in open angle glaucoma
47
**m**ethacholine--mechanism
* stimulates **m**uscarinic receptors in airway when inhaled
48
methacholine--use
* challenge test for diagnosis of asthma
49
**pilo**carpine--mechanism
* contracts ciliary muscle of eye--open angle glaucoma
* pupillary sphincter--closed angle glucoma
* resistant to AChE
* "You cry, drool, and sweat on your **pilo**w"
50
pilocarpine--use
* potent stimulator of sweat, tears, saliva
* open angle and closed angle glaucoma
* xerostomia--Sjorgren syndrome
51
name the 7 indirect cholinomimetic agents (anticholinesterases)
* donepezil
* galantamine
* rivastigmine
* edrophonium
* neostigmine
* physostigmine
* pyridostigmine
52
donepezil, galantamine, rivastigmine--mechanism
* inc ACh
53
donepezil, galantamine, rivastigmine--use
* Alzheimer disease
54
edrophonium--mechanism
* inc ACh
55
edrophonium--use
* historically, diagnosis of myasthenia gravis--extremely short acting
* myasthenia now diagnosed by anti AChR Ab (anti acetylcholine receptor antibody) test
56
**neo**stigmine--mechansm
* inc ACh
* "**Neo** CNS = **No** CNS penetration (quaternary amine)
57
neostigmine--use
* postoperative and neurogenic ileus and urinary retention
* myasthenia gravis
* reversal of neuromuscular junction blockade--postoperative
58
physostigmine--mechanism
* inc ACh
* "**Phy**sostigmine '**phy**xes' atropine overdose"
59
physostigmine--use
* anticholinergic toxicity
* crosses blood brain barrier --\> CNS (tertiary amine)
60
pyridostigmine--mechanism
* inc ACh
* inc muscle strength
61
pyridostigmine--use
* myasthenia gravis (long acting)
* "Py**rid**osti**gm**ine gets **rid** of **m**yasthenia **g**ravis"
* does not penetrate CNS--quaternary amine
62
what is important to watch for when administering any cholinomimetic agents?
* exacerbation of COPD
* asthma
* peptic ulcers
63
what causes cholinesterase inhibitor poisoning?
* often due to organophosphates, such as parathion, that *irreversibly* inhibit AChE
64
in which population is cholinesterase inhibitor poisoning usually seen and why?
* farmers b/c organophosphates are often components of insecticides
65
what does cholinesterase inhibitor poisoning cause?
* **D**iarrhea
* **U**rination
* **M**iosis
* **B**ronchospasm
* **B**radycardia
* **E**xcitation of skeletal muscle and CNS
* **L**acrimation
* **S**weating
* **S**alivation
* "**DUMBBELSS**"
* may lead ot respiratory failure if untreated
66
what is the antidote for cholinesterase inhibitor poisoning?
* atropine (competitive inhibitor) + pralidoxime (regenerates AChE if given early)
67
name the muscarinic antagonists
* atropine, homatropine, tropicamide
* benztropine
* glycopyrrolate
* hyoscyamine, dicyclomine
* ipratropium, tiotropium
* oxybutynin, solifenacin, tolterodine
* scopolamine
68
atropine, homatropine, tropicamide--organ system and use
* eye
* produce mydriasis
* produce cyclopegia
69
benztropine--organ system and use
* CNS
* **Park**inson dz
* "**park** my **B****enz**"
* acute dystonia
70
glycopyrrolate--organ system and use
* GI
* drooling
* peptic ulcer
* respiratory
* preoperative use to reduce airway secretions
71
hyoscyamine, dicyclomine--organ system and use
* GI
* antispasmodics for irritable bowel syndrome
72
ipratropium, tiotropium--organ system
* respiratory
* COPD
* asthma
* "**I pra**y I can breathe soon"
73
oxybutynin, solifenacin, tolterodine--organ system and use
* genitourinary
* reduce bladder spasms
* urge urinary incontinence
* overactive bladder
74
scopolamine--organ system and use
* CNS
* motion sickness
75
atropine--drug class and use
* muscarinic antagonist
* used to treat bradycardia and for ophthalmic applications
76
what is the action of atropine on the eyes?
* increase pupil dilation
* cycloplegia
77
what is the action of atropine on the airway?
* decreased secretions
78
what is the action of atropine on the stomach?
* decreased acid secretion
79
what is the action of atropine on the gut?
* decrease motility
80
what is the action of atropine on the bladder?
* decreased urgency in cystitis
81
atropine and cholinesterase inhibitor poisoning
* blocks **DUMBB**e**LSS** in cholinesterase inhibitor poisoning
* diarrhea
* urination
* miosis
* bronchospasm
* bradycardia
* lacrimation
* sweating
* salivation
* DOES NOT block excitation of skeletal muscle and CNS
* mediated by nicotinic receptors
82
atropine--toxicity
* incresed body **temperature**--due to dec sweating
* rapid pulse
* dry mouth
* **dry, flushed skin**
* **cycloplegia**
* constipation
* **disorientation**
* ****"**Hot** as a hare"
* **"Dry** as a bone"
* "**Red** as a beet"
* "**Blind** as a bat"
* "**Mad** as a hatter"
* can cause acute angle closure glaucoma in elderly due to mydriasis
* can cause urinary retention in men with prostatic hyperplasia
* can cause hyperthemia in infants
83
name the direct sympathomimetics
* albuterol, salmeterol
* dobutamine
* dopamine
* epinephrine
* fenoldopam
* isoproterenol
* midocrine
* norepinephrine
* phenylephrine
84
albuterol, salmeterol--mechanism
* beta 2 \> beta 1
85
albuterol, salmeterol--use
* albuterol for acute asthma or COPD
* salmeterol for long term asthma or COPD control
86
dobutamine--mechanism
* beta 1 \> beta 2, alpha
87
dobutamine--use
* heart failure (HF) -- inotropic \> chronotropic
* cardiac stress testing
88
dopamine--mechanism
* D1 = D2 \> beta \> alpha
89
dopamine--use
* unstable bradycardia
* HF
* shock
* inotropic and chronotropic effects at lower doses due to beta effects
* vasoconstriction at high doses to alpha effects
90
epinephrine--mechanism
* beta \> alpha
91
epinephrine--use
* anaphylaxis
* asthma
* open angle glaucoma
* alpha effects predominate at high doses
* significantly stronger effect at beta2 receptors than norepinephrine
92
fenoldopam--mechanism
* D1
93
fenoldopam--use
* postoperative hypertension
* hypertensive crisis
* vasodilator--coronary, peripheral, renal, splanchnic
* promotes natriuresis
94
fenoldopam--toxicity
* hypotension
* tachycardia
95
isoproterenol--mechanism
* beta1 \> beta2
96
isoproterenol--use
* electrophysiologic evaluation of tachyarrhythmias
* can worsen ischemia
97
midodrine--mechanism
* alpha1
98
midodrine--use
* autonomic insufficiency
* postural hypotension
99
midodrine--toxicity
* may exacerbate supine hypertension
100
norepinephrine--mechanism
* alpha1 \> alpha2 \> beta1
101
norepinephrine--use
* hypotension
* septic shock
102
phenylephrine--mechanism
* alpha1 \> alpha2
103
phenylephrine--use
* hypotension (vasoconstrictor)
* ocular procedures (mydriatic)
* rhinitis (decongestant)
104
name the indirect sympathomimetics
* amphetamine
* cocaine
* ephedrine
105
amphetamine--mechanism
* indirect general agonist
* reuptake inhibitor
* releases stored catecholamines
106
amphetamine--use
* narcolepsy
* obesity
* ADHD
107
cocaine--mechanism
* indirect general agonist
* reuptake inhibitor
108
cocaine--use
* causes vasoconstriction and local anesthesia
109
what to remember about cocaine intoxication?
* never give beta blockers
* can lead to unopposed alpha1 activation and extreme hypertension
110
ephedrine--mechanism
* indirect general agonist
* releases stored catecholamines
111
ephedrine--use
* nasal decongestion
* urinary incontinence
* hypotension
112
norepinephrine vs. isoproterenol
* norepinephrine inc systolic and diastolic pressures as a result of alpha1 mediated vasoconstriction --\> inc mean arterial pressure --\> reflex bradycardia
* isoproterenol--not commonly used anymore
* has little alpha effect but causes beta2 mediated vasodilation --\> dec mean arterial pressure and inc heart rate thru beta1 and reflex activity
113
name the sympatholytics alpha2 agonists
* clonidine, guanfacine
* alpha methyldopa
114
clonidine, guanfacine--use
* hypertensive urgency (limited situations)
* ADHD
* tourette syndrome
115
clonidine, guanfacine--toxicity
* CNS depression
* bradycardia
* hypotension
* respiratory depression
* miosis
116
alpha methyldopa--use
* hypertension during pregnancy
117
alpha methyldopa--toxicity
* direct Coombs + hemolysis
* SLE like syndrome
118
name the non-selective alpha blockers
* phenoxybenzamine (irreversible)
* phentolamine (reversible)
119
phenoxybenzamine--use
* pheochromocytoma (used preoperatively) to prevent catecholamine (hypertensive) crisis
120
phenoxybenzamine--toxicity
* orthostatic hypotension
* reflex tachycardia
121
phentolamine--use
* give to patients on MAO inhibitors who eat tyramine containing foods
122
phentolamine--toxicity
* orthostatic hypotension
* reflex tachycardia
123
name the alpha1 selective alpha blockers
* -osin ending
* Prazosin, terazosin, doxazosin
* tamsulosin
124
Prazosin, terazosin, doxazosin--use
* urinary symptoms of BPH
* PTSD--prazosin
* hypertension
125
Prazosin, terazosin, doxazosin--toxicity
* 1st dose orthostatic hypotension
* dizziness
* headache
126
tamsulosin--use
* urinary symptoms of BPH
127
tamsulosin--toxicity
* 1st dose orthostatic hypotension
* dizziness
* headache
128
name the alpha2 selective alpha blockers
* mirtazapine
129
mirtazapine--use
* depression
130
mirtazapine--toxicity
* sedation
* inc serum cholesterol
* inc appetite
131
alpha blockade of epinephrine vs. phenylephrine
* effects of an alpha blocker like phentolamine on blood pressure responses to epinephrine and phenylephrine
* epinephrine response exhibits reversal of the mean blood pressure change, from a net inc (alpha response) to a net decrease (beta 2 response)
* the response to phenylephrine is suppressed but not reversed b/c phenylephrine is a "pure" alpha agonist w/o beta action
132
name the beta blockers
* acebutolol
* atenolol
* betaxolol
* carvedilol
* esmolol
* labetalol
* metoprolol
* nadolol
* nebivolol
* pindolol
* propranolol
* timolol
133
beta blockers--use
* angina pectoris
* MI
* SVT (metoprolol, esmolol)
* hypertension
* HF
* glaucoma (timolol)
* variceal bleeding (nadolol, propranolol)
134
how do beta blockers work for angina pectoris?
* dec heart rate and contractility
* results in dec O2 consumption
135
how do beta blockers work for MI?
* dec mortality
136
how do beta blockers work for SVT?
* only metoprolol, esmolol
* dec AV conduction velocity
* class II antiarrhythmic
137
how beta blockers work for hypertension?
* dec cardiac output
* dec renin secretion
* due to beta1 receptor blockade on JGA cells
138
how do beta blockers work for HF?
* dec mortality
* with bisoprolol, carvedilol, metoprolol
139
how do beta blockers work for glaucoma?
* only timolol
* dec secretion of aqueous humor
140
how do beta blockers work for variceal bleeding?
* only nadolol, propranolol
* dec hepatic venous pressure gradient and portal hypertension
141
beta blockers--toxicity
* erectile dysfunction
* cardiovascular adverse effects--bradycardia, AV block, HF
* CNS adverse effects--seizures, sedation, sleep alterations
* dyslipidemia
* with metoprolol
* asthma/COPD exacerbations
142
beta blockers and cocaine users
* use with caution in cocaine users due to risk of unopposed alpha-adrenergic receptor agonist activity
143
beta blockers and diabetics
* despite theoretical concern of masking hypoglycemia in diabetics, benefits likely outweight the risks
* NOT contraindicated
144
name the beta1 selective antagonists (beta1 \> beta2)
* **a**cebutolol--partial agonist
* **a**tenolol
* **b**etaxolol
* **e**smolol
* **m**etoprolol
* "selective antagonists mostly go from **A** to **M**--beta1 with **1**st half of alphabet"
145
name the non selective antagonists (Beta1 = beta2)
* **N**adolol
* **P**indolol--partial agonist
* **P**ropranolol
* **T**imolol
* **N**onselective antagonists mostly go from **N** to **Z**--beta2 with **2**nd half of alphabet
146
name the nonselective alpha and beta antagonists
* carvedilol
* labetalol
* both have modifed suffixes--instead of "-olol"
147
nebivolol--selectivity
* combines cardiac selective beta1 adrenergic blockade with stimulation of beta3 receptors which activate nitric oxide synthase in the vasculature
148
name the 3 ingested seafood toxins
* tetrodotoxin
* ciguatoxin
* histamine--scombroid poisoning
149
tetrodotoxin--source
* pufferfish
150
tetrodotoxin--mechanism
* highly potent toxin
* binds fast voltage gated Na channels in cardiac/nerve tissue
* prevents depolarization
151
tetrodotoxin--symptoms
* nausea
* diarrhea
* paresthesias
* weakness
* dizziness
* loss of reflexes
152
tetrodotoxin--treatment
mostly supportive
153
ciguatoxin--source
* reef fish such as barracuda, snapper, moray eel
154
ciguatoxin--mechanism
* opens Na channels which causes depolarization
155
ciguatoxin--symptoms
* symptoms mimic cholinergic poisoning
156
ciguatoxin--treatment
primarily supportive
157
histamine (scombroid poisoning)--source
* spoiled dark meat fish such as tuna, mahi mahi, mackerel, bonito
158
histamine (scombroid poisoning)--mechanism
* bacterial histidine decarboxylase converts histidine to histamine
* frequently misdiagnosed as a fish allergy
159
histamine (scombroid poisoning)--symptoms
* mimics anaphylaxis:
* acute burning sensation of mouth
* flushing of face
* erythema
* urticaria
* itching
* may progress to:
* bronchospasm
* angioedema
* hypotension
160
histamine (scombroid poisoning)--treatment
* antihistamines
* albuteral and epinephrine if needed
