Drugs for fungal infections, head lice, hyperhidrosis, hair growth and pigmentation - Sweatman Flashcards
what is the unique, significnat adverse effect of ketoconazole use that were the subject of a recent FDA article?
Adrenal insufficiency - ketoconazoles ability to disrupt steroid synthesis
what are 2 common adverse effects shared by all azoles
Hepatotoxicity
Drug-drug interactions via CYP interactions
what are 3 BBW associated with Itraconazole use? Why does it carry these?
Heart Failure
Ventricular dysfunction
Co-administration with drugs (CYP)
Itraconazole produces negative inotropic effects on the heart
Are azoles safe in pregnancy?
no
Are azoles safe in breast feeding?
no - potential of the drug to pass to infant
which azoles produce QT prolongation?
Fluconazole, Psoaconazole, Voriconazole
Which azole are you worried about visual disturbances due to optic neuritis?
Voriconazole
Which azole are you worried about photosensitization of skin?
Voriconazole
which azole must be administered with a full meal for adequate bioavailability?
Posaconazole
This is a potential test question
You have a pt that has a fungal infection and renal failure - what azole can you not give, or at least need to dose adjust?
Fluconazole
most azoles are extensively hepatically metabolized, but fluconazole is metabolized and eliinated renally
which azoles have access to CSF?
Fluconazole and Voriconazole
What is the MOA of Griseofulvin?
binds microtubules, disrupts the mitotic spindle - thus inhibits fungal growth
what is the effect of Griseofulvin on CYP?
it is a CYP3A4 inducer (azoles are inhibitors)
is Griseofulvin safe in pregnancy?
no
What drug allergy in a pt would make you not want to give Griseofulvin?
Penicillin allergy
commonality in structure with Beta lactams
What is the MOA of Terbinafine and Naftifine (allylamines)?
inhibit squalene epoxidase, a step in ergosterol synthesis
is terbinafine safe in pregnancy?
yes
what precautions do you need to take with Terbinafine?
CBCs and LFTs
what is an important point about the allylamines and azoles in combination therapy?
both classes work to block ergosterol incorporation into fungal cell walls - there is no gain in combining the two classes
what is the route of delivery for Ciclopirox and Amorolfine?
TOPICAL ONLY
for review only, what is the MOA of azoles? what enzyme do they inhibit?
inhibit the cytochrome P450 enzyme sterol 14 demethylase
blocks production of ergosterol
for review only, what is the MOA of capsofungin (and Echinocandin)
inhibits 1,3-B-glucan synthase
results in disruption of cell wall integrity
for review only, what is the MOA of amphotericin B?
binds ergosterol and creates pores in the fungal cell membrane
what is the general mechanism used to treat hyperhidrosis?
anti-cholinergics
from the CNS, what causes activation of Eccrine (thermoregulatory) sweat glands?
sympathetic innervation with Ach as neurotransmitter, rather than customary NE
(the nerves innervating eccrine, or thermoregulatory, sweat glands are sympathetic cholinergic nerves, this is unique)
so an M2 student has sweaty armpits in anticipation of being pimped by Sweatman in class (eh, eh?) what is the post-synaptic neuro-effector receptor responsible for the sweating?
Muscarinic M2
the nerves innervating eccrine, or thermoregulatory, sweat glands are sympathetic cholinergic nerves, this is unique
what are the affects of cholinergic agonists or AchE inhibitors? what is the pneumonic?
DUMBBELS Diarrhea Urination Miosis/muscle weakness Bronchorrhea Bradycardia Emesis Lacrimation Salivation/sweating
what is first line treatment for hyperhidrosis (i.e. early stages)
start with general antiperspirants, such as aluminum chloride
what is second line treatment for hyperhidrosis (i.e. no response to antiperspirants)?
botulinum toxin
what is the treatment modality (3rd line) used for hyperhidrosis if there is no response to botulinum toxin?
systemic anticholinergics
or surgery with sympathectomy
what is the MOA of Aluminum Chloride
short-term occlusion of eccrine and apocrine sweat gland ducts
What is the MOA of botulinum toxin
cleaves SNARE proteins, prevents fusion of vesicle containing Ach and the presynaptic membrane - prevents Ach release into the cleft
what is a rare but impt BBW associated wiht Botulinum Toxin
systemic botulism is rare, but reported
for systemic anti-muscarinic therapy used for the treatment of hyperhidrosis, what type of drugs and what drug names do we want to choose, and why
we want to choose drugs that cannot cross the BBB, so as to not cause anti-muscarinic sedation and delirium
need quaternary ammonium compounds
glycopyrrolate, propantheline
what drugs can you use to diminish the central emotionally impacted sympathetic causation of sweating
propranolol (beta blocker) or clonidine (a2 agonist)
what are the two general divisions of head lice treatment types?
chemical and physical
in general, what is the effect of chemical methods to treat head lice
result in paralysis of louse and result in its demise from dehydration
in general, what is the effect of physical methods to treat head lice
suffocation of the little shits
Malathion - MOA and what does it treat?
AchE inhibitor
Chemical method to treat head lice
What should you admin in the event that Malathion is ingested (instead of applied topically, as indicated)
use atropine
muscarinic antagonist to help reduce the Ach overstimulation caused by Malathion
Permethrin - MOA and what does it treat?
blocks volt gated Na channels - slows and stops nervous system activity
chemical method to treat head lice
(also first line for scabies)
Ivermectin - MOA and what does it treat?
binds glutamate receptors gating chloride - leads to hyperpolarization of cell
also may act as agonist for GABA
used to treat head lice, and is a broad spectrum antiparasitic agent
In broad generalities, what is your approach to treatment of head lice? what all do you need to eradicate and how many treatments?
more than one treatment may be necessary in order to eradicate all adult and nit louse
What is the mechanism of resistance by lice to the chemical agents?
typical mechanisms common to other drugs
decreased concentration at target, increased rate of inactivation / removal, point mutations in targets
i.e. knock down resistance from point mutations in targets like the volt gate sodium channel (permethrin target)
What is dimethicone? what is it used to treat? what is its MOA?
a mechanical (physical) methd of lice treatment
it is a silicon based polymer that lubricates hair and aids in removal of lice and nits
and causes suffocation of lice
what is Air Alle, what is it used to treat?
mechanical treatment of hair lice, application of heat causes dehydration of louse leads to death
what drug treats hair conditions by inhibiting 5-alpha dihydrotestosterone production?
Finasteride (propecia)
what drug used for the treatment of hair conditions requires activation by UV light
Methoxsalen
What drugs block the production of melanin when used to treat hair conditions?
hydroquinone, Tretinoin
what is the danger of the practice of scalp cooling? (used to prevent alpecia following CTX)
preservation of scalp micrometastases
what is the MOA of minoxidil?
it is a potent oral vasodilator - mechanism of topical application leading to hypertrichosis is unknown
you are thinking about prescribing Finasteride (propecia) to somebody with alopecia; what herbal supplement do you need to ask them if they are taking, because it acts by a similar mechanism as finasteride
Saw Palmetto - used for BPH
what is a potential, debilitating side effect of Finasteride or saw palmetto?
sexual dysfunction / infertility
what is Eflornithine used to treat?
topical drug to reduce unwanted female facial hair growth
What is the MOA of Eflornithine used to treat unwanted female facial hair
inhibits ornithine decarboxylase - a mandatory step in polyamine production - causes decreased cell division and differentiation
what else, besides unwanted female facial hair growth, can Eflornithine be used to treat?
given IV, is trypanostatic - employed in tx of sleeping sickness
what 3 drug regimen is used in the treatment of melasma, or facial skin darkening caused by hormonal changes, prgnancy, OCs or HRT?
Fluocinolone, Hydroquinone, Tretinoin
what is the MOA of Fluocinolone? (part of 3 drug regimen to treat melasma)
anti-inflammatory corticosteroid
what is the MOA of Hydroquinone? (part of 3 drug regimen for melasma)
inhibits melanin formation, blocking melanocyte enzymatic oxidation of tyrosine to DOPA
what is the MOA of tretinoin? (part of 3 drug regimen for melasma?)
modulates skin growth and pigmentation
it is a retinoid, so it just does retinoid things
when on the 3 drug regimen for melasma Fluocinolone, Hydroquinone, Tretinoin, what do pts need to be cautioned about
increased sensitivity to UV, protection is necessary
What is the MOA of Methoxsalen? used to treat a number of different skin conditions
activated by exposure to UV light
conjugation and cross-linking of DNA - cell death
in cases of CTX induced alopecia, regrowth often occurs, via stem cells located where in the hair follicle
stem cells located in the bulge
what is the mechanism of CTX induced hair loss
apoptotic cell death, a result of dec BCL2, and inc Bax and p53
