Pharmacology8-2 Flashcards
What is the mechanism of action for a benzodiazepine?
Benzo’s bind to the GABA-A receptor-chloride channels in the CNS and increase the frequency at which they open.
This results in: (1) anxiolytic (2) anticonvulsant (3) muscle relaxant & (4) sedative-hypnotic effects
Glanzmann thrombasthenia is a rare bleeding disorder that typically presents in childhood with mucocutaneous bleeding. Peripheral blood smear would show no platelet clumping. What type of anti-coagulation drugs most closely mimic Glanzmann thrombasthenia?
Individuals with GT lack a functional glycoprotein IIb/IIIa platelet surface receptors. Anti-coagulant drugs that block the GPIIb/IIIa receptor (i.e Abciximab) would most closely resemble this illness.
Treatment:
Mycobacterial infection in a patient on HAART
Rifabutin
Typically, rifampin is used for mycobacterial infections; however, in patients concurrently taking a protease inhibitor, rifampin is contraindicated due to it’s ability to induce the activity of P-450. Rifampin would result in decreased serum levels of protease inhibitor.
What are the shared side effects of protease inhibitors?
(-avir)
- Lipodystrophy
- Hyperglycemia
- Inhibition of P-450
Each protease inhibitor has additional side effects. For example, idinavir also causes nephrotoxicity and nephrolithiasis.
Which organisms are not covered by cephalosporins?
The LAME ones. (1) Listeria (2) Atypicals (chlamydia & Mycoplasma) & (3) Enterococci
Mechanism of Action:
Penicillins
- covalently bind the active site of transpeptidase
- prevent crosslinking of peptidoglycan cell wall
- weak cell wall integrity causes osmotic lysis of the bacterium
Penicillins are structural analogs of D-Ala-D-Ala.
Diagnosis:
Your patient has a history of schizophrenia, treated with risperidone, and presents with (1) breast tenderness & (2) no menstrual periods for 3 months
Drug induced amenorrhea
Risperidone is an atypical antipsychotic. Many antipsychotics cause hyperprolactinemia due to their anti-dopaminergic actions
Pathogenesis:
Risperidone induced amenorrhea
- Risperidone is an antipsychotic with anti-dopaminergic actions.
- Decreased dopamine releases the inhibitory break on prolactin production.
- Excess prolactin will shut down the HPA axis, preventing the production of GnRH, LH & FSH.
Why might you consider prescribing a beta blocker to a patient on a anti-psychotic?
Anti-psychotic medications have some side effects: (1) Extrapyramidal side effects (2) Tardive dyskinesia & (2) Neuroleptic malignant syndrome. The beta-blocker would be helpful for a patient experiencing akathisia, a extrapyramidal side effect.
What the extrapyramidal side effects associated with anti-psychotic usage?
(1) Extrapyramidal side effects: acute dystonic reaction, akathisia & drug-induced parkinsonism
(2) Tardive dyskinesia
(3) Neuroleptic malignant syndrome
Mechanism of Action:
Carbamazepine
blocks voltage gated Na channels in cortical neurons
Side effects: (1) Bone marrow suppression (2) hepatoxicity & (3) SIADH
Carbamazepine may be used to treat: (1) simple partial (2) complex partial & (3) tonic-clonic seizures
Treatment:
Status epilepticus
- IV lorazepam (simultaneously load phenytoin)
- Phenobarbital if refractory
- Intubation and general anesthesia if still refractory
Function:
Phenytoin
Phenytoin inhibits neuronal firing by reducing the ability of the sodium channels to recover from inactivation. Thus, at high frequency firing rates, the neuron is refractory to reactivation an seizure activity is reduced.
Why are benzodiazepines first line therapy for status epilepticus over phenytoin?
Benzodiazepines have a rapid onset of action. Phenytoin takes approximately 15 minutes.
Name that antifungal!
Alters the fungal cell membrane composition by inhibiting the demethylation of lanosterol into ergosterol
(-azoles) Ketoconazole, fluconazole, itraconazole, voriconazole
This drugs also increase the serum concentration of drugs metabolized by liver P-450 enzymes like: warfarin, cyclosporine, tacrolimus, phenytoi, isoniazid, rifampin, oral hypoglycemics and others.
Name that antifungal!
Causes pore formation and ultimately lysis by binding ergosterol in the fungal cell membrane
Polyene antifungals (i.e. Amphotericin B & nystatin)
Name that antifungal!
Decreases the synthesis of ergosterol by inhibiting the fungal enzyme squalene-2, 3, epoxidase
Terbinafine
Terbinafine is used to treat dermatophytoses as it accumulates in the skin and nails.
Name that antifungal!
Inhibits fungal mitosis by binding polymerized microtubules and disrupting the fungal mitotic spindle
Griseofulvin
Griseofulvin is only effective for dermatophytosis because it accumulates in the skin and appendages.
How do cholinomimetics affect the smooth muscle tone of the detrusor muscle in the bladder?
Cholinomimetics would cause contraction of the detrusor muscle and promote urination.
Which anticonvulsant is most commonly used for seizure prophylaxis?
Valproate (Valproic acid)
What drug is indicated to treat (1) major depression (2) obsessive-compulsive disorder & (3) anxiety disorders?
Sertraline (SSRI)
Do not prescribe sertraline to a bipolar person. It may induce mania.
Mechanism of Action:
Valproate
- Blocks Na channels
- Enhances GABA synthesis and release
How would a muscarinic agonist affect the GI sphincter?
Muscarinic AGONISTS will increase tone in the visceral smooth muscle (i.e. GI tract). This promotes motility and GI secretions.
An anticholinergic drug would relax the GI wall and increase the contraction of the sphincters to cause constipation. (sympathetic activity slows down the GI tract!)
How would a muscarinic agonist affect the peripheral blood vessels?
- Endothelial cells have muscarinic receptors that when activated promote NO release (aka endothelium-derived relaxing factor/EDRF)
- NO activates guanylate cyclase
- intracellular cGMP is increased
- cGMP activates a Ca pump that causes Ca efflux from the cells
- Decrease in calcium concentration causes vascular wall smooth muscle relaxation
Name that antifungal!
Prevents fungal cell wall formation by blocking synthesis of 1,3-beta-D-glucan
Caspofungin and other echinocandin antifungals
1,3-beta-D-glucan is the main component of Candida and Aspergillus cell walls.
Name that antifungal!
Inhibits fungal DNA and RNA synthesis by replacing uracil with 5-fluorouracin in fungal mRNA.
Flucytosine (antimetabolite that is transformed into 5-fluorouracil in the fungal cell)
Flucytosine is often used with Amphotericin B to produce a synergistic response. This treatment is commonly used for cryptococcal meningitis.
What are the most signifcant side effects of metformin treatment?
- Gastrointestinal upset
- Lactic acidosis
In what subset of patients would metformin be contraindicated?
Patients with renal failure due to the increased risk of lactic acaid accumulation.
It is also contraindicated in patients with liver dysfunction, congestive heart failure, alcoholism and sepsis.
What type of antidote would you give to a patient suffering from cyanide poisoning?
Oxidizing nitrite agents, like amyl nitrite.
Nitrities cause methemoglobinemia, which avidly binds cyanide. This consumption of cyanide by methemoglobin reduces cyanides ability to bind iron-containing enzymes like cytochrome a-a3, a complex critical for electron transport during oxidative phosphorylation.
Diagnosis:
(1) decreased visual acuity
(2) central scotoma
(3) color blindness
optic neuritis due to ethambutol toxicity
Mechanism of Action:
Ethambutol (antimycobacterial)
- inhibits carbohydrate polymerization (arabinose to arabinan to arabinogalactan; via arabinosyl transferase)
- prevents peptidoglycan cell wall synthesis
What are the adverse effects of ethambutol therapy?
- hepatotoxicity (all antimycobacterial agents)
- ototoxicity
What is the ONLY antituberculous drug that inhibits mycolic acid synthesis?
Isoniazid
Reflex sympathetic activation (i.e. tachycardia and edema) is an adverse effect seen with which type of antihypertensive medications?
Direct arteriolar vasodilators (i.e. hydralazine and minoxidil) cause significant arterial vasodilation and reflex sympathetic activation.
What additional drugs might you administer to a patient receiving hydralazine to prevent reflex sympathetic activation?
Sympatholytics or diuretics
Hydralazine is a direct arteriolar vasodilator that can lead to tachycardia and edema due to reflex sympathetic activation.
Your patient is a burn victim with an oxidase-positive, non-lactose fermenting pathogen infection in his skin tissue. Which penicillin or cephalosporin drugs can you give to treat this patient?
(1) penicillin: ticarcillin, piperacillin
(2) cephalosporins: ceftazidime, cefepime
Note, you can also give aminoglycosides, fluoroquinolones (ciprofloxacin, levofloxacin) and carbapenems (imipenem, meropenem).
Your patient is a 24-year-old female with low energy, decreaes appetite, 8lb weight loss in one month and insomnia. Her mother has a history of “mood swings”. This patient clearly seems depressed. Should you give her Venlafaxine?
You might, but be aware that venlafaxine is an SNRI antidepressant that has an increased risk of mood switches into mania in patients with undiagnosed bipolar disorder. This patients family history suggest that she may have bipolar. If the patient becomes manic you might want to consider a mood stabilizer and discontinue the use of anti-depressants.
Which antidote would you administer to reverse organophosphate stimulation of BOTH muscarinic and nicotinic cholinergic receptors?
Pralidoxime, is the ONLY medication that can reverse the muscarinic and nicotinic effects of organophosphates. Atropine will only reverse the muscarinic effects. Thus if you administer atropine to a patient with organophosphate poisoning they will still be at risk for muscle paralysis due to increase spastic activity.
Mechanism of action:
Niacin
Niacin inhibits VLDL production (i.e. Cholesterol –> VLDL). It is often prescribed to increase HDL.
Which cholesterol lowering medication upregulates LDL receptors by inhibiting cholesterol synthesis?
Statins inhibit cholesterol synthesis in the hepatocytes (i.e. acetyl-CoA –> cholesterol). This upregulates LDL receptors on the liver cell membrane.
Which medication is superior to aspirin in the treatment of peripheral arterial disease?
Cilostazol, a phosphodiesterase inhibitor. Cilostazol has two functions: (1) inhibition of platelet aggregation & (2) direct arterial vasodilation.
What physiological effect is common to the following:
1. Atropine
2. TCA
3. H1 receptor antagonists
4. Neuroleptics
5. Antiparkinsonian drugs
antimuscarinic effects (eg flushed skin, mydriasis)
antimetabolite drug that is similar to folic acid
methotrexate
Which enzyme is inhibited by methotrexate
dihydrofolate reductase
Function:
Methotrexate
Competitively inhibits dihydrofolate reductase from synthesizing tetrahydrofolate. Thus, dihydrofolic acid polyglutamate accumulates in the tissues
Why are sulfonamide drugs selective for prokaryotes?
Sulfonamide drugs are para-aminobenzoic acid analogues. They block dihydropteroate synthetase from converting PABA into folic acid. Humans lack the ability to convert PABA into folic acid. Their folate is accquired from the diet. Thus, sulfonamide antibiotics selectively kill bacteria.
Function:
Sulfonamide antibiotics
prevent bacterial replication by blocking the dihydropteroate synthesase conversion of PABA to folic acid.
Treatment of choice for early (
Methotrexate
Rescue therapy for cancer patients receiving MTX and other types of chemotherapy
Folinic acid (leucovorin)
Leucovorin can be used to synthesize purines and thymidylate without first being converted by DHF.
List the 8 drugs that can increase the risk of osteoporosis.
Aromatase inhibitors-Decrease estrogen
Medroxy progesterone-Decrease estrogen
GnRH agonists-Decrease testosterone and estrogen
Anticonvulsants (CYP450 inducers: phenobarbital, phenytoin, carbamazepine)- Increase Vit D catabolism
Proton pump inhibitors-Decrease calcium absorption
Glucocorticoids-Decrease bone formation
Unfractionated heparin-Decrease bone formation
Thiazolidinediones-Decrease bone formation
Which receptor types use Gs, Gq & Gi 2nd messenger systems?
Q=alpha-1, M1, M3, H1, V1
S=beta-1, beta-2, D1, H2, V2
I=alpha-2, M2, D2
Kiss (Qiss) and kick (qiq) until you are sick (siq) of super quinky sex (sqs). [a,b,m, d, h, v]
How would the log dose-response curve be affected if a reversible competitive antagonist were added to a pure agonist?
- Right shift: the pure agonist drug would need to be present in higher concentrations to reach the same efficacy (ED50)
- Potency (or height) of the log dose-response curve would be unaffected (Emax)
Clinical Manifestation:
Atropine poisoning (mneumonic)
“Blind as a bat, mad as a hatter, red as a beet, hot as a hare, dry as a bone, the bowel and bladder lose their tone, and the heart runs alone.”
